Adrenal insufficiency may occur because of primary failure of the adrenal cortex but can also arise through a secondary failure of ACTH drive to the adrenal. 'Endogenous' suppression of the adrenal cortex may occur in patients with structural abnormalities affecting the hypothalamus/pituitary and in other patients with deficiency of pituitary ACTH secretion and action including those recovering from successful treatment of Cushing's syndromes. 'Exogenous' suppression is found in patients taking supraphysiological doses of corticosteroids; approximately 1% of the UK population is taking chronic corticosteroid therapy that involves numerous different preparations through many routes (oral, rectal, topical, inhalation, ocular, nasal, synovial). This can occur in any patient taking the equivalent of 7.5mg/day prednisolone for greater than 3 weeks; the suppressive effects are both dose- and duration of treatment-dependant.
The diagnosis might be inferred on clinical grounds with patients demonstrating features of adrenal insufficiency (tiredness, joint and muscle aches and pains, dizziness, hyponatraemia) but mineralocorticoid secretion is preserved and signs and symptoms may be subtle. Debate surrounds the optimal biochemical diagnostic test. The insulin tolerance test is regarded as the 'gold standard' but requires close medical in-patient supervision. We have advocated the use of the conventional 250ug dose short synacthen test (SST); based on normative data a +30 minute cortisol of >550 nmol/L in our centre indicates an intact HPA axis - however this result is heavily assay specific. Although the correlation between peak cortisol response to an ITT and SST is excellent, individual discrepancies are reported, though very few reflect a false-positive SST. Nevertheless in a patient with an underlying diagnosis of Cushing's disease or a recent insult to the HPA axis, the response to SST may be falsely elevated. Other tests including the low dose SST (1ug), metyrapone test and CRF test have been advocated but confer no advantage to the conventional SST.