Vandetanib successfully controls medullary thyroid cancer-related Cushing syndrome in an adolescent patient

Abstract

Context: Ectopic Cushing syndrome due to ACTH secretion from metastatic medullary thyroid cancer (MTC) is associated with significant morbidity and mortality.

Objective: The aim of the study was to describe the first case of Cushing syndrome associated with MTC in a pediatric patient and the successful reversal of Cushing syndrome with tyrosine kinase inhibitor (vandetanib) therapy.

Patient and methods: A 17-year-old Brazilian adolescent presented with metastatic MTC and associated ACTH-dependent ectopic Cushing syndrome in the context of multiple endocrine neoplasia type 2B. When the patient was treated with the tyrosine kinase inhibitor vandetanib, rapid decrease in serum cortisol and improvement of clinical symptoms were observed.

Conclusion: We describe the first pediatric case of clinical and biochemical improvement of paraneoplastic MTC-related Cushing syndrome after treatment with vandetanib. Vandetanib and possibly other tyrosine kinase inhibitors may be a novel beneficial option in patients with neuroendocrine tumor-related ectopic Cushing syndrome.

Trial registration: ClinicalTrials.gov NCT00514046.

Figure 1.

Serum morning cortisol (AM cortisol), ACTH, calcitonin, and UFC concentrations during treatment. Gray zone represents the normal ACTH reference range (0–46 pg/mL). Other normal reference ranges are: UFC, 4–56 μg/24 h; serum AM cortisol, 5–25 μg/dL; and calcitonin, 0–15.9 pg/mL. *, Vandetanib dose was reduced from 200 to 125 mg a day, due to intolerable diarrhea.

Figure 2.

Adrenal parenchyma with clusters of neuroendocrine neoplasm (A, hematoxylin and eosin; ×100) stains positive for calcitonin (B, immunohistochemistry stain; ×100) in agreement with the diagnosis of metastatic MTC. Immunohistochemistry stain for ACTH shows weak positivity in neoplastic cells (C, ×400).