<b><i>Introduction:</i></b> Tyrosine kinase inhibitors have been a breakthrough in the treatment of advanced medullary thyroid cancer (MTC), and they can prolong progression-free survival (PFS). <b><i>Case Presentation:</i></b> A patient with MTC and metastatic spread to the lymph nodes, lungs, bones, breast, and cerebellum started treatment with vandetanib. During treatment, she developed secondary adrenal insufficiency and hypogonadotropic hypogonadism. After 9 years of vandetanib therapy, the disease has not progressed and the patient maintains a complete response of the breast metastases and a partial response of the other metastatic lesions. <b><i>Conclusion:</i></b> To our knowledge, this is the first reported case of secondary adrenal insufficiency and hypogonadotropic hypogonadism related to therapy with vandetanib. Moreover, the prolonged PFS and the complete disappearance of some of the metastatic lesions in this patient are truly unusual.