(CSEMP054) ADRENAL INSUFFICIENCY FOLLOWING SUCCESSFUL TREATMENT OF ECTOPIC CUSHING'S SYNDROME IN MEDULLARY THYROID CANCER WITH SELPERCATINIB

Abstract:

Background: Medullary thyroid cancer (MTC) is a rare neuroendocrine cancer that arises from the parafollicular cells of the thyroid gland and can be either hereditary or sporadic. All hereditary MTC have rearranged during transfection (RET) mutations, as well as nearly half of all sporadic cases. Selpercatinib is a selective RET-inhibitor that has shown promising results in the treatment of MTC. In rare cases, paraneoplastic Cushing’s syndrome may develop in patients with MTC secondary to excess ectopic ACTH production. Here, we discuss a patient with paraneoplastic Cushing’s syndrome due to MTC that developed adrenal insufficiency following successful treatment with Selpercatinib.

Case: A 72-year-old female, previously healthy, presented with hypokalemia, bilateral leg swelling, and proximal muscle weakness. Elevated 24-hour urine cortisol (1533 nmol/d) and ACTH (21 pmol/L), along with non-suppressed 8 mg dexamethasone suppression test (AM cortisol 968 nmol/L) confirmed Cushing’s syndrome. CT chest demonstrated a large solid mass arising from the left lobe of the thyroid gland. Fine needle aspiration of the thyroid mass demonstrated medullary thyroid cancer. Molecular testing revealed somatic p.Cys620Arg mutation of the RET proto-oncogene. Surgical resection was deemed too risky as the thyroid mass encased the carotid artery. The patient began treatment with Selpercatinib and had rapid clinical improvements in fatigue and muscle weakness. Morning cortisol levels fell as low as 20 nmol/L, necessitating initiation of hydrocortisone replacement. Levels of the tumour markers carcinoembryonic antigen and calcitonin decreased from baseline. After 5 months of treatment, Selpercatinib elicited sustained clinical and radiographic changes. The patient remains adrenally insufficient at this time.

Discussion: Selpercatinib is an emerging treatment option for patients with ectopic Cushing’s syndrome due to medullary thyroid cancer, especially when other treatment modalities are contraindicated. This case illustrates the possibility of prolonged hypocortisolism following treatment with Selpercatinib. Further understanding of the time to recovery of adrenal function following treatment with Selpercatinib will help guide appropriate monitoring for patients with paraneoplastic Cushing’s undergoing RET-inhibitor treatment.