the adrenal glands

FRCS (Gen Surgery): A Road to Success.1st Edition, Doctors Academy Publications, Cardiff, UK, December 2013

The adrenal glandsPradip K Datta

139

Pradip K DattaTHE ADRENAL GLANDS

Questions with regard to the adrenal glands may be encountered in any part of the examination. In the critical care oral the role of therenin-angiotensin-aldosterone system in metabolic response to trauma is asked. The candidate must be well versed with the basicphysiology of the adrenal gland. Surgical conditions affecting the adrenal cortex and medulla may be asked including principles ofoperative surgery, particularly laparoscopic adrenalectomy. In the clinicals a patient with Cushings from adrenal disease (preoperative orpostoperative) may be shown as may a surgically treated phaeochromocytoma patient.

Synopsis

The following conditions are discussed. You are expected to match the diagnosis with the clinical features.

1. Addison’s disease

2. Conn’s syndrome

3. Cushing’s syndrome

4. Incidentaloma

5. Phaeochromocytoma

Diagnoses

Clinical features

A. A 48-year-old man underwent an abdominal CT scan for clinical features of chronic pancreatitis. Besides confirming the findingssuggestive of chronic pancreatitis, the scan also showed a mass in his right adrenal gland.

B. A 45-year-old man complains of headaches, palpitations and sweating and a general feeling of malaise and weakness from time totime over the last six months. Before that on a couple of occasions some of these symptoms came on while training in the gym.His general practitioner (GP) found he had a blood pressure of 180/120 mm Hg.

C. A 38-year-old woman presents with unexplained increase in weight over the last six months. Her family noticed that her facelooked puffy and she noticed some changes in the appearance of her abdominal skin reminiscent of her pregnancy several yearsago. She is embarrassed by growth of hair on her upper lip and has recently become a type 2 diabetic and has amenorrhoea.

D. A 52-year-old woman complains of lethargy, weight loss (10 kgs in 4 months), diarrhoea, intermittent vomiting and vague colickyabdominal pain and muscle cramps for three months. Recently she developed patchy greyish-brown pigmentation on her back,face and nails. She underwent a mastectomy for breast carcinoma 3-years-ago and a hemiarthroplasty of her hip for secondariesa-year-ago.

E. A 40-year-old woman complains of increased thirst, passing increased amounts of urine, episodes of feeling weak with musclecramps. The muscle weakness can be severe enough for her to feel as though there is episodic paralysis. Her GP performedroutine biochemical blood tests which showed serum potassium ranging from 1.8 – 2.4 mmol/L repeatedly and a blood pressureof 150/90 mm Hg.

140 The adrenal glandsPradip K Datta


Answer to question 1 : D

Addison’s disease

Questions

1. What are the causes of this condition?

2. Describe the management.

3. Describe briefly the physiology of the adrenal gland.

Answers

1. Addison’s disease causes hypoadrenalism, the clinical features being the outcome of adrenocortical deficiency. For symptoms tobe apparent, almost 90% of the gland has to be diseased; diagnosis is often not made promptly. Because of the negative feedback,ACTH levels are raised; this may manifest as circumoral hyperpigmentation and also of the skin. The cause of Addison’s diseasein the majority is due to an autoimmune process. In areas where tuberculosis is common, it is often a cause; HIV infection alsomay lead to this. In this patient it is almost certainly from secondary metastasis. A third of patients with cancer will have adrenalsecondaries although few will exhibit hypoadrenalism.

The condition may rarely occur acutely as a complication of meningococcal septicaemia. Other emergency presentation may bein a patient who has the disease undiagnosed and falls ill from septic shock.

2. The management is to confirm the diagnosis and the presence of adrenal secondaries. This can be proven by a CT scan. Bloodinvestigations will show a high basal ACTH level and a low plasma cortisol which fails to respond to administartion of ACTH. Thepatient needs to be under the care of an endocrinologist. Lifelong glucocorticoid and mineralococorticoid therapy is instituted.The patient must carry a ‘steroid card’ with advice to increase the dose in case of any medical emergency.

3. The physiology of the adrenal gland is described in Figures 16.1, 16.2 (a, b, c, d) and 16.3 (a, b).

Diagnoses matched with clinical features and images

Anterior Pituitary

Adrenocorticotrophic Hormone (ACTH) acts on Adrenal Cortex

MineralocorticoidAldosterone(from zona

glomerulosa)

GlucocorticoidCortisol and Corticosterone

(from zona fasciculata

Sex hormonesDehydroepiandrosterone Androstenidione

(from zonareticularis)

Figure 16.1: Adrenal Gland.

Angiotensin II byRAS (Renin-Angiotensin-System) also controls



141

Adrenal Cortex : secretes steroid hormones derived from cholesterol

Zona GlomerulosaProduces Mineralocorticoids

Aldosterone

Zona FasciculataProduces Glucocorticoids

(cortisol/steroids)

Zona ReticularisProduces sex hormones

Figure 16.2a: Adrenal Gland.

Mineralocorticoid(from zona glomerulosa)

RAS (Angiotensin II) Aldosterone

↑ Reabsorption of Na from distal convoluted tubule

↑ Water reabsorption, ECF and plasma

↑ Systemic filling pressure, venous return, CO and BP

Helps in long term BP regulation

Figure 16.2b: Adrenal Gland.

Glucocorticoid(from zona fasciculata)

• Utilisation of protein in muscles → increased plasma amino acid levels → thus helpingin heat and energy production

• Increased gluconeogenesis• Inhibition of ACTH by negative feedback• Helps in stress response – essential for survival: Stress → ↑ACTH → ↑Glucocorticoids

→ Metabolic Response to Trauma• Anti-allergic• Anti-inflammatory• Increased RBC, WBC and platelets

Figure 16.2c: Adrenal Gland.

Sex Hormones(from zona reticularis)

• Contributes to 20% of androgenic activity• Exerts very little masculinising effect in normal amounts• Promotes protein metabolism and growth• Androstenidione is converted into oestrogens but the amount is too small to have any

physiologic effect

Figure 16.2d: Adrenal Gland.



Secretion is under the control of SympatheticNervous System80% of cells secrete Adrenaline20% of cells secrete Noradrenailne and Dopamine

Stress

Hypothalamus

Medulla oblongata

Preganglionicsympathetic nerves

Adrenaline

Figure 16.3a: Adrenal Gland.

Adrenal medulla is responsible for‘Fight or Flight Function’

• Constricts cutaneous blood vessels → Pallor• Dilates arterioles of skeletal muscle• Excites cardiac muscle → Tachycardia and increase in cardiac output• Relaxes bronchiolar muscles → more air to alveoli• Stimulates respiration• Inhibits digestive tract• Mobilises muscle and liver glycogen – increases blood sugar: diabetes of stress• Increases BMR• Contracts gut sphincters• Contracts ureters• Inhibits wall of urinary bladder• Increases blood coagulability

Figure 16.3b: Adrenal Gland.



143

Answer to question 2 : E

Conn’s syndrome (Primary hyperaldosteronism)

Questions

1. How would you confirm the diagnosis?

2. What is the treatment?

Answers

1. The condition is strongly suspected when the patient has hypokalaemia in the presence of hypertension. Muscle weakness and fatigue is from hypokalaemia. Polyuria and polydypsia result from inability of the kidney to concentrate urine. However, thesepatients may be on antihypertensives and diuretics; these should be stopped for four weeks prior to repeating the biochemicalinvestigations. At the same time the aldosterone to plasma renin activity ratio is assessed; a reading of > 50 is diagnostic ofprimary hyperaldosteronism.

Imaging to localise the pathology is performed by CT and MRI scanning to distinguish between adenoma and micronodularhyperplasia. Adenomas usually are 1 to 2 cm in size and the vast majority are detected by CT. Selective adrenal venous samplingmay be resorted to in case of doubt. But this investigation is invasive and hazardous because adrenal haemorrhage and necrosisare complications.

2. The treatment in bilateral hyperplasia is medical with spironolactone and antihypertensive drugs. In case of adenoma, laparoscopicadrenalectomy is the treatment of choice although, in a minority, the hypertension might persist albeit to a lesser degree. Sutotaladrenalectomy, removing only the tumour, may be feasible in some cases.



Figure 16.4b: Adrenal tumour(same patient).

Answer to question 3 : C

Cushing’s syndrome

Figure 16.4a: Preoperative.



145

Figure 16.4c: Postoperative patient.Courtesy of: Dr. Nissanka Jayawardhana MB BS ,MS, FRCSEd, Consultant General Surgeon, District General HospitalKegalle, Sri Lanka.

Questions

1. How is this condition caused?

2. How will you confirm the diagnosis?

3. What is the treatment?

Answers

1. Cushing’s syndrome results from excessive secretion of cortisol. The disease predominantly affects females. The majority (85%) ofcases are caused by increased ACTH secretion from a pituitary adenoma when the condition is referred to as Cushing’s disease. Inapproximately 15% the condition is caused by an adrenocortical adenoma (Figure 16.4a, b, c) when the ACTH levels are low. Rarecauses of ACTH-dependent disease are paraneoplastic syndromes where ectopic ACTH is produced from small cell lung cancer,carcinoid tumours and medullary thyroid carcinoma.

2.

Figure 16.5a: Clinical features of Cushing’s syndrome.



After thorough clinical examination (Figure 16.5a, b), confirmation of diagnosis is by two sets of investigations: Blood tests andimaging studies.

Blood tests

• The common cause, ie., an ACTH dependent tumour from a pituitary adenoma must first be excluded. Plasma ACTH level ismeasured by radioimmunoassay – adrenal cause will show low or undetectable ACTH level (< 10 pg/ml); those with pituitaryadenomas will have normal or high levels whilst ectopic ACTH tumours will demonstrate very high levels.

• Circadian rhythm of plasma cortisol levels: samples taken in the morning and midnight show marked variation in normalsubjects. In Cushings high levels are seen in midnight samples and the diurnal rhythm is lost.

• Dexamethasone suppression test: there will be no fall in cortisol levels in adrenal and ectopic ACTH lesions. Pituitary disease(ACTH-dependent) will produce low cortisol levels.

Imaging

• In the presence of normal or elevated ACTH levels, the pituitary is imaged by MRI scan which will localise up to 85% of thetumours. If the MRI scan is normal it raises the possibilty of a pituitary microadenoma. Then bilateral selective venous samplingof inferior petrosal sinus (by a vascular radiologist) is carried out. A CT of the chest and abdomen is performed to excludeectopic ACTH producing tumour. In the presence of low ACTH levels, a CT and /or MRI will detect an adrenal tumour.

3. The treatment is surgical. However, prior to surgery preoperative optimisation is essential to contol diabetes and hypertension;precautions are taken against hospital-acquired infections, deep vein thrombosis and pulmonary embolism. Laparoscopicadrenalectomy is the procedure of choice. However, tumours larger than 7 cm are removed by open procedure.

Ectopic ACTH producing tumour is resected if possible. Cushing’s syndrome from a pituitary adenoma is treated by trans-sphenoidal resection.

Figure 16.5b: Diagrammatic representation of clinical features of a patient withCushing’s syndrome ‘Lemon on match-sticks’.



147

Answer to question 4 : A

Incidentaloma

Questions

1. What do you understand by incidentaloma?

2. What is the management?

Answers

1. As the terminology implies, an incidentaloma is a space-occupying lesion found incidentally. This happens in 1% of patients whena CT scan is carried out for a reason other than suspected adrenal disease. However, at post mortems the incidence ofunsuspected adrenal masses can be up to 6%. Almost three-quarters of these masses are benign non-functioning adenomas.However, very rarely, every type of adrenal pathology has been known to have been discovered in this manner. It is said that 4%of incidentalomas turn out to be phaeochromocytomas.

If a patient is known to have been treated for cancer, an adrenal metastasis may be the likely cause of the mass. The larger themass, the greater are the chances of it being an adrenocortical carcinoma.

2. The management depends on the size; 4 cm is regarded as the cut-off point when any mass that is larger should merit furtherinvestigations. A detailed history and clinical examination followed by biochemical and hormonal investigations on the linesdetailed above are carried out. CT and MRI are performed. If the patient is known to have been treated for cancer which has apotential for distant metastases, consideration should be given to a CT-guided biopsy. However, this should never be done untilphaeochromocytoma has been definitely excluded.

If there has been a good recurrence free period following removal of the primary cancer, and the adrenal is the sole site of distantmetastasis, then adrenalectomy should be considered for a worthwhile cancer-free future. Breast, colon, lung, melanoma andkidney have been known to metastasise to the adrenals.

When the incidentaloma is less than 4 cm without any proof of endocrine or other sinister pathology, observation by annualscreening to monitor the size is acceptable after full informed consent. However with the advent of laparoscopic adrenalectomy,the threshold for the removal of incidentalomas is becoming less than 4 cm.



Answer to question 5 : B

Phaeochromocytoma

Questions

1. What is this tumour and how would you confirm the diagnosis?

2. Outline your management.

3. Discuss the approaches to adrenalectomy.

Answers

1. This is a catecholamine producing tumour, 90% of them arising from the adrenal medulla whilst the remainder arise from extra-adrenal sites of chromaffin cells. Because of its particular nature of originating in extra-adrenal tissue in 10%, bilateral in 10%,malignant in 10%, seen in children in 10% and familial in 10% where it is a part of MEN syndromes 2A and 2B, the tumour is oftencalled a ’10 per cent tumour’. Hypertension, sustained or episodic and resistant to antihypertensives, should alert one to thepresence of this tumour. Episodes of a combination of palpitations, headaches, sweating, tachycardia, abdominal pain andvomiting – a reflection of a sudden release of catecholamines is typical of the condition.

The diagnosis is confirmed by biochemical studies followed by imaging.

• Biochemical tests of urinary metabolities – breakdown products of adrenaline and noradrenaline in 24-hour urine collection ismeasured. Metanephrine (0-6.5 ìmol/24 hr) and vanillylmandelic acid (0-35 ìmol/24 hr) estimations should be done on twoseparate occasions, the former being much more sensitive.

• Imaging – MRI scan is preferred to CT because contrast used for the latter may provoke an acute hypertensive episode. Theformer is regarded as better in identifying extra-adrenal tumours. 123 I-MIBG (metaiodobenzylguanidine) single photon emissiontomography will identify the vast majority of primary tumours and those of extra-adrenal origin.

2. Pre-operative: The diagnosis having been made, successful management requires close team-working between the surgeon,endocrinologist and the anaesthetist. Pre-operative optimisation is essential. This may commence as soon as the diagnosis is madeand whilst awaiting localisation of the tumour. Initially blood pressure is controlled by a course of α-adrenergic blocker(phenoxybenzamine) which allows intravascular volume expansion. After adequate α-blockade, the patient is next treated with β-blockers to control tachycardia.

Peri-operative: The critical periods in the operating theatre when hypertensive or hypotensive crises may arise are when anaesthesiais being induced, during intubation and per-operative tumour handling. Meticulous intra-operative monitoring with CVP andarterial lines, ECG and urinary catheter are mandatory; the use of a Swan-Ganz catheter may be considered in case of catecholaminecardiomyopathy.

The operation: For the approach, see below. Minimal tumour handling and meticulous haemostasis are the key features of surgicaltechnique.

Postoperative period: The patient should be in the ICU with careful monitoring of the patient’s preload and cardiac function.Postoperative hypotension should be very closely monitored. Hypotension should not always be presumed to be due to vasodilatationfollowing loss of vasoconstrictor tone due to removal of the tumour; persistent hypotension should alert the surgeon to secondaryhaemorrhage. Blood glucose is also closely monitored to prevent hypoglycaemia.

3. The size of the tumour permitting, the ideal approach nowadays is by the laparoscopic route which is regarded as the gold standardfor benign adrenal tumours. Some centres are now adopting this approach for malignant tumours with good oncological outcomes.However, for malignant tumours, open operation is still the favoured approach because of the large size of the tumour.Retroperitoneoscopic approach through the lumbar route is another approach which gives a good view and proponents maintainthat vascular control is simpler.

Laparoscopic adrenalectomy is often performed by the hepatobiliary surgeon because of the experience of laparoscopic surgeryand hepatic mobilisation in right-sided procedures. Experience and careful dissection should prevent iatrogenic damage to theinferior vena cava, renal vein, tail of pancreas or spleen. A team management with a dedicated anaesthetist and an endocrinephysician is essential for successful laparoscopic adrenal surgery. Open surgery is performed through a midline or a subcostalincision. Bilateral tumours are approached by rooftop incision. Ectopic tumours are approached by the appropriate incisiondictated by the exact site of the tumour.

the adrenal glands

Documents