Endocrine Abstracts

Introduction: Multiple endocrine neoplasia, type 2A (MEN 2A) is a hereditary syndrome characterized by medullary carcinoma of the thyroid, pheochromocytoma, parathyroid hyperplasia or adenomas due to mutation in RET oncogene on chromosome 10. Complications can occur as a result of ectopic ACTH causing Cushings syndrome. We present here a case initially presenting to hospital with worsening shortness of breath on a background of metastatic medullary thyroid cancer and family history of MEN2A syndrome.

Case Presentation: A 57-year-old male presented to the hospital with a left-sided pleural effusion along with pericardial effusion, refractory hypokalemia and hypocalcemia. A pleural tap confirmed Chylothorax effusion. He also developed in-patient psychosis and subsequent investigations confirmed Cushings syndrome due to ectopic ACTH as seen on urinary collections (>27000 nmol/24hr) and overnight dexamethasone suppression test revealing cortisol >4000 nmol/l with high ACTH (290ng/l). He was started on metyrapone titrated up to the maximum recommended dosage, and steroids along with ketoconazole. He was discussed with surgeons and oncology for bilateral adrenalectomy but given the extent of disease spread and progressive frailty, this was deemed inappropriate. He was also offered tyrosine kinase inhibitor therapy (Selpercatinib) but was unable to complete the same due to worsening frailty. He developed chronic diarrhea due to high calcitonin levels and bile salt malabsorption and was eventually commenced on palliative treatment.

Conclusion: This case highlights the complications and challenges of managing a complex MEN2A syndrome. Despite quiescent disease for years, rapid deterioration despite treatment contributed to the patient’s overall decline and frailty. A newer option would be the new drug osilodrostat (11-beta hydroxylase inhibitor). Although there is limited clinical experience in it, studies have shown promising results in controlling cortisol levels. This along with further details like complications of Cushings secondary to malignancy, challenges of managing these and their associated mortality would be discussed further.