One percent of the UK population takes 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 Cushings becomes a major health issue. High doses of medroxyprogesterone acetate can cause glucocorticoid effects and drug interactions may impair the metabolism of some glucocorticoids (e.g. fluticasone), thereby increasing their potency. In each case, patients may develop the classical features of Cushings including growth failure (nb childhood asthma) osteoporosis, myopathy and CVS risk factors all of which contribute to an increased mortality rate.
Through the HPA feedback mechanism, iatrogenic Cushings leads to adrenal suppression and low endogenous cortisol levels. A further specific example of this is the tertiary adrenal failure that occurs in patients recovering from surgical treatment of Cushings syndrome either selective removal of an ACTH-secreting pituitary tumour or a unilateral autonomous cortisol-secreting adrenal adenoma. Here, adrenal suppression may last many months/years until the residual pituitary corticotrophs awaken.
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. Single courses of high dose glucocorticoids given for three weeks or less are unlikely to cause clinically significant adrenal suppression.
The diagnosis is made on the basis of a low circulating cortisol concentration that fails to rise adequately (in our centre <525 nmol/l) following a short synacthen test (250 μg ACTH). Circulating ACTH concentrations may be reduced as are ACTH dependent steroids such as DHEAS. Other stimulation tests such as insulin tolerance test and CRF tests have been used to diagnose adrenal suppression.
In a patient taking the daily equivalent of 7.5 mg prednisolone, clinical features of adrenal withdrawal are unlikely; 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 tiredness, poor sleep, impaired QoL, troublesome arthralgia and have a real risk of an adrenal crisis. All such patients should be issued with a Steroid Alert card and carefully counselled regarding increasing steroid doses with stress/intercurrent illness. Switching patients to tailored and more physiological doses of hydrocortisone with regular assessment of HPA function through basal cortisol measures off treatment and SSTs is recommended. In some cases, despite best efforts complete withdrawal of corticosteroids is not possible and long term replacement therapy is then required.