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multiple endocrine neoplasia type-2 (MEN-2)

Uncommon inherited cancer syndrome. Pathology: - predisposition to medullary thyroid carcinoma & pheochromocytoma - hyperparathyroidism (MEN2A) (20-30%) - mucosal neuromas - ganglioneuromas of the intestine tract Genetics: 1) inheritance: autosomal dominant 2) high penetrance 3) RET gene is mutated in 95-98% of patients -> cysteine mutation at boundary of extracellular space & transmembrane region is frequently affected Clinical manifestations: - marfanoid habitus (MEN2B) - skeletal & ophthalmic abnormalities - palpable neck mass may be present - disease progresses rapidly with the development of metastatic medullary thyroid carcinoma & pheochromocytoma in 50% of cases - diarrhea resulting from high plasma calcitonin associated with medullary thyroid carcinoma - hypertension & palpitations associated with pheochromcytoma Laboratory: 1) DNA analysis for RET mutations 2) basal & provoked calcitonin level a) pentagastrin or calcium used for provocation b) annually: age 3-35 years 3) urinary fractionated catecholamines, metanephrines & vanillylmandelic acid (VMA) (annually) 4) serum Ca+2 (ionized or albumin-adjusted) 5) serum parathyroid hormone (PTH) 6) fine-needle aspiration 7) see ARUP consult [6] Management: 1) thyroidectomy for medullary carcinoma of the thyroid 2) palliative role for external radiotherapy 3) begin screening in early childhood before age 5 4) GLP-1 receptor agonists (incretin mimetics, glutides) are contraindicated in patients with medullary thyroid cancer or MEN2 [7]

Related

proto-oncogene tyrosine-protein kinase receptor ret; C-ret; (RET, CDHF12)

Specific

multiple endocrine neoplasia type-2A (MEN-2A); Sipple syndrome multiple endocrine neoplasia type-2B (MEN-2B)

General

multiple endocrine neoplasia (MEN)

Database Correlations

OMIM 162300

References

  1. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 270-71
  2. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 16, 18. American College of Physicians, Philadelphia 1998, 2006, 2012, 2018.
  3. Brandi ML, Gagel RF, Angeli A, Bilezikian JP Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab. 2001 Dec;86(12):5658-71. PMID: 11739416
  4. Moline J, Eng C. Multiple endocrine neoplasia type 2: an overview. Genet Med. 2011 Sep;13(9):755-64 PMID: 21552134
  5. Krampitz GW, Norton JA RET gene mutations (genotype and phenotype) of multiple endocrine neoplasia type 2 and familial medullary thyroid carcinoma. Cancer. 2014 Jul 1;120(13):1920-31. Review. PMID: 24699901 Free Article
  6. ARUP Consult: Multiple Endocrine Neoplasia Type 2 https://arupconsult.com/ati/multiple-endocrine-neoplasia-type-2
  7. NEJM Knowledge+ Endocrinology