Medullary thyroid carcinoma
Medullary thyroid carcinoma is a neuroendocrine tumor of the parafollicular C cells that secretes calcitonin and is familial (RET-mutant, part of MEN2A or MEN2B) in about 25% of cases. First-line treatment is total thyroidectomy with central neck lymph node dissection, with any coexisting pheochromocytoma resected first, followed by lifelong levothyroxine replacement and calcitonin/CEA surveillance; selpercatinib, a RET kinase inhibitor, is used for unresectable or metastatic RET-mutant disease.
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What this article covers
- Overview
Definition: medullary thyroid carcinoma (MTC) is a neuroendocrine malignancy arising from the parafollicular C cells of the thyroid, which produce calcitonin, rather than from the follicular…
- Epidemiology
Uncommon relative to differentiated thyroid cancer: papillary carcinoma accounts for 80-90% of thyroid cancer and follicular carcinoma for 10-15%, leaving MTC and anaplastic carcinoma as the smaller remaining share of thyroid malignancy.
- Risk factors
A germline RET proto-oncogene mutation: the driving risk factor for the familial forms, transmitted in an autosomal dominant pattern as part of MEN2A, MEN2B, or isolated familial MTC.
- Pathophysiology
MTC arises from parafollicular C cells, which are neural-crest-derived cells embedded within the thyroid that normally secrete calcitonin in response to rising serum calcium.
- Clinical features
A palpable thyroid nodule or a dominant nodule in a multinodular goiter is the most common presentation, sometimes with a firm, enlarging neck mass.
- Differential diagnosis
Papillary thyroid carcinoma: arises from follicular epithelium and is markedly more common; unlike MTC, it is not associated with calcitonin elevation and its cytology shows psammoma bodies and…
- Diagnosis
The clinching basis for diagnosis is an elevated serum calcitonin in a patient with a thyroid nodule, confirmed by FNA cytology showing neuroendocrine features, with immunohistochemical staining for…
- Management
First, if RET testing or biochemical screening reveals a pheochromocytoma, resect it before any thyroid surgery, following standard pheochromocytoma perioperative blockade, established in this order…
- Complications
Postoperative hypoparathyroidism and hypocalcemia from inadvertent removal of or damage to the parathyroid glands during total thyroidectomy.
- Prognosis
Intermediate between differentiated thyroid cancer and anaplastic carcinoma: median survival for MTC is shorter than for papillary or follicular carcinoma but considerably better than for anaplastic thyroid carcinoma.
- Prevention
Offer RET genetic testing to every patient newly diagnosed with MTC, since identifying a familial mutation allows cascade testing of first-degree relatives and pre-symptomatic prophylactic thyroidectomy in mutation carriers.
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Related articles
- Multiple endocrine neoplasia type 2A
Multiple endocrine neoplasia type 2A (MEN2A) is an autosomal dominant RET-mutation syndrome causing medullary thyroid carcinoma, pheochromocytoma, and primary hyperparathyroidism. First-line treatment is total thyroidectomy for medullary thyroid carcinoma and surgical resection of pheochromocytoma, always after preoperative alpha-then-beta adrenergic blockade if pheochromocytoma coexists.
- Multiple endocrine neoplasia type 2B
Multiple endocrine neoplasia type 2B is an autosomal dominant RET proto-oncogene disorder producing early, aggressive medullary thyroid carcinoma, pheochromocytoma, mucosal neuromas, and a marfanoid habitus, without the parathyroid disease seen in MEN2A. First-line treatment is prophylactic total thyroidectomy at the earliest safe age, with pheochromocytoma resected first if both lesions are present, after alpha blockade.
- Thyroid nodules
A thyroid nodule is a discrete structural lesion within an otherwise normal thyroid gland, found on ultrasound in about 40% of the United States population though palpable in far fewer, and malignant in roughly 5%. Evaluation begins with a thyroid-stimulating hormone (TSH) level and thyroid ultrasonography, and management is surveillance for benign or low-risk nodules, with lobectomy or total thyroidectomy reserved for cytology suspicious for or diagnostic of malignancy.
- Papillary thyroid carcinoma
Papillary thyroid carcinoma is the most common thyroid malignancy, arising from thyroid follicular cells and typically spreading to cervical lymph nodes with a low risk of distant metastasis. Diagnosis rests on ultrasound risk stratification and fine-needle aspiration biopsy, and treatment is thyroid lobectomy or total thyroidectomy, with postoperative radioactive iodine and thyroid-stimulating-hormone-suppressive levothyroxine reserved for intermediate to high risk disease.