Predictive Accuracy of Delta Cortisol on Recovery of Adrenal Function in Patients With Drug Induced Cushing’s Syndrome With Secondary Adrenal Insufficiency

Abstract

There is a growing concern upon the finding of many drug induced Cushing’s syndrome because of inadvertent use of glucocorticoids (GC) either prescribed or as alternative medicine in Myanmar. These patients are presenting with diversity of clinical problems ranging from hypertension, diabetes to acute adrenal crisis due to hypothalamic-pituitary-adrenal (HPA) axis suppression and secondary adrenal insufficiency (AI). The present study aimed to assess the delta cortisol (the degree of cortisol increments) during the first short Synacthen test (SST) as a factor predictive of adrenal function recovery in patients with drug induced Cushing’ syndrome with secondary AI and to determine the proportion of patients who recovered from AI within six-month follow-up. This was a hospital based prospective analytical study that enrolled a total of 52 patients with drug induced Cushing’s syndrome with secondary AI from January 2018 to June 2019. Secondary AI is defined by morning basal serum cortisol ≤ 400 nmol/L with Synacthen stimulated peak cortisol level ≤ 550 nmol/L and serum ACTH < 60 pg/ml. The follow-up SSTs were performed at three-month and six-month after first SST, and the patients with morning basal serum cortisol > 400 nmol/L (or) Synacthen stimulated peak serum cortisol > 550 nmol/L during follow-up SSTs are defined as recovered adrenal function group. In this study, a total of 52 patients were treated with modified regimen of physiological dose of prednisolone with tapering schedule or stress dose GC based on the basal serum cortisol levels up to six months. Among them, nearly half (n=25 / 48.1%) of the patients with drug induced Cushing’s syndrome with secondary AI achieved normal adrenal function within six-month follow-up. It was found that mean values for delta cortisol were not statistically significant between recovered and non-recovered groups, 118.6 nmol/L (SD 72.3) and 97.2 nmol/L (SD 64.2) respectively. The delta cortisol during the first SST could not predict strongly (AUC - 0.6, 95% CI - 0.44 to 0.76, P = 0.2) the recovery of adrenal function in patients with drug induced Cushing’s syndrome with secondary AI and it was inconsistent with previous studies. The older age of the patients, oral route of administration of drugs causing Cushing’s syndrome and comorbid hypertension were found to be more significant in the non-recovered group. In conclusion, the present study did not support the evidence that the delta cortisol during the first SST could predict adrenal function recovery in patients with drug induced Cushing’ syndrome with secondary AI. Reference: (1) Baek et al., 2016; Recovery of Adrenal Function in Patients with Glucocorticoids Induced Secondary AI. Endocrinol Metab.31, pp. 153–160. (2) Pofi et al., 2018; The Short Synacthen Test Can Be Used to Predict Recovery of HPA Axis Function. J Clin Endocrinol Metab.103(8), pp. 3050–3059.