Endocrine Abstracts

Background: Hypokalaemia is a common biochemical presentation caused by increased potassium loss, intracellular shift, or reduced intake. Common causes include diuretic use and gastrointestinal losses. Rarer aetiologies involve sustained activation of mineralocorticoid receptors by elevated levels of circulating cortisol, as seen in Ectopic ACTH Syndrome (EAS).

Case Presentation: A 60-yr old lady presented with severe refractory hypokalaemia (1.8-2.9 mmol/l), psychosis and hypomania. There were no somatic features of Cushing’s syndrome. The patient had been diagnosed with small cell lung cancer (SCLC) 3 months prior. Ectopic ACTH secretion from SCLC was suspected in view of hypokalaemia refractory to treatment with intravenous and oral potassium supplements. Investigations showed marked hypercortisolaemia (midnight cortisol 4283 nmol/l), elevated ACTH (120 pmol/l), and a markedly raised ACTH precursor concentration (1712 pmol/l; normal < 40 pmol/l), indicating ACTH-dependent hypercortisolaemia. Low-dose 48-hour overnight dexamethasone suppression test showed unsuppressed cortisol (3658 nmol/l), confirming a syndrome of cortisol excess. Pituitary MRI and adrenal CT were normal. Treatment with Metyrapone was initiated to inhibit steroid synthesis and serum cortisol improved from 3658 to 1345 nmol/l after 9 days of therapy and potassium levels normalized in parallel. Adrenal blockade was combined with rescue Hydrocortisone therapy. The patient was referred for palliative radiotherapy.

Discussion: Ectopic ACTH secretion from a bronchogenic carcinoma may be associated with florid hypercortisolaemia without any somatic features of Cushing’s syndrome, due to malignancy induced cachexia. Refractory hypokalaemia in this context is highly indicative of ectopic ACTH-dependent hypercortisolaemia but the diagnosis may be challenging in the non-specialist environment of a general medical ward. ACTH precursors characterize EAS and are disproportionately elevated compared to serum ACTH. Patients with malignancy induced ectopic ACTH secretion and hypercortisolaemia have a uniformly poor prognosis. A high index of suspicion remains the cornerstone of diagnosis.