Множественная эндокринная неоплазия 2-го типа

Наследственная форма феохромоцитомы отличается склонностью к рецидиву, двустороннему, мультицентричному и первично-множественному поражению. Для пациентов с синдромом множественных эндокринных неоплазий 2-го типа не характерны вненадпочечниковая локализация феохромоцитомы и наличие метастазов. Обследование и лечение данной категории пациентов необходимо проводить с учетом этих особенностей. На примере семьи с синдромом множественных эндокринных неоплазий 2-го типа освещены вопросы ведения пациентов с генетически-детерминированной феохромоцитомой.

множественная эндокринная неоплазия 2-го типа, феохромоцитома, мутация гена RET, медуллярный рак щитовидной железы

1. Takahashi M., Ritz J., Cooper G.M. Activation of a novel human transforming gene, ret, by DNA rearrangement. Cell 1985; 42: 2: 581-588.

2. Raue F., Frank-Raue K. Multiple endocrine neoplasia type 2. Horm Res 2007; 68: 101-104.

3. Kouvaraki M.A., Shapiro S.E., Perrier N.D. et al. RET proto-oncogene: a review and update of genotype-phenotype correlations in hereditary medullary thyroid cancer and associated endocrine tumors. Thyroid 2005; 15: 531-544.

4. Mulligan L.M., Kwok J.B., Healey C.S., Elsdon M.J., Eng C., Gardner E., Love D.R., Mole S.E., Moore J.K., Papi L., Ponder M.A., Telenius H., Tunnacliffe A., Ponder B.A.J. Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A. Nature 1993; 363: 458-460.

5. Donis-Keller H., Dou S., Chi D., Carlson K.M., Toshima K., Lairmore T.C., Howe J.R., Moley J.F., Goodfellow P., Wells S.A.Jr. Mutations in the RET proto-oncogene are associated with MEN 2A and FMTC. Hum Mol Genet 1993; 2: 851-856.

6. de Groot J.W., Links T.P., Plukker J.T., Lips C.J., Hofstra R.M. RET as a diagnostic and therapeutic target in sporadic and hereditary endocrine tumors. Endocr Rev 2006; 27: 535-560.

7. Romei C., Elisei R., Pinchera A., Ceccherini I., Molinaro E., Mancusi F., Martino E., Romeo G., Pacini F. Somatic mutations of the ret protooncogene in sporadic medullary thyroid carcinoma are not restricted to exon 16 and are associated with tumor recurrence. J Clin Endocrinol Metab 1996; 81: 1619-1622.

8. Elisei R., Cosci B., Romei C., Bottici V., Renzini G., Molinaro E., Agate L., Vivaldi A., Faviana P., Basolo F., Miccoli P., Berti P., Pacini F., Pinchera A. Prognostic significance of somatic RET oncogene mutations in sporadic medullary thyroid cancer: a 10-year follow-up study. J Clin Endocrinol Metab 2008; 93: 682-687.

9. Carlson K.M., Bracamontes J., Jackson C.E., Clark R., Lacroix A., Wells S.A.Jr., Goodfellow P.J. Parent-of-origin effects in multiple endocrine neoplasia type 2B. Am J Hum Genet 1994; 55: 1076-1082.

10. Schuffenecker I., Ginet N., Goldgar D., Eng C., Chambe B., Boneu A., Houdent C., Pallo D., Schlumberger M., Thivolet C., Lenoir G.M. Prevalence and parental origin of de novo RET mutations in multiple endocrine neoplasia type 2A and familial medullary thyroid carcinoma. Le Groupe d'Etude des Tumeurs a Calcitonine. Am J Hum Genet 1997; 60: 233-237.

11. Kaufman F.R., Roe T.F., Isaacs H.Jr., Weitzman J.J. Metastatic medullary thyroid carcinoma in young children with mucosal neuroma syndrome. Pediatrics 1982; 70: 263-267.

12. Roman S., Lin R., Sosa J.A. Prognosis of medullary thyroid carcinoma: demographic, clinical, and pathologic predictors of survival in 1252 cases. Cancer 2006; 107: 2134-2142.

13. Wygoda Z., Oczko-Wojciechowska M., GubaŁa E., Pawlaczek A., Kula D., Wiench M., WŁoch J. Medullary thyroid carcinoma: the comparison of the hereditary and sporadic types of cancer. Endokrynol Pol (Polsh) 2006; 57: 407-414.

14. Vasen H.F., Nieuwenhuijzen Kruseman A.C., Berkel H., Beukers E.K., Delprat C.C., Van Doorn R.G., Geerdink R.A., Haak H.R., Hackeng W.H., Koppeschaar H.P. et al. Multiple endocrine neoplasia syndrome type 2: the value of screening and central registration. A study of 15 kindreds in The Netherlands. Am J Med 1987; 83: 5: 847-52. PMID:2890300.

15. Howe J.R., Norton J.A., Wells S.A.Jr. Prevalence of pheochromocytoma and hyperparathyroidism in multiple endocrine neoplasia type 2A: results of long-term follow-up. Surgery 1993; 114: 6: 1070-1077. PMID: 7903003.

16. Lee N.C., Norton J.A. Multiple endocrine neoplasia type 2B-genetic basis and clinical expression. Surg Oncol 2000; 9: 3: 111-118. Review. PMID: 11356339.

17. Skinner M.A., Safford S.D., Freemerman A.J. RET tyrosine kinase and medullary thyroid cells are unaffected by clinical doses of STI571. Anticancer Res 2003; 23: 5A: 3601-3606. PMID:14666655.

18. Danko M.E., Skinner M.A. Surgical intervention in children with multiple endocrine neoplasia type 2. Curr Opin Pediatr 2006; 18: 3: 312-315. Review. PMID: 16721155.

19. Kakudo K., Carney J.A., Sizemore G.W. Medullary carcinoma of thyroid. Biologic behavior of the sporadic and familial neoplasm. Cancer 1985; 55: 2818-2821.

20. Ponder B.A., Ponder M.A., Coffey R. et al. Risk estimation and screening in families of patients with medullary thyroid carcinoma. Lancet 1988; 1: 8582: 397-401.

21. Poston G.J. Medullary carcinoma of the thyroid. In: Surgical Endocrinology. Eds. J. Lynn, S.R. Bloom. Oxford: Butterworth-Heinemann 1993; 270-276.

22. Phay J.E., Moley J.F., Lairmore T.C. Multiple endocrine neoplasias. Seminars. Surg Oncol 2000; 18: 324-332.

23. Clayman G.L., El-Baradie T.S. Medullary thyroid cancer. Otolaryngol Clin North Am 2003; 36: 91-105.

24. Gagel R.F., Tashjian A.H.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; 318: 478-484.

25. Pacini F., Fontanelli M., Fugazzola L., Elisei R., Romei C., DiCoscio G., Miccoli P., Pinchera A. Routine measurement of secum calcitonin in nodular thyroid disease allows the preoperative diagnosis of unsuspected sporadic medullary thyroid carcinoma. J Clin Endocrinol Metabol 1994; 78: 826-829.

26. Heshmati H.M., Ghabib H., van Heerden J.A., Sizemore G.W. Advances and controversies in the diagnosis and management of medullary thyroid carcinoma. Am J Med 1997; 103: 60-69.

27. Niccoli P., Wion-Barbot N., Caron P., Henry J.F., de Micco C., Saint Andre J.P., Bigorgne J.C., Modigliani E., Conte-Devolx B. Interest of routine measurement of serum calcitonin: study in a large series of thyroidectomized patients. The French Medullary Study Group. J Clin Endocrinol Metab 1997; 82: 338-341.

28. Cohen R., Campos J.M., Salaun C., Heshmati H.M., Proye C., Sarfati E., Henry J.F., Niccoli-Sire P., Modigliani E. Preoperative calcitonin levels are predictive of tumor size and postoperative calcitonin normalization in medullary thyroid carcinoma. J Clin Endocrinol Metabol 2000; 85: 919-922.

29. Skinner M.A., Moley J.A., Dilley W.G., Owzar K., Debenedetti M.K., Wells S.A.Jr. Prophylactic thyroidectomy in multiple endocrine neoplasia type 2A. N Engl J Med 2005; 353: 11: 1105-1113.

30. Brandi M.L., Gagel R.F., Angeli A. et al. Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab 2001; 86: 12: 5658-5671.

31. Samaan N.A., Draznin M.B., Halpin R.E., Bloss R.S., Hawkins E., Lewis R.A. Multiple endocrine syndrome type IIb in early childhood. Cancer 1991; 68: 1832-1834.

32. Skinner M.A., DeBenedetti M.K., Moley J.F., Norton J.A., Wells S.A.Jr. Medullary thyroid carcinoma in children with multiple endocrine neoplasia types 2A and 2B. J Pediatr Surg 1996; 31: 177-181; discussion 172-181.

33. Farndon J.R., Leight G.S., Dilley W.G. et al. Familial medullary thyroid carcinoma without associated endocrinopathies, a distinct clinical entity. Br J Surg 1986; 73: 4: 278-281.

34. Modigliani E., Cohen R., Campos J.M. et al. Prognostic factors for survival and for biochemical cure in medullary thyroid carcinoma, results in 899 patients. The GETC Study Group. Groupe d'etude des tumeurs a calcitonine. Clin Endocrinol (Oxf) 1998; 48: 3: 265-273.

35. Papotti M., Botto Micca F., Favero A., Palestini N., Bussolati G. Poorly differentiated thyroid carcinomas with primordial cell component. A group of aggressive lesions sharing insular trabecular and solid patterns. Am J Surg Pathol 1993; 17: 291-301.

36. Kebebew E., Ituarte P.H., Siperstein A.E., Duh Q.Y., Clark O.H. Medullary thyroid carcinoma, clinical characteristics, treatment, prognostic factors, and a comparison of staging systems. Cancer 2000; 88: 5: 1139-1148.

37. Quayle F.J., Moley J.F. Medullary thyroid carcinoma, including MEN 2A and MEN 2B syndromes. J Surg Oncol 2005; 89: 3: 122-129.

38. Lodish M., Stratakis С. RET oncogene in MEN2, MEN2B, MTC, and other forms of thyroid cancer: molecular genetics and therapeutic advances. Exp Rev Anticancer Ther 2008; 8: 4: 625-632.

39. You Y.N., Lakhani V., Wells S.A.Jr. New directions in the treatment of thyroid cancer. J Am Coll Surg 2007; 205: 4: Suppl:S45-S48.

40. Gimm O., Koch C.A., Januszewicz A., Opocher G., Neumann H.P. The genetic basis of pheochromocytoma. Front Horm Res 2004; 31: 45-60.

41. Kaltsas G.A., Papadogias D., Grossman A.B. The clinical presentation (symptoms and signs) of sporadic and familial chromaffin cell tumours (phaeochromocytomas and paragangliomas). Front Horm Res 2004; 31: 61-75.

42. Frank-Raue K., Kratt T., Hoppner W., Buhr H., Ziegler R., Raue F. Diagnosis and management of pheochromocytomas in patients with multiple endocrine neoplasia type 2-relevance of specific mutations in the RET proto-oncogene. Eur J Endocrinol 1996; 135: 222-225.

43. Kloos R.T. et al. Medullary thyroid cancer: management guidelines of the American Thyroid Association. Thyroid 2009; 19: 6: 565-612.

44. Schuffeneker I., Virally-Monod M., Brohet R., le Groupe D'Etude des Tumeurs a Calcitonine. 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. J Clin Endocrinol Metab 1998; 83: 487-491.

45. Kraimps J.L., Denizot A., Carnaille B., Henry J.F., Proye C., Bacourt F., Sarfati E., Dupond J.L., Maes B., Travagli J.P., Boneu A., Roger P., Houdent C., Barbier J., Modigliani E. Primary hyperparathyroidism in multiple endocrine neoplasia type IIa: retrospective French multicentric study. Groupe d'Etude des Tumeurs a` Calcitonine (GETC, French Calcitonin Tumors Study Group), French Association of Endocrine Surgeons. World J Surg 1996; 20: 808-812; discussion 803-812.

46. Raue F., Kraimps J.L., Dralle H., Cougard P., Proye C., Frilling A., Limbert E., Llenas L.F., Niederle B. Primary hyperparathyroidism in multiple endocrine neoplasia type 2A. J Int Med 1995; 238: 369-373.

47. 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: 943-951.

48. Romeo G., Ceccherini I., Celli J., Priolo M., Betsos N., Bonardi G., Seri M., Yin L., Lerone M., Jasonni V., Martucciello G. Association of multiple endocrine neoplasia type 2 and Hirschsprung disease. J Intern Med 1998; 243: 515-520.

49. Mulligan L.M., Eng C., Attie T., Lyonnet S., Marsh D.J., Hyland V.J., Robinson B.G., Frilling A., Verellen-Dumoulin C., Safar A., Venter D.J., Munnich A., Ponder B.A.J. Diverse phenotypes associated with exon 10 mutations of the RET protooncogene. Hum Mol Genet 1994; 3: 2163-2167.

50. O'Riordain D.S., O'Brien T., Crotty T.B., Gharib H., Grant C.S., van Heerden J.A. Multiple endocrine neoplasia type 2B: more than an endocrine disorder. Surgery 1995; 118: 936-942.

51. Leboulleux S., Travagli J.P., Caillou B., Laplanche A., Bidart J.M., Schlumberger M., Baudin E. Medullary thyroid carcinoma as part of a multiple endocrine neoplasia type 2B syndrome: influence of the stage on the clinical course. Cancer 2002; 94: 44-50.

52. Smith V.V., Eng C., Milla P.J. Intestinal ganglioneuromatosis and multiple endocrine neoplasia type 2B: implications for treatment. Gut 1999; 45: 143-146.

53. Unruh A., Fitze G., Janig U., Bielack S., Lochbuhler H., Coerdt W. Medullary thyroid carcinoma in a 2-month-old male with multiple endocrine neoplasia 2B and symptoms of pseudo-Hirschsprung disease: a case report. J Pediatr Surg 2007; 42: 1623-1626.

54. Yin M., King S.K., Hutson J.M., Chow C.W. Multiple endocrine neoplasia type 2B diagnosed on suction rectal biopsy in infancy: a report of 2 cases. Pediatr Dev Pathol 2006; 9: 56-60.

55. Carney J.A., Go V.L., Sizemore G.W., Hayles A.B. Alimentary-tract ganglioneuromatosis. A major component of the syndrome of multiple endocrine neoplasia, type 2b. N Engl J Med 1976; 295: 1287-1291.

56. Pacak K. Preoperative management of the pheochromocytoma patient. J Clin Endocrinol Metab 2007; 92: 4069-4079.

57. Lenders J.W., Pacak K., Walther M.M., Linehan W.M., Mannelli M., Friberg P., Keiser H.R., Goldstein D.S., Eisenhofer G. Biochemical diagnosis of pheochromocytoma: which test is best? JAMA 2002; 287: 1427-1434.

58. Eisenhofer G., Goldstein D.S., Walther M.M., Friberg P., Lenders J.W., Keiser H.R. et al. Biochemical diagnosis of pheochromocytoma: how to distinguish true- from false-positive test results. J Clin Endocrinol Metab 2003; 88: 2656-2666.