Critical illness may cause marked activation of the hypothalamic-pituitary-adrenal axis, mimicking ACTH-dependent Cushing syndrome, particularly when coinciding with incidental pituitary pathology.

A 67-year-old man underwent Hartmann's procedure for perforated diverticulitis after recent traumatic rib and scapular fractures. His postoperative course was complicated by wound dehiscence, intra-abdominal Candida infection, and 12 subsequent operations. Investigation for secondary hypothyroidism (TSH 0.05 mIU/L, fT4 2.0 pmol/L) revealed hypogonadotrophic hypogonadism, cortisol 2778 nmol/L, and ACTH 60 pmol/L. Cortisol failed to suppress following 8 mg dexamethasone (727 nmol/L; ACTH 32.6 pmol/L). He developed severe hypokalaemia (2.4 mmol/L) with suppressed renin and aldosterone, and new diabetes requiring temporary insulin therapy.

MRI demonstrated a 20 × 16 × 27 mm pituitary macroadenoma contacting the optic chiasm with bilateral cavernous sinus invasion. Whole-body CT identified no ectopic ACTH source. Despite the biochemical profile, serial examinations demonstrated no cushingoid features. Persistent hypercortisolaemia at 6 weeks (24-hour urinary free cortisol 1798 nmol/day; late-night salivary cortisol 17 nmol/L) prompted ketoconazole therapy for adrenal steroidogenesis inhibition.

Cortisol concentrations progressively declined, allowing cessation of ketoconazole on day 149. By day 182, serum cortisol, urinary free cortisol, and late-night salivary cortisol had normalised, with recovery of the hypothalamic-pituitary-gonadal axis, although ACTH remained mildly elevated. Visual fields remained intact and neurosurgical intervention was deferred.

This case demonstrates that profound, prolonged hypercortisolaemia during critical illness can closely mimic ACTH-dependent Cushing syndrome, particularly in the presence of an incidental pituitary macroadenoma. Although transient hypercortisolaemia is common in critically ill patients, the magnitude and duration observed in this case are unusual (1). The spontaneous resolution of hypercortisolaemia and recovery of pituitary function support a physiological stress response rather than autonomous cortisol excess. When clinically safe, endocrine abnormalities identified during critical illness should be reassessed following recovery before irreversible interventions, including pituitary surgery, are undertaken.