Vitamin D in thyroid tumorigenesis and development

Besides its classical role in bone and calcium homeostasis, 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃), the active form of vitamin D, has many non-classical effects; antiproliferative, anti-apoptotic and prodifferentiating effects of 1,25(OH)₂D₃ have been described in several tumour types in preclinical models. This review focuses on the insights gained in the elucidation of the role of 1,25(OH)₂D₃ in the normal thyroid and in the pathogenesis, progression and treatment of thyroid cancer, the most common endocrine malignancy. An increasing amount of observations points towards a role for impaired 1,25(OH)₂D₃-VDR signalling in the occurrence and progression of thyroid cancer, and a potential for structural analogues in the multimodal treatment of dedifferentiated iodine-resistant thyroid cancer. A role for vitamin D in thyroid-related autoimmunity is less convincing and needs further study. Altered 1,25(OH)₂D₃-VDR signalling does not influence normal thyroid development nor thyrocyte function, but does affect C-cell function, at least in rodents. If these findings also apply to humans deserves further study.