Endocrine Abstracts

Background: Long-term glucocorticoids can result in iatrogenic Cushing’s syndrome with adrenal suppression. Most patients reactivate their hypothalamic-pituitary-adrenal axis once they’re weaned off glucocorticoids. During glucocorticoid withdrawal, many clinicians switch patients to hydrocortisone to benefit from its short half-life¹. However, in some patients, hypothalamic-pituitary-adrenal axis recovery is delayed despite the above. It is unclear whether this could be related to persistent ongoing hydrocortisone overexposure. To investigate, we measured waking salivary cortisone (WSC), ACTH levels, blood pressure (BP), and body mass index (BMI) in patients on physiological doses of prednisolone and hydrocortisone with and without adrenal suppression after being weaned off high-dose glucocorticoids.

Method: A total of 99 patients on low-dose oral glucocorticoids (prednisolone≤5 mg/day, or immediate-release hydrocortisone≤25 mg/day) were assessed in a cross-sectional study. All patients were on glucocorticoids for more than 12 months. Patients with WSC levels >17 nmol/l were considered adrenal-sufficient, whereas those with levels<7 nmol/l, were adrenal-insufficient (AI). Patients with levels >7 nmol/l and<17 nmol/l had an ACTH-stimulation test, with a 30-minute post-Synacthen cortisol level >430 nmol/l confirming adrenal sufficiency. ACTH, BP, and BMI were measured on the day WSC was done.

Results: 58.6% (n=58) of this cohort had AI. 22% (n=13) of the AI cohort had a suppressed ACTH (<5 ng/l). In contrast, no adrenal-sufficient patients had a suppressed ACTH(<5 ng/l) (P=0.0006). Systolic BP (P=0.226), diastolic BP (P=0.968), and BMI (P=0.133) did not differ significantly between patients with AI and adrenal sufficiency. 48.3% (n=28) of patients with AI and 31.7%(n=13) with adrenal sufficiency were on hydrocortisone whilst the remaining were on prednisolone(P=0.146). Patients on hydrocortisone with AI had a significantly lower WSC than patients on prednisolone (median WSC:3.68 nmol/l [IQR:0.74-4.43] vs median WSC:6.94 nmol/l [IQR:1.40-8.34], respectively; P=0.0164) and 84.6%(n=11) of AI patients with a suppressed ACTH(<5 ng/l), were on hydrocortisone thrice daily(P=0.0046).

Conclusion: Our study suggests that overall adrenal suppression in patients on physiological glucocorticoid doses is unlikely to be related to continuing steroid overexposure as only 22% of the AI cohort had a suppressed ACTH(<5 ng/l) and steroid biomarkers were not raised. Conversely, patients on multiple immediate-release hydrocortisone doses were more likely to have adrenal suppression, as evidenced by a fully suppressed ACTH (<5 ng/l) and a lower WSC level when compared to patients on prednisolone, indicating a greater risk of overexposure which could delay adrenal recovery.

Reference: 1. Suehs et al. Oral Corticosteroids Tapering Delphi Expert Panel. Expert Consensus on the Tapering of Oral Corticosteroids for the Treatment of Asthma. A Delphi Study. Am J Respir Crit Care Med. 2021 Apr 1;203(7):871-881.