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medullary thyroid carcinoma

Rare tumor derived from calcitonin-secreting C-cells of the thyroid. Epidemiology: - rare - 80% sporadic - peak incidence in 6th & 7th decades of life - 20% familial - multiple endocrine neoplasia-2A (MEN-2A) - multiple endocrine neoplasia-2B (MEN-2B) - familial form NOT associated with multiple endocrine neoplasia; medullary thyroid carcinoma only manifestation Pathology: - calcitonin-secreting C-cells are malignant cells in the thyroid [3] - amyloid deposition resulting from excess procalcitonin - metastases to cervical lymph nodes - tumor & involved lymph nodes tend to calcify - 30% of patients with sporadic form & 100% of patients with inherited form have bilateral disease [3] Genetics: - 3 autosomal dominant hereditary forms - implicated genes INSM1, RET Clinical manifestations: - manifestations of MEN-2A, MEN-2B - headaches, sweating, palpitations (pheochromcytoma) - nephrolithiasis, hypercalcemia (hyperparathyroidism) - marfenoid habitus & ganglioneuromas on the tongue, lips & eyelid (MEN-2B) - diarrhea resulting from high plasma calcitonin Laboratory: - serum calcitonin elevated - confirms diagnosis - marker for residual disease & tumor burden - serum procalcitonin - elevated - unclear how the assay for serum calcitonin vs serum procalcitonin differs - urinary fractionated catecholamines, metanephrines & vanillylmandelic acid (VMA) (rule out pheochromocytoma*) - plasma normetaneprhine & plasma free metaphrine is suggested in ref [3] - serum calcium & serum PTH - RET gene mutation* including family members - also see multiple endocrine neoplasia type-2 * patients with medullary thyroid carcinoma & a pathologic variant RET gene need a rule-out of pheochromocytoma prior to surgery [6] Radiology: - plain radiograph of neck may show calcifications of thyroid & involved lymph nodes - nodule is 'cold' on radioactive iodine uptake test Management: - total thyroidectomy with neck dissection - rule out MEN-2* & associated pheochromocytoma BEFORE attemting surgery so as to avoid hyperadrenergic crisis - external irradiation & chemotherapy palliative for residual or recurrent disease * 131-I is not taken up by C-cells thus not a treatment option for medullary thyroid carcinoma [3] * MEN-2: medullary thyroid carcinoma, pheochromocytoma, hyperparathyroidism - GLP-1 receptor agonists (incretin mimetics, glutides) are contraindicated in patients with medullary thyroid cancer or MEN2 [6]

Interactions

disease interactions

Related

amyloid multiple endocrine neoplasia type-2 (MEN-2)

Specific

familial medullary thyroid carcinoma

General

neuroendocrine carcinoma thyroid carcinoma

Database Correlations

OMIM 155240

References

  1. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 210, 275
  2. Harrison's Principles of Internal Medicine, 13th ed. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1994, pg 1947
  3. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, 16, 17, 18. American College of Physicians, Philadelphia 1998, 2006, 2009, 2012, 2015, 2018. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  4. American Thyroid Association Guidelines Task Force, Kloos RT, Eng C, Evans DB et al Medullary thyroid cancer: management guidelines of the American Thyroid Association. Thyroid. 2009 Jun;19(6):565-612 PMID: 19469690
  5. Wells SA Jr, Asa SL, Dralle H et al Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid. 2015 Jun;25(6):567-610. Review. PMID: 2581004
  6. NEJM Knowledge+ Endocrinology