Endocrine Abstracts

Case history: A 53 year old lady was admitted with aggressive behaviour and confusion. Past medical history: Treated breast cancer 2017, no recurrence on mammogram 2021. Lifelong smoker. Initial investigations: persistent hypokalaemia with metabolic alkalosis, negative septic screen, unremarkable CT and MRI brain, failed lumbar puncture. Hypokalaemia only corrected with SandoK and spironolactone. She was empirically treated for encephalitis. CT TAP (septic screen): extensive mediastinal and hilar lymphadenopathy and bilateral bulky adrenals. Random cortisol, requested 15 days into admission, was 3059 nmol/l. O/E: Facial plethora, increased skin pigmentation, proximal myopathy and centripetal obesity.

Investigations: 24hr UFC >5000 nmol, ACTH 529 ng/l, 1 mg ODST cortisol >3300 nmol/l, TSH 1.5 mIU/l, HbA1c 44 mmol/mol.

Results and treatment: The diagnosis was ectopic Cushing’s syndrome. Metyrapone was started and uptitrated to 2 gm/day. She was moved to HDU for acute heart failure and severe agitation, where etomidate infusion was started. Rapid cortisol control was achieved with etomidate. A request for osilodrostat was made on compassionate grounds. Due to delay in procuring osilodrostat, she was initiated on mitotane, while etomidate was weaned. She was stepped down from HDU on metyrapone and mitotane. However, hypokalaemia and psychosis recurred with rising cortisol levels. Mitotane was stopped (potential neuropsychiatric toxicity) and metyrapone increased to 3 gm/day, while awaiting osilodrostat. Rapid deterioration ensued with desaturation and progressive CXR changes, without evidence of infection or heart failure. PCP prophylaxis was ongoing. She remained too unwell for bilateral adrenalectomy or invasive tissue diagnosis (EBUS or mediastinoscopy). Interval CT showed significant disease progression with new hepatic metastases. US-guided liver biopsy revealed metastatic small cell lung cancer, the likely source of ectopic ACTH secretion. Osilodrostat was only briefly given, as she deteriorated and passed away within a few days.

Conclusions and points for discussion: The clinical features of intense hypercortisolism include refractory hypokalaemia and metabolic alkalosis, as well as neuropsychiatric manifestations. Failure to recognise this constellation of features can lead to delay in diagnosing and managing both hypercortisolism and the underlying cause, often resulting in significant morbidity and even mortality. This case also illustrates the complexity in managing severe hypercortisolism with multiple agents which target the steroidogenesis pathway at different levels. 11 β-hydroxylase inhibitors include metyrapone and osilodrostat. Etomidate, an inhibitor of side chain cleavage and 11 β-hydroxylase, can achieve rapid cortisol control but requires administration in HDU. Mitotane, an adrenolytic agent, induces "chemical adrenalectomy".