We present 78-year-old man who presented to Ryde hospital with two weeks of generalised malaise, breathlessness and lower limb oedema. On presentation, serum potassium was 2.1 mmol/L, falling to 1.8 mmol/L despite IV replacement. Fasted morning bloods showed ACTH 242ng/L (0 – 47), and cortisol 1,590nmol/L (140 – 630). Overnight dexamethasone suppression test (DST) showed no reduction in cortisol. 24-hour urinary free cortisol was 4,818nmol (60–270). High-dose DST with 2mg QDS for 2 days returned cortisol of 1,230nmol and 1,360nmol. Abdominal ultrasound US showed three echogenic lesions in the liver. Subsequent triple phase CT scan revealed a right upper lobe primary bronchogenic neoplasm with hepatic and bilateral adrenal metastases. Biopsy of a liver lesion was consistent with small-cell lung cancer. Immunohistochemistry stained positive for synaptophysin, chromogranin, INSM1, CD 56, TTF1 but additional stain for ACTH was negative.
The patient required daily 90 mmol IV potassium and 84 mmol oral potassium for maintenance. He commenced 11b-hydroxylase inhibitors to block cortisol biosynthesis and control symptoms, initially with metyrapone 250 mg BD and subsequently, ketoconazole 200 mg BD. He responded with greatly reduced potassium replacement requirements. The patient tolerated the treatment well. Through extensive consultations with Endocrinology and Oncology services, he eventually declined definitive management with bilateral adrenalectomy or chemotherapy and was managed palliatively with continued medical management of hypercortisolism and remained comfortable throughout his end-of-life-care.
Endogenous Cushing’s syndrome is rare, with an incidence of 0.7–2.4 per million population per year. Ectopic ACTH producing tumours are responsible for approximately 5–10% of these cases. The prognosis for ectopic ACTH syndrome depends on the source of ACTH production however outcomes are shown to be favourable when curative treatment is undertaken. When curative treatment is not possible, medical management is highly effective at managing the symptoms and improving the quality of life of the patient.