Endocrine Abstracts

A 68-year-old gentleman presented with proximal myopathy in association with severe hypokalaemia (K+ 2.3mmol/l) and metabolic alkalosis. He had recently been diagnosed with type 2 diabetes. His random cortisol was 1045nmol/l. His 24-h urinary free cortisol was 3536nmol/24 h, and midnight cortisol was 85nmol/l. On a low dose dexamethasone suppression test, his cortisol failed to suppress (cortisol 1195–983nmol/l, ACTH 275ng/l), consistent with ACTH-dependent Cushing’s syndrome. He was commenced on a block and replace regime with metyrapone and prednisolone; eplerenone was started to manage his hypokalaemia. His MRI pituitary was unremarkable. CT imaging showed bulky adrenal glands and a 2cm left supraclavicular lymph node (low level uptake on FDG-PET). This was biopsied and histology demonstrated a well-differentiated neuroendocrine tumour with a Ki-67 proliferation index of 2%. Immunohistochemistry was positive for calcitonin, TTF1 and CEA. A significantly raised plasma calcitonin of >38,000ng/l confirmed a diagnosis of medullary thyroid cancer with ectopic ACTH secretion. A total thyroidectomy was not possible owing to significant mediastinal involvement and therefore a large open biopsy was undertaken instead. Molecular analysis confirmed the presence of a somatic RET mutation. He was commenced on a tyrosine kinase inhibitor (Cabozantinib) and despite a substantial fall in his plasma calcitonin, he was unable to tolerate maximal therapy due to progressive side effects. Ten months into treatment, the decision was made to switch to Selpercatinib with subsequent normalisation of plasma calcitonin (11ng/l) and all lesions decreased in size on CT. Furthermore, he was able to stop metyrapone and dynamic testing confirmed remission of his Cushing’s syndrome. A new diagnosis of Cushing’s syndrome may present in a variety of different ways. This case illustrates a rare presentation in association with medullary thyroid carcinoma that had an excellent response to tyrosine kinase inhibitors.