Endocrine Abstracts

Selpercatinib is a specific RET inhibitor, highly effective in the treatment of advanced RET-mutant medullary thyroid carcinoma (MTC). The consequences of selpercatinib administration in MTC patients who have not undergone thyroid surgery are still unknown. We report the case of an 84-year-old man undergoing investigations for worsening diarrhea and weight loss. Upon a neck ultrasound scan and blood exams that pointed out high levels of both calcitonin (CT, 20.583 ng/l) and carcinoembryonic antigen (CEA, 246 µg/l), he was diagnosed with locally advanced MTC. The Next-Generation Sequencing analysis identified the somatic RET M918T mutation. Due to the patient age, his comorbidities, and the tumor burden, surgery was excluded and neoadjuvant treatment with selpercatinib 160 mg twice per day was started. The US examination and blood exams performed after two weeks of treatment displayed a significant reduction of both primary and metastatic lesions, along with a considerable decrease of both CT and CEA. During the fourth week of treatment, the patient experienced weakness, nausea, vomiting, oliguria, and blunted consciousness. Blood exams detected severe hypocalcemia, hyperphosphatemia, hyperkalemia, hyperuricemia, and acute kidney injury on pre-existing chronic kidney disease (CKD). As the Cairo-Bishop criteria were satisfied, a tumor lysis syndrome (TLS), secondary to the systemic anti-tumor therapy, was diagnosed. Accordingly, the patient withdrew selpercatinib and received high-volume intravenous expansion with crystalloid fluids, along with the administration of calcium, rasburicase, phosphorus- and potassium-binding agents. Nevertheless, he experienced renal function worsening and life-threatening metabolic abnormalities. After unsuccessful treatment with furosemide and ethacrynic acid, he underwent intermittent renal replacement therapy. After nine days of dialysis, a significant clinical improvement was obtained, leading to replacement treatment interruption. Upon discharge, the patient re-started selpercatinib at the dose of 80 mg twice per day. After 11 months, the patient is still well tolerating the treatment, renal function is stable and neither new manifestations of TLS nor any other AE appeared. Tumor lesions were further reduced and stable, with stable serum levels of CT and CEA. To the best of our knowledge, this is the first case report of selpercatinib-induced TLS during treatment of MTC. The case is of particular interest also due to the long-term stability of the MTC obtained in a patient who was not operated on. This evidence could pave the way for future application of selpercatinib in this subset of patients.