Clínica y genética de la neoplasia endocrina multiple 1 y 2

Christopher Febres-Aldana, Anthony Febres-Aldana, Ruth Fernández-Ruiz, Miguel Villasmil

Resumen


El término Neoplasia Endocrina Múltiple (NEM) abarca múltiples síndromes hereditarios autosómicos que se expresan como endocrinopatías. Estos pacientes son portadores de mutaciones en líneas germinales que poseen elevada penetrancia y predisponen al desarrollo tumoral en células endocrinas. En la NEM tipo 1, las mutaciones del gen supresor de tumor MEN1 incrementan el riesgo de adenoma paratiroideo, tumores pancreáticos y tumores de la hipófisis anterior, mientras que en la NEM tipo 2, las mutaciones del protooncogen RET incrementan el riesgo de carcinoma medular de tiroides, tumores de paratiroides y feocromocitoma. La presencia de habito Marfanoide y neuromas mucosos permite la diferenciación entre NEM tipo 2B y tipo 2A. El reconocimiento y diagnóstico preciso de los individuos y familias que están a riesgo de poseer una mutación de RET en línea germinal es fundamental para la prevención y el manejo de neoplasias potencialmente mortales. En esta revisión, se resumen las características clínicas, estrategias diagnósticas, patogénesis, y aspectos relacionados con el asesoramiento genético de las NEM tipo 1 y tipo 2.


Palabras clave


Síndrome Neoplásico; Neoplasia Endocrina Múltiple; Asesoramiento Genético

Texto completo:

PDF

Referencias


Brandi ML, Gagel RF, Angeli A, et al. Consensus: Guidelines for Diagnosis and Therapy of MEN Type 1 and Type 2. J Clin Endocrinol Metab. 2001;86(12):5658-71.

Wermer P. Genetic aspects of adenomatosis of endocrine glands. Am J Med. 1954;16(3):363-71.

Sipple JH. The association of pheochromocytoma with carcinoma of the thyroid gland 1961;31:163-6.

Khairi MR, Dexter RN, Burzynski NJ, et al. Mucosal neuroma, pheochromocytoma and medullary thyroid carcinoma: multiple endocrine neoplásica type 3. Medicine (Baltimore) 1975;54(2):89-112.

Stratakis CA. Genetics of Carney complex and related familial lentiginoses, and other multiple tumor syndromes. Front Biosci. 2000;5:D353-66.

Carney JA, Gordon H, Carpenter PC, et al. The complex of myxomas, spotty pigmentation, and endocrine overactivity. Medicine (Baltimore). 1985;64:270-83.

Marinoni I, Pellegata NS. p27kip1: a new multiple endocrine neoplásica gene? Neuroendocrinology. 2011:93(1):19-28.

Marini F, Falchetti A, Del Monte F, et al. Multiple endocrine neoplasia type 1. Orphanet J Rare Dis. 2006;2:1:38.

Eng C. Seminars in Medicine of the Beth Israel Hospital, Boston: The RET Proto-Oncogene in Multiple Endocrine Neoplasia Type 2 and Hirschsprung's Disease. N Engl J Med. 1996;335(13):943-51.

Pujol RM, Matias-Guiu X, Miralles J, et al. Multiple idiopathic mucosal neuromas: a minor form of multiple endocrine neoplasia type 2B or a new entity? J Am Acad Dermatol. 1997;37(2 Pt 2):349-52.

Frank K, Raue F, Gottswinter J, et al. Importance of early diagnosis and follow-up in multiple endocrine neoplasia (MEN II B). Eur J Pediatr. 1984;143(2):112-16.

Toledo SPA, Cortina MA, Toledo RA, Lourenço, DM. Impact of RET proto-oncogene analysis on the clinical management of multiple endocrine neoplasia type 2. Clinics. 2006:61(1);59-70.

O’Riordain DS, O’Brien T, Crotty TB, et al. Multiple endocrine neoplasia type 2B: More than an endocrine disorder. Surgery. 1995;118:936-42.

Agarwal SK, Lee BA, Sukhodolets KE, et al. Molecular pathology of the MEN1 gene. Ann NY Acad Sci. 2004;1014:189-98.

Marx SJ. Molecular genetics of multiple endocrine neoplasia types 1 and 2. Nat Rev Cancer. 2005;5(5):367-75.

Kim H, Lee JE, Cho EJ, et al. Menin, a tumor suppressor, represses JunD-mediated transcriptional activity by association with an mSin3A-histone deacetylase complex. Cancer Res. 2003;63(19):6135-9.

Hughes CM, Rozenblatt-Rosen O, Milne TA, et al. Menin associates with a trithorax family histone methyltransferase complex and with the hoxc8 locus. Mol Cell. 2004;13(4):587-97.

Lin SY, Elledge SJ. Multiple tumor suppressor pathways negatively regulate telomerase. Cell. 2003;113(7):881-9.

Francis J, Lin W, Rozenblatt-Rosen O, et al. The menin tumor suppressor protein is phosphorylated in response to DNA damage. PLoS One. 2011;6(1):e16119.

Tomassetti P, Cometa G, Del Vecchio E, et al. Chromosomal instability in multiple endocrine neoplasia type 1. Cytogenetic evaluation with DEB test. Cancer Genet Cytogenet. 1995;79:123-26.

Gracanin A, Dreijerink KM, van der Luijt RB, et al. Tissue selectivity in multiple endocrine neoplasia type 1-associated tumorigenesis. Cancer Res. 2009;69(16):6371-4.

Mulligan LM, Ponder BA. Genetic basis of endocrine disease: multiple endocrine neoplasia type 2. J Clin Endocrinol Metab. 1995; 80(7): 1989-1995.

Frilling A, Weber F, Tecklenborg C, et al. Prophylactic thyroidectomy in multiple endocrine neoplasia: the impact of molecular mechanisms of RET protooncogene. Langenbecks Arch Surg. 2003;388(1):17-26.

Lorenzo M, Eng C, Mulligan L, et al. Multiple mRNA isoforms of the human RET prom-oncogene generated by alternative splicing. Oncogene. 1995;10:1377-83.

Nakamura T, Ishizaka Y, Nagao M, et al. Expression of the ret proto-oncogene product in human normal and neoplastic tissues of neural crest origin. J Path. 1994;172:255-60.

Eng C, Smith D, Mulligan L, et al. Activation of RET as a dominant transforming gene by germline mutations of MEN2A and MEN2B. Science. 1995;267:381-83.

Landsvater RM, Jansen RP, Hofstra RM, et al. Mutation analysis of the RET proto-oncogene in Dutch families with MEN 2A, MEN 2B and FMTC: two novel mutations and one de novo mutation for MEN 2A. Hum Genet. 1996;97(1):11-4.

Carlson K, Bracamontes J, Jackson C, et al. Parent-of-origin effects in multiple endocrine neoplasia type 2B. Am J Hum Genet. 1994;55:1076-82.

Cooper MS. Disorders of calcium metabolism and parathyroid disease. Best Pract Res Clin Endocrinol Metab. 2011;25(6):975-83.

Scarsbrook AF, Thakker RV, Wass JA, et al. Multiple endocrine neoplasia: spectrum of radiologic appearances and discussion of a multitechnique imaging approach. Radiographics. 2006;26(2):433-51.

Schreinemakers JM, Pieterman CR, Scholten A, et al. The optimal surgical treatment for primary hyperparathyroidism in MEN1 patients: a systematic review. World J Surg. 2011;35(9):1993-2005.

Pieterman CR, van Hulsteijn LT, den Heijer M, et al. Primary Hyperparathyroidism in MEN1 Patients: Preferred Surgical Procedure and

Relation With Genotype--a Cohort Study With Long-Term Follow-Up. Ann Surg. 2012 Mar 30. [En Prensa]

Piecha G, Chudek J, Więcek A. Primary hyperparathyroidism in patients with multiple endocrine neoplasia type 1. Int J Endocrinol. 2010;2010:928383.

Tonelli F, Marcucci T, Giudici F, et al. Surgical approach in hereditary hyperparathyroidism. Endocr J. 2009;56(7):827-41.

Piecha G, Chudek J, Wiecek A. Multiple Endocrine Neoplasia type 1. Eur J Intern Med. 2008;19(2):99-103.

Wada M, Furuya Y, Sakiyama J, et al. The calcimimetic compound NPS R-568 suppresses parathyroid cell proliferation in rats with renal insufficiency. Control of parathyroid cell growth via a calcium receptor. J Clin Invest. 1997;100:2977-83.

Moyes VJ, Monson JP, Chew SL, et al. Clinical Use of Cinacalcet in MEN1

Hyperparathyroidism. Int J Endocrinol. 2010;2010:906163.

Marcocci C, Cetani F. Update on the use of cinacalcet in the management of primary hyperparathyroidism. J Endocrinol Invest. 2012;35(1):90-5.

Falchetti A, Cilotti A, Vagelli L, et al. A patient with MEN1-associated hyperparathyroidism, responsive to cinacalcet. Nat Clin Pract Endocrinol Metab. 2008;4(6):351-7.

Veldhuis JD, Norton JA, Wells SA, et al. Surgical Versus Medical Management of Multiple Endocrine Neoplasia (MEN) Type I. J Clin Endocrinol Metab. 1997;82(2):357-64.

Scholten A, Schreinemakers JM, Pieterman CR, et al. Evolution of surgical treatment of primary hyperparathyroidism in patients with multiple endocrine neoplasia type 2A. Endocr Pract. 2011;17(1):7-15.

Lewis RB, Lattin GE Jr, Paal E. Pancreatic endocrine tumors: radiologic-clinicopathologic correlation. Radiographics. 2010;30:1445-64.

Virgolini I, Ambrosini V, Bomanji JB, et al. Procedure guidelines for PET/CT tumour imaging with 68Ga-DOTA-conjugated peptides: 68Ga-DOTA-TOC, 68Ga-DOTA-NOC, 68Ga-DOTA-TATE. Eur J Nucl Med Mol Imaging. 2010;37:2004-10.

McLean A. Endoscopic ultrasound in the detection of pancreatic islet cell tumours. Cancer Imaging. 2004;4:84-91.

Triponez F, Goudet P, Dosseh D, et al. Is surgery beneficial for MEN-1 patients with small (=2 cm), nonfunctioning pancreaticoduodenal endocrine tumor? An analysis of 65 patients from the GTE. World J Surg. 2006;30:654–62.

Kouvaraki MA, Shapiro SE, Cote GJ, et al. Management of pancreatic endocrine tumors in multiple endocrine neoplasia type 1. World J Surg. 2006;30:643-53.

Fendrich V, Langer P, Waldmann J, Bartsch DK, Rothmund M.

Management of sporadic and multiple endocrine neoplasia type 1 gastrinomas. Br J Surg. 2007;94(11):1331-41.

Akerström G, Hellman P. Surgery on neuroendocrine tumours. Best Pract Res Clin Endocrinol Metab. 2007;21(1):87-109.

Norton JA, Fang TD, Jensen RT. Surgery for gastrinoma and insulinoma in multiple endocrine neoplasia type 1. J Natl Compr Canc Netw. 2006;4(2):148-53.

Akerström G, Hessman O, Hellman P, Skogseid B. Pancreatic tumours as part of the MEN-1 syndrome. Best Pract Res Clin Gastroenterol. 2005;19(5):819-30.

Corbetta S, Pizzocaro A, Peracchi M, et al. Multiple endocrine neoplasia type 1 in patients with recognized pituitary tumours of different types. Clin Endocrinol. 1997;47:507-12.

O'Brien T, O'Riordan DS, Gharib H, et al. Results of treatment of pituitary disease in multiple endocrine neoplasia, type I. Neurosurgery. 1996;39:273-9.

Bevan JS, Webster J, Burke CW, et al. Dopamine agonists and pituitary tumor shrinkage. Endocr Rev. 1992;13:220-40.

Hoff AO, Hoff PM. Medullary thyroid carcinoma. Hematol Oncol Clin North Am. 2007;21(3):475-88.

Frank-Raue K, Rondot S, Schulze E, et al. Change in the spectrum of RET mutations diagnosed between 1994 and 2006. Clin Lab. 2007;53(5-6):273-82.

Byard RW, Thorner PS, Chan HS, et al. Pathological features of multiple endocrine neoplasia type IIb in childhood. Pediatr Pathol. 1990;10(4):581-92.

Skinner MA, DeBenedetti MK, Moley JF, et al. Medullary thyroid carcinoma in children with multiple endocrine neoplasia types 2A and 2B. J Pediatr Surg. 1996;31(1):177-181.

Hassett S, Costigan C, McDermott M, et al. Prophylactic thyroidectomy in the treatment of thyroid medullary carcinoma. Age for surgery? Eur J Pediatr Surg. 2000;10(5):334-6.

Moley JF, DeBenedetti MK, Dilley WG, et al. Surgical management of patients with persistent or recurrent medullary thyroid cancer. J Intern Med. 1998;243:521-6.

Heshmati HM, Gharib H, van Heerden JA, et al. Advances and controversies in the diagnosis and management of medullary thyroid carcinoma. Am J Med. 1997;103:60-9.

Barakat MT, Meeran K, Bloom SR. Neuroendocrine tumours. Endocr Relat Cancer. 2004;11:1–18.

Skinner MA, MA, Dilley WiG, et al. Prophylactic Thyroidectomy in Multiple Endocrine Neoplasia Type 2a. N Engl J Med. 2005;353:1105-13.

Machens A, Ukkat J , Brauckhoff M, et al. Advances in the management of hereditary medullary thyroid cancer. J Intern Med. 2005;257:50-9.

Neumann HP, Vortmeyer A, Schmidt D, et al. Evidence of MEN-2 in the original description of classic pheochromocytoma. N Engl J Med. 2007;357(13):1311-5.

Hes FJ, Höppener JWM, Lips CJM. Clinical Review 155: Pheochromocytoma in Von Hippel-Lindau Disease. 2003;88(3):969-74.

Raue F, Frank-Raue K. Multiple endocrine neoplasia type 2: 2007 update. Horm Res. 2007;68(Suppl 5):101-4.

Frank-Raue K, Kratt T, Hoppner W, et al. Diagnosis and management of pheochromocytomas in patients with multiple endocrine neoplasia type 2: relevance of specific mutations in the RET protooncogene. Eur J Endocrinol. 1996;135:222-5.

Heshmati HM, Hofbauer LC. Multiple endocrine neoplasia type 2: recent progress in diagnosis and management. Eur J Endocrinol. 1997;137:572-8.

Lenders JW, Keiser HR, Goldstein DS, et al. Plasma metanephrines in the diagnosis of pheochromocytoma. Ann Intern Med. 1995;123(2):101-9.

Kudva YC, Sawka AM, Young WF. Clinical Review 164. The Laboratory Diagnosis of Adrenal Pheochromocytoma: The Mayo Clinic Experience. J Clin Endocrinol Metab. 2003 88(10):4533-9.

Bravo EL, Tagle R. Pheochromocytoma: State-of-the-Art and Future Prospects Endocr Rev. 2003;24(4):539-53.

Eisenhofer G, Lenders JW, Timmers H, et al. Measurements of plasma methoxytyramine, normetanephrine, and metanephrine as discriminators of different hereditary forms of pheochromocytoma. Clin Chem. 2011;57(3):411-20.

Bravo EL. Pheochromocytoma: Current Perspectives in the Pathogenesis, Diagnosis, and Management. Arq Bras Endocrinol Metab. 2004;48(5):746-50.

Ilias I, Pacak K. Clinical Problem Solving: Current Approaches and Recommended Algorithm for the Diagnostic Localization of Pheochromocytoma. J Clin Endocrinol Metab. 2004;89(2):479-91.

Ilias I, Pacak K. Diagnosis, localization and treatment of pheochromocytoma in MEN 2 syndrome. Endocr Regul. 2009;43(2):89-93.

Dennehy PJ, Feldman GL, Kambouris M, et al. Relationship of familial prominent corneal nerves and lesions of the tongue resembling neuromas to multiple endocrine neoplasia type 2B. Am J Ophthalmol. 1995;120:456-61.

Smith VV, Eng C, Milla PJ. Intestinal ganglioneuromatosis and multiple endocrine neoplasia type 2B: implications for treatment. Gut. 1999;45:143-6.

Geist JR, Gander DL, Stefanac SJ. Oral manifestations of neurofibromatosis

types I and II. Oral Surg Oral Med Oral Pathol. 1992;73(3):376-82.

Grobmyer SR, Guillem JG, O’Riordain DS, et al. Colonic manifestation of multiple endocrine neoplasia type 2B. Report of four cases. Dis Colon Rectum. 1999;42:1216-9.

Winship IM, Dudding TE. Lessons from the skin—cutaneous features of familial cancer. Lancet Oncol. 2008;9:462-72.

Asgharian B, Turner ML, Gibril F, et al. Cutaneous tumors in patients with multiple endocrine neoplasia type 1 (MEN1) and gastrinomas: prospective study of frequency and development of criteria with high sensitivity and specificity for MEN1. J Clin Endocrinol Metab. 2004;89:5328-36.

Xia Y, Darling TN. Rapidly growing collagenomas in multiple endocrine neoplasia type I. J Am Acad Dermatol. 2007;56:877-80.

Saggini A, Brandi ML. Skin lesions in hereditary endocrine tumor syndromes. Endocr Pract. 2011;17(Suppl 3):47-57.

Ceccherini I, Romei C, Barone V, et al. Identification of the Cys634—>Tyr mutation of the RET proto-oncogene in a pedigree with multiple endocrine neoplasia type 2A and localized cutaneous lichen amyloidosis. J Endocrinol Invest.1994;17:201-4.

Newey PJ, Thakker RV. Rol of multiple endocrine neoplasia type 1 mutational analysis in clinical practice. Endocr Pract. 2011;17(Suppl3):8-17.

Giraud S, Choplin H, Teh BT, et al. A large multiple endocrine neoplasia type 1 family with clinical expression suggestive of anticipation. J Clin Endocrinol Metab. 1997;82:3487-92.

Marini F, Falchetti A, Del Monte F, et al. Multiple endocrine neoplasia type 2. Orphanet J Rare Dis. 2006;2:1:45.





Se encuentra actualmente indizada en:
  

Creative Commons License
Todos los documentos publicados en esta revista se distribuyen bajo una
Licencia Creative Commons Atribución -No Comercial- Compartir Igual 4.0 Internacional.
Por lo que el envío, procesamiento y publicación de artículos en la revista es totalmente gratuito.