anger and anxiety in patients with primary...

ANGER AND ANXIETY IN PATIENTS WITH PRIMARY ALDOSTERONISM TREATED WITH AMILORIDE HYDROCHLORIDE OR SPIRONOLACTONE OR

ADRENALECTOMY.

Robin Sherill Armstrong. RN, Dip. App. Sci. (Nsg Edn), BHSc.(Nsg) Institute of Health and Biomedical Innovation

School of Public Health Queensland University of Technology.

Thesis for Master of Applied Science (Research) 2007.

Robin S Armstrong M App Sci Thesis 2

Abstract

Background

In Primary Aldosteronism (PAL) excessive amounts of aldosterone cause sodium

and water retention and, in many individuals, this leads to moderate to severely high

blood pressure. Although the chemistry and physiology are increasingly well

understood, including the outcomes of treatment on physical health, there has been

no systematic study of the psychological dimension of PAL. Anecdotally, patients

exhibit symptoms such as angry outbursts, irritability, anxiety and defensiveness, and

partners of these patients sometimes mention poor anger control and brittle or

unpredictable moods. This thesis reports a systematic study of anger and anxiety

among patients undergoing treatment for PAL.

Eighty-three patients were recruited over an 11-month period to a prospective, pre-

post design study to determine if treatment was associated with change in

psychological state.

Method

Participants completed the State-Trait Anger Expression Inventory (STAXI-2),

State-Trait Anxiety Inventory (STAI) and Psychosocial Adjustment to Illness Scale

(PAIS) questionnaires. Adrenal Vein Sampling confirmed overproduction of

aldosterone in one or both adrenal glands. Patients with Aldosterone Producing

Adenoma (APA) were offered adrenalectomy. As per usual treatment protocols,

patients with Bilateral Adrenal Hyperplasia (BAH) were prescribed spironolactone or

amiloride depending predominantly on severity of blood pressure and potassium


levels. Post-test questionnaires were completed after 6-8 months. Analysis was by

mixed design (between-within subjects) ANOVA.

Participant numbers in the adrenalectomy group fell far short of expectations.

Fourteen past patients who had undergone unilateral adrenalectomy completed a

retrospective semi-structured questionnaire. This qualitative data was analysed to

identify themes similar to quantitative data.

Results

At baseline, ‘non-completers’ (ie those who did not complete the post-test; n=19),

were significantly more angry than ‘completers’ (n=50) in State Anger (p< .01), Trait

Anger (p< .05) and Anger Expression Index (p< .001). Trait Anxiety was also higher

(p< .05), as was Psychological Distress (p< .05).

Among those who participated at both interviews, there was small but statistically

significant adverse treatment effect with higher scores for State Anger (p< .05), and

Feeling Angry (p< .05). However for Trait Anger (p< .01), and 2 of its 3 sub-scales

Angry Temperament (p< .05) and Angry Reaction (p< .01) there was a slight to

moderate decrease in negative affect with treatment. Psychological Distress scores

also improved (p< .05). Across all ANOVAs, there were no significant interaction

effects, suggesting that any treatment effect was equivalent for the two drugs.

Qualitatively collected data elucidated participants’ changes in approach to life and

relationships since adrenalectomy. Themes that emerged in the data included

improved ability to cope with external stress, better control of emotions, more

relaxed relationships and attitude to work, and a greater vitality and quality of life.


Generally the comments were consistent with the drug treatments; there was

noticeable benefit, including perceived better anger control and less anxiety.

Conclusions

Positive psychological effects of treatment observed in the two drug groups were

triangulated with data from a qualitative study. The combined evidence suggests that

when excess circulating aldosterone is reduced (adrenalectomy), or blocked

(spironolactone), or aldosterone’s salt and water retaining effects are minimised

(amiloride), then nervous irritability and its subsequent psycho-behavioural

manifestations are reduced. The effect however is slight and the conclusions are

weakened by an apparent attrition bias, and the absence of a control group.

Implications for further research are discussed.


Table of Contents Chapter 1: Introduction and Literature Review. 12

Rationale for the study. 18

Evolution of the quantitative study. 19

Objectives. 22

Chapter 2: Method (Study 1). 23

Rationale for this study 23

Null Hypothesis 25

Design. 25

Sample. 25

Measurement. 33

Procedures. 38

Statistical analysis. 40

Ethical considerations. 41

Chapter 3: Results (Study 1). 42

Discussion. 57

Conclusion. 61

Chapter 4: Qualitative inquiry into the effects of adrenalectomy (Study 2).

Patient perceptions of behavioural, emotional, physical

And lifestyle change, 6-24 months post-adrenalectomy

for aldosterone producing adenoma: A qualitative study.

Introduction. 63

Method. 64

Analysis. 69

Results. 71

Discussion (Study 2). 81


Chapter 5: Conclusion. The combined quantitative and

qualitative study. 85

Reference list. 88

Appendix 1: Psychometric Analysis - modified STAI – Form Y. 96

Appendix 2: Qualitative Study questionnaire. 112


List of Tables and Figures. Chapter 2: Method (Study 1)

Table 2.1: Descriptive characteristics of participants in spironolactone and

amiloride groups at baseline ___________________________________________30

Table 2.2: Concomittant medication use by participants in spironolactone and

amiloride groups at baseline. __________________________________________ 32

Table 2.3: Scale and sub-scale definitions taken from STAXI-2 Professional

Manual (Spielberger, 1996).___________________________________________ 35

Chapter 3: Results (Study 1)

Table 3.1: Comparison at baseline of mean State Anger and Mean State Anxiety

scores of participants who subsequentlydid complete (completers) and did not

complete (non-completers) the post-test questionnaire. ______________________42

Table 3.2: Comparison at baseline of mean Trait Anger and mean Trait Anxiety

scores of participants who subsequently did complete (completers) and did not

complete (non-completers) the post-test questionnaire. ______________________43

Table 3.3: Comparison at baseline of mean Anger Expression and mean Anger

control scores of participants who subsequently did complete (completers) and did

not complete (non-completers) the post test questionnaire. ___________________44

Table 3.4: Comparison of mean PAIS baseline scores for participants who did or did

not complete the post-test questionnaire. _________________________________45

Table 3.5: Comparison of treatment groups spironolactone and amiloride at

baseline.___________________________________________________________46

Table 3.6: Variables significantly differing by gender at baseline. _____________47

Table 3.7: Post-test differences in scores that were significantly different at baseline,

grouped by gender and treatment group. _________________________________47

Table 3.8: Mixed between-within analysis of variance (ANOVA). State Anger and

State Anxiety._______________________________________________________49

Figure 3.1: Change in mean State Anger scores from pre-test to post-test.________49

Figure 3.2: Change in mean Feeling Angry scores from pre-test to post-test. _____50

Table 3.9: Mixed between-within analysis of variance (ANOVA). Trait Anger,

Anger Expression, Anger Control and Trait Anxiety. _______________________ 51

Figure 3.3: Change in mean Trait Anger scores pre-test to post-test.____________52


Figure 3.4: Change in mean Angry Temperament scores pre-test to post-test._____52

Figure 3.5: Change in mean Angry reaction scores pre-test to post-test._________ 53

Table 3.10: Mixed between-within analysis of variance (ANOVA). Psychosocial

Adjustment to Illness Scale (PAIS). _____________________________________53

Figure 3.6: Change in mean (PAIS) Psychological Distress scores pre-test to

post-test. __________________________________________________________55

Table 3.11: Mixed between-within analysis of variance (ANOVA). Serum Potassium

and Systolic Blood Pressure.___________________________________________56

Chapter 4 : Qualitative enquiry into the effects of adrenalectomy

Table 4.1: Participant perceptions of their ability to cope with external stress.____73

Table 4.2: Participant perceptions of their improved emotional control. ________ 75

Table 4.3: Participant perceptions of positive changes in their spouse/partner,

family and social relationships, and work._________________________________76

Table 4.4: Participant perceptions of improvement in their vitality and quality of

life._______________________________________________________________78

Table 4.5: Participant perceptions of most important physical change. _________ 79

Table 4.6: Participant blood pressure and medications.______________________80

Appendix 1:Psychometric analysis of State-Trait Anxiety Inventory (STAI).

Table 1.1: Pre-test State Anxiety modified 8-item form. ____________________ 97

Table 1.2: Pre-test Trait Anxiety modified 8-item form. ____________________ 98

Table 1.3: Post-test State Anxiety modified 8-item form. ___________________ 98

Table 1.4: Post-test Trait Anxiety modified 8-item form. ___________________ 99

Table 1.5: Pre-test State Anxiety – same 8 items used in modified version from

participants who completed the 20-item form-Y.__________________________ 100

Table 1.6: Pre-test State Anxiety – 20-item form-Y._______________________ 101

Table 1.7: Pre-test Trait Anxiety – same 8 items used in modified version from

participants who completed the 20-item form-Y.__________________________102

Table 1.8: Pre-test Trait Anxiety –20-item form-Y ________________________103

Table 1.9: Post-test State Anxiety – same 8 items used in modified version from


Table 1.10: Post-test State Anxiety – 20-item form-Y._____________________105


Table 1.11: Post-test Trait Anxiety – same 8 items used in modified version from


Table 1.12: Post-test Trait Anxiety – 20-item form-Y._____________________107

Table 1.13: Correlation of 8-item modified scale total score with PAIS (vii)

Psychological Distress score and correlation of 20-item version with PAIS (vii)

Psychological distress score. __________________________________________108

Figure 1.1: Total score correlation of pre-test State Anxiety 1-8 with matched

PAIS (vii) item Psychological Distress.__________________________________109

Figure 1.2: Total score correlation of pre-test Trait Anxiety 1-8 with matched


Figure 1.3: Total score correlation of post-test State Anxiety 1-8 with matched


Figure 1.4: Total score correlation of post-test Trait Anxiety 1-8 with matched



Statement of Original Authorship

“The work contained in this thesis has not been submitted for a degree or

diploma at any other higher education institution. To the best of my

knowledge and belief, this thesis contains no material previously

published or written by another person except where due reference is

made.”

Signed: ………………………………………

Robin S Armstrong RN, Dip App Sci (Nsg Edn) BHSc (Nursing)

Date: …………………………………………


Acknowledgements.

Thankyou to Dr Diana Battistutta for making me think that I could do the study and

being there for my seminar presentation. Thanks to Professor Michael Dunne for

taking on my supervision though I am sure there were many times he wished he

hadn’t. Thanks for your patience and guidance and for hanging in through the ups

and downs. Many thanks also to Professor Ross Young for his unyielding optimism

and assistance over and above the call of duty. Thanks to Mr Simon Kitto for

guidance in constructing the qualitative questionnaire. Also acknowledged is the

psychological support for the underlying idea of the study given by Dr Nik Nikwan

(cardiologist) and thanks to Dr Michael Stowasser (physician) for early guidance in

the design assistance with recruitment.

Thankyou to the many patients who shared their feelings with me over the 14 years

that I worked in Hypertension, and particularly those who participated in both of the

studies. Greatly acknowledged is the assistance of the Queensland Hypertension

Association for financial help in purchase of the study questionnaires.

Thanks to Robyn Huttenmeister who didn’t mind my breaking the 5am peace of the

Brisbane river when I needed to talk about things that would have been most

uninteresting, and for her kind encouragement.

Finally and mostly, I would like to thank my husband Greg and children Ebony and

Imogen who believed in me, let me have the computer, and let me get on with it.


Anger and anxiety in patients with primary aldosteronism treated

with amiloride hydrochloride, spironolactone or adrenalectomy.

Chapter 1: Introduction and literature review.

The aim of this study was to examine anger, anxiety and quality of life in individuals

living with a form of sodium-dependent hypertension known as primary

aldosteronism (PAL) and to examine the effects of three current treatment modalities

for that condition.

Aldosterone, a hormone produced by the adrenal glands, acts via specific receptors

located in cells within the kidney, colon and sweat glands to cause these tissues to

retain sodium rather than to excrete it into the urine, faeces and sweat. In primary

aldosteronism (PAL), the adrenal glands secrete excessive amounts of aldosterone,

resulting in sodium and water retention that is excessive to the body’s needs and this

typically leads to hypertension. Studies over the last 15 years have suggested that

excessive production of aldosterone, in addition to causing hypertension, may have

adverse consequences on the cardiovascular system that are independent of its effect

on blood pressure. These include autonomic imbalance (Barr & Struthers, 1994) and

electrolyte abnormalities contributing to altered cardiac function and problems of

cardiac rhythm (Struthers, 2002), and cardiovascular remodelling and fibrosis

(Weber & Brilla, 1991). Studies conducted by Brilla and Weber (1992) on rats

administered large doses of exogenous aldosterone, demonstrated that the presence

of sodium was required for development of myocardial remodelling and fibrosis in

the aldosterone treated animals.


Within the brain, aldosterone is thought to act on neurones in centres responsible for

receiving and integrating information on electrolyte, fluid and cardiovascular status,

to bring about alterations in central sympathetic nervous system output (Gomez-

Sanchez, 1997). Zhang et al (2002) demonstrated that in Sprague Dawley rats with

ischaemia induced heart failure, the renin angiotensin aldosterone system (RAAS)

drives paraventricular nucleus neuronal activity, “likely increasing sympathetic drive

and volume accumulation”. As well, Huang et al (a, 2005) showed that intracerebral

infusion of aldosterone into Dahl salt-sensitive rats induced sympathetic

hyperactivity and hypertension. Huang and Leenen (b, 2005) in a separate study on

Wistar rats post-myocardial infarction found that blockade of mineralocorticoid

receptors (aldosterone receptor sites) and sodium channels prevented sympathetic

hyper-reactivity. These studies suggest a relationship between aldosterone, sodium

and sympathetic nervous system hyperactivity.

It is not certain if there are any psychological effects resulting from the action of

aldosterone on receptors in the brain. However, there are reasonable grounds to

expect this may be the case. For example, it is known that aldosterone levels are

raised in the luteal (premenstrual) phase of the menstrual cycle (O’Brien et al, 1980).

Many of the affective and somatic symptoms stated in the American College of

Gynaecologist’s diagnostic criteria for pre-menstrual tension (PMS) (ACOG, 2000 in

Rapkin, 2003) overlap with those observed by this investigator and by patients seen

over many years. These symptoms include depression, angry outbursts, irritability,

anxiety, social withdrawal, headache and abdominal bloating. Raised aldosterone and

salt and water retention are phenomena common to PMS and PAL.


The aetiology of premenstrual syndrome is unknown and the pathophysiology is

likely to be complex (Breckwoldt & Keck, 2002). There has been a plethora of

pharmacologic and non-pharmacologic treatments proposed over the past few

decades and some of these (low sodium diet, Vitamin B6) have been aimed at

minimising sodium and water retention in this phase of the menstrual cycle (Rapkin,

2003).

Halbreich (2003) lists the aldosterone antagonist spironolactone as an effective

treatment for PMS. In the same article however it is stated that data are conflicting

and spironolactone may be effective mostly for bloatedness and fluid related

symptoms. Burnet and colleagues (1991) in their double blind, placebo controlled,

randomised crossover study failed to find a significant difference in somatic or

neuropsychiatric symptoms of women with PMS assessed on or off spironolactone.

However, other authors have found spironolactone (an aldosterone blocker) to have a

broad effectiveness in the treatment of PMS. Significant improvement in negative

mood symptoms was demonstrated by O’Brien et al (1979) in a double blind

crossover trial over four menstrual cycles in 28 women with premenstrual syndrome

(PMS). They found that spironolactone reduced weight and relieved psychological

symptoms in more than 80% of the symptomatic group. Wang et al (1995) included

35 women with PMS in a double blind placebo controlled crossover trial. They found

that spironolactone not only reduced somatic symptom scores for breast tenderness,

feeling of swelling, and food cravings (p < .001), but also significantly (p < .001)

decreased negative mood symptom scores for irritability and depression.

Furthering the plausibility of a connection between aldosterone, sodium and water

retention and mood symptoms is more recent work in PMS and menopause with


drospirenone, a mineralocorticoid receptor antagonist and derivative of

spironolactone. Drospirenone blocks, or at least reduces, aldosterone effects on the

renin angiotensin system allowing increased sodium and water excretion which can

result in weight and blood pressure reduction. Drospirenone also appears to control

PMS (Ylikorkala, 2005).

Successful treatment of PMS and menopause is also achieved by use of drospirenone

in combination with oestrogen (Oelkers, 2004). According to Foidart (2005), the

improvements in negative affect and feelings of wellbeing attributable to

drospirenone are likely to improve treatment compliance in women suffering from

PMS and menopausal symptoms.

In the last decade, a number of studies have demonstrated behavioural changes in

“sodium sensitive” individuals challenged with sodium loading versus a placebo. A

sodium (salt) sensitive person can be described as one whose blood pressure rises

after a period of oral or parenteral sodium loading. A salt resistant person however

has no change in blood pressure with the same period and amount of sodium loading.

Deter et al (1997) recruited 16 “salt-sensitive”and 16 “salt-resistant” healthy,

normotensive (blood pressure within normal range) participants and measured their

response to mental stress. They found an increased level of irritation, a greater rise in

blood pressure and pulse wave velocity, higher levels of anxiety and lower levels of

anger control in “salt-sensitive” individuals. Bucholz et al (1999) administered

several standardised psychological questionnaires to the same cohort and found an

increased level of emotional irritation in the same “salt-sensitive” group. Deter et al

(1997) suggest from the results of their study assessing psychological reactivity in


“salt-sensitive” normotensive subjects, that psychophysiological traits may play a

role in the development of “salt-sensitive” hypertension.

An early study linking sodium and sympathetic nervous system stimulation by

Rankin et al (1981) demonstrated an increased blood pressure response to

noradrenaline infusion in normotensive (normal blood pressure) human subjects who

had been sodium loaded for 5 days. This raised the possibility that sodium loading

alters sympathetic nervous system function, and possibly other aspects of neural

activity. Hunyor and Henderson (1996) cite studies in which hypertension was not

evoked in dogs and rats in response to shock stress until a high sodium diet was

given to the rats or saline infused into the dogs, again illustrating a link between

increased blood pressure and sympathetic nervous system only after sodium was

added. Conversely, Skrabal et al (1984) demonstrated reduced cardiovascular

response to noradrenaline infusion and mental arithmetic by maintaining

normotensives (individuals with normal blood pressure) on low sodium, high

potassium diet for 4 weeks. This illustrated that the reverse could be induced and it

was thought by Scrabal and colleagues (1984) that there may be a link between

noradrenergic activity and salt sensitivity.

Light et al (1983) also found that psychological stress induced sodium and water

retention in men who had one or two parents with hypertension or, had borderline

hypertension (determined by the mean of 8 systolic seated blood pressure readings

during a one hour rest period being 140 mmHg or greater). Deter et al (1997) also

cite studies on humans, baboons, dogs and rats that suggest that behavioural stress

has an antinatriuretic (sodium retaining) effect. In this study we are exploring the

concept that if we have a sodium and water loaded state as there is in PAL, could this


be the cause of the irritability described earlier in PAL patients or is it the direct

action of aldosterone on the brain.

The association between hypertension, anger and anxiety has been the subject of

debate over many decades (van der Ploeg, 1985, Pickering, 1993). Crane (1981) in

her dissertation on “The role of anger, hostility and aggression in essential

hypertension” cites reports of case studies from as early as 1939 in which the

aggressive, hostile impulses of hypertensive patients typically appeared in

connection with anxiety. Williams et al (2003) reviewed the association between

psychosocial risk factors and cardiovascular disease and suggested that not all

components of the now devalued concept of the global Type A behaviour pattern

should be discounted. They stated that hostility was the component most associated

with coronary heart disease risk. Williams et al (2003) also cited Yan and colleagues

(2003) who studied hostility and time urgency/impatience (TUI), both components of

the Type A behaviour pattern. This prospective study of 3308 black and white young

adults (the CARDIA study) found that TUI and hostility were associated with a two-

fold increase in the incidence of hypertension in young adults (matched for age, sex,

ethnicity and education) over a 15 year period.

The evidence that overactivity of the sympathetic nervous system plays a role in

early stage development of hypertension is extensive (Pickering, 1997). However not

all individuals with hypertension are angry or anxious or pressured and not all

individuals who are angry, anxious or pressured have hypertension. It may be that

hypertension (because of common nervous system pathways) occurs in parallel with

the psychological symptoms due to sodium and water retention common to both.


Hunyor and Henderson (1996) suggested that it may be only in subsets of individuals

with hypertension that bio-behavioural factors play a significant role. The concept

that aldosterone excess may be associated with psychological function remains

largely unexplored. Aldosterone may act either directly via receptors in the brain,

indirectly through sodium and water retention or may simply effect alterations in

nervous system activity.

Rationale for this study.

Patients who have hypertension associated with primary aldosteronism appear to

exhibit more anger, irritability and emotionality than do patients with hypertension

from other causes. The experience of ward nurses who care for these patients,

patients’ family members and the patients themselves have frequently concurred with

this observation. During blood pressure self-measurement and life-style

modifications teaching sessions that include discussion of issues such as dietary salt

reduction, weight loss, exercise and stress management; many patients indicated that

they have a low threshold for stress and anxiety.

Conversely, file notations and comments from (some) patients and (some) family

members of patients, who have had surgical removal of an adrenal gland for

aldosterone-producing adenoma (APA) suggest a comparative calmness after

surgery. The need to find evidence for this clinical impression was the initial

motivation for this study. Does aldosterone either directly or indirectly through salt

and water retention, have a role in heightening the experience of psychological

symptoms of persons suffering from this condition?


The establishment of a retained sodium and water environment (as seen in PAL due

to excessive production of aldosterone through mechanisms other than stress), may

promote a heightened nervous system responsiveness or nervous irritability that

manifests as anger, anxiety and increased emotional irritability. Alternatively,

aldosterone may have an effect on the brain and nervous system independent of the

role in sodium and water retention.

The primary physiological outcome of each of the treatment modes for primary

aldosteronism is increased sodium and water excretion. Adrenalectomy for

aldosterone producing adenoma (Discussed in Chapter 4) reduces excess levels of

circulating aldosterone hence less sodium and water is retained. Spironolactone acts

by blocking aldosterone receptors thus preventing aldosterone action, again less

sodium and water is retained. Amiloride (not known to block the aldosterone

receptor) prevents reabsorption of sodium and water by inhibiting sodium channels

in the distal renal tubules (and other aldosterone responsive tissues) that have been

stimulated by aldosterone (Oberleithner et al, 2004).

By comparing the effect of amiloride with that of other treatment modalities, this

project has the potential to differentiate the role of sodium retention alone from that

of other putative effects of aldosterone excess.

Evolution of the quantitative study. The initial design of the study was to be a comparison of anger, anxiety and quality

of life outcomes of 3 treatment modalities for primary aldosteronism; spironolactone,

amiloride and adrenalectomy. Spironolactone, an aldosterone antagonist, inhibits the


action of aldosterone by blocking its receptor (Delyani et al, 2001). Amiloride

antagonises the sodium retaining effects of aldosterone by inhibiting the sodium

channels that are normally activated in response to the binding of aldosterone to the

receptor (Haddy & Pamnani, 1987). Adrenalectomy for aldosterone producing

adenoma (APA) reduces excess levels of circulating aldosterone hence less sodium

and water is retained, blood pressure is mostly (60% by 12 months) returned to

normal and potassium loss is minimised (Stowasser & Gordon, 2004). Recent

clinical loads and advice from consulting physicians suggested that one third of

patients with PAL were candidates for adrenalectomy (Stowasser et al, 2001) and

thus about 30 patients could be expected in each group.

Unfortunately the recruitment of adrenalectomy patients did not proceed as planned

and there were insufficient adrenalectomy patients to be followed over 6 months in

parallel with the other treatment modes. Recruitment to the spironolactone and

amiloride groups was quite successful. Seventeen were medicated with

spironolactone and 33 participants were medicated with amiloride, but over that time,

only 5 participants were diagnosed with unilateral aldosterone producing adenoma

(APA) and were thus potential recruits to the adrenalectomy group. This drop in

numbers was unexpected and only one of these five participants went on to have an

adrenalectomy during the period of the study. The remaining four participants with

APA chose either to delay their surgery because of social reasons or they chose

alternative treatment options. This unexpected reduction in participant numbers

necessitated an alternative method of collecting appropriate data from patients who

had undergone this method of treatment. It was not possible to collect prospective

data hence a retrospective design was developed to gather qualitative information


from patients who had undergone adrenalectomy for APA in the preceding 6-24

months. Full Ethics Committee approval was obtained for this additional study both

from the University Human Research Ethics Committee and the Ethics Committee of

the hospital where the study was conducted.

The assistance of the Director of the Hypertension Unit was sought to provide

contact details of potential participants for this study. A semi-structured

questionnaire was developed to explore anger, anxiety and quality of life, including

psycho-social and behavioural changes participants had noticed in the 6-24 months

since their adrenalectomy. A retrospective qualitative sub-study (reported in Chapter

4) was conducted to obtain data thematically comparable to that quantitatively

measured in the amiloride and spironolactone groups reported below.


Objectives.

1. To compare differences in participant’s experience of anger and anxiety as

effected by two current medical treatment modalities for primary

aldosteronism. (Chapter 3)

2. To examine the impact on quality of life by utilising the Psychosocial

Adjustment to Illness Scale (PAIS) to measure participant’s responses before

and after 6-8 months of treatment with amiloride hydrochloride and before

and after 6-8 months treatment with spironolactone. (Study 1, Chapter 3)

3. To examine patient perceptions of changes following adrenalectomy in order

to triangulate results and confirm quantitative findings with qualitative data.

(Study 2, Chapter 4)


Chapter 2: Method (Study 1)

Rationale for this study.

The principal investigator worked for many years within a specialist hypertension

investigation unit. Her clinical impression is that patients who have hypertension

associated with primary aldosteronism exhibit more anger, irritability and

emotionality than do patients with hypertension from other causes. An early thought

was that the males were exhibiting behaviour similar to that of premenstrual

syndrome. Ward nurses’ experiences supported these observations and their

descriptions of patients’ behaviour included ‘hard to handle’, ‘quick to rise’,

‘intense’, ‘emotional’ and ‘short fuse’.

When discussing their condition with the investigator, many patients used words and

phrases such as ‘impatient’, ‘fly off the handle’, ‘I get angry over nothing’, ‘my

brothers and sisters hate it’, and speak also of ’overwhelming anxiety with no due

cause’ and ‘feeling like I’m going to burst with anxiety … couldn’t explain why it

was happening or what it was that was happening … very weepy all the time… felt

angry with everyone at times’. File notations and comments from (some) patients

and family members of patients who have had an adrenalectomy (surgical removal of

an adrenal gland) for aldosterone-producing adenoma (APA) suggest a comparative

calmness after surgery. The need to find evidence for this clinical impression was the

initial motivation for this study.

The establishment of a retained sodium and water environment (as seen in PAL due

to excessive production of aldosterone through mechanisms other than stress), may

promote a heightened nervous system responsiveness or nervous irritability that


manifests as anger, anxiety and increased emotional irritability. Alternatively,

aldosterone may have an effect on the brain and nervous system independent of the

role in sodium and water retention. The primary physiological outcome of each of

the treatment modes for primary aldosteronism is increased sodium and water

excretion. Adrenalectomy for aldosterone producing adenoma reduces excess levels

of circulating aldosterone hence less sodium and water is retained. Spironolactone

acts by blocking aldosterone receptors thus preventing aldosterone action, again less

sodium and water is retained. Amiloride prevents reabsorption of sodium and water

by inhibiting sodium channels in the distal renal tubules (and other aldosterone

responsive tissues) that have been stimulated by aldosterone (Oberleithner et al,

2004). By comparing the effect of amiloride with that of other treatment modalities,

this project has the potential to differentiate the role of sodium retention alone from

that of other putative effects of aldosterone excess.

There is indirect evidence to support the hypothesis that adrenalectomy reduces

anger and anxiety. The proposed mechanisms include (1) reduced circulating

aldosterone resulting in increased excretion of excess sodium and water, or (2)

reduced circulating aldosterone resulting in stimulation of brain aldosterone

receptors. It is also hypothesised that in participants taking spironolactone,

improvement in anger and anxiety scores may be due to (1) blocking the salt-

retaining action of aldosterone thus promoting excretion of sodium and water or (2)

blocking other putative effects of aldosterone, including possible direct effects on the

brain. Improvement in anger and anxiety scores in the group treated with amiloride

which promotes sodium and water excretion (but is not known to block the

aldosterone receptor), may indicate that a salty intra or extracellular environment is


the means by which aldosterone excess promotes anger, anxiety and irritability. This

study examines outcomes from three different treatments with three distinct

mechanisms of action to see if the outcomes illuminate the nature of the bio-

behavioural interaction between aldosteronism and psychological state.

Summary of variables.

The independent (and grouping) variable is the treatment modality for PAL, either

spironolactone or amiloride. The dependent variables are anger, anxiety and quality

of life scores, serum Potassium levels and Systolic Blood Pressure.

Null Hypothesis.

Change in anger, anxiety and quality of life scores will not differ by treatment

modality (amiloride or spironolactone) for PAL.

Design.

A pre-test – post-test quasi experimental design is used to measure change in state –

trait anger, state – trait anxiety and quality of life in a cohort of patients with PAL

who are undergoing one of two treatment modalities for this condition. Hypothesis

testing is two-tailed.

Sample. Process of Recruitment.

The clinical coordinator role in the Hypertension Unit included liaising and

providing information regarding Fludrocortisone Suppression Test (FST) procedures.

Information regarding upcoming bookings for FSTs was thus readily accessible to


the principal investigator. Patients were informed about the study by phone and it

was explained that participation was voluntary. Those agreeing by phone were

invited to participate on day one of the admission for FST. Patients reaching this

stage of their diagnostic work-up have had at least two abnormal (high) aldosterone-

renin ratios (ARR). This pathological finding is an early indicator of PAL. As well,

each patient reaching this stage has been screened for all other known causes of

hypertension.

The Fludrocortisone Suppression Test (FST) is a definitive diagnostic test for PAL

(Stowasser et al, 2001). Patients are administered a synthetic form of aldosterone

(fludrocortisone) over a four day period. Fludrocortisone normally suppresses normal

adrenal production of aldosterone. Other factors that affect aldosterone production

such as potassium, sodium and posture are controlled according to a strict test

protocol. As well, the potential for stimulating adrenocorticotrophic hormone

(ACTH) is monitored by serum cortisol estimation at the same time as aldosterone,

renin and potassium samples are collected. A positive FST is one in which

aldosterone continues to be produced autonomously despite complete suppression of

renin. Renin stimulates aldosterone’s normal chronic regulator, Angiotensin II

(Stowasser et al, 2001).

Sampling Strategy and Size.

Based on figures from the previous two years there were approximately 40-60

admissions yearly to the Hypertension Unit for FST. This study aimed to recruit 90-

100 participants over 2 years. Discussions with physicians indicated that in past

years, excess aldosterone production in approximately one third of patients


(Stowasser et al, 2001) lateralised to one gland only, most commonly due to

aldosterone producing adenoma (APA).

Estimates of the occurrence of aldosterone producing adenoma (APA) were based

not only on physicians’ judgements and recent clinical workloads, but also were

consistent with the literature. International figures (Mulatero et al, 2004) provide

mixed results, as many patients do not undergo adrenal vein sampling (AVS). The

absence of this diagnostic procedure precludes diagnosis of APAs that are not

detectable on Computer Axial Tomography (CT) scan. These figures from the last

decade in four international centres suggest that the percentage of the primary

aldosterone (PAL) population that had APA confirmed by AVS to be; Torino, Italy –

30% or 18.9 per year, Rochester Minnesota – 28% or 34 patients in 1999, Brisbane,

Australia – 29.6% or 17 per year, Singapore, Republic of Singapore – 50% or 12.6

per year, and Santiago, Chile – 9.1% or 2 per year (at this centre AVS was not

performed on any patients). On this basis, it was expected that the patient recruitment

in Brisbane at that time would include about 30% of PAL patients where surgery was

appropriate. This did not occur, and the clinical staff did not have a clear explanation

of why there was such a dramatic shift.

These patients would if surgically suitable, be offered adrenalectomy. The remaining

two-thirds of patients would most commonly have bilateral adrenal hyperplasia and

thus be pharmacologically treated. Approximately one-third would receive amiloride

and one-third would receive spironolactone.


Eighty-five eligible persons were admitted for the fludrocortisone suppression test

and invited to participate in the study, two declined and 83 participants completed

the pre-test phase over an 11- month period. Thirteen participants were excluded for

not meeting protocol requirements leaving 70 participants remaining. An additional

five participants indicated that they were currently too busy or wanted to opt for

medical treatment leaving a potential cohort of 65 however, fourteen participants did

not respond to an invitation or reminder phone call or letter leaving 51 participants in

the final sample. Thirty-three participants were medicated with amiloride and 17

medicated with spironolactone.

One participant only, underwent adrenalectomy for APA. (Five participants were

actually diagnosed with APA but 4 chose other treatment options). This paucity of

participants in the adrenalectomy treatment group necessitated the development of

the retrospective qualitative study described in Chapter 4.

Inclusion criteria.

Participants were included if they had at least two, raised aldosterone-renin ratios and

progressed to a positive fludrocortisone suppression test to definitively diagnose

PAL. The aldosterone renin ratio is accepted internationally as a valid means of

successfully diagnosing Primary Aldosteronism (Brown et al 1996, Lim et al, 2002).

The use of this ratio is reported to have increased the detection of this condition from

1% to 12% of hypertensive patients (Mulatero et al 2004). In this study all

participants had had other secondary causes of hypertension excluded and ARR

performed under conditions recommended for accuracy. These conditions preclude


known factors that can cause false positives or false negatives in the ARR (Stowasser

& Gordon, 2004).

Participants were required to have an adequate understanding of English and

cognitive ability to understand and complete the questionnaires and provide informed

consent was also necessary.

Exclusion criteria.

Patients suffering from the rare hybrid gene Familial Hyperaldosteronism Type 1

(FH-I) are identified genetically. This glucocorticoid-remediable form of PAL is

treated with dexamethasone (Stowasser et al, 2001); the sub-group is rare and not

included in the study. Patients found not to have PAL by way of negative FST are

also excluded from the study. One of the 83 pre-test participants had negative FST.

Withdrawal criteria.

Participants wishing to withdraw from the study were able to do so at any time. If a

participant was to express feelings of significant distress due to answering the

questionnaires they could be withdrawn. Commencement on medications known to

affect aldosterone renin ratio was also criterium for withdrawal.

Attrition.

Nineteen participants who enrolled in the first phase of the study (pre-test) did not

respond to reminders for the follow-up phase (post-test). Of the19 non-responders

(termed ‘non-completers’ in this study), five either did not return for treatment , did


not wish to proceed to adrenal vein sampling, or chose no treatment or usual anti-

hypertensive treatment. Two were subsequently treated with spironolactone and

twelve with amiloride hydrochloride.

Characteristics of the sample.

The mean age of participants in each group is similar but gender is significantly

different across groups. Thirteen males and 4 females comprised the spironolactone

group whereas in the amiloride group there were 26 females and 7 males. There was

no gender specific reason for this as treatment is prescribed according to severity of

blood pressure and evidence of potassium wasting. Other significant differences

between the groups were in the biological variables (Table 2.1) Systolic Blood

Pressure (SBP) (p< .05) and Serum Potassium (Se K+) (p< .001).

Table 2.1: Descriptive characteristics of participants in spironolactone and amiloride groups at baseline.

spironolactone amiloride Variable n Min. Max. Mean SD n Min. Max. Mean SD DEMOGRAPHIC Age (17) 43 76 58.76 8.46 (33) 39 70 54.42 7.78 BIOLOGICAL SBP (17) 132 182 154.29* 13.5 (33) 118 174 144.42* 16.67 DBP (17) 65 105 82.00 10.5 (33) 38 110 80.30 11.41 Se K+ (17) 3.00 4.3 3.84*** 0.35 (33) 3.5 4.9 4.24*** 0.33 Se ALDO (17) 350 1640 688 304 (33) 69 1310 621 289.6 Se RENIN (17) 1.10 13.00 5.60 3.2 (33) 2.00 15.00 5.69 3.6 ARR (17) 7.07 20.98 12.24 4.35 (33) 1.95 20.78 11.28 4.04 *p < .05. **p < .01. ***p < .001. All variables not Normally distributed were transformed for analysis.


Concomittant Medication. There are many medications taken concomitantly by patients in both treatment

groups and as medications may often affect mood and behaviour all medications

being taken by participants at baseline have been documented in Table 2.2.

Anxiolytic / antidepressant use was much the same between groups.


Table 2.2: Concomittant medication use by participants in spironolactone and amiloride groups at baseline. (Medications were classified according to National Health Survey Users’ Guide. Appendix 6 – Classification of type of medication 4363.0.55.001). spironolactone amiloride Concomitant medication n % n % 1. Anti-adrenergic agents peripherally acting 9 52 1 3 (prazosin) 2. Arteriolar smooth muscle relaxing agents 14 82.4 12 36.4 (hydralazine) 3. Calcium channel blockers 15 88.2 30 90.9 (verapamil – SR) 4. HRT / Oral contraceptive pill - - 8 24.2 (Premarin / Microgynon) 5. Serum lipid lowering agents 5 29.4 7 21.2 (Lipitor / gemfibrozil) 6. Potassium replacement supplements 1 5.9 - - 7. Drugs acting on Upper GIT 2 11.8 3 9.1 8. Drugs acting on Lower GIT 1 5.9 - - 9. Anti-platelet therapy 5 29.4 6 18.2 (Cartia / Plavix / Aspirin) 10. Anti-asthma 2 11.8 4 12.1 11. Beta-blockers 3 17.6 - - (atenolol / betaloc) 12. Antibiotics 2 11.8 2 6.1 13. Anxiolytics 1 5.9 - - (Ducene / Ativan) 14. Antidepressants 2 11.8 3 9.1 (Effexor/ Luvox) 15. Anti-HIV agents 1 5.9 - - 16. Anti-convulsants - - - - 17. Potassium sparing diuretics - - - - 18. Analgesia - - 1 3.0 19. Vitamins / minerals/ other hormones 3 17.6 6 18.2 20. Uric acid reducing agents 3 17.6 2 6.1 21. Hypoglycaemic agents 2 11.8 - - 22. ACE Inhibitors / AII receptor antagonists 2 11.8 - - (trandolapril / irbesartan) 23. Non-potassium sparing diuretics - - - - 24. Non Steroidal Anti-inflammatory Drugs - - 1 3.0 (Mobic)


Measurement.

The State-Trait Anger eXpression Inventory – 2nd Edition (Spielberger, 1996) is a

57 item self-report questionnaire that provides concise measures of the experience,

expression and control of anger and takes 10-15 minutes to complete. Table 2.3

(Spielberger, 1996) defines the nature of the information measured by each scale and

sub-scale. Also provided are the number of items in and the possible range of scores

obtainable for each.

The STAXI was first published in 1979 and has generated valid norm-referenced

data in adolescent, college student, and adult samples along with general medical and

surgical patient, male and female groups. Deffenbacher and colleagues (1990) used

the STAXI in a pre-post design with a 5 week and 12 month follow-up to measure

the effectiveness of an anger reduction program in 29 college students. Hains (1992)

used the STAXI in a randomised, controlled pre-post design to measure the

effectiveness of two cognitive behavioural interventions to help adolescent boys cope

with stress and other negative emotional arousal. The STAXI-2 has been successfully

used in anger testing in cardiac disease and hypertension (Spielberger, 1996).

Whilst we found no normative data on such a definitively diagnosed sub-group of

hypertensives (hypertension due to PAL, mean age 55.90 in current sample), other

researchers have used STAXI (an earlier version of STAXI-2) to investigate the

relationship of anger type manifestations in ‘essential’ (cause not found)

hypertensive’ populations. Jula et al (1999) used STAXI in a Finnish study to

demonstrate a lack of correlation of anger expression with high blood pressure in 237

newly diagnosed hypertensives and 147 normotensive controls. The mean age of

participants in their study was 10 years younger and participants were all newly


diagnosed, untreated hypertensives. The researchers found no difference in State-

Trait Anger scores between the hypertensives and age / gender matched controls.

Mann and Gerber (2000) used STAXI in a study on 22 hypertensive patients to

measure psychological characteristics and responses to anti-hypertensive drug

therapy. Interestingly they found that Anger-out scores were positively correlated

with a diuretic (hydrochlorothiazide) induced fall in blood pressure.

Crane (1981) used a very early version of the STAXI called State-Trait Personality

Inventory (STPI), to compare levels of State and Trait anger and anxiety in a

population of 88 US Veterans Administration patients diagnosed with essential

hypertension. The control group of 47 general medical patients had no history of

hypertension or heart disease but differed significantly (p < .001) from the

hypertensive group in their time on active duty and marital status (p < .05). Crane

found that hypertensive patients scored significantly higher on State and Trait anger

scales, Angry Reaction sub-scale and State and Trait Anxiety.

The differing participant groups, different levels of development of the scales used in

the published literature and different numbers of items used in each version to

measure State-Trait anger and its sub-sets, make difficult the establishment of

normative data for hypertensive patients and those with hypertension due to PAL.


Table 2.3: Scale and sub-scale definitions taken from STAXI-2 Professional Manual (Spielberger, 1996). Scale/Subscale Items Range Description State Anger 15 15–60 Measures the intensity of angry feelings and the (S-Ang) extent to which a person feels like expressing anger at a particular time. Feeling Angry 5 5–20 Measures the intensity of the angry feelings the (S-Ang/F) person is currently experiencing. Feel Like Expressing 5 5-20 Measures the intensity of current feelings Anger Verbally related to the verbal expression of anger. (S-Ang/V) Feel like Expressing 5 5-20 Measures the intensity of current feelings Anger Physically related to the physical expression of anger. (S-Ang/P) Trait Anger 10 10-40 Measures how often angry feelings are (T-Ang) experienced over time. Angry Temperament 4 4-16 Measures the disposition to experience anger (T-Ang/T) without specific provocation. Angry Reaction 4 4-16 Measures the frequency that angry feelings are (T-Ang/R) experienced in situations that involve frustration and/or negative evaluations. Anger Expression-Out 8 8-32 Measures how often angry feelings are (AX_O) expressed in verbally or physically aggressive behaviour. Anger Expression-In 8 8-32 Measures how often angry feelings are (AX-I) experienced but not expressed (suppressed). Anger Control –Out 8 8-32 Measures how often the person controls the (AC-O) outward expression of angry feelings. Anger Control –In 8 8-32 Measures how often a person attempts to (AC-I) to control angry feelings by calming down or cooling off. Anger Expression 32 0-96 Provides a general index of anger expression Index based on responses to the AX-O, AX-I, AC-O (AX-Index) and AC-I items.

The State-Trait Anxiety Inventory – STAI – Form Y (Spielberger et al 1983) consists

of two, twenty item self-report scales designed to measure anxiety proneness (trait),

as well as the current level of tension and apprehension (state) and takes 15- 20


minutes to complete. The STAI has been used extensively in research on anxiety in

cardiovascular disease. Lane and colleagues (2002) used this scale to study 288

patients in the UK for the prevalence and persistence of anxiety after myocardial

infarction.

The STAI has also been used successfully in pre-post treatment studies. Linden and

colleagues (2001) in a randomised, controlled trial, used the STAI to assess an

individualised stress management program in 60 primary hypertensive patients.

Systolic blood pressure reduction in this study correlated positively with reductions

in psychological stress. Wilk and Turkoski (2001) in a small randomised, controlled

pilot study measured the effects of progressive muscle relaxation on anxiety in 14

patients enrolled in a cardiac rehabilitation program, using the STAI. Reduction in

anxiety correlated well with reduction in heart rate. In another pre-post design using

the STAI, Khatri and colleagues (2001) demonstrated that hypothermia during

coronary artery bypass surgery was associated with increased incidence of anxiety

and depression at 6 weeks and 6 months after surgery.

In the current study, a modified version of the STAI – Form Y was used. Eight items

measured trait anxiety and eight items measured state anxiety. Item analysis and

basic psychometric data indicated a high comparability to the 20-item version (Form-

Y). STAI scores in the modified version were also compared to anxiety scores in the

PAIS-SR Psychological distress section and again found to be comparable.

(Appendix 1).


The Psychosocial Adjustment to Illness Scale – Self Report – PAIS-SR (Derogatis &

Lopez, 1983) is a 46 item multi-dimensional assessment of psychological and social

adjustment of medical patients to their illness in a self-report format. The scale

addresses seven domains of health care orientation, vocational environment,

domestic environment, sexual relationships, extended family relationships, social

environment and psychological distress.

The PAIS-SR has been extensively used to assess adjustment to illness in chronic

medical conditions (Streisand et al, 1999). Such studies include patients having

haemodialysis (DeNour, 1982), diabetics with lower limb disability (Carrington et al,

1996), psychosocial adjustment of patients with HIV infection (Morer et al 1998),

patients with prostate cancer (Lilleby et al, 1999) and patients with chronic psoriasis

(Adams et al, 2001).

Two further studies have used the PAIS-SR in a prospective pre-post design as in

this study in primary aldosteronism. Langeluddecke and colleagues (1989) measured

change in psychological and psychosocial impairment before and 6 months after by-

pass graft surgery. Geevarghese et al (1998) administered the PAIS-SR to 100 liver

transplant patients 6 months and then yearly for 5 years post-transplantation. The

validity of the PAIS-SR is supported by strong correlations with other adjustment

measures commonly used in the assessment of adults with chronic physical

conditions. (Rodrigue et al, 2000).


Procedures.

Phase 1 – Pre-test. For those patients who agreed to participate in the study,

Participant Information, Informed Consent, STAXI-2, STAI-Form Y (modified

version) and PAIS-SR forms were given on the 1st day of admission for FST. This

ensured that all baseline data were collected at a similar time in the diagnostic

process. Each participant’s set of forms was given a three-digit code for

identification.

Biological data included blood pressure measurements, weight, basal day FST serum

aldosterone-renin and ratio and biochemical profile. A brief medical history was

obtained from the hospital file in order to identify other medical conditions and

concomitant medications which may impact on anger and anxiety scores.

After FST results confirmed a diagnosis of PAL (usually 1 week later), participants

were contacted to book an admission for Adrenal Vein Sampling (AVS) to

differentiate between unilateral and bilateral adrenal gland over-production of

aldosterone.

Prescription of treatment regimes determining treatment groups.

Adrenal Vein Sampling is performed under skilled radiological guidance via a

Femoral Vein puncture. A fine catheter is progressed through to the very small

Adrenal Vein from which 2-3 samples of adrenal outflow blood are collected for

measurement of aldosterone and cortisol. A higher level of cortisol (also produced by

the adrenal cortex) than in the simultaneously collected peripheral sample, helps to

ensure that the sample is from the adrenal vein. This procedure differentiates


between unilateral over-production, usually aldosterone producing adenoma, and

bilateral overproduction, usually bilateral adrenal hyperplasia, (Daunt, 2005).

Comparison of adrenal and peripheral venous serum aldosterone and cortisol levels,

is the most reliable means of determining whether autonomous excessive aldosterone

production is confined to one gland or is occurring in both glands (Stowasser et al,

2001). Unilateral over-production (usually found in approximately one third of

patients) gives the patient the choice of surgery (unilateral adrenalectomy of the

over-producing gland) in their treatment options. When excess aldosterone

production does not lateralise to one side on AVS, or the patient is unfit or not ready

for surgery or prefers pharmacological treatment; specific drugs, spironolactone and

amiloride are used (Stowasser et al, 2001).

Phase 2 – Treatment.

Following detailed discussion with the participant, the decision regarding treatment

is made by the physician. This decision though independent of the study, determined

the treatment group of the participant in the study. Time of initiation of treatment

was the date of commencement of amiloride or spironolactone as determined by the

clinic visit when the drug was prescribed. Information regarding concomitant

medications was collected and participants were asked to contact the study

coordinator if there was any change in treatment during the 6-8 month treatment

period so that Phase 3 post-test could be carried out before commencing the new

drug. In this study two participants forgot to inform the study coordinator prior to

commencement of the alternative treatment. These participants were subsequently

withdrawn from the study.


Phase 3 – Post-test.

Six to eight months after commencement of Phase 2, participants were interviewed

by phone or in person in order to update information such as change in medications,

average home blood pressures and current weight. Recent pathology results were

collected from hospital files and follow-up STAXI, STAI and PAIS forms were

posted or completed on site.

Statistical Analysis.

Variables not normally distributed were transformed using the square root formula.

The post-test pair of the same variable was also transformed.

Changes (from pre-test to post-test) in mean anger, anxiety and quality of life scores

were analysed using a mixed design (between – within) ANOVA. Blood pressure

and serum potassium levels were included in this analysis. Between subjects analysis

determines the effect of each drug on dependent variables. Within subjects

determines difference in the effects of spironolactone or amiloride on the above

variables over time. An interaction effect indicates whether the change in scores over

time is different for the 2 groups (Pallant, 2005).

Gender differences at baseline were analysed using an Independent samples T-Test.

Changes over time were analysed using the Paired Samples T-Test.

Participants who did not return post-test surveys (non-completers), were compared at

baseline with the group who did respond (completers). An independent samples T-

Test was used to identify significant differences between these two groups.


Ethical Considerations.

It is not in the interest of participant wellbeing to have a ‘no treatment’ PAL control

group as a component of the study. Many patients with PAL have moderate to

severe, resistant hypertension that is often the reason for referral. Participants were

informed that they were able to withdraw from the study at any time without

compromise to the staff-patient relationship or medical treatment.

Confidentiality was maintained using a three-digit code on all study documents and

database files. Data collection in the pre-test phase did not intrude greatly on

participant time as they were an in-patient with much time on their hands between

requirements of the protocol. The post-test requirements however required one to one

and half hours of participants time to complete questionnaires.

Risks to participants or staff are not in excess of standard clinical practice.

Information and consent forms for participants were constructed according to

guidelines in Booklet 11 of the QUT Human Research Ethics Committee and

guidelines of the Ethics Committee of the Greenslopes Private Hospital. The study

was formally approved by both of the above Ethics Committees.


Chapter 3: Results.

Baseline comparison of participants who did and those who did not complete the study.

The first step in the analysis was to assess the attrition effect. This was done by

comparing the two groups; “completers” (n=50) and “non-completers” (n=19). Most

baseline STAXI-2 anger sub-scale scores indicated that the non-completer group was

significantly more angry in State (Table 3.1) and Trait (Table 3.2) domains than

completers, and in particular the Anger Expression Index (Table 3.3). As well, Trait

Anxiety scores (Table 3.2) and Psychological Distress scores (Table 3.4) were also

higher in the non-completer group.

Table 3.1: Comparison at baseline of mean State Anger and State Anxiety scores of participants who subsequently did complete (completers) and did not complete (non-completers) the post-test questionnaire. Variable Completers Non-completers T-test & (range) (mean) (mean) State Anger – total [trans.] 15.14 18.11 -3.10** (S-Ang) (15-60) Feeling Angry [trans.] 5.20 6.74 -3.25** (S-Ang/F) (5-20) Feel Like Expressing [trans.] 5.02 5.89 -2.41* Anger Verbally (S-Ang/V) (5-20) Feel like Expressing [trans.] 5.00 5.47 -1.34 Anger Physically (S-Ang/P) (5-20) State Anxiety 12.53 14.83 -1.782 (SANXTY) (8-32) *p < .05. **p < .01. ***p < .001. All variables not Normally distributed were transformed for analysis [trans.] Sub-scales in Italics.


Spielberger (1999) defines state anger as a psychobiological emotional state

characterised by subjective feelings of varying intensity from mild irritation to rage.

The Total State Anger scores in those who did not complete the post-test were

significantly higher than those who did complete the study. The sub-scales Feeling

Angry and, Feeling Like Expressing Anger Verbally scores were also significantly

higher in those who did not complete. State Anxiety scores were not significantly

different however. These scores suggest that the group who subsequently did not go

on to complete the post-test experienced more anger than those who stayed and this

state was confirmed by Trait Anger scores (Table 3.2).

Table 3.2: Comparison at baseline of mean Trait Anger and Trait Anxiety scores of participants who subsequently did complete (completers) and did not complete (non-completers) the post-test questionnaire. Variable Completers Non-completers T-test & (Range) (mean) (mean) Trait Anger – total 16.76 20.89 -2.51* (T-Ang) (10-40) Angry Temperament [trans.] 6.16 8.89 -2.53* (T-Ang/T) (4-16) Angry Reaction 7.80 9.42 -2.13* (T-Ang/R) (4-16) Trait anxiety 14.22 17.11 -2.15* (TANXTY) ((8-32) *p < .05. **p < .01. ***p < .001. All variables not Normally distributed were transformed for analysis [trans.] Sub-scales in Italics.

The Anger Expression Index provides an overall measure of the expression and

control of anger (Spielberger, 1999). The difference in this score between the

completers and non-completers was highly significant.


Table 3.3: Comparison at baseline of mean Anger Expression and Anger Control scores of participants who subsequently did complete (completers) and did not complete (non-completers) the post-test questionnaire. Variable Completers Non-completers T-test & (Range) (mean) (mean) Anger Expression – Out 13.14 15.79 -3.01** (AX-O) (8-32) Anger Expression - In 16.70 18.53 -1.70 (AX-I) ((8-32) Anger Control -Out 24.40 20.42 2.98** (AC-O) (8-32) Anger Control –In 23.62 20.05 2.57* (AC-I) (8-32) Anger Expression Index 29.62 41.95 -3.36*** (AXIndex) (0-96) *p < .05. **p < .01. ***p < .001.

The difference in Trait Anxiety scores between the groups was significant (Table

3.2). This higher level of Trait Anxiety or ‘anxiety proneness’ (Spielberger, 1983) in

the non- completer group was consistent with significantly higher average scores on

the Psychological Distress component of the PAIS (Table 3.4). This sub-scale is

made up of 7 items that measure dysphoric thoughts and feelings that accompany the

patient’s illness. Major indicators measured are anxiety, depression, hostility, guilt,

worry, self-devaluation and body image (Derogatis, 1983). It should be noted

however that there were no group differences for the other six subscales of the PAIS.


Table 3.4: Comparison of PAIS baseline scores of participants who did or did not complete the post-test questionnaire. Variable Completers Non-completers T-test (mean) (mean) Health Orientation 5.06 6.21 -1.66 Vocational Environment 3.18 4.68 -1.35 Domestic Environment 3.08 4.63 -1.61 Sexual Relationships 3.08 4.63 -1.59 Extended Family Relationships [trans.] 0.92 1.58 -1.63 Social Environment 3.37 4.16 -0.63 Psychological Distress 5.49 8.47 -2.54* All variables not Normally distributed were transformed for analysis. [trans.] *p < .05. **p < .01. ***p < .001. Comparison of treatment groups at baseline.

Of the 50 participants who did complete the study, 17 were treated with

spironolactone and 33 were treated with amiloride hydrochloride. An Independent

Samples T-test was performed on both groups at baseline.

No significant baseline difference was found between the groups on any anger,

anxiety or psychosocial variable (Table 3.5). Nor was there any significant difference

between the two groups in the incidence of potential side effects. However, analysis

of biological variables found mean serum potassium significantly lower and systolic

blood pressure significantly higher in the spironolactone group.


Table 3.5: Comparison of treatment groups spironolactone and amiloride at baseline. Scale / Subscale spironolactone amiloride T-test State Anger [trans] 15.29 15.06 1.23 Feeling Angry [trans] 5.24 5.18 0.34 Feel Like Expressing [trans] 5.06 5.00 1.00 Anger Verbally Feel like Expressing [trans] 5.00 5.00 1.23 Anger Physically

17.41 16.42 0.06

Angry Temperament [trans] 6.71 5.88 0.73 Angry Reaction 7.82 7.79 1.10 Anger Expression - Out 12.76 13.33 0.627 Anger Expression - In 16.71 16.70 0.01

Anger Control -Out 23.88 24.67 0.53 Anger Control -In 23.41 23.73 0.21 Anger Expression Index 30.24 29.30 0.24

State Anxiety 11.82 12.93 0.90 Trait anxiety 14.41 14.12 0.17 Health Orientation 5.12 5.03 0.12 Vocational Environment [trans] 3.94 2.78 0.95 Domestic Environment [trans] 4.00 2.59 1.23 Sexual Relationships 3.82 2.69 1.12 Extended Family [trans] 1.00 0.88 0.30 Relationships Social Environment 3.76 3.16 0.45 Psychological Distress 5.94 5.25 0.47 Serum Potassium 3.84 4.2 3.849*** Systolic Blood Pressure 154.29 144.42 2.106* *p < .05. **p < .01. ***p < .001. All variables not normally distributed were transformed for analysis. [trans]


Analysis to determine gender differences at baseline.

Baseline scores were examined using an Independent T-Test to determine any

systematic differences. Only variables reaching significance have been tabled.

Table 3.6: Variables significantly differing by gender at baseline. Variable Male Female T (mean) (mean) Feeling angry 5.4* 5.07 2.25 (SANGF) Sexual r/ships 4.32* 2.30 2.01 (SEXUAL) Weight 89.90** 76.23 3.10 (WEIGHT) Serum Potassium 3.91** 4.23 -3.08 (SEK) *p < .05. **p < .01. ***p < .001. At baseline males felt slightly more angry than females. They were also more

dissatisfied with their sexual relationships, significantly heavier and had lower serum

potassium levels (Table 3.6).

Table 3.7: Post-test differences in scores that were significantly different at baseline, grouped

by gender and treatment group. Variable Male (means) Female (means) Pre-test // Post-test T Pre-test // Post-test T Feeling angry SPIRO. 5.31 6.23 -1.39 5.00 5.25 -1.00 AMIL. 5.57 5.14 1.44 5.08 5.84 -1.70 Sexual relationships SPIRO. 4.15 5.00 -1.05 2.75 1.50 1.99 AMIL. 4.67 3.50 1.47 2.23 2.53 -.63 Weight SPIRO. 91.43 90.48 1.33 82.02 83.6 -2.15 AMIL. 88.39 87.62 .69 74.78 75.20 -.627 Serum Potassium SPIRO. 3.78 4.46*** -5.05 3.97 4.22 -1.89 AMIL. 4.10 4.64** -4.15 4.28 4.57*** -4.01 *p < .05. **p < .01. ***p < .001.


By post-test, all differences between males and females at baseline had resolved

except for serum potassium. This is a treatment effect of both drug groups.

Spironolactone blocks aldosterone and so conserves potassium. Amiloride

hydrochloride is a potassium sparing diuretic so does not waste potassium while

promoting salt and water excretion.

Analyses to determine difference in effect of spitonolactone or amiloride. State Anger and Feeling Angry. A mixed design (between-within subjects) ANOVA

found significant treatment effects over time in State Anger (Figure 3.1) and Feeling

Angry (Figure 3.2). In this scale and sub-scale there was a moderate increase in the

mean score from pre-test to post test (Table 3.8) suggesting perhaps that treatment

increased ‘… participants intensity of angry feelings and the extent to which they felt

like expressing anger at a particular time’ (Spielberger, 1999). Alternatively, patients

may just become angrier over time independent of treatment. This could only be

established with a non-treatment control group and/or more frequent monitoring of

anger / anxiety. There was a small insignificant increase in anxiety for the

spironolactone group whilst anxiety in the amiloride group decreased but as well was

not significant.


Table 3.8: Mixed between-within analysis of variance (ANOVA). STATE anger and STATE anxiety. Variable Pre-test Post-test F F F & (range) (mean) (mean) spiro. amil. spiro. amil. (B) (W) (I) State Anger –total [trans] 15.29 15.06 17.12 16.09 0.78 3.99* .23 (S-Ang) (15-60) Feeling Angry [trans] 5.24 5.18 6.00 5.70 0.41 4.39* .21 (S-Ang/F) (5-20) Feel Like Exp. [trans] 5.06 5.00 5.47 5.33 0.17 1.86 .02 Anger Verbally (S-Ang/V) (5-20) Feel like Exp. [trans] 5.00 5.00 5.65 5.06 1.45 2.35 .45 Anger Physically (S-Ang/P) (5-20) State Anxiety 11.82 12.93 12.35 11.41 0.01 0.59 2.10 (SANXTY) (8-32) *p < .05. **p < .01. ***p < .001. All variables not Normally distributed were transformed for analysis. [trans] (B = between, W = within, I = interaction). Subscales in Italics.

Figure 3.1: Change in mean STATE ANGER scores from pre-test to post-test.

C h ange in m ean S T A T E A N G E R sco res p re -te s t to pos t-tes t.

14

15

16

17

18

19

P re -test P ost-test

Mea

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ores sp irono lac tone

am ilo ride


Figure 3.2. Change in mean FEELING ANGRY scores from pre-test to post-test.

Trait Anger (Figure 3.3) incorporates the sub-scales Angry Temperament (Figure

3.4) and Angry Reaction (Figure 3.5). Spielberger (1999. p1) defines Trait Anger

‘…in terms of individual differences in the disposition to perceive a wide range of

situations as annoying or frustrating and by the tendency to respond to such

situations with elevations in state anger’.

C h a n g e in m e a n F E E L IN G A N G R Y s c o re s p re -te s t to p o s t- te s t .

22 .5

33 .5

44 .5

55 .5

66 .5

7

P re - te s t P o s t- te s t

Mea

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ores s p iro n o la c to n e

a m ilo r id e


Table 3. 9: Mixed between-within analysis of variance (ANOVA). TRAIT anger, Anger Expression, Anger Control and TRAIT anxiety. Variable Pre-test Post-test F F F (& range) (mean) (mean) spiro amil spiro amil (B) (W) (I) Trait Anger - total 17.41 16.42 15.47 15.48 0.20 7.80** 0.94 (T-Ang) (10-40) Angry Temperament [trans] 6.71 5.88 5.65 5.61 0.58 5.75* 1.63 (T-Ang/T) (4-16) Angry Reaction [trans] 7.82 7.79 7.06 7.18 0.01 7.76** 0.05 (T-Ang/R) (4-16) Anger Exp. – Out 12.76 13.33 12.71 13.15 0.40 0.12 0.03 (AX-O) (8-32) Anger Exp. - In 16.71 16.70 15.88 20.27 0.23 0.01 0.36 (AX-I) ((8-32) Anger Control -Out 23.88 24.67 23.53 25.18 0.79 0.01 0.39 (AC-O) (8-32) Anger Control –In 23.41 23.73 24.65 23.70 0.05 0.83 0.91 (AC-I) (8-32) Anger Exp. Index 30.24 29.30 28.29 27.64 0.05 1.32 0.01 (AXIndex) (0-96) Trait anxiety 14.41 14.12 14.06 13.26 0.133 1.90 0.41 (TANXTY) ((8-32) *p < .05. **p < .01. ***p < .001. All variables not Normally distributed were transformed for analysis [trans]. (B = between, W = within, I = interaction). Sub-scales in Italics


Figure 3.3: Change in mean TRAIT ANGER scores from pre-test to post-test.

Figure 3.4: Change in ANGRY TEMPERAMENT scores from pre-test to post-test.

C h a n g e in m e a n T R A I T A N G E R s c o r e s p r e - t e s t t o p o s t - t e s t .

1 4

1 5

1 6

1 7

1 8

1 9

P r e - te s t P o s t - te s t

Mea

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ores

s p ir o n o la c to n e

a m ilo r id e

C h a n g e in m e a n A N G R Y T E M P E R A M E N T s c o r e s

p r e - te s t to p o s t - te s t .

3

4

5

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Mean scores for Trait Anger (and two of the 3 sub-scales, Angry Temperament and

Angry Reaction) decreased significantly from pre-test to post-test (Table 3.9). The

Trait Anger scale ‘measures how often angry feelings are experienced over time’.

The Angry Temperament scale ‘measures the disposition to experience anger without

Figure 3.5: Change in ANGRY REACTION scores from pre-test to post-test.

specific provocation’. The Angry Reaction scale ‘measures the frequency that angry

feelings are experienced in situations that involve frustration and/or negative

evaluations’ (Spielberger, 1996). These scores suggest that participants experienced

anger less often, with lesser intensity and were less likely to react after treatment, but

there was no difference between each treatment group in this effect.

C h a n g e in m e a n A N G R Y R E A C T IO N s c o re s p re -te s t to p o s t-te s t

4

5

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For Anger Expression-In, Anger Expression-Out, Anger Control-In and Anger

Control-Out scales (Table 3.9), no significant treatment effects on STAXI-2 scores

were found. As well, there was no significant treatment effect on State Anxiety

(Table 3.8) or Trait Anxiety (Table 3.9).

The Treatment effect did reach significance however (Table 3.10) in the

Psychosocial Adjustment to Illness Scale (PAIS) Psychological Distress domain in

which mean scores decreased from pre-test to post-test (Figure 3.6). This suggests

improvement in the major indicators measured in this composite domain; anxiety,

depression, hostility, self esteem, body image and inappropriate guilt (Derogatis,

1983). This general improvement in psychological wellbeing was similar for both

groups. However, there was no apparent treatment effect on the six other of the seven

domains measured in this scale. Overall the psychological impact is small.

Table 3.10: Mixed between-within analysis of variance (ANOVA). Psychosocial Adjustment to Illness Scale (PAIS). Variable Pre-test Post-test F F F (mean) (mean) spiro amil spiro amil (B) (W) (I) Health Orientation 5.12 5.03 4.71 3.94 0.43 3.71 0.76 Vocational Environ. [trans] 3.94 2.78 2.71 2.24 0.38 2.80 0.33 Domestic Environ. [trans] 4.00 2.59 3.88 2.21 2.45 1.91 0.63 Sexual Relationships 3.82 2.69 4.18 2.79 1.71 0.25 0.18 Ext. Family R/ships [trans] 1.00 0.88 1.18 0.85 0.34 0.23 0.13 Social Environment 3.76 3.16 3.76 2.21 0.87 0.75 0.75 Psychological Distress 5.94 5.25 4.24 3.94 0.19 5.08* 0.14 *p < .05. **p < .01. ***p < .001. All variables not Normally distributed were transformed for analysis. [trans] (B = between, W = within, I = interaction)


Figure 3.6: Change in mean PAIS Psychological Distress scores from pre-test to post-test.

Across all ANOVAs, none of the interaction effects were significant, suggesting that

any treatment effect was equivalent for the two drugs.

Change in mean (PAIS) PSYCHOLOGICAL DISTRESS scores pre-test to post-test

2

3

4

5

6

7

Pre-test Post-test

Mea

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core

s.

spironolactoneamiloride


Biological variables.

Only biological variables reaching significant change were included in the

analysis. Change in means of serum potassium (Se K+) (Figure 3.7) and systolic

blood pressure (SBP) (Figure 3.11) reached significance (p < .001) from pre-test to

post-test (Table 3.11). The increase in Se K+ was significantly greater for the

spironolactone group but this may be because baseline Se K+ in this group was lower

which may have influenced the treatment group to which these participants were

assigned. There was no interaction effect found for Se K+ with other variables.

Table 3.11: Mixed between-within analysis of variance (ANOVA). Serum Potassium and Systolic Blood Pressure. Variable Pre-test Post-test F F F (mean) (mean)

Spiro amil spiro amil (B) (W) (I) Se. Potassium. 3.84 4.2 4.4 4.59 12.57*** 56.94*** 3.48 Systolic B P. 154.29 144.42 138.47 134.72 4.03* 25.35*** 1.31 *p < .05. **p < .01. ***p < .001. (B = between, W = within, I = interaction)


Discussion (Study 1)

The intent of this study was to illustrate a relationship between anger and anxiety and

excessive aldosterone production. This hormone may have either a direct

neurochemical effect upon emotionality or an indirect effect through salt and water

retention causing nervous irritability.

One of the proposed biological influences discussed, that of sodium and water

retention, is not easy to examine in any depth. Total body sodium is difficult to

measure non-invasively, and blood sodium level even when sodium intake is

abnormal, is kept within an acceptable range by the kidneys. As well, there is no

clinically tested and agreed, commonly applied measure of circulating fluid volume

or interstitial volume (Boyle et al, 2007).

Given the paucity of psychological information from patients with PAL, an attempt

was made to draw parallels with other conditions where there is salt and water

retention and psychological irritability such as pre-menstrual tension and menopause.

Variation in levels of other hormones such as testosterone and cortisone may cause

psychological manifestations such as mood changes, irritability, hostility, and

depression. In this study hormonal overproduction was assessed prior to adrenal

surgery as part of routine pre-operative procedure. Testing for excess production of

other hormones is also performed on clinical indication.

The observed slight changes in psychological state may have occurred due to reasons

other than improved control over aldosterone. In many patients, blood pressure was


reduced and sometimes medication levels were reduced; both of these factors would

have made patients feel physically and psychologically well. However, many

participants remained on much the same amount of medication and their blood

pressure had not been affected much at all, perhaps because of the relatively short

time since commencement on medication.

This study had mixed results. There are modest trends in the data that support the

original hypothesis that treatment for primary aldosteronism is effective in reducing

emotionality, especially anger expressiveness. Given the strong finding that

treatment is associated with reduced blood pressure and increased potassium

retention, it is possible that either or both of these biological changes contribute to

improved mood.

However, the findings of reduced trait anger following treatment are not clear-cut,

because of the data showing increased state anger over time. There is no clear reason

as to why we might find such opposite trends. Given that all significant statistical

effects were modest in size (except those for blood pressure and potassium levels), it

may simply be that the trends for psychological effects are unstable. Thus, we must

conclude that there is no strong evidence for the central hypothesis of this study.

There are numerous reasons why the study failed to detect the expected effects. First,

it may be that the original clinical insights were not valid and therefore that the

hypotheses were not justified. Against this view is the prior research which suggests

the link between aldosteronism and mood state is feasible.


A second explanation is that the study was weakened because of attrition bias. There

was a very substantial effect of attrition: lost from the study were those patients who

were most angry to begin with. Therefore, we could not determine whether treatment

has been most effective among those who were lost. It is possible that it was not, as

they may have remained highly angry and this is manifested in their refusal to

participate further (by most who were lost). On the contrary, it is possible that the

most angry had benefited the most, and having ‘recovered’ they were less likely to

feel the need to participate in research that was related to a previous illness.

A major limitation of the study is the absence of a non-treatment control group.

It is assumed that the reduction in anger and distress is associated with drug

treatment. However, it must be recognised that without a non-treatment control group

(which ethically could not be justified in this particular study) it cannot be certain

that change over time is caused by the treatment. In designing the study a non-

placebo control group was considered. For example, patients with low aldosterone

and renin but high total body sodium such as those who have undergone unilateral

nephrectomy, or patients with high aldosterone and renin but low total body sodium

such as those with renal artery stenosis could have been recruited. However,

sufficient numbers of such controls was beyond the resources available for this

thesis. The loss of the adrenalectomy group from the quantitative analysis also limits

the study. Physicians were not able to explain the unexpected drop in numbers over

this time period.

The two drug treatment groups differed in gender comparison. There were more

males in the spironolactone group and more females in the amiloride group. Because

of the similarity of symptoms with PMS and menopause, the influence of gender was


examined and found not to have an impact on outcomes. This difference may be

random and simply reflect the constituents of the cohort at the time. As well,

numbers in the amiloride group were higher and this may reflect the early snapshot

in time in the chronological progression of treatment for this condition. Many

patients who did not have severely high blood pressure or potassium wasting might

be commenced on small doses of the lesser strength medication, amiloride. Patients

with more severely high blood pressure and evidence of potassium wasting might be

placed on small doses of spironolactone.

A recognised difficulty in studies of this type is not only the definition of terms but

also the variety of measurement tools used making comparison of studies difficult

(Barefoot & Lipkus, 1994). Pickering (1993) points out that even though views

regarding outcomes of anger studies are often conflicting, the resulting confusion

should in no way invalidate the concept. Pickering (1993) believes that a major

disadvantage of measurement in this domain is the reliance on self-report scales

wherein subjects have a tendency to portray themselves as they would choose to be

perceived.

This study is strengthened by the pre-test scores component of STAXI-2, STAI and

PAIS-SR which is a control in itself. These widely validated tools have been used in

multiple health research studies. To date there appears not to be any state-trait anger,

anxiety or quality of life data collected on such definitively diagnosed (PAL)

hypertensives.


This research adds substantially to the currently limited knowledge in this field. To

date, there appears to be only one small study (Sonino et al, 2006) that addresses

psychological aspects of Primary Aldosteronism. In that Italian study of 10 patients

with PAL, 5 male and 5 female aged 45 +/-6.6 yrs; 7 suffered from

Anxiety disorder. This prevalence was much higher than in the general population.

The present study of PAL is the largest survey of mental health in primary

aldosteronism patients (with 50 people completing both phases and a further 19

contributing phase 1 data). Even though the primary hypotheses are not strongly

supported, the study is valuable as it is because it provides descriptive data on

psychological states of an understudied population

Conclusion from study 1:

Overall the findings of this study do not provide support for the central hypothesis.

However, it is important now to reflect on why that hypothesis developed in the first

place. The author’s clinical experience with adrenalectomy patients suggested that

anger and hostility were reduced by removal of the adrenal glands. The original

intention of the study was to compare, systematically, a group of adrenalectomy

patients with two non-surgical treatment controls (spironolactone and amiloride).

Contrary to the expectations of the author and clinical supervisor, and due to

circumstances that could not be controlled; after commencement of the study the

numbers of eligible adrenalectomy patients fell significantly short of the predicted

level. Inclusion of this key group in the treatment follow-up study was therefore not

possible. On the advice of supervisors however, the study continued with the

comparison of the two non-surgical treatment groups to assess whether there were

differential effects of those treatments.


Rather than discard the original question because of this methodological and logistic

problem, another approach was taken to examine whether adrenalectomy may reduce

anger. This was done by asking former adrenalectomy patients to recall their

experiences in the time since surgery. The method chosen was a semi-structured

qualitative survey, which aimed to identify prominent themes in their recall of mood

state. This is described in chapter 4.


Chapter 4. Qualitative inquiry into effects of adrenalectomy.

Patient perceptions of behavioural, emotional, physical and lifestyle change, 6-24 months post adrenalectomy for aldosterone producing

adenoma: A qualitative study.

Introduction.

Scientific literature on adrenalectomy over the last three decades has addressed long-

term outcomes, including hypertension post-surgery. The focus of most research has

typically included biochemical, physiological and patho-physiological parameters

only (Ferris et.al. 1975, Groth et.al.1985, Horky et.al. 1987, Obara et.al. 1992, Jeck

et.al.1994, Stowasser et.al. 1994, Celen et.al.1996, Proye et.al. 1998, Siren et.al.

1998, Ichikawa et.al. 2000, Brunt et.al. 2001, Gordon et.al.2001, Sawka et.al. 2001,

Sywack & Pasieka 2002, Harris et.al. 2003, Goh et.al. 2004, Lumachi et.al. 2005 and

Meyer et.al. 2005). To date, there has been an absence of studies that include

emotional and behavioural data after the removal of an overactive adrenal gland.

Clinical impressions and patient comments over many years (file notes and personal

communications) suggest relatively calm, less pressured, more content individuals

after adrenalectomy. In the absence of prospective data from the proposed

adrenalectomy group in the quantitative study; retrospective qualitative data was

collected from a cohort of patients who had undergone adrenalectomy in the previous

6-24 months for aldosterone producing adenoma (APA) a form of Primary

Aldosteronism (PAL).

The original intention of this research project was to quantitatively assess outcomes

of adrenalectomy. However, due to circumstances beyond the researcher’s control it


was not possible to recruit sufficient numbers in this group. This study describes a

cohort of patients’ perceptions of behavioural, emotional and physical changes since

their adrenalectomy. The purpose is to triangulate the findings with data from study

1, to more rigorously examine the hypothesis.

Method.

Theoretical approach.

An interpretive phenomenological approach was taken to describe and detect themes

in behavioural, emotional and social interaction change after surgical removal of an

adrenal gland. The focus of this approach is to understand the patient’s experience of

life (Fossey et al, 2002). Interpretive phenomenology involves understanding and

interpreting phenomena and helps us make sense of the world (Maggs-Rapport,

2001), thus descriptions of individuals’ perceptions of change in the essence of their

everyday experiences since their adrenalectomy (Liamputtong & Ezzy, 2005) are

presented within the psycho-social-physical framework developed for the focus of

the study.

Design

A retrospective semi-structured questionnaire required participants to recall and

describe their experience of change (or not) in behavioural, emotional and physical

parameters and approach to life, in the 6-24 months since surgical removal of their

adrenal gland for aldosterone producing adenoma (APA) or Conn’s syndrome. The

open-response questionnaire was developed with the aim of examining whether

thematically comparable data to that measured quantitatively in the main study by

the STAXI-2 (Speilberger, 1996), STAI Form Y (Speilberger, 1983), PAIS


(Derogatis 1983) could be elicited. A framework was developed (with later template

analysis in mind) which encompassed concepts of current and usual anger and anger

expression, current and usual anxiety state, and quality of life. In addition, the

concept of feeling ‘pressured’ (identified in the clinical impressions of the principal

investigator) was also explored. Information on patient perceptions of physical

change, current blood pressure and medication was also collected.

The information regarding participants’ perception of physical change since

adrenalectomy was pursued because patients often think of improvement in physical

terms. The intention was to give opportunity to express this parameter but

differentiate it from the psychological parameters as stated above. Blood pressure

data was collected to reflect on success of treatment and its possible influence on

feelings. Medication information was collected to illustrate to the reader interested in

this information, the total treatment and other medications taken to attain the stated

blood pressure and psychological outcome. This information provides a richer

picture and helps the reader qualify the participant’s perception of physical change.

Participants

A purposive sampling strategy (Fossey et al, 2002) was used. Eligible patients were

those who underwent surgical treatment for unilateral aldosterone producing

adenoma.

Inclusion into the study required the participants to meet the following criteria:


1. Unilateral excess production of aldosterone confirmed by Adrenal Vein

Sampling.

2. Unilateral adrenalectomy performed in the previous 6-24 months. This time

frame was considered by the research team to be a reasonable time for

retrospectively collected data to be recalled by the participant.

3. The adrenalectomy was performed for the purpose of removing an

aldosterone producing adenoma.

Excluded from the study were participants who had undergone unilateral

adrenalectomy for adenoma which were not producing abnormal amounts of

aldosterone but the size being greater than 2.5cm has a greater malignant potential

(Stowasser et al, 2001). As well, persons who had undergone unilateral

adrenalectomy but had bilateral disease and medical treatment was not effective in

controlling severe symptoms of high blood pressure, ventricular hypertrophy and

potassium depletion.

Fifteen potential participants were contacted by phone over a 6-week period

(between 23/9/05 and 2/11/05) and invited to take part in the study. All agreed to

receive information about the study by mail. Consent, survey forms and stamped

addressed envelopes for return of completed forms were also included. Reminder

calls were made to three participants on 4/2/06 and by 8/2/06 a total of fourteen

responses were received. Twelve of the 14 participants now had low to normal blood

pressure and 6 were no longer on any anti-hypertensive medication.


Measurement

So as not to further reduce potential participant numbers, the questionnaire was

piloted on four patients who had PAL and had undergone unilateral adrenalectomy

within the same time frame but did not meet entry criteria for other reasons.

Responses to questions were analysed and appropriate changes made to promote user

friendliness and elicit the desired information in a valid and open manner.

The five-page questionnaire (see Appendix 2) has ample space for the written

response to each question. There was further option to turn to the back of the page if

more space was required. Based on participant reports from the pilot study

completion of the questionnaire took 20-30 minutes. Participants were asked whether

they had, in the last 6-24 months since their adrenalectomy, noticed any change in

their relationships with (i) those with whom they worked, (ii) spouse or person they

felt closest too, (iii) family and (iv) social relationships. Participants were also asked

whether their spouse or the person closest to them had reported any change in the

participant’s relationships in the above parameters (the spouse was not specifically

required to enter this response). In addition, the participant was asked whether they

felt this change was related to the removal of their adrenal gland.

Physical changes for better or worse were requested in descending order of

importance to the participant. Ample space was given for up to five changes. Change

in consistency of moods and intensity of emotional reactions were required to be

described along with whether a spouse or person closest to the participant reported

noticing this. The concept of feeling less or more ‘pressured’ or ‘driven’ was

explored by asking participants to describe any difference in the way they


approached their day since having their adrenalectomy. This was a manifestation that

in the clinical experience of the principal investigator seemed to occur relatively

frequently in PAL.

Difference in the level and frequency of feeling anger and changes in the way that

participants expressed anger were also sought. As well, participants were asked to

describe change in their levels of anxiety, how often they became anxious and the

types of things they became anxious about. A list of current medications was

requested to assess the potential effects of mood altering drugs or re-occurrence of

PAL. Recent blood pressure measurements were also sought.

Ethical considerations and approval.

Ethics approval for the study was given by the University Human Research Ethics

Committee and the Hospital Ethics Committee was notified. Potential suitable

participant names were obtained from the director of the Hypertension Unit and

contact details obtained through the medical records department. All participants

were known to the principal investigator through past clinical contact during the

diagnostic and treatment process. Participants were contacted by phone and received

study documents during September, October and early November 2005.

Confidentiality was maintained by identifying each participant’s questionnaire with a

3-digit code. Documents sent to the participant were identified with this and

participants were requested not to identify themselves on the questionnaire.


Analysis.

The qualitative information obtained in the open-ended questionnaire was analysed

using a Template (thematic) Analysis approach (King, 2003). Development of this

thematic template is described to illustrate transparency and support validity (Green

& Thorogood, 2004). Themes, according to King (2003) are aspects of participant’s

accounts that characterise particular perceptions and/or experiences that the

researcher sees as relevant to the research question.

The analysis process often but not always begins with presumptive themes strongly

expected to be relevant in the analysis (King, 2003). A similar style was used by

Kent (2000) to elicit psychological manifestations of a cohort of sufferers of

vertiligo. That study’s pre-selected areas also were determined by theorists who had

developed conceptual frameworks in Kent’s area of interest such as stigma, social

anxiety and social skills. In the current study the early ideas underlying the

subsequent themes were seeded from clinical observations of patient’s emotions,

behaviours and physical changes described earlier. From these observations, and

along similar lines to the concepts examined in the quantitative study, the

questionnaire was developed.

The initial template for the analysis included concepts of anger and anger expression,

anxiety-state, quality of life and any experience of feeling pressured. These concepts

were examined within a framework of change since adrenalectomy in ‘relationships

at work’, ‘relationships with family’, ‘social relationships’ and ‘relationships with

spouse or partner. As well, change in frequency of moods and intensity of emotional


reactions was explored. Themes substantiated by recurring similar phenomena are

identified and coded. Coding is the process of identifying themes in accounts and

attaching labels (codes) to index them (King, 2003).

As the data was read, transcribed and coded, some of the early categories such as

work, family and social relationships merged to form one of the final themes

reported as ‘impact on relationships and work’. As well, new themes evolved.

Transcriptions indicating ‘feeling better’, ‘not so tired’, ‘able to do more’ and many

others similar, evolved into the final theme of ‘vitality’.

In many cases it was the way in which the participant described the change, that

determined the coding of the transcript. This explains what may seem to some as a

lack of clarity amongst the themes. For example, if the participant spoke of ‘less

anger’, ‘increased calmness’, ‘more tolerant’ this was likely to be coded under

‘emotional control’. If the participant spoke of ‘stress’, ‘coping’, ‘managing’,

‘tension’ or ‘pressure’; they were more likely to be coded to ‘coping with external

stress’. Coding was also modified by which question the answer was in response to.

The information derived from the Physical Changes section of the questionnaire was

not elicited thematically. These data were responses to the question asked of

participants regarding change in their physical health since removal of their adrenal

gland. Participants were asked for up to five changes and asked to describe the

change most important to them first. Whilst it is realised that this question has a

quantitative feel; it was aimed at eliciting quality in the response, not just any of a


number of physical changes that sprang to mind. Only the first response of each

participant is reported.

Results.

Actual transcriptions and parts of transcriptions are reported to promote rigour (Rice

& Ezzy, 1999). Four principal themes were elicited from the responses. (1) Coping

with external stress, (2) Emotional control, (3) Impact on relationships at work and

(4) Vitality. The theme; ‘most important physical changes’ as determined by the

participant was prompted by the fifth section of the questionnaire. One third of

spouses verified changes for the better either in statements themselves or statements

made to the participants.

Where participant responses are inconsistent with the theme they are discussed in the

accompanying text. Validity is promoted by reporting of discontinuity in the

evidence and reporting of deviant cases (Green & Thorogood, 2004).

1. Coping with external stress.

Almost half of participants mentioned improvement in their ability to cope with

external stress. One participant indicated a dampening of the reactiveness that he had

previously experienced. However, one participant indicated that there was a

worsening in this aspect of his behaviour. His statement ‘my wife believes I have

become more snappy but this could be a factor with age’ was verified by his spouse

‘ … because I react to smaller things’. A second participant whose spouse’s

statement included ‘ … appears to be easily irritated. Can appear to be fine then

something apparently minor will cause a reaction which (to me) seems to be


irrational’, did not include a statement supportive of their spouse’s view. These

conflicting response statements are not unlike the mixed anger effects seen in the

quantitative study.

Another participant when responding to the question regarding any difference in the

level of anxiety that they felt, stated ‘I get anxious if I look like being late for

appointments. I get anxious if I have to go back and do things twice. I get anxious

with people who cause me grief!!!’ This participant did not indicate whether for

them, this was an improvement or worsening of this manifestation. Statements

depicted in Table 4.1 illustrate participant perceptions of their improvement.


Table 4.1: Participant perceptions of their improved ability to cope with external stress. Theme: Coping with external stress. Quotes: ‘We have a son on drugs and I have been able to talk to him honestly about the way

I feel … whereas before I said nothing and just bottled it up and stressed about it’ ‘probably less pressured’ ‘I move away from fights with other people. Before, I would get involved and end up

being violent and abusive.’ ‘ … I would panic and get anxious about not getting things done … apparently I

would just go, go, go all the time.’ ‘I deal better with people’ ‘I am now far more mellow, sometimes I feel too mellow.’ ‘Prior to the operation I remember getting so angry watching a war film on the TV

and thinking at the time how ridiculous, but could not stop being angry.’ ‘Because I realised I was getting angry at little things, I started to drink a lot of

alcohol to reduce the anger. I no longer have that problem.’ ‘Because I now feel that I can cope with most things, now I don’t feel so anxious

shopping and driving etc.’ ‘I just cope better with problems all round.’ ‘Yes exactly (less pressured)’ ‘Yes, despite extreme provocation at times I believe I am now managing anger

better.’

2. Emotional control.

Half of participants indicated improved emotional control. Participant statements in

response to questions regarding change in intensity of their emotional reactions and

whether their spouse had noticed any change illustrated a broad range in change in

emotional feelings. This spectrum included feelings of being more reserved and

calmer to no longer being angry, violent or abusive. Almost all spouses (according to

participant statements) of those who indicated positive change verified the change for

the better. One participant stated in response to the question regarding change in


intensity of emotional reactions; ‘people know how I feel – I hide less’. This

statement was difficult to definitely interpret in a positive or negative way. There

was no indication ‘of control’ only of no longer bottling emotions up for which there

was no suitable theme. King highlights this facet of template analysis as a potential

problem in that some important data could be missed and go unreported if it doesn’t

fit into the template (King, 2003). Another participant interpreted this question from

a personal emotion perspective and stated ‘I seem to want more emotional

interaction with my wife. This was probably an issue all along but seems to be

more so now’. This statement as well as the one quoted above may indicate more of

a tendency to express emotions more freely but (in the investigator’s opinion) are

insufficient in themselves to code into the identified themes.


Table 4.2: Participant perceptions of their improved emotional control.

Theme: Emotional control. Quotes: ‘I think that I am now more tolerant and less hassled … more “go with the flow” ‘

‘tend to be more reserved’ ‘I do not get excited as often or as readily’

‘just more open – more assertive rather than angry’

‘If I had alcohol, one or two drinks, my behaviour could be unpredictable. I wanted to jump off the roof and the police came. I don’t know why I did it. The same day I ran on to the road in front of cars. I was arrested for hitting my partner and throwing a frypan at him.’

‘I tend not to be so destructive …’

‘(anger ) level is less … not as often’. ‘(anger expression) more constructive’.

‘I used to get angry very quickly … since removal I am more calm, takes a lot longer to get stressed.’

‘I feel a lot better and a lot more calmer.’

‘ … and also a longer fuse meaning it takes a lot longer to get me heated.’

‘I feel anger a lot less’ ‘I seem to have a calmer outlook on life. It doesn’t worry me so much.’ ‘Yes, I guess you’d have to say I am more resigned to my fate now. Emotional thoughts do surface but are under better control now I think.’

3. Impact on relationships and work.

In response to questions regarding change in relationships at work and with spouse

and family, half of participants indicated a positive change. There was more

openness and willingness to become closer, participants were more able to talk and

express themselves and there was an increase in or want for more emotional

interaction. Many found work less stressful now, or did not allow work issues to

cause them stress.

In some participants it was not possible to separate the inter-relatedness of the

changes; many had significant impact on other aspects of life. For example, one


participant who was so tired by 11am. Often left the workplace to take naps in her

car. Some days this participant couldn’t get out of bed to put a load of washing on.

This had an enormous impact on her relationships at work and with the family and as

well contributed to poor emotional control and ability to deal with external stress.

After the adrenalectomy this participant was ‘not as tired so able to do more, more

patient’ and was said by spouse to be ‘more ambitious and work harder’.

Table 4.3: Participant perceptions of positive change in their spouse/partner, family and social relationships and work.

Theme: Impact on relationships and work. Quotes: ‘… Its been an easier year at work…’ ‘… I now speak my mind instead of bottling up … no more “walking on eggshells”

and not expressing my feelings.’

‘Yes but only marginally, I think before I yell at … for little things, I listen more.’ ‘(at work) I was falling asleep at 11am and going to sleep in my car for naps or sneaking home. I had a lot of sick leave and even used all my holiday.’ ‘more in touch with emotions and able to talk about them’ ‘have become closer because of time spent together’ ‘I try not to get anxious … I try not to pre-empt work to be done later’ ‘I had no real problem whilst at work, the problem came when I tried to rest.’ ‘Yes I am more tolerant, less tired.’ ‘Yes less stress and pressure on my body and as I feel better therefore it passes on.’ ‘I don’t get stressed as much about work any more and I leave work problems at work.’ ‘ … despite the stressful nature of … I still think I am coping better with the stress than would have been the case prior to my surgery.’ ‘Yes, in fact on the work front I have never been able to cope so easily with the pressure of work and deadlines. They don’t phase me any more.’


4. Vitality. Almost half of participants indicated an increase in vitality and an improvement in

the quality of their life due to how well they now felt. Being less tired, having more

energy, no more headaches were major factors. Other contributing factors included

now considering themselves more and being more able to take part in family life and

social activities. One participant after her adrenalectomy took up a demanding sport

at a veteran’s level and another stated that the adrenalectomy enabled him to have a

healthy lifestyle.

Table 4.4: Participant perceptions of improvement in their vitality and quality of life. Theme: Vitality. Quotes: ’Because my health is so much better I am less tired in the afternoons after work.

The removal of the adrenal gland meant an immediate improvement in health. Blood pressure problems no longer exist, therefore no headaches etc. That has contributed to feeling less stressed therefore better physically and mentally.’

‘I am heaps better now, have more energy and can do more. I was always tired,

moody and withdrawn.’ ‘Less stress, change of life style.’ ‘I often suffered very bad headaches on my days of rest away from work. This had

an impact socially.’ ‘After 15 years of high blood pressure, the difference in the way I feel is

remarkable.’ ‘Being a lot more calmer I am probably a lot more pleasant and I enjoy myself

more.’ ‘a lot more happy in myself’


Physical change.

Participants were asked to describe up to five physical changes they had noticed

since their adrenalectomy in order of importance. The diversity of these physical

improvements was important in itself in that it indicated such a broad influence on

quality in so many different aspects of the participants lives. The descriptions are too

numerous to include. The only factor mentioned more than once was that of being

less tired or having more energy, and this was stated by three participants as being

most important. Table 4.5 includes only the change indicated by each participant as

most important. Table 4.6 depicts (in the same order as table 4.5) average blood

pressure at time of completion of the questionnaire (in most cases taken at home),

and an account of all current medications being taken at that time. These later factors

are included because of their potential effect on how participants may feel.

There were however some reports of physical change for the worse. One participant

who now did ‘tasks at a slower pace’did not enjoy this slower pace. As well, he tired

more easily and had gained 8 kilograms. This participant’s blood pressure had

significantly improved but he had been commenced on amiloride as there was not a

total cure of his primary aldosteronism. This may also have had a negative

psychological effect. Another participant found that he became ‘extremely sensitive

to warm environments’, suffered ‘excessive sweating after minimal physical

activity even on cool days’, also suffered ‘night cramps, never experienced prior to

adrenal gland removal’ and ‘decreased exercise tolerance, surprisingly short of

breath after relatively short period of low level physical exertion’. This participant’s

medications included two antihypertensive drugs – Isoptin SR and Gopten, an

antidepressant – Aropax, and, dexamphetamine because of a head injury 3 years

prior to the study. A third participant had a mixture of positive and negative


responses to this question. With regards to the current medications the answer was

‘nil! And this is the best part. I feel liberated after 15 years of BP medication with

awful side effects’. The most important physical change was ‘low blood pressure

(better)’ but negative changes included ‘less energy (worse), difficulty

concentrating (worse) …, Mild neuralgia type pain at site of surgery …’, and an

excerpt from the participant’s journal ‘at 12 months after the surgery I am

beginning to slowly regain energy, but not the energy I had prior to my surgery …’

One other participant reported weight gain, umbilical hernia around previous surgical

scar and lack of energy, amongst his positive reports of ‘no further need to take

Span K– a BIG PLUS and an almost complete absence of irregular heart rhythms

is a definite POSITIVE’. All other participants reported positive changes.

Table 4.5: Participant perceptions of most important physical change. Theme: Most important (to participant) physical change. Quote: ‘My activity level had dropped and so I do tasks at a slower pace.’

‘more energy - this year particularly… played (sport) energetically for three days (and partied too!)’

‘no’.

‘less tired’

‘no toilet trips during the night – used to go 4-5 times’

‘extremely sensitive to warm environments’ .

‘low blood pressure (better)’

‘mental attitude has changed’

‘potassium levels are now normal thus energy levels do not drop to zero.’

‘not as tired’ ‘no’ .

‘headaches have gone’

‘I enjoy life more’

‘an almost complete absence of irregular heart rhythms. This is a definite positive.


Table 4.6: Participant blood pressure and medications. Theme: Physical change. Blood Current Pressure Medications 126/91 carvedilol, candesartan, lercanidipine,

amiloride, allopurinol, atorvastatin, colchicine. 110/70 nil 150/89 verapamil (slow release),raloxifene,

atorvastatin, calcium carbonate. ‘very normal’ Premarin (congugated oestrogens),

ibuprofen, acetylsalacylic acid, paracetamol. 134/88 salbutamol (puffer), budesonide (spray). 132/84 paroxetine, verapamil SR, trandolapril, dexamphetamine. 108/72 nil 120/79 nil 116/86 irbesartan, low dose aspirin, Atorvastatin. 125/82 irbesartan, diltiazem, omeprazole, allopurinol. 125/81 verapamil SR, atorvastatin, low dose aspirin. no longer nil takes blood pressure. ‘normal’ enalapril, atorvastatin. 145/85 metoprolol, hydralazine, atorvastatin.


Discussion (Study 2).

Participants’ statements indicated that they felt significantly better, interacted more

effectively, did not get upset as easily or as often, and generally coped far better with

the stresses of life and work, than they did prior to the removal of their over-

productive adrenal gland. Two women participants drew similarities between

symptoms of this condition and those associated with menopause. This is interesting

and lends support to early clinical impressions (discussed in Chapter 1) regarding the

commonality of symptoms of sodium and water retention. One participant states in

response to the question; “Has your spouse or person whom you feel closest to

noticed any change in your relationship with them?” ‘Yes, I guess there have been

some changes. Once again, being active has helped. It is hard to distinguish how

much is due to post adrenalectomy or post menopause – as these occurred in the

same year! The second participant makes a comparison between how well she felt

post adrenalectomy and when menopause occurred she felt back where she started

illustrating a similarity in symptoms of the two conditions as perceived by these two

women. This second participant said ‘Yes, initially I felt like a new person. I feel

menopause has really set me back. I feel like I am back there. Menopause has hit

and I am very impatient and moody.’ These menopause like symptoms seem similar

to those common with pre-menstrual syndrome and as described earlier in this study

appeared to manifest in male and female patients who had the condition of primary

aldosteronism.

The work of other researchers also supports the idea that sodium and water may

cause or exacerbate nervous system irritability. Deter and colleagues in 1997

described an increased responsiveness of the blood pressure to mental stress and an


increased level of irritation in salt sensitive normotensive individuals. They also

found higher levels of anxiety and lower levels of anger control in these salt sensitive

individuals compared to salt-resistant, age, BMI and family history of hypertension,

matched participants. In a separate analysis Deter et al (2001) found that the most

important predictor for rise in blood pressure response to stress was the degree of salt

sensitivity of the individual. As well, the findings of Bucholz et al (1999) on the

same cohort indicate an increased level of emotional irritation in the salt-sensitive

group.

The Deter and Bucholz studies suggest that the psychological traits described may

play a role in the development of salt-sensitive hypertension. Light and colleagues

(1983) however demonstrated a reduction in the amount of sodium excreted in the

urine of men exposed to the stress of arithmetical tasks suggesting a partnership (or

common sympathetic nervous system pathway) between stress and sodium retention.

The findings of our study are consistent with this idea adding the involvement of

aldosterone to the equation by way of its function in sodium and water retention. In

situations such as this study where excessive circulating aldosterone has been

reduced by removal of the overproductive adrenal gland, the subsequent reduction in

circulating aldosterone and salt and water retention results in a substantial

improvement in symptoms not only partially described by the above researchers but

in rich qualitative form by patients who have had their over-productive adrenal gland

removed.


This study could not determine whether emotional irritability in PAL (and PMS) is

due to increased salt and water retention, that induces a constant state of readiness to

respond to fight or flight stimulus, or whether this irritable, angry state is due to the

direct action of hormone aldosterone in PAL (and progesterone in luteal phase of

menstrual cycle in PMS). However it is clear, that substantial numbers of participants

indicated that after removal of their over-productive adrenal gland they had better

emotional control and ability to cope with external stress and also reported improved

vitality and improvements in their relationships with family, spouses, socially and at

work.

It is a weakness of the study that there was no validation undertaken of qualitative

findings. This was because there were so few adrenalectomy patients available who

met entry criteria.

Triangulation of findings from the qualitative and quantitative studies. Spielberger (1996) describes the Trait Anger scale as measuring ‘… how often angry

feelings are experienced over time’. The decrease in scores in this scale concurs with

participant statements in the qualitative study such as ' feel anger a lot less’, ‘(anger)

level is less … not as often’. The Angry Temperament scale is described as

measuring ‘the disposition to experience anger without specific provocation’. The

decrease in scores in this scale is also consistent with statements from participants in

the qualitative study such as ‘because I realised I was getting angry at little things, I

started to drink a lot of alcohol to reduce the anger. I no longer have this problem’.

As well, ‘Prior to the operation I remember getting so angry watching a war film

on the TV and thinking at the time how ridiculous, but could not stop being

angry’.


Spielberger’s (1996) second sub-scale of Trait Anger, Angry Reaction’ measures ‘

the frequency that angry feelings are experienced in situations that involve frustration

and/or negative evaluations’. Improvement in these scores also concur with

statements in the qualitative study such as ‘... also a longer fuse meaning it takes a

lot longer to get me heated. ‘I used to get angry very quickly… since removal I am

more calm, takes a lot longer to get stressed’, and ‘I just cope better with problems

all round’.

Patients who had undergone adrenalectomy in the qualitative study had in the main,

improved emotional control, improved ability to cope with external stress, improved

relationships and greater vitality. A salty intra or extracellular environment may be

the means by which aldosterone excess promotes anger, anxiety and irritability.


Chapter 5: Conclusion

The combined quantitative and qualitative study.

The primary aim of this study was to explore the concept that aldosterone excess

either by acting directly via receptors in the brain, indirectly through sodium and

water retention, or by influencing alterations in sympathetic nervous system activity,

may be associated with psychological function. Because there was no significant

difference in the treatment effect between spironolactone and amiloride; the blocking

of aldosterone receptors with spironolactone did not elicit a direct effect of reducing

aldosterone action on the brain which would have been attributable if there was a

significant treatment effect with spironolactone over amiloride. Amiloride promotes

sodium and water excretion but is not known to block the aldosterone receptor. The

overall improved treatment effect on Trait Anger and Psychological Distress from

(assumed) sodium and water depletion via the action of both drugs has further

suggested an association between sodium and water retention and adverse

behavioural symptoms.

Triangulating these behavioural outcomes was the retrospective, qualitatively

collected data that concurs with quantitatively measured slight to moderate

improvements in anger, anxiety and quality of life on patients who had undergone

adrenalectomy. This group also shared the common outcome of reduced sodium and

water retention. Participants indicated that they felt much more active and interested

in their lives and that their interactions at all levels were more effective and

satisfying. As well, they were less likely to to get upset as easily or as often and


generally coped far better with work and life’s stresses than they did prior to the

removal of their over-productive adrenal gland.

The outcomes of this study may promote broader thinking by health professionals

who may take into account other symptoms that the patient may be experiencing and

investigate for primary aldosteronism before commencing anti-hypertensive

medications which interfere with the interpretation of the aldosterone-renin ratio, the

first diagnostic indicator for primary aldosteronism. More efficient and specific

screening for specific causes of hypertension can facilitate earlier diagnosis and

treatment minimising not only years of inadequate treatment on non specific

medications but also the minimising the experience of anger and anger expression

and its consequential ramifications on sufferers’ relationships, work and physical

health

This is a small study and was carried out for a relatively short period of time in the

usual gradually progressive course of drug treatment for primary aldosteronism.

Further research is needed to determine whether a longer period on medications or a

higher dose does in fact elicit more definitive change in psychological status. More

research is also necessary to determine whether anger does in fact manifest more in

patients with primary aldosteronism than those with ‘essential hypertension’. This

would best be achieved by implementing at the GP level to a very large cross section

of the population, urban and rural, a newly developed questionnaire (and return

envelope) that could be given to the newly diagnosed hypertensive before

commencement on medication. The additional diagnostic tests specific to the study

would include 2 aldosterone-renin ratios and these would be analysed with the scores

of the questionnaire to assess its accuracy in identifying high blood pressure due to


aldosterone excess and thus channel investigations along this path thus saving

patients many years of end organ damage from uncontrolled blood pressure, many

years high cost of blood pressure medication, much psychological and social cost as

depicted in this paper.

It is clear that many people with this disorder have severe and troubling

psychological symptoms and need careful management by nurses and physicians and

allied health workers. This study indicates that these symptoms improve with

treatment specific to salt sensitivity rather than the non-specific antihypertensive

treatment that participants were on prior to the study.

Further extrapolation of this salt sensitivity / anger concept may reveal an association

between salt sensitivity, hypertension and our ever increasingly high salt diet of

processed foods. This study adds to the body of knowledge about salt sensitivity and

hypertension.


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Appendix 1: Psychometric Analysis of State-Trait Anxiety Inventory (STAI).

A psychometric analysis was performed to determine the adequacy of the eight item

modified version of the STAI compared with the 20 item version of the scale (Polit

& Hungler, 1999). Internal consistency was determined by calculation of

Chronbach’s Alpha for the whole scale in order to compare the modified 8–item

State and Trait scales of the State-Trait Anxiety Inventory (STAI- Form Y), with the

same eight items completed within the 20-item version of the scale. As well the same

analyses (below) were conducted for the 20-item scale as a whole and the same

comparisons made.

External validity for the 8-item modified scale was determined by Pearson’s product

moment correlation coefficient (Pearson’s r) which explores the strength of the

relationship between two continuous variables. The 8-item modified version was

compared with the anxiety measure (Psychological distress) in the Psychosocial

Adjustment to Illness Scale (PAIS) collected at the same time points in the study.

Calculation of Cronbach’s coefficient alpha, total-item correlation and means for

State and Trait scales in both Pre-test and Post-test data was performed. Cronbach’s

coefficient alpha measures internal consistency or the extent to which the items

making up the scale all measure the same underlying attribute (Pallant, 2005). This

statistic gives an indication of the average correlation among all of the items that

make up the scale. Values range from 0 to 1 with higher values indicating greater

reliability. Nunally (1978, cited in Pallant, 2005) recommends the value of this

statistic be a minimum of 0.7.


In this study, Cronbach’s coefficient alpha for the modified 8-item version ranged

between .873 and .945 for both State and Trait scales in pre and post test data

(Appendix tables 1.1, 1.2, 1.3 and 1.4) indicating that all items were sound.

Appendix Table 1.1: Pre-test State Anxiety modified 8-item form. (cases N=16) STAI State Item Mean Cronbach’s Alpha Item total if item deleted. Correlation I feel calm 1.38 .878 .409 I am tense 1.31 .880 .428 I feel upset 1.13 .872 .513 I feel frightened 1.19 .847 .736 I feel nervous 1.50 .824 .894 I am relaxed 1.63 .840 .784 I am worried 1.69 .839 .788 I feel confused 1.13 .867 .535 Cronbach’s Alpha - .873 Mean = 0.636


Appendix Table 1.2: Pre-test Trait Anxiety modified 8-item form. (cases N=17) STAI Trait Item Mean Cronbach’s Alpha Item total if item deleted. Correlation I feel nervous and restless. 1.82 .943 .762 I feel satisfied with myself. 1.82 .938 .789 I feel that difficulties are 1.65 .929 .911 piling up so that I cannot overcome them. I feel like a failure. 1.53 .932 .898 I have disturbing thoughts. 1.65 .936 .834 I lack self-confidence. 1.88 .938 .797 I feel secure. 1.71 .930 .909 I worry too much about 2.35 .952 .617 something that really does not matter. Cronbach’s Alpha - .945 Mean = 0.814 Appendix Table 1.3: Post-test State Anxiety modified 8-item form. (cases N=17) STAI StateItem Mean Cronbach’s Alpha Item total if item deleted. Correlation I feel calm 1.47 .888 .704 I am tense 1.29 .874 .847 I feel upset 1.06 .918 .215 I feel frightened 1.12 .878 .844 I feel nervous 1.29 .890 .682 I am relaxed 1.53 .902 .609 I am worried 1.35 .879 .798 I feel confused 1.12 .878 .844 Cronbach’s Alpha - .902 Mean = 0.693


Appendix Table 1.4: Post-test Trait Anxiety modified 8-item form. (cases N=17) STAI Trait Item Mean Cronbach’s Alpha Item total if item deleted. Correlation I feel nervous and restless. 1.94 .907 .564 I feel satisfied with myself. 1.88 .897 .709 I feel that difficulties are 1.53 .886 .819 piling up so that I cannot overcome them. I feel like a failure. 1.53 .884 .857 I have disturbing thoughts. 1.53 .898 .722 I lack self-confidence. 1.94 .899 .667 I feel secure. 1.94 .896 .753 I worry too much about 2.06 .897 .696 something that really does not matter. Cronbach’s Alpha - .908 Mean = 0.723 Reliability of the scale is further confirmed by item-total correlation. This figure

provides an indication as to how well each item correlates with the total score and

should not be higher than the final alpha for the scale. In this study there were no

inter-item correlations higher than the final alpha (Appendix tables 1.1, 1.2, 1.3 and

1.4).


Comparison of means. Item means were comparable across the 3 analyses; the 8-item modified version, the

same 8 items in the 20-item scale and the 20 items 20-item scale at each data

collection time. Means for the 8-item modified version are presented above

(Appendix tables 1.1, 1.2, 1.3 and 1.4).

Presented below are data for (i) the same 8 items in the 20-item scale and (ii) the 20

items in the 20-item scale for the 3 analyses. Two sets of data are presented for Pre-

test State Anxiety (Appendix tables 2.1 and 2.2), Pre-test Trait Anxiety (Appendix

tables 3.1 and 3.2), Post-test State Anxiety (Appendix tables 4.1 and 4.2) and Post-

test Trait Anxiety (Appendix tables 5.1 and 5.2).

PRE-TEST – STATE ANXIETY Appendix Table 1.5: Pre-test State Anxiety same 8 items used in modified version from participants who completed the 20-item Form-Y. (cases N=36) STAI StateItem Mean Cronbach’s Alpha Item total if item deleted. Correlation I feel calm 1.75 .783 .707 I am tense 1.92 .787 .652 I feel upset 1.19 .810 .509 I feel frightened 1.28 .812 .472 I feel nervous 1.58 .808 .499 I am relaxed 1.89 .789 .635 I am worried 1.69 .802 .552 I feel confused 1.25 .822 .379 Cronbach’s Alpha - .823 Mean = 0.551


Appendix Table 1.6: Pre-test State Anxiety 20-item Form-Y. (cases N=33) STAI State Item Mean Cronbach’s Alpha Item total if item deleted. Correlation I feel calm. 1.76 .918 .757 I feel secure. 1.55 .918 .726 I am tense. 1.97 .918 .690 I feel strained. 1.39 .920 .634 I feel at ease. 1.79 .917 .753 I feel upset. 1.21 .923 .477 I am presently worried over possible misfortunes. 1.58 .923 .483 I feel satisfied. 1.85 .920 .631 I feel frightened. 1.30 923 .476 I feel comfortable. 1.88 .925 .407 I feel self-confident. 1.88 .918 .691 I feel nervous. 1.64 .924 .404 I am jittery. 1.30 .925 .342 I feel indecisive. 1.42 .921 .583 I am relaxed. 1.91 .918 .722 I feel content. 1.76 .921 .565 I am worried. 1.76 .919 .663 I feel confused. 1.27 .924 .431 I feel steady. 1.76 .917 .742 I feel pleasant. 1.73 .919 .649 Cronbachs’ Alpha - .924

Chronbachs’ Alpha = 0.873 for 8-item version and 0.823 for 8 items within the 20- item form are reasonably similar to the 20-item value 0.924 above.


PRE-TEST TRAIT ANXIETY Appendix Table 1.7 Pre-test Trait Anxiety same 8 items used in modified version from

participants who completed the 20- item Form-Y. (cases N=38) STAI Trait Item Mean Cronbach’s Alpha Item total if item deleted. Correlation I feel nervous and restless. 1.92 .832 .347 I feel satisfied with myself. 1.92 .807 .578 I feel that difficulties are 1.61 .818 .492 piling up so that I cannot overcome them. I feel like a failure. 1.37 .821 .470 I have disturbing thoughts. 1.53 .814 .521 I lack self-confidence. 1.89 .781 .744 I feel secure. 1.53 .796 .655 I worry too much about 2.08 .800 .635 something that really does not matter. Cronbach’s Alpha - .830 Mean = 0.555


Appendix Table 1.8: Pre-test Trait Anxiety 20-item Form-Y. (cases N=38) STAI Trait Item Mean Cronbach’s Alpha Item total if item deleted. Correlation I feel pleasant. 1.71 .918 .643 I feel nervous and restless. 1.92 .923 .354 I feel satisfied with myself. 1. 92 .917 .679 I wish I could be as happy 1.63 .924 .390 as others seem to be. I feel like a failure. 1.37 .922 .455 I feel rested. 2.53 .923 .434 I feel calm, cool and collected. 2.34 .915 .739 I feel that difficulties are 1.61 .920 .515 piling up so that I cannot overcome them. I worry too much about 2.08 .917 .670 something that really does not matter. I am happy. 1.74 .917 .708 I have disturbing thoughts. 1.53 .920 .532 I lack self-confidence. 1.89 .916 .721 I feel secure. 1.53 .917 .689 I make decisions easily 2.03 .921 .507 I feel inadequate. 1.71 .923 .410 I am content. 1.76 .920 .559 Some unimportant thought 1.71 .919 .608 runs through my mind and bothers me. I take disappointments so 1.76 .915 .768 keenly that I can’t put them out of my mind. I am a steady person. 1.74 .913 .828 I get in a state of tension or 1.84 .919 .576 turmoil as I think over my recent concerns and interests.

Cronbachs’ Alpha - .923

Chronbachs’ Alpha = 0.945 for 8-item version and 0.830 for 8 items within the 20- item form are reasonably similar to the 20-item value 0.923 above.


POST-TEST STATE ANXIETY. Appendix Table 1.9: Post-test State Anxiety same 8 items used in modified version from participants who completed the 20- item Form-Y. (cases N=38) STAI StateItem Mean Cronbach’s Alpha Item total if item deleted. Correlation I feel calm 1.76 .887 .810 I am tense 1.71 .899 .684 I feel upset 1.34 .904 .610 I feel frightened 1.26 .900 .704 I feel nervous 1.53 .896 .706 I am relaxed 1.89 .898 .697 I am worried 1.63 .892 .754 I feel confused 1.29 .894 .779 Cronbach’s Alpha - .908 Mean = 0.718


Appendix Table 1.10: Post-test – State Anxiety 20 Item Form-Y. (cases N=37) STAI StateItem Mean Cronbach’s Alpha Item total if item deleted. Correlation I feel calm. 1.76 .949 .885 I feel secure. 1.49 .951 .826 I am tense. 1.68 .953 .618 I feel strained. 1.62 .951 .751 I feel at ease. 1.84 .951 .806 I feel upset. 1.30 .954 .592 I am presently 1.57 .953 .636 worried over possible misfortunes. I feel satisfied. 1.84 .955 .517 I feel frightened. 1.27 .953 .669 I feel comfortable. 1.57 .951 .809 I feel self-confident. 1.89 .952 .741 I feel nervous. 1.49 .953 .674 I am jittery. 1.32 .954 .570 I feel indecisive. 1.59 .952 .688 I am relaxed. 1.89 .951 .796 I feel content. 1.81 .953 .671 I am worried. 1.62 .952 .712 I feel confused. 1.30 .951 .806 I feel steady. 1.78 .953 .652 I feel pleasant. 1.70 .952 .710 Cronbachs’ Alpha - .954 Chronbachs’ Alpha = 0.902 for 8-item version and 0.908 for 8 items within the 20- item form are similar to the 20-item value 0.954 above.


POST-TEST TRAIT ANXIETY. Appendix Table 1.11: Post-test Trait Anxiety same 8 items used in modified version from participants who completed the 20- item Form-Y. (cases N=37) STAI Trait Item Mean Cronbach’s Alpha Item total if item deleted. Correlation I feel nervous and restless. 1.68 .852 .697 I feel satisfied with myself. 1.84 .844 .759 I feel that difficulties are 1.54 .858 .656 piling up so that I cannot overcome them. I feel like a failure. 1.30 .861 .632 I have disturbing thoughts. 1.38 .865 .593 I lack self-confidence. 1.70 .877 .458 I feel secure. 1.54 .848 .722 I worry too much about 1.84 .861 .625 something that really does not matter. Cronbach’s Alpha - .874 Mean = 0.643


Appendix Table 1.12: Post-test Trait Anxiety 20-item Form-Y. (cases N=36) STAI Trait Item Mean Cronbach’s Alpha Item total if item deleted. Correlation I feel pleasant. 1.69 .914 .757 I feel nervous and restless. 1.67 .915 .758 I feel satisfied with myself. 1.83 .914 .739 I wish I could be as happy 1.89 .950 .000 as others seem to be. I feel like a failure. 1.31 .918 .612 I feel rested. 2.50 .918 .554 I feel calm, cool and collected. 2.22 .912 .795 I feel that difficulties are 1.56 .917 .685 piling up so that I cannot overcome them. I worry too much about 1.83 .916 .640 something that really does not matter. I am happy. 1.72 .913 .793 I have disturbing thoughts. 1.36 .917 .698 I lack self-confidence. 1.69 .920 .446 I feel secure. 1.56 .915 .723 I make decisions easily 1.92 .915 .716 I feel inadequate. 1.61 .920 .457 I am content. 1.72 .912 .840 Some unimportant thought 1.56 .916 .701 runs through my mind and bothers me. I take disappointments so 1.75 .916 .659 keenly that I can’t put them out of my mind. I am a steady person. 1.83 .914 .728 I get in a state of tension or 1.61 .915 .708 turmoil as I think over my recent concerns and interests. Cronbachs’ Alpha - .921 Chronbachs’ Alpha = 0.908 for 8-item version and 0.874 for 8 items within the 20- item form are reasonably similar to the 20-item value 0.921 above.


External validity of scale.

External validity for the 8-item modified scale was determined by Pearson’s product

moment correlation coefficient (Pearson’s r) which explores the strength of the

relationship between two continuous variables to Psychosocial Adjustment to Illness

Scale) used in this study. This comparison is particularly valid for this comparison

because the data were collected at the same time points as the State and Trait Anxiety

data.

Appendix Table 1.13: Correlation of 8-item modified scale total score with PAIS (vii) Psychological Distress score and correlation of 20-item version with PAIS (vii) Psychological Distress score. Data collection point. Pearson’s r Pearson’s r

8-item modified scale 20-item original version

Pre-test State Anxiety .912** .631**

Pre-test Trait Anxiety .837** .712**

Post-test State Anxiety .921** .733**

Post-test Trait Anxiety .827** .327*

** correlation is significant at the 0.01 level (2-tailed) * correlation is significant at the 0.05 level (2-tailed)

In this study there was significant (p < .01) relationship between each 8-item score

and the PAIS Psychological distress score for the same data collection point.

Visual representations of these relationships are depicted in following scatterplots

(Figures 1.1, 1.2, 1.3 and 1.4).


Appendix Figure 1.1: Total score correlation of pre-test State Anxiety 1- 8 (cases N=17) with matched PAIS Psychological Distress item (cases N=17).

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Appendix Figure 1.2: Total score correlation of pre-test Trait Anxiety 1- 8 (cases N=17) with matched PAIS Psychological Distress item (cases N=17).

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Appendix Figure 1.3: Total score correlation of post-test State Anxiety 1- 8 (cases N=17) with matched PAIS Psychological Distress item (cases N=17).

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psyc

h di

stre

ssCorrelation:

PAIS psych distress (item vii) & STAI State post-test items 1-8


Appendix Figure 1.4: Total score correlation of post-test Trait 1- 8 (cases N=17) with matched PAIS Psychological Distress item (cases N=17).

25201510

trait total score 1-8

12.5

10

7.5

5

2.5

0

pais

vii p

sych

dis

tres

sCorrelation:

PAIS psych distress (item vii) & STAI Trait post-test items 1-8


Appendix 2.

ID CODE: ………………..

SCHOOL OF PUBLIC HEALTH QUT and the HYPERTENSION UNIT GREENSLOPES PRIVATE HOSPITAL DATE: ………………... 6-24 MONTHS POST-ADRENALECTOMY SUB-STUDY In the 6 to 24 months since you have had your adrenal gland removed … 1.0 Have you noticed any changes in your relationships with others at work? Yes /No 1.1 If you have answered “yes” please describe. _______________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ 1.2 Do you feel that these changes are in the main related to the removal of your

adrenal gland? Yes / No 1.3 Please state the reasons for your response.

___________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________

In the 6-24 months since you have had your adrenal gland removed…

2.0 Have you noticed any change in your relationship with your spouse or person you feel closest to? Yes / No 2.1 If you have answered “yes” please describe. _________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ 2.2 Do you feel that these changes are in the main related to the removal of your adrenal gland? Yes / No 2.3 Please state the reasons for your response. __________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ In the 6-24 months since you have had your adrenal gland removed…

3.0 Have you noticed any change in your relationships with your family? Yes / No


3.1 If you have answered “yes” please describe. _______________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ 3.2 Do you feel that these changes are in the main related to the removal of your adrenal gland? Yes / No 3.3 Please state the reasons for your response. ________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ In the 6-24 months since you have had your adrenal gland removed…

4.0 Have you noticed any changes in your social relationships? Yes / No 4.1 If you have answered “yes” please describe. _________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ 4.2 Do you feel that these changes are in the main related to the removal of your adrenal gland? Yes / No 4.3 Please state the reasons for your response. ___________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ In the 6-24 months since you have had your adrenal gland removed…

5.0 Has your spouse or person you feel closest to, noticed any change in your relationship with them? Yes / No 5.1 If you have answered “yes” please describe. ________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________6.0 Has your spouse or person you feel closest to noticed any change in your relationships at work? Yes / No 6.1 If you have answered “yes” please describe. _________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________


7.0 Has your spouse or person you feel closest to noticed any change in your relationships with the family? Yes / No 7.1 If you have answered “yes” please describe. ________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ 8.0 Has your spouse or person you feel closest to noticed any change in your relationships socially? Yes / No 8.1 If you have answered “yes” please describe. _______________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ In the 6-24 months since you have had your adrenal gland removed…

9.0 Have you noticed any changes (for better or worse) in your physical health? Yes / No 9.1 If you have answered “yes” please describe up to 5 physical changes (noting whether this change is for the better or the worse) beginning with the most important to you. 1._______________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ _____________________________________________________________2.___________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ _____________________________________________________________3.________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ 4.___________________________________________________________________ ________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ 5.___________________________________________________________________ ________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________



10.0 Have you noticed any change in the consistency of your moods? Yes / No 10.1 If you answered “yes” please describe. ____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ 11.0 Has your spouse or person to whom you feel closest noticed any change in the consistency of your moods? Yes / No 11.1 If you have answered ‘yes’ please describe. ____________________________________________________________________ ____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ 12.0 Have you noticed any change in the intensity of your emotional reactions? Yes

/ No 12.1 If you answered “yes” please describe. ____________________________________________________________________ ____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ 13.0 Has your spouse or person to whom you feel closest noticed any change in the intensity of your emotional reactions? Yes / No 13.1 If you answered “yes” please describe. ____________________________________________________________________ ____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ 14.0 Have you noticed any difference in the way you approach your day? For example, do you feel less or more “pressured” or “driven” since you have had your adrenal gland removed? Please describe. ____________________________________________________________________ ____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________



15.0 Have you noticed any difference in (i) the level of anger that you feel or (ii) how often you feel angry? Please describe. ____________________________________________________________________ (i)______________________________________________________________________________________________________________________________________ ii)______________________________________________________________________________________________________________________________________ 15.1 Have you noticed any change in the way/s in which you express your anger? Please describe. ____________________________________________________________________ ____________________________________________________________________________________________________________________________________________________________________________________________________________ In the 6-24 months since you have had your adrenal gland removed…

16.0 Have you noticed any difference in (i) the level of anxiety that you feel or (ii) how often you feel anxious? Please describe. (i)______________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ ii)______________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ 16.1 Is there a difference in the types of things you get anxious about? Please describe. ________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ Please do not write your name on this document, it is coded for confidentiality. IF YOU DO NOT HAVE ENOUGH ROOM TO WRITE ALL THAT YOU WISH, PLEASE NUMBER THE QUESTION YOU ARE REFERRING TO AND CONTINUE ON THE BACK OF THE PAGES. Thankyou. 17.0 Please include a record of 2-3 days of home blood pressure measurements done within the last month.


18.0 Please include a list of all of the medications that you are currently taking for any condition at all. Thankyou.