Диагностика медуллярного рака щитовидной железы и тактика ведения пациентов при отсутствии лабораторной ремиссии

Успешное лечение медуллярного рака щитовидной железы возможно только при его раннем выявлении. Представлен анализ результатов исследований, посвященных различным методам диагностики этого заболевания и особенностям длительного ведения пациентов при отсутствии ремиссии.

медуллярный рак щитовидной железы, кальцитонин, раковоэмбриональный антиген, мутации гена RET

1. Hundahl S.A., Fleming I.D., Fremgen A.M., Menck H.R. A National Cancer Data Base report on 53,856 cases of thyroid carcinoma treated in the US 1985-1995. Cancer 1998; 83: 2638-2648.

2. Kloos R.T., Eng Ch., Evans D.B., Francis G.L., Gagel R.F., Gharib H., Moley J.F., Pacini F., Ringel M.D., Schlumberger M., Wells S.A.Jr. Medullary thyroid cancer: management guidelines of the American Thyroid Association. Thyroid 2009; 19: 6: 565-612.

3. Cai S., Liu H., Li W., Ouyang Y., Zhang B., Li P., Wang X., Zhang X., Li J., Jiang Y. Ultrasonographic features of medullary thyroid carcinoma and their diagnostic values. Chin Med J 2010; 123: 21: 3074-3078.

4. Kim S.H., Kim B.S., Jung S.L., Lee J.W., Yang P.S., Kang B.J., Lim H.W., Kim J.Y., Whang I.Y., Kwon H.S., Jung C.K. Ultrasonographic findings of medullary thyroid carcinoma: a comparison with papillary thyroid carcinoma. Korean J Radiol 2009; 10: 101-105.

5. Lee S., Shin J.H., Han B.K., Ko E.Y. Medullary thyroid carcinoma: comparison with papillary thyroid carcinoma and application of current sonographic criteria. Am J Roentgenol 2010; 194: 1090-1094.

6. Chang T.C., Wu S.L., Hsiao Y.L. Medullary thyroid carcinoma: pitfalls in diagnosis by fine needle aspiration cytology and relationship of cytomorphology to RET protooncogene mutations. Acta Cytolog 2005; 49: 477-482.

7. Papaparaskeva K., Nagel H., Droese M. Cytologic diagnosis of medullary carcinoma of the thyroid gland. Diagn Cytopathol 2000; 22: 351-358.

8. Bugalho M.J., Santos J.R., Sobrinho L. Preoperative diagnosis of medullary thyroid carcinoma: fine needle aspiration cytology as compared with serum calcitonin measurement. J Surg Oncol 2005; 91: 56-60.

9. 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.

10. Elisei R., Bottici V., Luchetti F., Di Coscio G., Romei C., Grasso L., Miccoli P., Iacconi P., Basolo F., Pinchera A., Pacini F. Impact of routine measurement of serum calcitonin on the diagnosis and outcome of medullary thyroid cancer: experience in 10,864 patients with nodular thyroid disorders. J Clin Endocrinol Metab 2004; 89: 163-168.

11. Boi F., Maurelli I., Pinna G., Atzeni F., Piga M., Lai M.L., Mariotti S. Calcitonin measurement in wash-out fluid from fine needle aspiration of neck masses in patients with primary and metastatic medullary thyroid carcinoma. J Clin Endocrinol Metab 2007; 92: 6: 2115-2118.

12. Massaro F., Dolcino M., Degrandi R., Ferone D., Mussap M., Minuto F., Giusti M. Calcitonin assay in wash-out fluid after fine-needle aspiration biopsy in patients with a thyroid nodule and border-line value of the hormone. J Endocrinol Inv 2009; 32: 4: 308-312.

13. Chambon G., Alovisetti C., Idoux-Louche C., Reynaud Ch., Rodier M., Guedj A-M., Chapuis H., Lallemant J-G., Lallemant B. The Use of Preoperative Routine Measurement of Basal Serum Thyrocalcitonin in Candidates for Thyroidectomy due to Nodular Thyroid Disorders: Results from 2733 Consecutive Patients. J Clin Endocrinol Metab 2011, 96: 1: 75-81.

14. Cooper D.S., Doherty G.M., Haugen B.R., Kloos R.T., Lee S.L., Mandel S.J., Mazzaferri E.L., McIver B., Pacini F., Schlumberger M., Sherman S.I., Steward D.L., Tuttle R.M. Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid 2009; 9: 11: 1-48.

15. Gharib H., Papini E., Paschke R., Duick D.S., Valcavi R., Hegedüs L., Vitti P. American Association of Clinical Endocrinologists, Associazione Medici Endocrinologi, and European Thyroid Association Medical Guidelines for Clinical Practice for the Diagnosis and Management of Thyroid Nodules. Endocrine Pract 2010; 16: Suppl 1: 1-43.

16. Costante G., Meringolo D., Durante C., Bianchi D., Nocera M., Tumino S. Predictive value of serum calcitonin levels for preoperative diagnosis of medullary thyroid carcinoma in a cohort of 5817 consecutive patients with thyroid nodules. J Clin Endocrinol Metab 2007; 92: 450-455.

17. D'Herbomez M., Caron P., Bauters C. French Group GTE (Groupe des Tumeurs Endocrines). Reference range of serum calcitonin levels in humans: influence of calcitonin assays, sex, age, and cigarette smoking. Eur J Endocrinol 2007; 157: 749-755.

18. Kotzmann H., Schmidt A., Scheuba C. Basal calcitonin levels and the response to pentagastrin stimulation in patients after kidney transplantation or on chronic hemodialysis as indicators of medullary carcinoma. Thyroid 1999; 9: 943-947.

19. Erdogan M.F., Gullu S., Baskal N., Uysal A.R., Kamel N., Erdogan G. Omeprazole: Calcitonin stimulation test for the diagnosis follow-up and family screening in medullary thyroid carcinoma. J Clin Endocrinol Metab 1997; 82: 897-899.

20. LiVolsi V.A. C cell hyperplasia-neoplasia. J Clin Endocrinol Metab 1997; 82: 39-41.

21. Hahm J.R., Lee M.S., Min Y.K., Lee M.K., Kim K.W., Nam S.J., Yang J.H., Chung J.H. Routine measurement of serum calcitonin is useful for early detection of medullary thyroid carcinoma in patients with nodular thyroid diseases. Thyroid 2001; 11: 73-80.

22. Machens A., Hoffmann F., Sekulla C., Dralle H. Importance of gender-specific calcitonin thresholds in screening for occult sporadic medullary thyroid cancer. Endocr Relat Cancer 2009; 16: 1291-1298.

23. Wells S.A.Jr., Baylin S.B., Linehan W.M., Farrell R.E., Cox E.B., Cooper C.W. Provocative agents and the diagnosis of medullary carcinoma of the thyroid gland. Ann Surg 1978; 188: 139-141.

24. Gharib H., Kao P.C. Determination of silica-purified plasma calcitonin for the detection and management of medullary thyroid carcinoma: comparison of two provocative tests. Mayo Clin Proc 1987; 62: 373-378.

25. Doyle P., Duren C., Nerlich K., Verburg F.A., Grelle I., Jahn H., Fassnacht M., Mader U., Reiners C., Luster M. Potency and tolerance of calcitonin stimulation with high-dose calcium versus pentagastrin in normal adults. J Clin Endocrinol Metab 2009; 94: 2970-2974.

26. Colombo C., Verga U., Perrino M., Vicentini L., Beck-Peccoz P., Fugazzola L. High-dose calcium and pentagastrin tests in patients with cured or persistent medullary thyroid cancer and in controls: comparison of the efficacy and the tolerance. 14th Annual International Thyroid Congress. Paris 2010; Abstract P-0923.

27. Cheung K., Roman S.A., Wang T.S., Walker H.D., Sosa J.A. Calcitonin measurement in the evaluation of thyroid nodules in the United States: a cost-effectiveness and decision analysis. J Clin Endocrinol Metab 2008; 93: 2173-2180.

28. Redding A.H., Levine S.N., Fowler M.R. Normal preoperative calcitonin levels do not always exclude medullary thyroid carcinoma in patients with large palpable thyroid masses. Thyroid 2000; 10: 919-922.

29. Modigliani E., Cohen R., Campos J.M., Conte-Devolx B., Maes B., Boneu A., Schlumberger M., Bigorgne J.C., Dumontier P., Leclerc L., Corcuff B., Guilhem I. Prognostic factors for survival and for biochemical cure in medullary thyroid carcinoma: results in 899 patients. The GETC Study Group. Groupe d'ütude des tumeurs a` calcitonine. Clin Endocrinol 1998; 48: 265-273.

30. Engelbach M., Gorges R., Forst T., Pfutzner A., Dawood R., Heerdt S., Kunt T., Bockisch A., Beyer J. Improved diagnostic methods in the follow-up of medullary thyroid carcinoma by highly specific calcitonin measurements. J Clin Endocrinol Metab 2000; 85: 1890-1894.

31. Tisell L.E., Dilley W.G., Wells S.A. Progression of postoperative residual medullary thyroid carcinoma as monitored by plasma calcitonin levels. Surgery 1996; 119: 34-39.

32. Franc S., Niccoli-Sire P., Cohen R., Bardet S., Maes B., Murat A., Krivitzky A., Modigliani E. Complete surgical lymph node resection does not prevent authentic recurrences of medullary thyroid carcinoma. Clin Endocrinol 2001; 55: 403-409.

33. Shoback D., Strewler G. Disorders of the parathyroids and calcium metabolism. In: Pathophysiology of disease: an introduction to clinical medicine. Eds. S. McPhee, V.R. Lingappa, W. Ganong, J. Lange. 2nd ed. Stamford CT: Appleton and Lange 1995; 416-417.

34. Leboulleux S., Baudin E., Travagli J.P., Schlumberger M. Medullary thyroid carcinoma. Clin Endocrinol (Oxford) 2004; 61: 299-310.

35. Stepanas A.V., Samaan N.A., Hill C.S., Hickey R.C. Medullary thyroid carcinoma: importance of serial serum calcitonin measurement. Cancer 1979; 43: 825-837.

36. Fugazzola L., Pinchera A., Luchetti F., Iacconi P., Miccoli P., Romei C., Puccini M., Pacini F. Disappearance rate of serum calcitonin after total thyroidectomy for medullary thyroid carcinoma. Int J Biol Markers 1994; 9: 21-24.

37. Wells S.A., Baylin S.B., Gann D.S., Farrell R.E., Dilley W.G., Preissig S.H., Linehan W.M., Cooper C.W. Medullary thyroid carcinoma: relationship of method of diagnosis to pathologic staging. Ann Surg 1978; 188: 377-383.

38. Lundgren C.I., Delbridg L., Learoyd D., Robinson B. Surgical approach to medullary thyroid cancer. Arq Bras Endocrinol Metabol 2007; 51: 818-824.

39. Cohen M.S., Moley J.F. Surgical treatment of medullary thyroid carcinoma. J Intern Med 2003; 253: 616-626.

40. Kebebew E., Kikuchi S., Duh Q.Y., Clark O.H. Long-term results of reoperation and localizing studies in patients with persistent or recurrent medullary thyroid cancer. Arch Surg 2000; 135: 895-901.

41. Dralle H. Lymph node dissection and medullary thyroid carcinoma. Br J Surg 2002; 89: 1073-1075.

42. Fialkowski E., Debenedetti M., Moley J. Long-term outcome of reoperations for medullary thyroid carcinoma.World J Surg 2008; 32: 754-765.

43. Chatal J.F., Campion L., Kraeber-Bodere F., Bardet S., Vuillez J.P., Charbonnel B., Rohmer V., Chang C.H., Sharkey R.M., Goldenberg D.M., Barbet J. Survival improvement in patients with medullary thyroid carcinoma who undergo pretargeted anti-carcinoembryonic-antigen radioimmunotherapy: a collaborative study with the French Endocrine Tumor Group. J Clin Oncol 2006; 24: 1705-1711.

44. Wu L.T., Averbuch S.D., Ball D.W., de Bustros A., Baylin S.B., McGuire W.P. Treatment of advanced medullary thyroid carcinoma with a combination of cyclophosphamide, vincristine, and dacarbazine. Cancer 1994; 73: 432-436.

45. Schlumberger M., Abdelmoumene N., Delisle M.J., Couette J.E. Treatment of advanced medullary thyroid cancer with an alternating combination of 5 FU-streptozocin and 5 FU-dacarbazine. The Groupe d'Etude des Tumeurs a Calcitonine (GETC). Br J Cancer 1995; 71: 363-365.

46. Bajetta E., Rimassa L., Carnaghi C., Seregni E., Ferrari L., Di Bartolomeo M., Regalia E., Cassata A., Procopio G., Mariani L. 5-Fluorouracil, dacarbazine, and epirubicin in the treatment of patients with neuroendocrine tumors. Cancer 1998; 83: 372-378.

47. Wells S.A., Gosnell J.E., Gagel R.F., Moley J.F., Pfister D.G., Sosa J.A., Skinner M., Krebs A., Hou J., Schlumberger M. Vandetanib in metastatic hereditary medullary thyroid cancer: follow-up results of an open-label phase II trial. ASCO Annual Meeting Proceedings Part I 2007; 25: 6016.

48. Lam E.T., Ringel M.D., Kloos R.T., Collamore M., Arbogast D., Liang J., Hall N., Knopp M.V., Wright J., Shah M.H. Anti-tumor activity of Sorafenib in patients with Metastatic Medullary Thyroid Carcinoma. Proceedings of the American Association for Cancer Research 2009; Abstract 4513.

49. Salgia R., Sherman S., Hong D.S., Ng C.S., Frye J., Janisch L., Ratain M.J., Kurzrock R. A phase I study of XL184, a RET, VEGFR2, and MET kinase inhibitor, in patients (pts) with advanced malignancies, including pts with medullary thyroid cancer (MTC). J Clin Oncol 2008; 26: abstract 3522.

50. 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: 1139-1148.

51. Hyer S.L., Vini L., A'Hern R., Harmer C. Medullary thyroid cancer: multivariate analysis of prognostic factors influencing survival. Eur J Surg Oncol 2000; 26: 686-690.

52. Miyauchi A., Onishi T., Morimoto S., Takai S., Matsuzuka F., Kuma K., Maeda M., Kumahara Y. Relation of doubling-time of plasma calcitonin levels to prognosis and recurrence of medullary thyroid carcinoma. Ann Surg 1984; 199: 461-466.

53. Barbet J., Campion L., Kraeber-Bodere F., Chatal J.F. Prognostic impact of serum calcitonin and carcinoembryonic antigen doubling-times in patients with medullary thyroid carcinoma. J Clin Endocrinol Metab 2005; 90: 6077-6084.

54. Giraudet A.L., Al Ghulzan A., Auperin A., Leboulleux S., Chehboun A., Troalen F., Dromain C., Lumbroso J., Baudin E., Schlumberger M. Progression of medullary thyroid carcinoma: assessment with calcitonin and carcinoembryonic antigen doubling times. Eur J Endocrinol 2008; 158: 239-246.

55. Eng Ch., Mulligan L.M., Healey C.S. Heterogeneous Mutation of the RET Proto-oncogene in Subpopulations of Medullary Thyroid Carcinoma. Cancer Res 1996; 56: 2167-2170.

56. Schilling T., Burck J., Sinn H-P., Clemens A., Otto H.F., Hoppner W., Herfarth Ch., Ziegler R., Schwab M., Raue F. Pognostic value of codon 918 (ATG3ACG) RET proto-oncogene mutations in sporadic medullary thyroid carcinoma. Int J Cancer (Pred Oncol) 2001; 95: 62-66.

57. Elisei R., Barbara 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.

58. Moura M.M., Cavaco B.M., Pinto A.E., Domingues R., Santos J.R., Cid M.O., Bugalho M.J., Leite V. Correlation of RET somatic mutations with clinicopathological features in sporadic medullary thyroid carcinomas. Br J Cancer 2009; 100: 11: 1777-1783.

59. Zedenius J., Dwight T., Robinson B.G., Delbridge L., Backdahl M., Wallin G., Larsson C., Weber G. A rapid method for DNA extraction from fine-needle aspiration biopsies of thyroid tumors, and subsequent RET mutation analysis. Cancer Detect Prev 1998; 22: 6: 544-548.

60. Uchino S., Noguchi S., Yamashita H., Sato M., Adachi M., Yamashita H., Watanabe S., Ohshima A., Mitsuyama S., Iwashita T., Takahashi M. Somatic mutations in RET exons 12 and 15 in sporadic medullary thyroid carcinomas: different spectrum of mutations in sporadic type from hereditary type. Jpn J Cancer Res 1999; 90: 1231-1237.

61. Uchino S., Noguchi S., Adachi M., Sato M., Yamashita H., Watanabe S., Murakami T., Toda M., Murakami N., Yamashita H. Novel point mutations and allele loss at the RET locus in sporadic medullary thyroid carcinomas. Jpn J Cancer Res 1998; 89: 411-418.

62. Marsh D.J., Learoyd D.L., Andrew S.D., Krishnan L., Pojer R., Richardson A.L., Delbridge L., Eng C., Robinson B.G. Somatic mutations in the RET protooncogene in sporadic medullary thyroid carcinoma. Clin Endocrinol (Oxford) 1996; 44: 249-257.

63. Shan L., Nakamura M., Nakamura Y., Utsunomiya H., Shou N., Jiang X., Jing X., Yokoi T., Kakudo K. Somatic mutations in the RET protooncogene in Japanese and Chinese sporadic medullary thyroid carcinomas. Jpn J Cancer Res 1998; 89: 883-886.