HYPERADRENOCORTICISM

Jade Webster

Hyperadrenocorticism

Common endocrine condition Overproduction of cortisol

Results in signs of:PUPD PolyphagiaAlopeciaAbdominal distension

Types

Categorised into 2 types:

Pituitary Dependent Adrenal Dependent

Pituitary Dependent (PDH)

Overproduction of ACTH = Increased cortisol Majority of HAC dogs (85%) Mainly small breeds Middle aged – older (7-9yrs)

PDH

Radiotherapy Progression of disease : can form a

pituitary macroadenoma Neurological signs

Median survival time = 662-900 days (tx with trilostane)

Adrenal Dependent

Tumour of the Adrenal cortex produces excessive cortisol

Less common (15%) Large breeds Older dogs (11yrs) Median survival time = 353 days

ADH

50% benign and 50% malignant

Surgery: Adrenalectomy Progression of disease:

Malignancy is a possibility in 50% of these cases

Study

Involved 57 dogs from both first opinion (32 dogs) and referral hospitals (25 dogs)

All diagnosed with HAC Age Range = 4 – 17 years old Weight range = 2.3 - 38.5kg

Breeds involved Cross-breed (20) Jack Russell (7) Cocker Sp. (4) YRT (3) Shih-Tzu (3) WHWT (2) Springer Sp. (2) Bichon Frise (2) Schnauzer (2) Patterdale (1) Scottish Terrier (1)

Collie (2) SBT (1) Shetland Sheepdog (1) Affenpinscher (1) Beagle (1) Hungarian Viszla (1) CKCS (1) Flatcoat Ret. (1) Border Terrier (1) Red Setter (1) Shar Pei (1)

What tests were used to diagnose HAC?

Were the patients differentiated into PDH or ADH?

And if so, How were they differentiated?

Diagnostic tests

Cannot use basal cortisolNon-adrenal illness (NAI) can cause a high

circulating cortisol levelPulsatile action of ACTH

Therefore diagnosis of HAC based on other tests

Tests performed

ACTH LDDST 17-OH Urine Cortisol:Creatinine

ACTH Stimulation Test LDDST 17-OH Progesterone Urine Cortisol:Creatinine

ACTH stimulation test

HAC = exaggerated responsePost ACTH cortisol >600nmol/l

Sensitivity = 57-83% Specificity = 59-93%

ACTH Stimulation Test

ACTH Stim was performed on 45 dogs in the study

31 recorded as a positive result Positive Post ACTH ranged from 618-

1443 (mean 926) Negative Post ACTH ranged from 218-

651 (median 427)

LDDST

HAC response: either no suppression or suppression and then escape at 8h

8 hour >40nmol/l Sensitivity: 85-100% Specificity: 44-73%

LDDST performed in 20 dogs in study Of these 14 produced positive result

17-OH Progesterone

Precursor for cortisol

Increased in HAC and “atypical HAC”

Performed in 4 dogs in study

Urine cortisol:creatinine

Cortisol excreted in urine – reflection of cortisol release

Very sensitive (92%) Non-specific (21%)

Used in one case in the study as ACTH, LDDST and 17-OH were all negative but clinical signs strongly suggested HAC.

First Line Test

84%

16%

ACTH Stim Test LDDST

Test that confirmed diagnosis

67%

29%

2% 2%

ACTH LDDST17-OH TRILOSTANE

Differentiation

Ultrasound Endogenous ACTH LDDST

Differentiated

54% were differentiatedPDH = 25 cases (89%)ADH = 3 cases (11%)

29% cases in 1st opinion practice 90% cases in referral hospital

Ultrasound

PDH = Bilateral adrenomegaly ADH = Mass on adrenal gland

Ultrasound of adrenals performed in 24/53 dogs in study

95% of referral cases had adrenal ultrasound

15% of first opinion cases

Endogenous ACTH PDH = high ACTH (>28pg/ml) ADH = low ACTH (<5pg/ml) Used in 5 cases

All in referral centres Used alone in 2 of these

Rest were used in conjunction with ultrasound

LDDST

Suppression at 4hours and then escape suggest PDH

No suppression – either ADH or PDH Suggestive results were used to

differentiate alone in 7 cases6 in First opinion1 in Referral

Used in conjunction with ultrasound and endogenous ACTH

MRI

Used to diagnose PDH or following PDH diagnosis for planning of radiotherapy

Used in one case in the study as showed neuro signs and was diagnosed with a macroadenoma

Conclusions

ACTH was the most popular test of choice for diagnosing HAC

LDDST suggested as test of choiceHigher Sensitivity

Confusion over interpretation

UCCR

LDDST

17-OH

ACTH

Decreasing Sensitivity

Only 54% of dogs were differentiated

Simple test that can be performed in first opinion practice

Case Example - Sammy Diagnosed in first opinion practice with HAC

and was not differentiated The year following diagnosis

More PUPD Dx: diabetes insipidus. Responded to tx

6 months later represented for PUPD, weight loss and lethargyBelieved to be due to an over suppression

(Addisons) therefore decreased dose of trilostane 2 months later – presented for lying in lateral

recumbency and head banging

Limitations of Study

Assumptions of correct diagnosis History availability Information on diagnosis Absent values for Post ACTH/8hr

LDDST Assumptions of ultrasound

measurements made by first opinion vets

Important to differentiate

Not being done as often in first opinion practice as in referral hospitals

Endogenous ACTH – very simple

References Gould S.M, Baines E.A, Mannion P.A, Evans H and Herrtage M.E. (2001) Use of

endogenous ACTH concentration and adrenal ultrasonography to distinguish the cause of canine hyperadreocorticism. Journal of Small Animal Practice 42, 113-121

Behrend et al. (2012) Diagnosis of Spontaneous Canine Hyperadrenocorticism:ACVIM Consensus Statement (Small Animal). J Vet Intern Med 2013;27:1292–1304

Mooney C.T, Peterson M.E (2012) BSAVA Manual of Canine and Feline Endocrinology 4th ed.

Helm et al. (2011) A Comparison of Factors that Influence Survival in Dogs with Adrenal-Dependent Hyperadrenocorticism Treated with Mitotane or Trilostane. J Vet Intern Med 2011;25:251–260.

Chapman, P.S. et al (2003) Evaluation of the basal and post adrenocorticotrophic hormone serum concentrations of 17-hydroxyprogesterone for the diagnosis of hyperadrenocorticism in dogs. Veterinary Record 153, 77-775

Smiley L.E, Peterson M.E (1993) Evaluation of a urine cortisol:creatinine ratio as a screening test for hyperadrenocorticism in dogs. JVIM 7, 163-8

Ramsey I, Ristic J (2007) Diagnosis of canine hyperadrenocorticism. In Practice 2007;29:446-454

Acknowledgements

Thanks to Laura Cosgrove

Questions?