7713 Remission of Ectopic Cushing Syndrome Due to Medullary Thyroid Cancer with Selpercatinib
Authors: Davydov Emily , Severson Dawn , Athimulam Shobana 
Published: October 2024

Abstract
Disclosure: E. Davydov: None. D. Severson: None. S. Athimulam: None.
Introduction: Medullary thyroid cancer (MTC) accounts for less than 5% of all thyroid cancers. In less than 1% of these patients, cushing syndrome (CS) due to ectopic ACTH secretion can develop. Selpercatinib is a selective RET kinase inhibitor approved in 2020 for treatment of advanced medullary thyroid cancer with RET mutations. We present a case of a patient with MTC complicated by ectopic CS that resolved after treatment with Selpercatinib. Case: A 38-year old male presented to the ED with progressive left upper extremity swelling and erythema. Cross sectional CT imaging revealed a 9.6 x 8.8 cm ill-defined mediastinal mass encasing major blood vessels contiguous with the right thyroid lobe along with enlarged supraclavicular and upper abdominal lymph nodes and multiple hepatic masses consistent with metastatic malignant disease. Serum Calcitonin was 1,308 pg/mL (nl &lt; 18) and Carcinoembryonic antigen (CEA) was &gt;950 ng/mL (nl &lt; 6.1). Biopsy of a liver lesion confirmed metastatic MTC and molecular testing on biopsy specimen was positive for a RET mutation. Germline genetic testing was negative including the RET and MEN1 gene. While in the hospital, he was treated for persistently low potassium levels, new diagnosis of diabetes mellitus with hyperglycemia (HbA1c 6.9%) and hypertension. Serum cortisol following overnight - 1 mg dexamethasone suppression test (DST) was 50.1 mcg/dL, with baseline ACTH of 500 pg/mL (nl 7-63). 24-hour urine free cortisol was 15,168 mcg (nl &lt; 60). MRI brain was unremarkable. He was diagnosed with ectopic CS due to MTC and started on ketoconazole which was later switched to metyrapone due to uptrending liver enzymes. He was also provided prophylactic treatment for opportunistic infections and thromboembolism. In the outpatient setting, selpercatinib was initiated for treatment of MTC. Serum ACTH, cortisol, potassium, glucose, and blood pressure normalized and he discontinued metyrapone eleven days after initiation of selpercatinib. After 5 cycles of selpercatinib, repeat CT demonstrated a significant decrease in size of the hepatic metastases and the mediastinal mass (3.2 x 2.3cm). Serum calcitonin and CEA levels improved to 188 pg/mL and 73.3 ng/mL, respectively. Discussion: This case illustrates successful treatment of ectopic CS due to MTC after initiation of selpercatinib. Comorbidities associated with severe hypercortisolism can be fatal and rapid normalization of cortisol is imperative in these patients. There are multiple reported management strategies for ectopic CS in patients with MTC including surgical debulking, steroidogenesis inhibitors, bilateral adrenalectomies, and more recently the use of tyrosine kinase inhibitors. As demonstrated in our patient, the use of selpercatinib in patients with RET positive metastatic MTC can act as a non-invasive therapeutic option to treat ectopic CS, a rare associated paraneoplastic syndrome.
Presentation: 6/1/2024