Diagnosis of Cortisol deficiency Robert Schmidli www.schmidli.com.au “Lectures”

Causes Primary: destruction of adrenal glands (Addison’s disease) Autoimmune Infectious (Tb, Meningococcal etc) Metastatic Haemorrhagic Secondary: ACTH deficiency – hypopituitarism Hypothalamic (“tertiary”)

Acute adrenal insufficiency Clinical suspicion essential Consider in Peripheral vascular collapse Unexplained hypoglycaemia NEVER DELAY TREATMENT OF ACUTE ADRENAL INSUFFICIENCY WHILE DIAGNOSTIC TESTS ARE PERFORMED

Chronic adrenal insufficiency Often overlooked Fatigue, lassitude “chronic fatigue syndrome” GI complaints Hyperpigmentation not present in secondary (pituitary) adrenal insufficiency

Other features Hyponatraemia GI symptoms – vomiting, abdominal pain Weight loss Weakness Confusion/psychiatric Coma Postural hypotension Salt craving Arthralgia, myalgia Hypercalcaemia (rare)

Secondary adrenal failure: associated features Amenorrhoea Galactorrhoea Erectile dysfunction, loss of libido Loss of body hair (♂) Hypothyroidism (usually not severe) Diabetes insipidus Growth failure (children) Acromegaly

Laboratory diagnosis Cortisol level ACTH status Primary diagnosis High in primary Low-normal in secondary Primary diagnosis Autoimmune adrenalitis (adrenal Ab) Others: Tb, metastatic, haemorrhage, infectious Pituitary disease

Cortisol level Must be measured in the morning Low level normal later in day May be done 12-24hr after short-acting glucocorticoid (Hydrocortisone/Cortisone) Measure 1 day after Prednisone/Prednisolone Change to Hydrocortisone/Cortisone if patient on long-acting glucocorticoid Limited sensitivity even at correct time Synacthen test more sensitive

Diurnal cortisol release Morning peak at 9am Midnight trough 06:00 12:00 18:00 24:00 06:00

Pitfalls “Subclinical” primary adrenal insufficiency Protein binding Normal Cortisol with high plasma ACTH Normal cortisol with impaired ACTH response Protein binding ↑ Cortisol binding globulin with Estrogens – false negatives No response if patient on long-acting steroids eg. Dexamethasone Synacthen test may be negative in secondary adrenal insufficiency 24-hour urinary Cortisol useless (Cushing’s only)

Diagnosis of secondary adrenal insufficiency (ACTH deficiency) 8am cortisol Synacthen test Insulin tolerance test “Gold standard” Potentially dangerous Requires adequate hypoglycaemia Must be performed in specialist department Increasing sensitivity Synacthen test probably best

Hypopituitarism: pitfalls TSH may be normal or marginally low: measure FT4 GH secretion pulsatile: IGF-1 more useful LH/FSH may be normal: need Testosterone in males Premenopausal ♀: menstrual history Postmenopausal ♀: low LH/FSH

Glucocorticoid withdrawal Often determined more by underlying condition than adrenal insufficiency Test HPA axis if acute withdrawal required (eg surgery, psychosis, infection etc) Symptoms may be confused with relapse of underlying disease (eg. polymyalgia) Can be tapered over 2-3 months

Space-occupying lesions of the pituitary (UpToDate®) Pituitary adenomas – functional/non-functional Craniopharyngioma Meningioma Cysts Abscesses Malignant tumours/metastases A-V fistulas Lymphocytic hypophysitis

Case reports Giant internal carotid artery aneurysm simulating pituitary adenoma. Arq Bras Endocrinol Metabol. 2006 Jun;50(3):558-63. Giant intrasellar carotid aneurysm - an unusual cause of panhypopituitarism. Exp Clin Endocrinol Diabetes. 2005 Oct;113(9):551-3 A further case of giant intrasellar carotid aneurysm mimicking a pituitary adenoma: the relevance of a multivariate approach in differential diagnosis. Ital J Neurol Sci. 1994 Oct;15(7):369-72 Giant intrasellar aneurysm presenting with panhypopituitarism and subarachnoid hemorrhage: case report and literature review. Clin Investig. 1994 Mar;72(4):302-6. Review. Large suprasellar aneurysms imitating pituitary tumour. J Neurol Neurosurg Psychiatry. 1978 Jan;41(1):83-7.

Giant aneurysms in pituitary fossa May be associated with pituitary tumours May follow pituitary irradiation or surgery Significant risk of rupture during surgery MRI investigation of choice for pituitary tumours (don’t do CT)