1. Diagnosis of Cortisol deficiency
Robert Schmidli
“Lectures”

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

3. 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

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

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

6. 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

7. 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

8. 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

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

10. 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)

11. 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

12. 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

13. 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

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

15. Case reports
Giant internal carotid artery aneurysm simulating pituitary adenoma. Arq Bras Endocrinol Metabol Jun;50(3):
Giant intrasellar carotid aneurysm - an unusual cause of panhypopituitarism. Exp Clin Endocrinol Diabetes 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 Oct;15(7):369-72
Giant intrasellar aneurysm presenting with panhypopituitarism and subarachnoid hemorrhage: case report and literature review. Clin Investig Mar;72(4): Review.
Large suprasellar aneurysms imitating pituitary tumour. J Neurol Neurosurg Psychiatry Jan;41(1):83-7.

16. 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)