Альманах клинической медицины. 2017; 45: 326-332
Распространенность новообразований при акромегалии в Московской области
https://doi.org/10.18786/2072-0505-2017-45-4-326-332Аннотация
Актуальность. Распространенность новообразований при акромегалии, а также влияние на их развитие различных факторов риска, таких как возраст пациента, длительность и активность заболевания, изучены недостаточно.
Цель – оценить распространенность новообразований щитовидной железы, желудка и толстой кишки в зависимости от возраста, пола, длительности и активности заболевания у пациентов с впервые выявленной акромегалией.
Материал и методы. Проведен ретроспективный анализ данных амбулаторных карт
и стационарных историй болезни 108 пациентов (25 мужчин и 83 женщины). Медиана возраста составила 50,5 (39,3–59,0) года, медиана длительности акромегалии 5 (2–10) лет (за начало заболевания принимали момент появления первых изменений внешности). Девяносто шести пациентам было выполнено ультразвуковое исследование щитовидной железы, 92 – эзофагогастродуоденоскопия, 89 – фиброколоноскопия.
Результаты. Доброкачественные узловые новообразования щитовидной железы выявлены у 50% (48 из 96) больных акромегалией, злокачественные – у 6,2% (6 из 96). Процент превышения верхней границы нормы инсулиноподобного ростового фактора 1-го типа у больных раком щитовидной железы был в 2,3 раза выше, чем у больных без новообразований щитовидной железы и в 2 раза выше, чем у больных с доброкачественными новообразованиями (р = 0,012 и p = 0,03 соответственно). Злокачественные новообразования чаще наблюдались в пожилой возрастной группе (старше 60 лет) по сравнению со средней (45–60 лет) (в 30,8 и 4,3% случаев соответственно, р = 0,01). У мужчин злокачественные новообразования щитовидной железы выявлялись чаще, чем у женщин (в 11,1 и 5,1% случаев соответственно). Доброкачественные новообразования желудочно-кишечного тракта встретились у 51,7% больных (у 18% – желудка, у 37% – толстой кишки). Возраст больных с новообразованиями желудка и длительность акромегалии у них были больше, чем у пациентов без подобных новообразований (р = 0,015 и p = 0,036 соответственно). Новообразования толстой кишки были представлены в 33,7% случаев гиперпластическими полипами и в 3% случаев раком толстой кишки. Возраст больных с новообразованиями толстой кишки был на 11 лет выше, чем у больных без таких новообразований (р = 0,015).
Заключение. При установке диагноза акромегалии необходима комплексная диагностика состояния желудочно-кишечного тракта и щитовидной железы ввиду повышенного риска развития новообразований у этой категории больных. Взаимосвязь повышенных показателей инсулиноподобного ростового фактора 1-го типа с развитием рака щитовидной железы указывает на участие этого фактора в канцерогенезе и требует дальнейшего изучения.
Список литературы
1. Cats A, Dullaart RP, Kleibeuker JH, Kuipers F, Sluiter WJ, Hardonk MJ, de Vries EG. Increased epithelial cell proliferation in the colon of patients with acromegaly. Cancer Res. 1996;56(3): 523–6.
2. Yamamoto M, Fukuoka H, Iguchi G, Matsumoto R, Takahashi M, Nishizawa H, Suda K, Bando H, Takahashi Y. The prevalence and associated factors of colorectal neoplasms in acromegaly: a single center based study. Pituitary. 2015;18(3): 343–51. doi: 10.1007/s11102-014-0580-y.
3. Kauppinen-Mäkelin R, Sane T, Reunanen A, Välimäki MJ, Niskanen L, Markkanen H, Löyttyniemi E, Ebeling T, Jaatinen P, Laine H, Nuutila P, Salmela P, Salmi J, Stenman UH, Viikari J, Voutilainen E. A nationwide survey of mortality in acromegaly. J Clin Endocrinol Metab. 2005;90(7): 4081–6. doi: 10.1210/jc.2004-1381.
4. Baris D, Gridley G, Ron E, Weiderpass E, Mellemkjaer L, Ekbom A, Olsen JH, Baron JA, Fraumeni JF Jr. Acromegaly and cancer risk: a cohort study in Sweden and Denmark. Cancer Causes Control. 2002;13(5): 395–400.
5. Ron E, Gridley G, Hrubec Z, Page W, Arora S, Fraumeni JF Jr. Acromegaly and gastrointestinal cancer. Cancer. 1991;68(8): 1673–7. doi: 10.1002/1097-0142(19911015)68:8<1673::AID-CNCR2820680802>3.0.CO;2-0.
6. Kurimoto M, Fukuda I, Hizuka N, Takano K. The prevalence of benign and malignant tumors in patients with acromegaly at a single institute. Endocr J. 2008;55(1): 67–71. doi: http://doi.org/10.1507/endocrj.K07E-010.
7. dos Santos MC, Nascimento GC, Nascimento AG, Carvalho VC, Lopes MH, Montenegro R, Montenegro R Jr, Vilar L, Albano MF, Alves AR, Parente CV, dos Santos Faria M. Thyroid cancer in patients with acromegaly: a case-control study. Pituitary. 2013;16(1): 109–14. doi: 10.1007/s11102-012-0383-y.
8. Dagdelen S, Cinar N, Erbas T. Increased thyroid cancer risk in acromegaly. Pituitary. 2014;17(4): 299–306. doi: 10.1007/s11102-013-0501-5.
9. Dogan S, Atmaca A, Dagdelen S, Erbas B, Erbas T. Evaluation of thyroid diseases and differentiated thyroid cancer in acromegalic patients. Endocrine. 2014;45(1): 114–21. doi: 10.1007/s12020-013-9981-3.
10. Титаева АА, Терещенко СГ, Лукина ЕМ, Древаль АВ, Иловайская ИА. Фоновые изменения слизистой оболочки желудочно-кишечного тракта у больных акромегалией. Альманах клинической медицины. 2014;31:29–33. doi: 10.18786/2072-0505-2014-31-29-33.
11. Lois K, Bukowczan J, Perros P, Jones S, Gunn M, James RA. The role of colonoscopic screening in acromegaly revisited: review of current literature and practice guidelines. Pituitary. 2015;18(4): 568–74. doi: 10.1007/s11102-014-0586-5.
12. Mestron A, Webb SM, Astorga R, Benito P, Catala M, Gaztambide S, Gomez JM, Halperin I, Lucas-Morante T, Moreno B, Obiols G, de Pablos P, Paramo C, Pico A, Torres E, Varela C, Vazquez JA, Zamora J, Albareda M, Gilabert M. Epidemiology, clinical characteristics, outcome, morbidity and mortality in acromegaly based on the Spanish Acromegaly Registry (Registro Espanol de Acromegalia, REA). Eur J Endocrinol. 2004;151(4): 439–46. doi: 10.1530/eje.0.1510439.
13. Ituarte EA, Petrini J, Hershman JM. Acromegaly and colon cancer. Ann Intern Med. 1984;101(5): 627–8. doi: 10.7326/0003-4819-101-5-627.
14. Jenkins PJ, Frajese V, Jones AM, Camacho-Hubner C, Lowe DG, Fairclough PD, Chew SL, Grossman AB, Monson JP, Besser GM. Insulin- like growth factor I and the development of colorectal neoplasia in acromegaly. J Clin Endocrinol Metab. 2000;85(9): 3218–21. doi: 10.1210/jcem.85.9.6806.
15. Reverter JL, Fajardo C, Resmini E, Salinas I, Mora M, Llatjós M, Sesmilo G, Rius F, Halperin, Webb SM, Ricart V, Riesgo P, Mauricio D, Puig-Domingo M. Benign and malignant nodular thyroid disease in acromegaly. Is a routine thyroid ultrasound evaluation advisable? PLoS One. 2014;9(8):e104174. doi: 10.1371/journal.pone.0104174.
16. Katznelson L, Atkinson JL, Cook DM, Ezzat SZ, Hamrahian AH, Miller KK; American Association of Clinical Endocrinologists. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the diagnosis and treatment of acromegaly – 2011 update. Endocr Pract. 2011;17 Suppl 4:1–44.
17. Tan GH, Gharib H. Thyroid incidentalomas: management approaches to nonpalpable nodules discovered incidentally on thyroid imaging. Ann Intern Med. 1997;126(3): 226–31. doi: 10.7326/0003-4819-126-3-199702010-00009.
18. Guth S, Theune U, Aberle J, Galach A, Bamberger CM. Very high prevalence of thyroid nodules detected by high frequency (13 MHz) ultrasound examination. Eur J Clin Invest. 2009;39(8): 699–706. doi: 10.1111/j.1365-2362.2009.02162.x.
19. Hegedüs L. Clinical practice. The thyroid nodule. N Engl J Med. 2004;351(17): 1764–71. doi: 10.1056/NEJMcp031436.
20. Mandel SJ. A 64-year-old woman with a thyroid nodule. JAMA. 2004;292(21): 2632–42. doi: 10.1001/jama.292.21.2632.
21. Renehan AG, Bhaskar P, Painter JE, O'Dwyer ST, Haboubi N, Varma J, Ball SG, Shalet SM. The prevalence and characteristics of colorectal neoplasia in acromegaly. J Clin Endocrinol Metab. 2000;85(9): 3417–24. doi: 10.1210/jcem.85.9.6775.
Almanac of Clinical Medicine. 2017; 45: 326-332
Prevalence of neoplasms in acromegaly in the Moscow Region
https://doi.org/10.18786/2072-0505-2017-45-4-326-332Abstract
Rationale: Prevalence of neoplasms in patients with acromegaly and the effects of various risk factors on their development have been insufficiently studied.
Aim: To assess the prevalence of thyroid, gastric and colon neoplasms in patients with newly diagnosed acromegaly, depending on their age, gender, duration and activity of the underlying disease.
Materials and methods: We retrospectively analyzed data extracted from out- and in-patient medical files of 108 patients with acromegaly (25 male, 93 female). Their median age was 50.5 [range 39.3 to 59] years, median duration of acromegaly 5 [range 2 to 10] years (starting from the first appearance of the first physique abnormalities). Thyroid ultrasound was performed in 96 patients, gastroscopy in 92, and colonoscopy in 89.
Results: Benign thyroid nodules were found in 50% (48/96) of patients, malignant thyroid nodules in 6.2% (6/96). Insulinlike growth factor 1 (IGF-1) levels (calculated as a percentage above upper limit of the normal range) in patients with thyroid cancer was 2.3-fold higher than in patients without nodular thyroid disease and 2-fold higher than in patients with benign thyroid nodules (р < 0.012 and p < 0.03, respectively). Malignant neoplasms were more often seen in the elderly (above 60 years of age), compared to younger adults (45 to 60 years) (30.8% and 4.3% of patients, respectively, p = 0.01). Male patients had higher prevalence of thyroid cancer than female (11.1% and 5.1%, respectively). Benign gastrointestinal neoplasms were observed in 51.7% of patients (18% had gastric polyps and 37% colon polyps). Age and duration of acromegaly in patients with gastric neoplasms were higher, than in those without them (р = 0.015 and p = 0.036, respectively). Colon neoplasms consisted of hyperplastic polyps (33.7%) and colon cancer (3% of patients). Patients with colon neoplasms were 11 years older than those without it (p = 0.015).
Conclusion: Gastrointestinal tract and thyroid gland should be diagnostically assessed in all patients at diagnosis of acromegaly, because of the higher risk of the neoplasms in these patients. The association of higher IGF-1 levels with thyroid cancer indicates that this factor may contribute to carcinogenesis and requires further studies.
References
1. Cats A, Dullaart RP, Kleibeuker JH, Kuipers F, Sluiter WJ, Hardonk MJ, de Vries EG. Increased epithelial cell proliferation in the colon of patients with acromegaly. Cancer Res. 1996;56(3): 523–6.
2. Yamamoto M, Fukuoka H, Iguchi G, Matsumoto R, Takahashi M, Nishizawa H, Suda K, Bando H, Takahashi Y. The prevalence and associated factors of colorectal neoplasms in acromegaly: a single center based study. Pituitary. 2015;18(3): 343–51. doi: 10.1007/s11102-014-0580-y.
3. Kauppinen-Mäkelin R, Sane T, Reunanen A, Välimäki MJ, Niskanen L, Markkanen H, Löyttyniemi E, Ebeling T, Jaatinen P, Laine H, Nuutila P, Salmela P, Salmi J, Stenman UH, Viikari J, Voutilainen E. A nationwide survey of mortality in acromegaly. J Clin Endocrinol Metab. 2005;90(7): 4081–6. doi: 10.1210/jc.2004-1381.
4. Baris D, Gridley G, Ron E, Weiderpass E, Mellemkjaer L, Ekbom A, Olsen JH, Baron JA, Fraumeni JF Jr. Acromegaly and cancer risk: a cohort study in Sweden and Denmark. Cancer Causes Control. 2002;13(5): 395–400.
5. Ron E, Gridley G, Hrubec Z, Page W, Arora S, Fraumeni JF Jr. Acromegaly and gastrointestinal cancer. Cancer. 1991;68(8): 1673–7. doi: 10.1002/1097-0142(19911015)68:8<1673::AID-CNCR2820680802>3.0.CO;2-0.
6. Kurimoto M, Fukuda I, Hizuka N, Takano K. The prevalence of benign and malignant tumors in patients with acromegaly at a single institute. Endocr J. 2008;55(1): 67–71. doi: http://doi.org/10.1507/endocrj.K07E-010.
7. dos Santos MC, Nascimento GC, Nascimento AG, Carvalho VC, Lopes MH, Montenegro R, Montenegro R Jr, Vilar L, Albano MF, Alves AR, Parente CV, dos Santos Faria M. Thyroid cancer in patients with acromegaly: a case-control study. Pituitary. 2013;16(1): 109–14. doi: 10.1007/s11102-012-0383-y.
8. Dagdelen S, Cinar N, Erbas T. Increased thyroid cancer risk in acromegaly. Pituitary. 2014;17(4): 299–306. doi: 10.1007/s11102-013-0501-5.
9. Dogan S, Atmaca A, Dagdelen S, Erbas B, Erbas T. Evaluation of thyroid diseases and differentiated thyroid cancer in acromegalic patients. Endocrine. 2014;45(1): 114–21. doi: 10.1007/s12020-013-9981-3.
10. Titaeva AA, Tereshchenko SG, Lukina EM, Dreval' AV, Ilovaiskaya IA. Fonovye izmeneniya slizistoi obolochki zheludochno-kishechnogo trakta u bol'nykh akromegaliei. Al'manakh klinicheskoi meditsiny. 2014;31:29–33. doi: 10.18786/2072-0505-2014-31-29-33.
11. Lois K, Bukowczan J, Perros P, Jones S, Gunn M, James RA. The role of colonoscopic screening in acromegaly revisited: review of current literature and practice guidelines. Pituitary. 2015;18(4): 568–74. doi: 10.1007/s11102-014-0586-5.
12. Mestron A, Webb SM, Astorga R, Benito P, Catala M, Gaztambide S, Gomez JM, Halperin I, Lucas-Morante T, Moreno B, Obiols G, de Pablos P, Paramo C, Pico A, Torres E, Varela C, Vazquez JA, Zamora J, Albareda M, Gilabert M. Epidemiology, clinical characteristics, outcome, morbidity and mortality in acromegaly based on the Spanish Acromegaly Registry (Registro Espanol de Acromegalia, REA). Eur J Endocrinol. 2004;151(4): 439–46. doi: 10.1530/eje.0.1510439.
13. Ituarte EA, Petrini J, Hershman JM. Acromegaly and colon cancer. Ann Intern Med. 1984;101(5): 627–8. doi: 10.7326/0003-4819-101-5-627.
14. Jenkins PJ, Frajese V, Jones AM, Camacho-Hubner C, Lowe DG, Fairclough PD, Chew SL, Grossman AB, Monson JP, Besser GM. Insulin- like growth factor I and the development of colorectal neoplasia in acromegaly. J Clin Endocrinol Metab. 2000;85(9): 3218–21. doi: 10.1210/jcem.85.9.6806.
15. Reverter JL, Fajardo C, Resmini E, Salinas I, Mora M, Llatjós M, Sesmilo G, Rius F, Halperin, Webb SM, Ricart V, Riesgo P, Mauricio D, Puig-Domingo M. Benign and malignant nodular thyroid disease in acromegaly. Is a routine thyroid ultrasound evaluation advisable? PLoS One. 2014;9(8):e104174. doi: 10.1371/journal.pone.0104174.
16. Katznelson L, Atkinson JL, Cook DM, Ezzat SZ, Hamrahian AH, Miller KK; American Association of Clinical Endocrinologists. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the diagnosis and treatment of acromegaly – 2011 update. Endocr Pract. 2011;17 Suppl 4:1–44.
17. Tan GH, Gharib H. Thyroid incidentalomas: management approaches to nonpalpable nodules discovered incidentally on thyroid imaging. Ann Intern Med. 1997;126(3): 226–31. doi: 10.7326/0003-4819-126-3-199702010-00009.
18. Guth S, Theune U, Aberle J, Galach A, Bamberger CM. Very high prevalence of thyroid nodules detected by high frequency (13 MHz) ultrasound examination. Eur J Clin Invest. 2009;39(8): 699–706. doi: 10.1111/j.1365-2362.2009.02162.x.
19. Hegedüs L. Clinical practice. The thyroid nodule. N Engl J Med. 2004;351(17): 1764–71. doi: 10.1056/NEJMcp031436.
20. Mandel SJ. A 64-year-old woman with a thyroid nodule. JAMA. 2004;292(21): 2632–42. doi: 10.1001/jama.292.21.2632.
21. Renehan AG, Bhaskar P, Painter JE, O'Dwyer ST, Haboubi N, Varma J, Ball SG, Shalet SM. The prevalence and characteristics of colorectal neoplasia in acromegaly. J Clin Endocrinol Metab. 2000;85(9): 3417–24. doi: 10.1210/jcem.85.9.6775.
