Endocrine Abstracts

Background: Loperamide, a peripherally acting μ-opioid receptor agonist, is commonly used for diarrhoea management and control of high output stomas. Due to limited CNS penetration from P-glycoprotein efflux at the blood brain barrier, it is considered safe at therapeutic doses. However, in supra therapeutic doses, loperamide may cross the blood brain barrier and suppress the hypothalamic pituitary adrenal (HPA) axis, leading to central adrenal insufficiency (CAI). Such cases remain exceptionally rare (1).

Case Presentation: A 56-year-old woman presented with persistent hypotension, profound fatigue, and marked unintentional weight loss after emergency surgery with loop ileostomy for small bowel necrosis. Initial symptoms were attributed to postoperative stress and volume depletion. She was self administering loperamide up to 64 mg/day, four times the recommended maximum, to manage high stoma output. Despite adequate fluid and electrolyte optimisation, symptoms persisted. Endocrine evaluation demonstrated CAI (Table 1). Other pituitary axes were intact. Pituitary magnetic resonance imaging found a small 3.4 mm incidental Rathke’s cleft cyst deemed benign and stable with no mass effect.

Management and Outcome: Hydrocortisone replacement therapy led to rapid clinical improvement. Loperamide was tapered down to recommended limits. Over 12 months, adrenal function normalised (0/30 min cortisol 527/864 nmol/l), permitting successful hydrocortisone withdrawal.

Conclusion: This case highlights a rare but reversible form of CAI secondary to supratherapeutic loperamide use. Clinicians should maintain vigilance for drug induced HPA axis suppression in patients with unexplained fatigue or hypotension. Prompt recognition, steroid replacement, and rationalisation of therapy are critical for preventing morbidity and ensuring full endocrine recovery.

Reference: 1. Napier C, Gan EH, Pearce SH. Loperamide-induced hypopituitarism. BMJ Case Rep. 2016;2016:bcr2016216384. Published 2016 Sep 28. doi: 10.1136/bcr-2016-216384