problendoПроблемы ЭндокринологииProblems of Endocrinology0375-96602308-1430Endocrinology Research Centre10.14341/probl9854problendo-9854Research ArticleОригинальные исследованияOriginal StudiesДиагностика врожденной патологии полового развития у мальчиков с двусторонним паховым крипторхизмом в период мини-пубертатаDiagnosis of congenital sexual maldevelopment in boys with bilateral inguinal cryptorchidism during minipubertyhttps://orcid.org/0000-0003-0361-5329РайгородскаяНадежда ЮрьевнаRaygorodskayaNadezda Y.

д.м.н.

MD, PhD

nraygorodskaya@gmail.comhttps://orcid.org/0000-0002-8148-526XБолотоваНина ВикторовнаBolotovaNina V.

д.м.н., профессор

MD, PhD, Professor

kafedranv@mail.ruhttps://orcid.org/0000-0002-4056-2951ЧехонацкаяМарина ЛеонидовнаChekhonatskayaMarina L.

д.м.н.

MD, PhD, Professor

fax-1@yandex.ruhttps://orcid.org/0000-0001-6162-7884ПоляковВадим КонстантиновичPolyakovVadim K.

д.м.н., профессор

MD, PhD

polyakov_vk@mail.ruhttps://orcid.org/0000-0002-4667-8736СедоваЛюдмила НиколаевнаSedovaLudmila N.

к.м.н.

MD, PhD

sedovamila-2015@ya.ruСомоваВероника АндреевнаSomovaVeronika A.tigronika263pz@rambler.ruФГБУ ВО «Саратовский государственный медицинский университет им. В.И. Разумовского» Минздрава РоссииРоссияV.I. Razumovskiy Saratov State Medical UniversityRussian Federation201925102019654236242Copyright © Райгородская Н.Ю., Болотова Н.В., Чехонацкая М.Л., Поляков В.К., Седова Л.Н., Сомова В.А., 20192019Райгородская Н.Ю., Болотова Н.В., Чехонацкая М.Л., Поляков В.К., Седова Л.Н., Сомова В.А.Raygorodskaya N.Y., Bolotova N.V., Chekhonatskaya M.L., Polyakov V.K., Sedova L.N., Somova V.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.probl-endojournals.ru/jour/article/view/9854Обоснование

Обоснование. Крипторхизм ассоциирован с риском инфертильности и может быть симптомом врожденной патологии полового развития.

Цель

Цель: оценить функциональное состояние гипофиза и половых желез у мальчиков 1–6-месячного возраста с двусторонним паховым крипторхизмом; выявить врожденную патологию полового развития на этапе мини-пубертата.

Методы

Методы. Были обследованы 21 мальчик в возрасте 1–6 мес (период мини-пубертата) с изолированным двусторонним паховым крипторхизмом и 40 здоровых мальчиков в возрасте 2–3 мес (группа контроля). Оценивали состояние гонад, определяли концентрации половых гормонов в сыворотке и при наличии показаний проводили молекулярно-генетическое исследование.

Результаты

Результаты. На основании результатов гормонального анализа формировали 3 группы пациентов: 1-я – с нормальной концентрацией гонадотропинов и половых гормонов в сыворотке, 2-я – с повышенным уровнем гонадотропинов, низким уровнем антимюллерова гормона и ингибина B и 3-я – с нулевыми показателями гонадотропинов и тестостерона и низкой концентрацией АМГ и ингибина B. У пациентов 1-й группы не выявлено функциональных нарушений гипофизарно-гонадной системы; у пациентов 2-й группы обнаружено нарушение функции клеток Сертоли с высоким риском инфертильности; у пациентов 3-й группы диагностирован гипогонадотропный гипогонадизм, подтвержденный результатами молекулярно-генетического исследования.

Заключение

Заключение: гормональное обследование пациентов с двусторонним паховым крипторхизмом в период мини-пубертата делает возможным раннее выявление врожденной патологии полового развития.

BACKGROUND

BACKGROUND: Cryptorchidism is associated with the risk of infertility and can be a symptom of congenital sexual maldevelopment.

AIM

AIM: To assess the functional status of the pituitary gland and sexual glands in boys aged 1–6 months with bilateral inguinal cryptorchidism and to reveal the congenital sexual maldevelopment during minipuberty.

METHODS

METHODS: Twenty-one boys aged 1–6 months (the minipuberty period) with isolated bilateral inguinal cryptorchidism and 40 healthy boys aged 2–3 months (the control group) were examined. The gonadal status was assessed and serum levels of sex hormones were measured. Molecular genetic testing was performed if there were indications for it.

RESULTS

RESULTS: The results of hormone analysis were used to divide the patients into three groups: group 1 – patients with normal serum levels of gonadotropin and sex hormones; group 2 – patients with elevated gonadotropin level and low levels of anti-Müllerian hormone (AMH) and inhibin B, and group 3 – patients with zero gonadotropin and testosterone levels and low levels of AMH and inhibin B. Group 1 patients had no functional disturbances in the pituitary–gonadal system. Failure of Sertoli cells associated with a high risk of infertility was detected in group 2 patients. Group 3 patients were diagnosed with hypogonadotropic hypogonadism verified by molecular genetic tests.

CONCLUSION

CONCLUSION: Hormonal testing of patients with bilateral inguinal cryptorchidism during minipuberty makes it possible to early detect the congenital sexual maldevelopment.

двусторонний крипторхизммини-пубертат у мальчиковгипогонадотропный гипогонадизмbilateral cryptorchidismminipuberty in boyshypogonadotropic hypogonadismМолекулярно-генетические исследования были проведены в лаборатории отделения наследственных эндокринопатий ФГБУ «НМИЦ эндокринологии», при финансовой поддержке Фонда поддержки и развития филантропии «КАФ» в рамках Национальной благотворительной программы помощи детям с эндокринными заболеваниями «Альфа-Эндо».Molecular genetic studies were carried out in the laboratory of the department of hereditary endocrinopathies of the Federal State Budget Scientific Research Center for Endocrinology, with financial support from the Foundation for the Support and Development of Philanthropy KAF as part of the Alfa Endo National Charity Program for Helping Children with Endocrine Diseases.ReferencesHutson JM. Undescended testis: the underlying mechanism and the effects on germ cells that cause infertility and cancer. J Pediatr Surg. 2013;48(5):903–908. doi: https://doi.org/10.1016/j.jpedsurg.2013.02.001Hutson JM. Undescended testis: the underlying mechanism and the effects on germ cells that cause infertility and cancer. J Pediatr Surg. 2013;48(5):903–908. doi: https://doi.org/10.1016/j.jpedsurg.2013.02.001Pacenza N, Pasqualini T, Gottlieb S. Clinical presentation of Klinefelter’s syndrome: differences according to age. Int J Endocrinol. 2012;2012:324835. doi: https://doi.org/10.1155/2012/324835.Pacenza N, Pasqualini T, Gottlieb S. Clinical presentation of Klinefelter’s syndrome: differences according to age. Int J Endocrinol. 2012;2012:324835. doi: https://doi.org/10.1155/2012/324835.Ivell R, Hartung S. The molecular basis of cryptorchidism. Mol Hum Reprod. 2003;9(4):175–181. doi: https://doi.org/10.1093/molehr/gag025Ivell R, Hartung S. The molecular basis of cryptorchidism. Mol Hum Reprod. 2003;9(4):175–181. doi: https://doi.org/10.1093/molehr/gag025Bay K, Hartung S, Ivell R, et al. Insulin-like factor 3 serum levels in 135 normal men and 85 men with testicular disorders: relationship to the luteinizing hormone-testosterone axis. J Clin Endocrinol Metab. 2005;90(6):3410–3418. doi: https://doi.org/10.1210/jc.2004-2257Bay K, Hartung S, Ivell R, et al. Insulin-like factor 3 serum levels in 135 normal men and 85 men with testicular disorders: relationship to the luteinizing hormone-testosterone axis. J Clin Endocrinol Metab. 2005;90(6):3410–3418. doi: https://doi.org/10.1210/jc.2004-2257Huang Z, Rivas B, Agoulnik A. Insulin-like 3 signaling is important for testicular descent but dispensable for spermatogenesis and germ cell survival in adult mice. Biol Reprod. 2012;87(6):143. doi: https://doi.org/10.1095/biolreprod.112.103382Huang Z, Rivas B, Agoulnik A. Insulin-like 3 signaling is important for testicular descent but dispensable for spermatogenesis and germ cell survival in adult mice. Biol Reprod. 2012;87(6):143. doi: https://doi.org/10.1095/biolreprod.112.103382Foresta C, Zuccarello D, Garolla A, Ferlin A. Role of hormones, genes, and environment in human cryptorchidism. Endocr Rev. 2008;29(5):560–580. doi: https://doi.org/10.1210/er.2007-0042Foresta C, Zuccarello D, Garolla A, Ferlin A. Role of hormones, genes, and environment in human cryptorchidism. Endocr Rev. 2008;29(5):560–580. doi: https://doi.org/10.1210/er.2007-0042Wang Q, Ge X, Wang HX, et al. Association of androgen receptor gene CAG and GGN repeat polymorphism with cryptorchidism: a meta-analysis. Andrologia. 2018;50(3):e12909. doi: https://doi.org/10.1111/and.12909Wang Q, Ge X, Wang HX, et al. Association of androgen receptor gene CAG and GGN repeat polymorphism with cryptorchidism: a meta-analysis. Andrologia. 2018;50(3):e12909. doi: https://doi.org/10.1111/and.12909Svechnikov K, Landreh L, Weisser J, et al. Origin, development and regulation of human Leydig cells. Horm Res Paediatr. 2010;73(2):93–101. doi: https://doi.org/10.1159/000277141Svechnikov K, Landreh L, Weisser J, et al. Origin, development and regulation of human Leydig cells. Horm Res Paediatr. 2010;73(2):93–101. doi: https://doi.org/10.1159/000277141Choi J, Smitz J. Luteinizing hormone and human chorionic gonadotropin: distinguishing unique physiologic roles. Gynecol Endocrinol. 2014;30(3):174–181. doi: https://doi.org/10.1016/j.mce.2013.12.009Choi J, Smitz J. Luteinizing hormone and human chorionic gonadotropin: distinguishing unique physiologic roles. Gynecol Endocrinol. 2014;30(3):174–181. doi: https://doi.org/10.1016/j.mce.2013.12.009Bergadá I, Milani C, Bedecarrás P. Time course of the serum gonadotropin surge, inhibins, and anti-Müllerian hormone in normal newborn males during the first month of life. J Clin Endocrinol Metab. 2006;91(10):4092–4098. doi: https://doi.org/10.1210/jc.2006-1079Bergadá I, Milani C, Bedecarrás P. Time course of the serum gonadotropin surge, inhibins, and anti-Müllerian hormone in normal newborn males during the first month of life. J Clin Endocrinol Metab. 2006;91(10):4092–4098. doi: https://doi.org/10.1210/jc.2006-1079Main KM, Toppari J, Skakkebek NE. Gonadal development and reproductive hormones in infant boys. Eur J Endocrinol. 2006;155 Suppl 1:51–57. doi: https://doi.org/10.1530/eje.1.02237Main KM, Toppari J, Skakkebek NE. Gonadal development and reproductive hormones in infant boys. Eur J Endocrinol. 2006;155 Suppl 1:51–57. doi: https://doi.org/10.1530/eje.1.02237Grinspon RP, Rey RA. Anti-müllerian hormone and sertoli cell function in paediatric male hypogonadism. Horm Res Pediatr. 2010;73(2):81–92. doi: https://doi.org/10.1159/000277140Grinspon RP, Rey RA. Anti-müllerian hormone and sertoli cell function in paediatric male hypogonadism. Horm Res Pediatr. 2010;73(2):81–92. doi: https://doi.org/10.1159/000277140Rodríguez F, Vallejos C, Giraudo F, et al. Copy number variants of Ras/MAPK pathway genes in patients with isolated cryptorchidism. Andrology. 2017;5(5):923–930. doi: https://doi.org/10.1111/andr.12390Rodríguez F, Vallejos C, Giraudo F, et al. Copy number variants of Ras/MAPK pathway genes in patients with isolated cryptorchidism. Andrology. 2017;5(5):923–930. doi: https://doi.org/10.1111/andr.12390Boepple PA, Hayes FJ, Dwyer AA. Relative roles of inhibin B and sex steroids in the negative feedback regulation of follicle-stimulating hormone in men across the full spectrum of seminiferous epithelium function. J Clin Endocrinol Metab. 2008;93(5):1809–1814. doi: https://doi.org/10.1210/jc.2007-2450Boepple PA, Hayes FJ, Dwyer AA. Relative roles of inhibin B and sex steroids in the negative feedback regulation of follicle-stimulating hormone in men across the full spectrum of seminiferous epithelium function. J Clin Endocrinol Metab. 2008;93(5):1809–1814. doi: https://doi.org/10.1210/jc.2007-2450Kelsey TW, Miles A, Mitchel RT. A normative model of serum inhibin B in young males. PLoS One. 2016;11(4):e0153843. doi: https://doi.org/10.1371/journal.pone.0153843Kelsey TW, Miles A, Mitchel RT. A normative model of serum inhibin B in young males. PLoS One. 2016;11(4):e0153843. doi: https://doi.org/10.1371/journal.pone.0153843Bouvattier C, Maione L, Bouligand J, et al. Neonatal gonadotropin therapy in male congenital hypogonadotropic hypogonadism. Nat Rev Endocrinol. 2011;8(3):172–182. doi: https://doi.org/10.1038/nrendo.2011.164Bouvattier C, Maione L, Bouligand J, et al. Neonatal gonadotropin therapy in male congenital hypogonadotropic hypogonadism. Nat Rev Endocrinol. 2011;8(3):172–182. doi: https://doi.org/10.1038/nrendo.2011.164Lambert A, Bougneres P. Growth and descent of the testes in infants with hypogonadotropic hypogonadism receiving subcutaneous gonadotropin infusion. Int J Pediatr Endocrinol. 2016;2016:13. doi: https://doi.org/10.1186/s13633-016-0031-9Lambert A, Bougneres P. Growth and descent of the testes in infants with hypogonadotropic hypogonadism receiving subcutaneous gonadotropin infusion. Int J Pediatr Endocrinol. 2016;2016:13. doi: https://doi.org/10.1186/s13633-016-0031-9Main KM, Schmidt IM, Skakkebaek NE. A possible role for reproductive hormones in newborn boys: progressive hypogonadism without the postnatal testosterone peak. J Clin Endocrinol Metab. 2000;85(12):4905–4907. doi: https://doi.org/10.1210/jc.85.12.4905Main KM, Schmidt IM, Skakkebaek NE. A possible role for reproductive hormones in newborn boys: progressive hypogonadism without the postnatal testosterone peak. J Clin Endocrinol Metab. 2000;85(12):4905–4907. doi: https://doi.org/10.1210/jc.85.12.4905Falardeau J, Chung WC, Beenken A, et al. Decreased FGF8 signaling causes deficiency of gonadotropin-releasing hormone in humans and mice. J Clin Invest. 2008;118(8):2822–2831. doi: https://doi.org/10.1172/jci34538Falardeau J, Chung WC, Beenken A, et al. Decreased FGF8 signaling causes deficiency of gonadotropin-releasing hormone in humans and mice. J Clin Invest. 2008;118(8):2822–2831. doi: https://doi.org/10.1172/jci34538Miraoui H, Dwyer AA, Sykiotis GP. Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in individuals with congenital hypogonadotropic hypogonadism. Am J Hum Genet. 2013;92(5):725–743. doi: https://doi.org/10.1016/j.ajhg.2013.04.008Miraoui H, Dwyer AA, Sykiotis GP. Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in individuals with congenital hypogonadotropic hypogonadism. Am J Hum Genet. 2013;92(5):725–743. doi: https://doi.org/10.1016/j.ajhg.2013.04.008

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