Ectopic ACTH secretion due to malignant tumours is a rare cause of hypercortisolism. Induced metabolic disturbances are often serious and the management of such patients may be difficult. We report the case of a 50-yr-old man who had a sporadic medullary thyroid carcinoma (MTC) removed 2 years ago (Dec/2003). Calcitonin and CEA levels remained high postoperatively and a CT scan revealed liver metastases. In August 2005 he was referred to Endocrinology with symptoms of muscular weakness of lower limbs, easy bruising, peripheral oedema, polyuria and polydipsia. These symptoms had begun 2 months earlier and at that time he was diagnosed with diabetes mellitus. He had a Cushingoid appearance, with truncal obesity, moon facies and plethora. Laboratory studies revealed an elevated 24 h urine free cortisol (3209.6 μg/dl). Baseline serum cortisol was 77.8 μg/dl (6.219.4) and changed to 80.6 and 56.8 after 2 mg and 8 mg dexamethasone suppression, respectively. Plasma ACTH was 122.0 pg/ml (< 46) and changed to 153.0 and 79.0 after dexamethasone. An adrenal CT scan showed no changes and an octreoscan didnt reveal any anomalous fixation areas. However, a PET scan demonstrated metastatic disease to the liver and lymph nodes and adrenal hyperplasia. Liver biopsy confirmed metastatic MTC with positive immunohistochemical stain for calcitonin and ACTH. He started treatment with metyrapone (achieving 3 g/day) with partial regression of symptoms and diminished urinary cortisol levels. In conclusion: The clinical presentation was significant by the severity and the rapidity of the hypercortisolism. The differential diagnosis of ACTH-dependent Cushings syndrome in this case included pituitary disease or ectopic ACTH secretion. Metastatic MTC was confirmed as the source of ectopic ACTH, by positive immunohistochemical ACTH stain on liver metastasis. This is an extremely rare association with a poor prognosis, which treatment isnt clearly defined. Removal of the source of ACTH is the treatment of choice, but often not feasible. If adrenalytic medical therapy fails to control the disease bilateral adrenalectomy should be considered.
01 - 05 Apr 2006
European Society of Endocrinology