Acute severe hypocalcaemia after initiation of a selective RET-inhibitor in medullary thyroid cancer

• Published in: Endocrine oncology Vol. 5; no. 1; p. e240060
• Main Authors: Cheng, Leslie, Ghaznavi, Syeda Khadijah, Stevens, Jessica, Hoy, Sonja, Wong, Kee Howe, Malik, Tass, Newbold, Kate, Morganstein, Daniel
• Format: Journal Article
• Language: English
• Published: England Bioscientifica Ltd 01.01.2025; Bioscientifica
• Subjects: Case Report; hypocalcaemia; medullary thyroid cancer; ret-inhibitor; tyrosine kinase inhibitor; medullary thyroid cancer; tyrosine kinase inhibitor; hypocalcaemia; RET-inhibitor
• ISSN: 2634-4793; 2634-4793
• DOI: 10.1530/EO-24-0060

Medullary thyroid cancer (MTC) is a rare subtype of thyroid cancer originating from parafollicular C-cells of the thyroid. Tyrosine kinase inhibitors are used to treat patients with advanced MTC. Selpercatinib is a highly selective RET inhibitor used in the treatment of advanced RET-mutated MTC, having shown higher potency and fewer side effects compared to multikinase inhibitors in clinical trials. As a relatively new drug, its toxicity profile continues to be characterised. This report describes a case of severe acute hypocalcaemia in a 64-year-old male with advanced MTC treated with selpercatinib. The patient, who had stable hypoparathyroidism, experienced acute hypocalcaemia (corrected calcium 1.4 mmol/L) 2 weeks after initiating selpercatinib, requiring hospitalisation for calcium supplementation and monitoring. Selpercatinib was temporarily withheld and later reintroduced at a lower dose, successfully preventing recurrence of hypocalcaemia. Investigations excluded other common or important causes of hypocalcaemia, which led us to conclude that this could be a drug-related adverse event. This case highlights the need for careful monitoring of electrolyte disturbances in patients on selpercatinib, particularly those with pre-existing hypoparathyroidism. Although rare, the development of hypocalcaemia with RET inhibitors may necessitate dose interruptions and adjustments. Our experience has also illustrated that re-challenge with selpercatinib is feasible with appropriate management strategies.