A 77-year-old male presented with rapid onset peripheral oedema and proximal myopathy. Computed tomography revealed diffusely enlarged adrenal glands, liver metastases, and a small spiculated lung lesion. Cushing’s syndrome was confirmed with markedly elevated 24-hour urine free cortisol levels. The 8mg dexamethasone suppression test indicated an ectopic source of cortisol. FDG-PET revealed low grade uptake in the lung and hepatic lesions. Ga68-DOTATATE PET was negative. Core biopsy of a liver lesion confirmed metastatic neuroendocrine tumour (NET) with immunohistochemistry suggesting a primary lung origin. Metyrapone and ketoconazole successfully reduced 24-hour urine free cortisol but multiple complications of hypercortisolism still developed. The absence of DOTATATE uptake eliminated the possibility of peptide receptor radionuclide therapy (PRRT). Other management strategies of ectopic ACTH syndrome (EAS) were considered and bilateral adrenalectomy was ultimately performed. The metastatic NET was managed with active surveillance and remains stable after eight months.
EAS is a rare condition that reflects excessive ACTH secretion by NETs, most commonly by well-differentiated pulmonary NETs (1,2,3). Management of metastatic EAS requires consideration of the tumour risk against the hormonal risk. Options for tumour control are limited in metastatic EAS as there is minimal evidence for targeted therapies although PRRT may be effective (1,2,3). Management of hypercortisolism includes pharmacologic treatment, which is limited by tolerability and efficacy, or bilateral adrenalectomy, which is effective but associated with post-operative morbidity and permanent glucocorticoid requirement (1,2,4). In several large case series, bilateral adrenalectomy was required for most patients with metastatic disease and was associated with better survival (3,4,5,6). In conclusion, EAS is most commonly due to pulmonary NETs which often have an excellent tumour prognosis due to their indolent nature. In such cases, management of hypercortisolism is a priority and bilateral adrenalectomy may be required, particularly in patients with metastatic disease to provide effective long-term control.