ODP477 Ectopic Cushing's Syndrome Due to Medullary Thyroid Cancer
Authors: Mateen Abdul , Alameri Majid , Alnuaimi Abdulla , Marco Aimee D , Wernig Florian 
Published: November 2022

Introduction

Medullary thyroid carcinoma (MTC) is an uncommon aetiology of ectopic ACTH syndrome. Ectopic ACTH secretion has been reported in 0.7% of MTCs; it usually occurs in metastatic MTC and has been associated with increased mortality.

Case presentation

A 65-year-old male with a history of diabetes, hypertension and schizophrenia presented with confusion and upper respiratory symptoms. Initial evaluation showed hypokalaemia, hypocalcaemia, hypomagnesaemia and metabolic alkalosis with random plasma cortisol of 1045 nmol/L. He did not have any cushingoid features on examination. Clubbing of the fingers and proximal myopathy were noted on examination. 24-hour urinary free cortisol was elevated at 3536 nmol/day [NR 50-270] and midnight plasma cortisol was high 856 nmol/L. Low-dose dexamethasone suppression testing showed a cortisol of 1195 nmol/L at baseline and 983 nmol/L [NR &lt;50] at 48 hours. ACTH was significantly elevated at 275 ng/. Plasma metanephrines were normal. A pituitary MRI was normal and an adrenal CT showed bilateral hyperplastic adrenal glands with no discrete nodules. FDG PET/CT revealed nodularity in both upper lung lobes and 2 cm metabolically active left supraclavicular lymph node. He was started on potassium chloride, calcium carbonate with Ergocalciferol. Hypokalaemia worsened in spite of potassium replacement. He was commenced on Metyrapone and prednisolone as a block-and-replace. Ketoconazole has been avoided due to derangement of liver biochemistry. Normalisation of cortisol led to resolution of his confusion. Rivaroxaban 10mg once daily was started as DVT prophylaxis. Eplerenone was added for better control of the hypokalaemia. He underwent ultrasound-guided biopsy of his supraclavicular/cervical mass which showed findings consistent with metastatic MTC. Calcitonin was significantly elevated at 28,400 ng/L(NR &lt;11.8) and CEA level was 340ug/L (NR 0-5). Cytogenetics showed a somatic RET mutation. An attempted total thyroidectomy had to be abandoned as his disease was found to be too locally advanced with fixed area of tumour in the left root of the neck encasing the great vessels and extending down into the sternum. He was commenced on Cabozantinib with plan to re-explore total thyroidectomy option if the tumour shrinks. At follow up, biochemical and radiological assessment showed good response to treatment. The patient remains in good physical condition and is continuing treatment for his mental health problems.

Conclusion

MTC may infrequently present with paraneoplastic syndrome such as ectopic ACTH secretion. A high index of clinical suspicion is essential in diagnosing atypical cases of Cushing syndrome presenting with rapidly progressive clinical features of hypercortisolaemia, severe hypokalaemia, normal or high ACTH in the absence of a pituitary lesion on imaging. Targeted therapy such as Tyrosine kinase inhibitors (TKI) or selective RET inhibitors have led to improved treatment outcomes.

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