Steroid withdrawal syndrome, the leading cause of adrenocortical insufficiency, results from the abrupt cessation of steroid therapy. The clinical picture includes non-specific features such as malaise, lethargy, low-grade fever, headache, myalgia, arthralgia, mood changes, etc. The diagnosis is confirmed with biochemical testing.
Steroid withdrawal syndrome, the most frequent causative factor of acute adrenocortical insufficiency, occurs in the context of a normal hypothalamic-pituitary-adrenal axis (HPA) . Its manifestations are related to glucocorticoid deficiency, which is a consequence of endogenous suppression of cortisol as a result of steroid therapy . Glucocorticoids are prescribed for its anti-inflammatory and immunosuppressive effects  for the management of autoimmune and inflammatory conditions, allergic reactions, and neoplastic diseases . Symptoms can develop in patients who have discontinued steroid therapy whether the drug was taken in multiple doses or just once, and even in healthy people without disease . Overall, this syndrome is self-limiting and can be treated with small doses of glucocorticoids . A very important consideration for individuals who have completed treatment is that exogenous glucocorticoids should be gradually and slowly tapered off to prevent adrenal insufficiency and its sequelae.
The presentation of steroid withdrawal syndrome shares similar characteristics to that of adrenal insufficiency . Specifically, the clinical picture may include malaise, weakness, lethargy, hyposthenia, nausea, emesis, anorexia, weight loss, diffuse headaches, postural hypotension, myalgia, arthralgia, mood changes, and emotional lability   . Patients may also develop a temporary low-grade fever . Additionally, skin desquamation may be observed in affected individuals  .
Studies have reported steroid withdrawal syndrome in pulmonary tuberculosis patients who tapered off prednisone and adrenocorticotropic hormone (ACTH) after using these therapies for 3 months and tapering off steroids over a period of 3 weeks . Another investigation noted that patients taking cortisone for chronic asthma also developed symptoms after cessation . Additionally, children on dexamethasone experienced such effects following discontinuation of the steroid .
When evaluating cases presenting with the above non-specific symptoms, it is imperative to elicit the medication list including the duration, frequency, dose, and last use of all drugs. In addition, the patient's complete medical history and physical exam are key components of the workup. Very importantly, the diagnosis of steroid withdrawal syndrome should be confirmed through the appropriate studies that test the integrity of the HPA axis .
The clinician should differentiate glucocorticoid therapy withdrawal from other cause of adrenal insufficiency . This can be achieved by obtaining the measurement of the 9 am cortisol levels . Note that a cortisol value below 100nmol/l is indicative of cortisol insufficiency while levels above 450nmol/l are likely normal .
Those with a level between 100nmol/l and 449nmol/l warrant further testing with stimulation tests . These include the short Synacthen test (SST) (a synthetic ACTH), glucagon stimulation test (GST), and insulin tolerance test (ITT), and others that are not commonly used . These will examine various components of the HPA axis. Note that GST and ITT are more invasive. Additionally, the SST demonstrates sensitivity and specificity for adrenal insufficiency.
Other pertinent studies include a complete blood count (CBC), electrolyte panel and serum calcium, renal function test, and thyroid function tests. A fever workup should also be done which should include blood and urine cultures, as well as chest X-ray .
Other than chest radiography, computed tomography (CT) scan of the adrenals and head scan can be performed to rule out other causes of adrenal insufficiency.
An electrocardiograph (ECG) should be obtained in medical emergencies.
Courtney CH, McAllister AS, McCance DR, et al. Comparison of one week 0900 h serum cortisol, low and standard dose synacthen tests with a 4 to 6 week insulin hypoglycaemia test after pituitary surgery in assessing HPA axis. Clin Endocrinol (Oxf). 2000;53(4):431–436.