Endocrine Abstracts

1% of western populations take chronic oral corticosteroids and this rises to 3% in subjects aged over 70 years old. When inhaled, topical and parenteral steroids are added to this burden, iatrogenic Cushing’s becomes a major health issue. High doses of medroxyprogesterone acetate can cause glucocorticoid effects and drug interactions may impair the metabolism of some glucocorticoids (eg fluticasone), thereby increasing their potency. Patients may develop the classical features of Cushing’s including growth failure, osteoporosis, myopathy and CVS risk factors all of which contribute to increased mortality. In our unpublished meta-analysis of 128 studies comprising 51,380 patients with inflammatory disease taking corticosteroid therapy, SMR was 1.84 (CI 1.27-2.41) with dose of glucocorticoid associated with higher SMR. Through the HPA feedback mechanism, iatrogenic Cushing’s leads to adrenal suppression and low endogenous cortisol levels. Adrenal suppression depends upon the potency of preparation used, its dose, route and duration of administration. There are no “hard and fast rules”, but adrenal suppression should be anticipated in any patient taking the equivalent of 7.5 mg prednisolone/day for over 3 weeks. The diagnosis relies on a low circulating cortisol concentration that fails to respond adequately following a short synacthen test (250 mg ACTH). Circulating ACTH concentrations may be reduced as are ACTH dependent steroids such as DHEAS. In the absence of an evidence base for management, a “treat whilst we wait” policy seems the safest way forward. Patients taking the daily equivalent of 7.5 mg prednisolone are unlikely to experience clinical features of adrenal withdrawal; however supplemental doses of steroid may be required in the event of intercurrent illness in patients taking <20 mg prednisolone/day or equivalent. Patients withdrawing from corticosteroids frequently experience fatigue, poor sleep, impaired QoL, arthralgia and have a risk of adrenal crisis. Patients should be issued with a Steroid Alert card and counselled regarding increasing steroid doses with stress/ intercurrent illness. Switching patients to tailored and more physiological doses of hydrocortisone is advocated by some. Clinical trials of selective inhibitors of 11b-HSD1 are underway in an attempt to mitigate against iatrogenic Cushings. Finally, ongoing education around surveillance, diagnosis and risk of adrenal crisis across patients and other clinical specialists is urgently required.