Endocrine Abstracts

Background: Severe hypercortisolism from ectopic adrenocorticotropic (ACTH) secretion may be life-threatening. The lung is the most common site of ACTH secreting tumours, ranging from bronchial carcinoids to small cell lung carcinoma. Olfactory neuroblastomas (ONB) are rare malignant neuroectodermal tumours. They show neuroendocrine differentiation and may exhibit a wide variety of paraneoplastic syndromes including ectopic ACTH secretion (EAS). We report a case of EAS from a recurrent olfactory neuroblastoma.

Clinical Case: A 64-year-old male presented with an incidental laboratory finding of severe hypokalemia. He had a background of recurrent olfactory neuroblastoma with neck and dural metastases. He had undergone a resection of the tumour ten years ago, but subsequently experienced intracranial recurrence and slow progression of disease despite three lines of chemotherapy. He had been started on oral dexamethasone one week prior, to reduce the mass effect from the tumour edema. His potassium on admission was 2.2 mmol/l (reference range 3.6 – 5.0 mmol/l). It remained persistently low despite aggressive oral and intravenous replacements. Of note, his potassium level one month ago was normal. His main complaint was increasing lethargy and generalized weakness for the past one month. He had not been taking any new medications, supplements or licorice. Physical examination revealed marked cachexia with proximal myopathy, but no other discriminatory features of Cushing’s syndrome. Subsequent investigations revealed inappropriate urinary wasting of potassium. His 0800 hours cortisol (sample taken while on dexamethasone 8 mg twice daily) was 2996 nmol/l, with a markedly elevated ACTH at 429 pg/ml. 24 h urine cortisol collection returned at >18205 nmol/l (above the detection limit). Computed tomography imaging revealed unremarkable pulmonary parenchyma but noted interval development of diffuse bilateral adrenal thickening. Magnetic resonance imaging of the brain revealed progressive disease with enlarging dural metastases, and no sellar lesion. He was diagnosed with ectopic ACTH secretion secondary to recurrent olfactory neuroblastoma, resulting in rapid onset of hypokalemia and proximal myopathy, as well as ACTH-dependent bilateral adrenal hyperplasia. Dexamethasone was stopped promptly and he was commenced on oral ketoconazole. The dose was gradually escalated to 600 mg twice a day which achieved good control of his hypercortisolism, allowing for the oncologist to initiate systemic chemotherapy to control his disease.

Conclusion: Olfactory neuroblastoma is associated with a wide range of paraneoplastic syndromes including EAS. Aggressive tumours with EAS often present with rapid onset of clinical signs and symptoms including weight loss, hypokalemia and proximal myopathy. Ketoconazole is a useful therapeutic option in the management of EAS.