C cells

C cells, also called parafollicular cells, are derived from the neural crest (ultimobranchial body) rather than the endoderm that gives rise to thyroid follicular cells. They are located in the interstitial spaces between thyroid follicles, embedded within the basement membrane. C cells produce and secrete calcitonin, a peptide hormone that opposes the actions of parathyroid hormone (PTH) by inhibiting osteoclast activity, thereby decreasing bone resorption and lowering serum calcium levels. Calcitonin secretion is stimulated by hypercalcemia and gastrin. Clinically, C cells are important because they give rise to medullary thyroid carcinoma (MTC), a neuroendocrine tumor that secretes calcitonin (used as a tumor marker) and can also produce CEA. MTC can occur sporadically or as part of multiple endocrine neoplasia (MEN) syndromes, particularly MEN 2A and MEN 2B, which are associated with RET proto-oncogene mutations. Histologically, MTC shows amyloid deposits (derived from calcitonin) on Congo red staining. C-cell hyperplasia is often a precursor lesion to MTC in hereditary cases. Physiologically, calcitonin's role in normal calcium homeostasis is considered relatively minor compared to PTH and vitamin D, as evidenced by the lack of significant calcium abnormalities after thyroidectomy or in medullary thyroid carcinoma.