The search for ectopic ACTH production in a 9-year-old boy

Ectopic ACTH syndrome (EAS) is rare in children and is challenging to differentiate from Cushing's disease. A 9-year-old boy presented with a history of worsening fatigue, muscle weakness, weight gain and acne, and he appeared cushingoid with central obesity and hyperpigmentation of his palmar creases. Investigations demonstrated an elevated ACTH and an elevated morning cortisol that did not suppress with low or high dose dexamethasone suppression tests. Brain imaging inconsistently showed a small pituitary lesion. Chest and abdomen computed tomography (CT) showed adrenal hyperplasia and a liver hemangioma. [18F]fluorodeoxyglucose positron emission tomography CT was normal. Ultrasound and abdominal magnetic resonance imaging (MRI) also showed a liver hemangioma. Bilateral inferior petrosal sinus sampling, however, was consistent with ectopic ACTH production. An octreotide scan revealed a small focus of increased activity in the liver, which was the likely source of ectopic ACTH production. The patient was managed with metyrapone followed by a wedge liver resection. Pathology showed a well-differentiated neuroendocrine tumor (NET) that stained positive for ACTH. Post-operatively, the signs and symptoms of EAS are resolving and his hypothalamic-pituitary-adrenal axis is recovering. This case describes the first pediatric patient with EAS caused by a liver NET. It illustrates the challenges in localizing the source of ectopic ACTH and treating this rare condition.