ometendoОжирение и метаболизмObesity and metabolism2071-87132306-5524Endocrinology Research Centre10.14341/omet2015239-46ometendo-7223Research ArticleСлучай из практикиCase Report«Немые» аденомы гипофиза: обзор литературы и описание серии клинических случаевSilent pituitary adenomas: review and clinical casesЛипатенковаАнна КонстантиновнаLipatenkovaAnna Konstantinovna

PhD student

a.lipatenkova@gmail.comДзерановаЛариса КонстантиновнаDzeranovaLarisa Konstantinovna

MD, PhD, leading researcher at the Department of Neuroendocrinology and ostepaty

dzeranovalk@yandex.ruПигароваЕкатерина АлександровнаPigarovaEkaterina Aleksandrovna

Ph.D., senior researcher at the Department of Neuroendocrinology and ostepaty

kpigarova@gmail.comАстафьеваЛюдмила ИгоревнаAstaf'evaLudmila Igorevna

MD, PhD, a physicianat the 8th Neurosurgery department

LAst@nsi.ruГригорьевАндрей ЮрьевичGrigor'evAndrey Yur'evich

MD, PhD, head of the Neurosurgery department

medway26@me.comШишкинаЛюдмила ВалентиновнаShishkinaLudmila Valentinovna

PhD, Head of the  Neyropatomorfologii department

lshishkina@nsi.ruЧеребилоВладислав ЮрьевичCherebiloVladislav Yur'evich

врач-нейрохирург отделения нейрохиурргии

neurosurgeon at the Department of Neurosurgery

cherebillo@mail.ruЭктоваАнастасия ПавловнаEktovaAnastasiya Pavlovna

physicianat the Pathomorphology department

ektozz@gmail.comФГБУ «Эндокринологический научный центр» Минздрава РоссииРоссияEndocrinology Research CentreRussian FederationИнститут нейрохирургии им. академика Н.Н.БурденкоРоссияBurdenko Neurosurgery InstituteRussian FederationИнститут нейрохирургии им. академика Н.Н.БурденкоРоссияBurdenko Neurosurgery InstituteRussian FederationФедеральный медицинский исследовательский центр им. В.А. Алмазова МЗ РФРоссияAlmazov federal heart blood and endocrinology centreRussian FederationРоссийская детская клиническая больница МЗ РФРоссияRussian Pediatric Clinical HospitalRussian Federation2015270620151224046Copyright © Липатенкова А.К., Дзеранова Л.К., Пигарова Е.А., Астафьева Л.И., Григорьев А.Ю., Шишкина Л.В., Черебило В.Ю., Эктова А.П., 20152015Липатенкова А.К., Дзеранова Л.К., Пигарова Е.А., Астафьева Л.И., Григорьев А.Ю., Шишкина Л.В., Черебило В.Ю., Эктова А.П.Lipatenkova A.K., Dzeranova L.K., Pigarova E.A., Astaf'eva L.I., Grigor'ev A.Y., Shishkina L.V., Cherebilo V.Y., Ektova A.P.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.omet-endojournals.ru/jour/article/view/7223

Гормонально-неактивные аденомы гипофиза представляют собой морфологически гетерогенную группу и подразделяются на «немые» аденомы, обладающие иммунореактивностью к тропным гормонам и схожим строением с типичными аденоцитами, но не приводящие к развитию клинических признаков гормональной гиперсекреции («немые» гонадо-, кортико-, сомато-, тиро- и маммотропиномы), и опухоли, не имеющие специфических маркеров и сходства с аденогипофизарными клетками (ноль-клеточные опухоли и онкоцитомы). Согласно проводимым исследованиям, все типы «немых» аденом имеют различную биологическую активность, секреторный потенциал и исходы в послеоперационном периоде. Данная серия клинических случаев демонстрирует более «агрессивное» течение заболевания, высокий риск рецидива при «немых» кортико- и соматотропиномах гипофиза. Активное выявление «немых» кортико- и соматотропином при проведении иммуно-гистохимического анализа не только позволяет выявить пациентов из группы высокого риска рецидива заболевания, но и выработать оптимальную тактику лечения и дальнейшего наблюдения, определить показания и оценить целесообразность медикаментозной и лучевой терапии после проведенного нейрохирургического вмешательства.

Silent, or clinically nonfunctioning adenomas are morphologically heterogeneous group, characterized by positive immunoreactivity for one or more hormones classically secreted by normal pituitary cells but without clinical expression. Although in some occasions enhanced or changed secretory activity can develop over time. According to immunoreactivity they are divided into "silent" gonado-, cortico-, somato -, mammo – and thyrotropinomas, oncocytomas, «zero-cell» tumors. All types of "silent" adenomas have different biological activity, secretory capacity and outcomes in the postoperative period. This series of clinical cases shows more «aggressiveness», a higher risk of relapse for "silent" cortico- and somatotropinomas. Immunohistochemical analysis of residual tissue can be used to identify patients with high risk of recurrence, to develop optimal treatment and follow-up.

«немые» гонадо-кортико-сомато-тиро- и маммотропиномыноль-клеточные опухолионкоцитомыиммуно- гистохимический анализ.silent" gonado-cortico-somato-thyro- and mammotropinomy«zero-cell» tumorsoncocytomasimmunohistochemistryReferencesHorvath E, Kovacs K. Ultrastructural diagnosis of human pituitary adenomas. Microscopy Research and Technique. 1992;20(2):107-35. doi: 10.1002/jemt.1070200202Horvath E, Kovacs K. Ultrastructural diagnosis of human pituitary adenomas. Microscopy Research and Technique. 1992;20(2):107-35. doi: 10.1002/jemt.1070200202Mayson SE, Snyder PJ. Silent (clinically nonfunctioning) pituitary adenomas. Journal of Neuro-Oncology. 2014;117(3):429-36. doi: 10.1007/s11060-014-1425-2Mayson SE, Snyder PJ. Silent (clinically nonfunctioning) pituitary adenomas. Journal of Neuro-Oncology. 2014;117(3):429-36. doi: 10.1007/s11060-014-1425-2Melmed S. Pathogenesis of pituitary tumors. Nature Reviews Endocrinology. 2011;7(5):257-66. doi: 10.1038/nrendo.2011.40Melmed S. Pathogenesis of pituitary tumors. Nature Reviews Endocrinology. 2011;7(5):257-66. doi: 10.1038/nrendo.2011.40Fernandez A, Karavitaki N, Wass JAH. Prevalence of pituitary adenomas: a community-based, cross-sectional study in Banbury (Oxfordshire, UK). Clinical Endocrinology. 2010;72(3):377-82. doi: 10.1111/j.1365-2265.2009.03667.xFernandez A, Karavitaki N, Wass JAH. Prevalence of pituitary adenomas: a community-based, cross-sectional study in Banbury (Oxfordshire, UK). Clinical Endocrinology. 2010;72(3):377-82. doi: 10.1111/j.1365-2265.2009.03667.xDaly AF, Rixhon M, Adam C, Dempegioti A, Tichomirowa MA, Beckers A. High Prevalence of Pituitary Adenomas: A Cross-Sectional Study in the Province of Liège, Belgium. The Journal of Clinical Endocrinology & Metabolism. 2006;91(12):4769-75. doi: 10.1210/jc.2006-1668Daly AF, Rixhon M, Adam C, Dempegioti A, Tichomirowa MA, Beckers A. High Prevalence of Pituitary Adenomas: A Cross-Sectional Study in the Province of Liège, Belgium. The Journal of Clinical Endocrinology & Metabolism. 2006;91(12):4769-75. doi: 10.1210/jc.2006-1668Дедов И.И. Вакс В.В. Клиническая нейроэндокринология. - М.: 2011. [Dedov II. Vaks VV. Klinicheskaya neyroendokrinologiya. Moscow: 2011. (In Russ).]Дедов И.И. Вакс В.В. Клиническая нейроэндокринология. - М.: 2011. [Dedov II. Vaks VV. Klinicheskaya neyroendokrinologiya. Moscow: 2011. (In Russ).]Melmed S. Mechanisms for pituitary tumorigenesis: the plastic pituitary. Journal of Clinical Investigation. 2003;112(11):1603-18. doi: 10.1172/jci20401Melmed S. Mechanisms for pituitary tumorigenesis: the plastic pituitary. Journal of Clinical Investigation. 2003;112(11):1603-18. doi: 10.1172/jci20401Fernandez A, Karavitaki N, Wass JAH. Prevalence of pituitary adenomas: a community-based, cross-sectional study in Banbury (Oxfordshire, UK). Clinical Endocrinology. 2010;72(3):377-82. doi: 10.1111/j.1365-2265.2009.03667.xFernandez A, Karavitaki N, Wass JAH. Prevalence of pituitary adenomas: a community-based, cross-sectional study in Banbury (Oxfordshire, UK). Clinical Endocrinology. 2010;72(3):377-82. doi: 10.1111/j.1365-2265.2009.03667.xRaappana A, Koivukangas J, Ebeling T, Pirilä T. Incidence of Pituitary Adenomas in Northern Finland in 1992–2007. The Journal of Clinical Endocrinology & Metabolism. 2010;95(9):4268-75. doi: 10.1210/jc.2010-0537Raappana A, Koivukangas J, Ebeling T, Pirilä T. Incidence of Pituitary Adenomas in Northern Finland in 1992–2007. The Journal of Clinical Endocrinology & Metabolism. 2010;95(9):4268-75. doi: 10.1210/jc.2010-0537Rosenfeld MG. POU-domain transcription factors: pou-er-ful developmental regulators. Genes & Development. 1991;5(6):897-907. doi: 10.1101/gad.5.6.897Rosenfeld MG. POU-domain transcription factors: pou-er-ful developmental regulators. Genes & Development. 1991;5(6):897-907. doi: 10.1101/gad.5.6.897Holck, S., Wewer, U.M., and Albrechtsen, R. Heterogeneity of secretory granules of silent pituitary adenomas.Modern Pathology.1988; 3: 212–215Holck, S., Wewer, U.M., and Albrechtsen, R. Heterogeneity of secretory granules of silent pituitary adenomas.Modern Pathology.1988; 3: 212–215Kontogeorgos G, Horvath E, Kovacs K. Sex-Linked Ultrastructural Dichotomy of Gonadotroph Adenomas of the Human Pituitary: An Electron Microscopic Analysis of 145 Tumors. Ultrastructural Pathology. 1990;14(6):475-82. doi: 10.3109/01913129009076134Kontogeorgos G, Horvath E, Kovacs K. Sex-Linked Ultrastructural Dichotomy of Gonadotroph Adenomas of the Human Pituitary: An Electron Microscopic Analysis of 145 Tumors. Ultrastructural Pathology. 1990;14(6):475-82. doi: 10.3109/01913129009076134Kovacs K, Lloyd R, Horvath E, Asa S, Stefaneanu L, Killinger D, et al. Silent somatotroph adenomas of the human pituitary. A morphologic study of three cases including immunocytochemistry, electron microscopy, in vitro examination, and in situ hybridization. The American journal of pathology. 1989;134(2):345.Kovacs K, Lloyd R, Horvath E, Asa S, Stefaneanu L, Killinger D, et al. Silent somatotroph adenomas of the human pituitary. A morphologic study of three cases including immunocytochemistry, electron microscopy, in vitro examination, and in situ hybridization. The American journal of pathology. 1989;134(2):345.Ohta S, Nishizawa S, Oki Y, Yokoyama T, Namba H. Significance of absent prohormone convertase 1/3 in inducing clinically silent corticotroph pituitary adenoma of subtype I -immunohistochemical study. Pituitary. 2002;5(4):221-3. doi: 10.1023/a:1025321731790Ohta S, Nishizawa S, Oki Y, Yokoyama T, Namba H. Significance of absent prohormone convertase 1/3 in inducing clinically silent corticotroph pituitary adenoma of subtype I -immunohistochemical study. Pituitary. 2002;5(4):221-3. doi: 10.1023/a:1025321731790Saeger W, Ludecke DK, Buchfelder M, Fahlbusch R, Quabbe HJ, Petersenn S. Pathohistological classification of pituitary tumors: 10 years of experience with the German Pituitary Tumor Registry. European Journal of Endocrinology. 2007;156(2):203-16. doi: 10.1530/eje.1.02326Saeger W, Ludecke DK, Buchfelder M, Fahlbusch R, Quabbe HJ, Petersenn S. Pathohistological classification of pituitary tumors: 10 years of experience with the German Pituitary Tumor Registry. European Journal of Endocrinology. 2007;156(2):203-16. doi: 10.1530/eje.1.02326Yamada S, Ohyama K, Taguchi M, Takeshita A, Morita K, Takano K, et al. A Study of the Correlation between Morphological Findings and Biological Activities in Clinically Nonfunctioning Pituitary Adenomas. Neurosurgery. 2007;61(3):580-5. doi: 10.1227/01.neu.0000290906.53685.79Yamada S, Ohyama K, Taguchi M, Takeshita A, Morita K, Takano K, et al. A Study of the Correlation between Morphological Findings and Biological Activities in Clinically Nonfunctioning Pituitary Adenomas. Neurosurgery. 2007;61(3):580-5. doi: 10.1227/01.neu.0000290906.53685.79Young WF, Scheithauer BW, Kovacs KT, Horvath E, Davis DH, Randall RV. Gonadotroph adenoma of the pituitary gland: a clinicopathologic analysis of 100 cases. Mayo Clinic Proceedings. 1996;71(7):649-56. doi: 10.4065/71.7.649Young WF, Scheithauer BW, Kovacs KT, Horvath E, Davis DH, Randall RV. Gonadotroph adenoma of the pituitary gland: a clinicopathologic analysis of 100 cases. Mayo Clinic Proceedings. 1996;71(7):649-56. doi: 10.4065/71.7.649Sahli R, Christ ER, Seiler R, Kappeler A, Vajtai I. Clinicopathologic correlations of silent corticotroph adenomas of the pituitary: Report of four cases and literature review. Pathology - Research and Practice. 2006;202(6):457-64. doi: 10.1016/j.prp.2006.01.007Sahli R, Christ ER, Seiler R, Kappeler A, Vajtai I. Clinicopathologic correlations of silent corticotroph adenomas of the pituitary: Report of four cases and literature review. Pathology - Research and Practice. 2006;202(6):457-64. doi: 10.1016/j.prp.2006.01.007Scheithauer BW1,Jaap AJ, Horvath E, Kovacs K, Lloyd RV, Meyer FB, Laws ER Jr, Young WF Jr. Clinically silent corticotroph tumors of the pituitary gland. Neurosurgery. 2000 Sep;47(3):723-9 PMID:10981760Scheithauer BW1,Jaap AJ, Horvath E, Kovacs K, Lloyd RV, Meyer FB, Laws ER Jr, Young WF Jr. Clinically silent corticotroph tumors of the pituitary gland. Neurosurgery. 2000 Sep;47(3):723-9 PMID:10981760Cooper O, Ben-Shlomo A, Bonert V, Bannykh S, Mirocha J, Melmed S. Silent Corticogonadotroph Adenomas: Clinical and Cellular Characteristics and Long-Term Outcomes. Hormones and Cancer. 2010;1(2):80-92. doi: 10.1007/s12672-010-0014-xCooper O, Ben-Shlomo A, Bonert V, Bannykh S, Mirocha J, Melmed S. Silent Corticogonadotroph Adenomas: Clinical and Cellular Characteristics and Long-Term Outcomes. Hormones and Cancer. 2010;1(2):80-92. doi: 10.1007/s12672-010-0014-xPawlikowski M, Kunert-Radek J, Radek M. " Silent" corticotropinoma. Neuro endocrinology letters. 2008;29(3):347-50.Pawlikowski M, Kunert-Radek J, Radek M. " Silent" corticotropinoma. Neuro endocrinology letters. 2008;29(3):347-50.Webb KM, Laurent JJ, Okonkwo DO, Lopes MB, Vance ML, Laws ER. Clinical Characteristics of Silent Corticotrophic Adenomas and Creation of an Internetaccessible Database to Facilitate Their Multi-institutional Study. Neurosurgery. 2003;53(5):1076-85. doi: 10.1227/01.neu.0000088660.16904.f7Webb KM, Laurent JJ, Okonkwo DO, Lopes MB, Vance ML, Laws ER. Clinical Characteristics of Silent Corticotrophic Adenomas and Creation of an Internetaccessible Database to Facilitate Their Multi-institutional Study. Neurosurgery. 2003;53(5):1076-85. doi: 10.1227/01.neu.0000088660.16904.f7Melcescu E, Gannon AW,Parent AD, Fratkin JF, Nicholas WC, Koch CA, Galhom A. Silent or Subclinical Corticotroph Pituitary Macroadenoma Transforming Into Cushing Disease: 11-Year Follow-up. Neurosurgery. 2013;72(1):E144-6. doi:10.1227/NEU.0b013e3182750850Melcescu E, Gannon AW,Parent AD, Fratkin JF, Nicholas WC, Koch CA, Galhom A. Silent or Subclinical Corticotroph Pituitary Macroadenoma Transforming Into Cushing Disease: 11-Year Follow-up. Neurosurgery. 2013;72(1):E144-6. doi:10.1227/NEU.0b013e3182750850Baldeweg SE1, Pollock JR, Powell M, Ahlquist J. A spectrum of behaviour in silent corticotroph pituitary adenomas. Br J Neurosurg. 2005;19(1):38-42. doi:10.1080/02688690500081230Baldeweg SE1, Pollock JR, Powell M, Ahlquist J. A spectrum of behaviour in silent corticotroph pituitary adenomas. Br J Neurosurg. 2005;19(1):38-42. doi:10.1080/02688690500081230Wade AN, Baccon J, Grady MS, Judy KD, O'Rourke DM, Snyder PJ. Clinically silent somatotroph adenomas are common. Eur J Endocrinol 2011;165(1):39–44. doi:10.1530/EJE-11-0216Wade AN, Baccon J, Grady MS, Judy KD, O'Rourke DM, Snyder PJ. Clinically silent somatotroph adenomas are common. Eur J Endocrinol 2011;165(1):39–44. doi:10.1530/EJE-11-0216Mohammed S, Syro L, Abad V, Salehi F et. al. Silent somatotroph adenoma of the pituitary in an adolescent. Canadian Journal of Neurological Sciences 2009; (36):123–125. doi:10.1017/S0317167100006466Mohammed S, Syro L, Abad V, Salehi F et. al. Silent somatotroph adenoma of the pituitary in an adolescent. Canadian Journal of Neurological Sciences 2009; (36):123–125. doi:10.1017/S0317167100006466Trouillas J, Sassolas G, Loras B, Velkeniers B et. al. Somatotropic adenomas without acromegaly. Pathology, Research and Practice. 1991; (187):943–949.Trouillas J, Sassolas G, Loras B, Velkeniers B et. al. Somatotropic adenomas without acromegaly. Pathology, Research and Practice. 1991; (187):943–949.Heshmati HM, Turpin G, Kujas M. et al. The immunocytochemical heterogeneity of silent pituitary adenomas. Acta Endocrinologica. 1988; (4): 533–537. doi:10.1530/acta.0.1180533Heshmati HM, Turpin G, Kujas M. et al. The immunocytochemical heterogeneity of silent pituitary adenomas. Acta Endocrinologica. 1988; (4): 533–537. doi:10.1530/acta.0.1180533Naritaka H, Kameya T, Sato Y, Furuhata S, Otani M. Morphological characterization and subtyping of silent somatotroph adenomas. Pituitary. 1999; 1(3-4):233. doi:10.1023/A:1009942122673Naritaka H, Kameya T, Sato Y, Furuhata S, Otani M. Morphological characterization and subtyping of silent somatotroph adenomas. Pituitary. 1999; 1(3-4):233. doi:10.1023/A:1009942122673

The authors declare that there are no conflicts of interest present.