As síndromes de neoplasia endócrina múltipla (NEM) são relativamente raras.
A prevalência estimada é de 1 a 3 em 100,000.[8]Al-Salameh A, Cadiot G, Calender A, et al. Clinical aspects of multiple endocrine neoplasia type 1. Nat Rev Endocrinol. 2021 Apr;17(4):207-24.
https://www.doi.org/10.1038/s41574-021-00468-3
http://www.ncbi.nlm.nih.gov/pubmed/33564173?tool=bestpractice.com
Cerca de 90% dos pacientes desenvolvem hiperparatireoidismo primário (HPTP) e isso é frequentemente diagnosticado em uma idade mais jovem (20 a 25 anos) em comparação com as formas esporádicas de HPTP.[3]Thakker RV, Newey PJ, Walls GV, et al; Endocrine Society. Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). J Clin Endocrinol Metab. 2012 Sep;97(9):2990-3011.
https://academic.oup.com/jcem/article/97/9/2990/2536740
http://www.ncbi.nlm.nih.gov/pubmed/22723327?tool=bestpractice.com
Aproximadamente 40% a 70% dos pacientes com NEM1 têm tumores neuroendócrinos pancreáticos (TNEs), que podem ser funcionais (por exemplo, gastrinomas, insulinomas, glucagonomas, polipeptidomas intestinais vasoativos [síndrome de Verner-Morrison (VIPoma)]) ou não funcionais.[3]Thakker RV, Newey PJ, Walls GV, et al; Endocrine Society. Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). J Clin Endocrinol Metab. 2012 Sep;97(9):2990-3011.
https://academic.oup.com/jcem/article/97/9/2990/2536740
http://www.ncbi.nlm.nih.gov/pubmed/22723327?tool=bestpractice.com
Devido ao rastreamento de rotina em famílias com NEM1, TNEs pancreáticos não funcionais são agora o tipo mais comum de TNE pancreático no contexto de NEM1.[3]Thakker RV, Newey PJ, Walls GV, et al; Endocrine Society. Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). J Clin Endocrinol Metab. 2012 Sep;97(9):2990-3011.
https://academic.oup.com/jcem/article/97/9/2990/2536740
http://www.ncbi.nlm.nih.gov/pubmed/22723327?tool=bestpractice.com
[8]Al-Salameh A, Cadiot G, Calender A, et al. Clinical aspects of multiple endocrine neoplasia type 1. Nat Rev Endocrinol. 2021 Apr;17(4):207-24.
https://www.doi.org/10.1038/s41574-021-00468-3
http://www.ncbi.nlm.nih.gov/pubmed/33564173?tool=bestpractice.com
Os gastrinomas são os TNEs duodenopancreáticos funcionais mais comuns em NEM1, afetando 21% a 70% dos pacientes.[8]Al-Salameh A, Cadiot G, Calender A, et al. Clinical aspects of multiple endocrine neoplasia type 1. Nat Rev Endocrinol. 2021 Apr;17(4):207-24.
https://www.doi.org/10.1038/s41574-021-00468-3
http://www.ncbi.nlm.nih.gov/pubmed/33564173?tool=bestpractice.com
Cerca de 30% a 40% dos pacientes com NEM1 apresentam adenomas hipofisários.[3]Thakker RV, Newey PJ, Walls GV, et al; Endocrine Society. Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). J Clin Endocrinol Metab. 2012 Sep;97(9):2990-3011.
https://academic.oup.com/jcem/article/97/9/2990/2536740
http://www.ncbi.nlm.nih.gov/pubmed/22723327?tool=bestpractice.com
Prolactinomas são os mais comuns e ocorrem em 65% dos pacientes com adenomas hipofisários relacionados a NEM1.[8]Al-Salameh A, Cadiot G, Calender A, et al. Clinical aspects of multiple endocrine neoplasia type 1. Nat Rev Endocrinol. 2021 Apr;17(4):207-24.
https://www.doi.org/10.1038/s41574-021-00468-3
http://www.ncbi.nlm.nih.gov/pubmed/33564173?tool=bestpractice.com
Os adenomas hipofisários secretores de hormônio do crescimento (somatotróficos) e os adenomas não funcionais são os próximos adenomas hipofisários mais comuns relacionados ao NEM1.[8]Al-Salameh A, Cadiot G, Calender A, et al. Clinical aspects of multiple endocrine neoplasia type 1. Nat Rev Endocrinol. 2021 Apr;17(4):207-24.
https://www.doi.org/10.1038/s41574-021-00468-3
http://www.ncbi.nlm.nih.gov/pubmed/33564173?tool=bestpractice.com
Os tumores secretores de hormônio adrenocorticotrófico são menos comuns, ocorrendo em <5% dos pacientes com adenomas hipofisários relacionados a NEM1.[8]Al-Salameh A, Cadiot G, Calender A, et al. Clinical aspects of multiple endocrine neoplasia type 1. Nat Rev Endocrinol. 2021 Apr;17(4):207-24.
https://www.doi.org/10.1038/s41574-021-00468-3
http://www.ncbi.nlm.nih.gov/pubmed/33564173?tool=bestpractice.com
Tumores secretores de hormônio estimulador da tireoide e tumores secretores de gonadotróficos são adenomas hipofisários relacionados a NEM1 raros (<1%).[8]Al-Salameh A, Cadiot G, Calender A, et al. Clinical aspects of multiple endocrine neoplasia type 1. Nat Rev Endocrinol. 2021 Apr;17(4):207-24.
https://www.doi.org/10.1038/s41574-021-00468-3
http://www.ncbi.nlm.nih.gov/pubmed/33564173?tool=bestpractice.com
Tumores neuroendócrinos (TNEs) brônquicos e tímicos ocorrem cada em 2% dos pacientes com NEM1.[3]Thakker RV, Newey PJ, Walls GV, et al; Endocrine Society. Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). J Clin Endocrinol Metab. 2012 Sep;97(9):2990-3011.
https://academic.oup.com/jcem/article/97/9/2990/2536740
http://www.ncbi.nlm.nih.gov/pubmed/22723327?tool=bestpractice.com
TNEs tímicos mostram uma predominância masculina acentuada em pacientes com NEM1 de origem europeia e estão associados a uma alta mortalidade.[8]Al-Salameh A, Cadiot G, Calender A, et al. Clinical aspects of multiple endocrine neoplasia type 1. Nat Rev Endocrinol. 2021 Apr;17(4):207-24.
https://www.doi.org/10.1038/s41574-021-00468-3
http://www.ncbi.nlm.nih.gov/pubmed/33564173?tool=bestpractice.com
TNEs brônquicos apresentam uma evolução mais indolente.[3]Thakker RV, Newey PJ, Walls GV, et al; Endocrine Society. Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). J Clin Endocrinol Metab. 2012 Sep;97(9):2990-3011.
https://academic.oup.com/jcem/article/97/9/2990/2536740
http://www.ncbi.nlm.nih.gov/pubmed/22723327?tool=bestpractice.com
[9]de Laat JM, Pieterman CR, van den Broek MF, et al. Natural course and survival of neuroendocrine tumors of thymus and lung in MEN1 patients. J Clin Endocrinol Metab. 2014 Sep;99(9):3325-33.
http://www.ncbi.nlm.nih.gov/pubmed/24915123?tool=bestpractice.com
[10]Kamilaris CDC, Stratakis CA. Multiple endocrine neoplasia Type 1 (MEN1): An update and the significance of early genetic and clinical diagnosis. Front Endocrinol (Lausanne). 2019 Jun 11;10:339.
https://www.doi.org/10.3389/fendo.2019.00339
http://www.ncbi.nlm.nih.gov/pubmed/31263451?tool=bestpractice.com
Registrada em aproximadamente 1000 famílias no mundo todo em 2001.[5]Wells SA Jr, Pacini F, Robinson BG, et al. Multiple endocrine neoplasia type 2 and familial medullary thyroid carcinoma: an update. J Clin Endocrinol Metab. 2013 Aug;98(8):3149–64.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5399478
http://www.ncbi.nlm.nih.gov/pubmed/23744408?tool=bestpractice.com
A maioria dos casos é de NEM2A.
O câncer medular de tireoide se manifesta em quase todos os portadores genéticos de NEM2 na idade adulta se não for tratado com tireoidectomia profilática, e é o achado inicial mais comum na NEM2.[5]Wells SA Jr, Pacini F, Robinson BG, et al. Multiple endocrine neoplasia type 2 and familial medullary thyroid carcinoma: an update. J Clin Endocrinol Metab. 2013 Aug;98(8):3149–64.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5399478
http://www.ncbi.nlm.nih.gov/pubmed/23744408?tool=bestpractice.com
O feocromocitoma ocorre em aproximadamente 50% dos pacientes com NEM2A. O feocromocitoma é a primeira manifestação de NEM2 em 25% dos pacientes.[5]Wells SA Jr, Pacini F, Robinson BG, et al. Multiple endocrine neoplasia type 2 and familial medullary thyroid carcinoma: an update. J Clin Endocrinol Metab. 2013 Aug;98(8):3149–64.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5399478
http://www.ncbi.nlm.nih.gov/pubmed/23744408?tool=bestpractice.com
[11]Petri BJ, van Eijck CH, de Herder WW, et al. Phaeochromocytomas and sympathetic paragangliomas. Br J Surg. 2009 Dec;96(12):1381-92.
http://onlinelibrary.wiley.com/doi/10.1002/bjs.6821/full
http://www.ncbi.nlm.nih.gov/pubmed/19918850?tool=bestpractice.com
Os adenomas paratireoidianos multiglandulares se desenvolvem em até 30% dos pacientes com NEM2A.[5]Wells SA Jr, Pacini F, Robinson BG, et al. Multiple endocrine neoplasia type 2 and familial medullary thyroid carcinoma: an update. J Clin Endocrinol Metab. 2013 Aug;98(8):3149–64.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5399478
http://www.ncbi.nlm.nih.gov/pubmed/23744408?tool=bestpractice.com
[12]Gagel RF, Tashjian AH Jr, Cummings T, et al. The clinical outcome of prospective screening for multiple endocrine neoplasia type 2a. An 18-year experience. N Engl J Med. 1988 Feb 25;318(8):478-84.
http://www.ncbi.nlm.nih.gov/pubmed/2893259?tool=bestpractice.com
[13]Easton DF, Ponder MA, Cummings T, et al. The clinical and screening age-at-onset distribution for the MEN-2 syndrome. Am J Hum Genet. 1989 Feb;44(2):208-15.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1715408/pdf/ajhg00112-0034.pdf
http://www.ncbi.nlm.nih.gov/pubmed/2563193?tool=bestpractice.com
[14]Ponder BA, Ponder MA, Coffey R, et al. Risk estimation and screening in families of patients with medullary thyroid carcinoma. Lancet. 1988 Feb 20;1(8582):397-401.
http://www.ncbi.nlm.nih.gov/pubmed/2893198?tool=bestpractice.com
O HPTP é encontrado em subgrupos menores de pacientes com NEM2A.[15]Schuffenecker I, Virally-Monod M, Brohet R, et al. Risk and penetrance of primary hyperparathyroidism in multiple endocrine neoplasia type 2A families with mutations at codon 634 of the RET proto-oncogene. Groupe d'etude des Tumeurs a Calcitonine. J Clin Endocrinol Metab. 1998 Feb;83(2):487-91.
http://jcem.endojournals.org/cgi/content/full/83/2/487
http://www.ncbi.nlm.nih.gov/pubmed/9467562?tool=bestpractice.com
Variantes raras de NEM2A incluem doença de Hirschsprung e líquen amiloide cutâneo.[16]Donovan DT, Levy ML, Furst EJ, et al. Familial cutaneous lichen amyloidosis in association with multiple endocrine neoplasia type 2A: a new variant. Henry Ford Hosp Med J. 1989;37(3-4):147-50.
http://www.ncbi.nlm.nih.gov/pubmed/2576950?tool=bestpractice.com
[17]Verdy M, Weber AM, Roy CC, et al. Hirschsprung's disease in a family with multiple endocrine neoplasia type 2. J Pediatr Gastroenterol Nutr.1982;1(4):603-7.
http://www.ncbi.nlm.nih.gov/pubmed/6136579?tool=bestpractice.com
NEM2B é bastante raro (prevalência: 0.9 a 1.6 por milhão de indivíduos) e, em comparação com NEM2A, é notável por feocromocitoma mais agressivo e câncer medular de tireoide que se apresentam em idades mais precoces.[6]Castinetti F, Waguespack SG, Machens A, et al. Natural history, treatment, and long-term follow up of patients with multiple endocrine neoplasia type 2B: an international, multicentre, retrospective study. Lancet Diabetes Endocrinol. 2019 Mar;7(3):213-20.
https://www.doi.org/10.1016/S2213-8587(18)30336-X
http://www.ncbi.nlm.nih.gov/pubmed/30660595?tool=bestpractice.com
[18]Castinetti F, Moley J, Mulligan L, et al. A comprehensive review on MEN2B. Endocr Relat Cancer. 2018 Feb;25(2):T29-T39.
https://www.doi.org/10.1530/ERC-17-0209
http://www.ncbi.nlm.nih.gov/pubmed/28698189?tool=bestpractice.com