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Open Access 01-12-2018 | Review

Inhibin B in healthy and cryptorchid boys

Authors: Susanna Esposito, Marta Cofini, Donato Rigante, Alberto Leonardi, Laura Lucchetti, Clelia Cipolla, Lucia Lanciotti, Laura Penta

Published in: Italian Journal of Pediatrics | Issue 1/2018

Abstract

Background

Cryptorchidism, the most common male genital abnormality observed in paediatrics, might often be associated with long-term functional consequences and can even reoccur after a successful orchidopexy. Serum markers that identify cryptorchid boys with gonadal dysfunction early should be useful in a decision-making process. Inhibin B, produced during all of childhood but altered in cryptorchid subjects, appears strictly related to Sertoli cells, and its levels directly reflect the status of the testis germinative epithelium. Unfortunately, its precise roles in bilateral and unilateral cryptorchidism are still debated and being unravelled. Herein, we report the most current knowledge about inhibin B in both healthy boys and those with cryptorchidism to discuss and clarify its potential clinical applications.

Discussion

Inhibin B represents a simple and repeatable serum marker and it seems to well asses the presence and function of the testicular tissue. Testicular tissue in prepubertal age is largely made up of Sertoli cells; inhibin B, coming from working Sertoli cells, allows to indirectly evaluate their function. Besides, inhibin B is produced throughout childhood, even before puberty, in contrast with central hormones, and it is not influenced by androgens during puberty, in contrast with other testicular hormones. Although further studies are needed, low levels of inhibin B have been related with low testicular score and/or with consistent alterations of testicular parameters at histological examination. This means that inhibin B could be an indirect marker of testicular functions that could even replace testicular biopsies, but current data are inconsistent to confirm this potential role of inhibin B in cryptorchidism.

Conclusion

Inhibin B represents an effective candidate for early identification of testicular dysfunction after orchidopexy for cryptorchidism. Unfortunately, current data cannot exactly clarify the real role of inhibin B as a predictor of future testicular function in cryptorchidism and future long-term follow-up studies, with repeated inhibin B checks both in cryptorchid and in formerly cryptorchid children and adolescents, will permit to assess if previous normal levels of inhibin B would match with future normal pubertal development and fertility potential.

Klonisch T, Fowler PA, Hombach-Klonisch S. Molecular and genetic regulation of testis descent and external genitalia development. Dev Biol. 2004;270(1):1–18. https://doi.org/10.1016/j.ydbio.2004.02.018.CrossRefPubMed

Barthold JS, González R. The epidemiology of congenital cryptorchidism, testicular ascent and orchiopexy. J Urol. 2003;170(6 Pt 1):2396–401. https://doi.org/10.1097/01.ju.0000095793.04232.d8. CrossRefPubMed

Mathers MJ, Sperling H, Rübben H, Roth S. The undescended testis: diagnosis, treatment and long-term consequences. Dtsch Arztebl Int. 2009;106(33):527–32. https://doi.org/10.3238/arztebl.2009.0527. PubMedPubMedCentralCrossRef

Skakkebaek NE, Rajpert-De Meyts E, Main KM. Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects. Hum Reprod. 2001;16(5):972–8. http://www.ncbi.nlm.nih.gov/pubmed/11331648. Accessed 28 Mar 2017CrossRefPubMed

Gill B, Kogan S. Cryptorchidism. Current concepts. Pediatr Clin N Am. 1997;44(5):1211–27. http://www.ncbi.nlm.nih.gov/pubmed/9326959. Accessed 30 Mar 2017.CrossRef

Hadziselimovic F, Hoecht B. Testicular histology related to fertility outcome and postpubertal hormone status in cryptorchidism. Klin Padiatr. 2008;220(5):302–7. https://doi.org/10.1055/s-2007-993194.CrossRefPubMed

Feldmman Witchel S, Lee PA. Ambiguous genitalia. In: Sp MA, editor. Pediatric Endocrinology. 2nd ed. Ph; 2002. p. 111–33.

Main KM, Mortensen GK, Kaleva MM, et al. Human breast milk contamination with phthalates and alterations of endogenous reproductive hormones in infants three months of age. Environ Health Perspect. 2006;114(2):270–6. http://www.ncbi.nlm.nih.gov/pubmed/16451866. Accessed 30 Mar 2017CrossRefPubMed

Ahmed SF, Khwaja O, Hughes IA. The role of a clinical score in the assessment of ambiguous genitalia. BJU Int. 2000;85(1):120–4. http://www.ncbi.nlm.nih.gov/pubmed/10619959. Accessed 12 Sept 2017CrossRefPubMed

10.

Bertola DR, Yamamoto GL, Almeida TF, et al. Further evidence of the importance of RIT1 in Noonan syndrome. Am J Med Genet Part A. 2014;164(11):2952–7. https://doi.org/10.1002/ajmg.a.36722.CrossRef

11.

Zeidler C, Woelfle J, Draaken M, et al. Heterozygous FGF8 mutations in patients presenting cryptorchidism and multiple VATER/VACTERL features without limb anomalies. Birth Defects Res Part A Clin Mol Teratol. 2014;100(10):750–9. https://doi.org/10.1002/bdra.23278.CrossRefPubMed

12.

Weber S, Mir S, Schlingmann KP, et al. Gene locus ambiguity in posterior urethral valves/prune-belly syndrome. Pediatr Nephrol. 2005;20(8):1036–42. https://doi.org/10.1007/s00467-005-1977-7.CrossRefPubMed

13.

Liu L, Yu T, Wang L, Mo X, Yu Y. A novel CHD7 mutation in a Chinese patient with CHARGE syndrome. Meta Gene. 2014;2:469–78. https://doi.org/10.1016/j.mgene.2014.06.002.CrossRefPubMedPubMedCentral

14.

Cannistraci CV, Ogorevc J, Zorc M, Ravasi T, Dovc P, Kunej T. Pivotal role of the muscle-contraction pathway in cryptorchidism and evidence for genomic connections with cardiomyopathy pathways in RASopathies. BMC Med Genet. 2013;6(1):5. https://doi.org/10.1186/1755-8794-6-5. CrossRef

15.

Bergh A, Söder O. Studies of cryptorchidism in experimental animal models. Acta Paediatr Int J Paediatr. 2007;96(5):617–21. https://doi.org/10.1111/j.1651-2227.2007.00295.x.CrossRef

16.

Cortes D. Cryptorchidism--aspects of pathogenesis, histology and treatment. Scand J Urol Nephrol Suppl. 1998;196:1–54. http://www.ncbi.nlm.nih.gov/pubmed/9561565. Accessed 28 Mar 2017PubMed

17.

Suomi A-M, Main KM, Kaleva M, et al. Hormonal changes in 3-month-old cryptorchid boys. J Clin Endocrinol Metab. 2006;91(3):953–8. https://doi.org/10.1210/jc.2004-2318.CrossRefPubMed

18.

Hutson JM, Hasthorpe S. Testicular descent and cryptorchidism: the state of the art in 2004. J Pediatr Surg. 2005;40(2):297–302. https://doi.org/10.1016/j.jpedsurg.2004.10.033.CrossRefPubMed

19.

Thorup J, McLachlan R, Cortes D, et al. What is new in cryptorchidism and hypospadias--a critical review on the testicular dysgenesis hypothesis. J Pediatr Surg. 2010;45(10):2074–86. https://doi.org/10.1016/j.jpedsurg.2010.07.030.CrossRefPubMed

20.

Kolon TF, Herndon CDA, Baker LA, et al. Evaluation and treatment of cryptorchidism: AUA guideline. J Urol. 2014;192(2):337–45. https://doi.org/10.1016/j.juro.2014.05.005.CrossRefPubMed

21.

Virtanen HE, Bjerknes R, Cortes D, et al. Cryptorchidism: classification, prevalence and long-term consequences. Acta Paediatr Int J Paediatr. 2007;96(5):611–6. https://doi.org/10.1111/j.1651-2227.2007.00241.x.CrossRef

22.

Kollin C, Stukenborg JB, Nurmio M, et al. Boys with undescended testes: endocrine, volumetric and morphometric studies on testicular function before and after Orchidopexy at nine months or three years of age. J Clin Endocrinol Metab. 2012;97(12):4588–95. https://doi.org/10.1210/jc.2012-2325.CrossRefPubMed

23.

Lee PA, O’Leary LA, Songer NJ, Coughlin MT, Bellinger MF, LaPorte RE. Paternity after bilateral cryptorchidism. A controlled study. Arch Pediatr Adolesc Med. 1997;151(3):260–3. http://www.ncbi.nlm.nih.gov/pubmed/9080933. Accessed 28 Mar 2017CrossRefPubMed

24.

Lee PA, O’Leary LA, Songer NJ, Coughlin MT, Bellinger MF, LaPorte RE. Paternity after unilateral cryptorchidism: a controlled study. Pediatr. 1996;98(4 Pt 1):676–9. http://www.ncbi.nlm.nih.gov/pubmed/8885945. Accessed 28 Mar 2017

25.

Rune GM, Mayr J, Neugebauer H, Anders C, Sauer H. Pattern of Sertoli cell degeneration in cryptorchid prepubertal testes. Int J Androl. 1992;15(1):19–31. http://www.ncbi.nlm.nih.gov/pubmed/1347512. Accessed 28 Mar 2017CrossRefPubMed

26.

Müller J, Skakkebaek NE. Abnormal germ cells in maldescended testes: a study of cell density, nuclear size and deoxyribonucleic acid content in testicular biopsies from 50 boys. J Urol. 1984;131(4):730–3. http://www.ncbi.nlm.nih.gov/pubmed/6142966. Accessed 28 Mar 2017CrossRefPubMed

27.

Braga LH, Lorenzo AJ. The changing elaboration of inhibin B in patients with unilateral testicular maldescent vs vanished testis. J Urol. 2015;193(5):1465–6. https://doi.org/10.1016/j.juro.2015.02.076.CrossRefPubMed

28.

Lee PA, Coughlin MT. Fertility after bilateral cryptorchidism. Evaluation by paternity, hormone, and semen data. Horm Res. 2001;55(1):28–32. doi:49960PubMed

29.

Coughlin MT, Bellinger MF, Lee PA. Age at unilateral orchiopexy: effect on hormone levels and sperm count in adulthood. J Urol. 1999;162(3 Pt 2):986–8. discussion 989. http://www.ncbi.nlm.nih.gov/pubmed/10458417. Accessed 28 Mar 2017PubMed

30.

Valeri C, Schteingart HF, R a R. The prepubertal testis: biomarkers and functions. Curr Opin Endocrinol Diabetes Obes. 2013;20(3):224–33. https://doi.org/10.1097/MED.0b013e328360be2c.CrossRefPubMed

31.

Cabrol S, Ross JL, Fennoy I, Bouvattier C, Roger M, Lahlou N. Assessment of Leydig and Sertoli cell functions in infants with nonmosaic Klinefelter syndrome: insulin-like peptide 3 levels are normal and positively correlated with LH levels. J Clin Endocrinol Metab. 2011;96(4):E746–53. https://doi.org/10.1210/jc.2010-2103.CrossRefPubMedPubMedCentral

32.

Aksglaede L, Sørensen K, Boas M, et al. Changes in anti-Müllerian hormone (AMH) throughout the life span: a population-based study of 1027 healthy males from birth (cord blood) to the age of 69 years. J Clin Endocrinol Metab. 2010;95(12):5357–64. https://doi.org/10.1210/jc.2010-1207.CrossRefPubMed

33.

Miller KD, Coughlin MT, Lee PA. Fertility after unilateral cryptorchidism. Paternity, time to conception, pretreatment testicular location and size, hormone and sperm parameters. Horm Res. 2001;55(5):249–53. http://www.ncbi.nlm.nih.gov/pubmed/11740148. Accessed 1 Apr 2017PubMed

34.

Gaudino R, Cavarzere P, Camilot M, Teofoli F, Zampieri N, Tatò L. Prepubertal serum inhibin B in cryptorchid infants and in monorchid boys with compensatory testicular hypertrophy. Fertil Steril. 2008;90(6):2217–21. https://doi.org/10.1016/j.fertnstert.2007.10.017.CrossRefPubMed

35.

Andersson A-M, Juul A, Petersen JH, Müller J, Groome NP, Skakkebæk NE. Serum inhibin B in healthy pubertal and adolescent boys: relation to age, stage of puberty, and follicle-stimulating hormone, luteinizing hormone, testosterone, and estradiol levels ¹. J Clin Endocrinol Metab. 1997;82(12):3976–81. https://doi.org/10.1210/jcem.82.12.4449.PubMedCrossRef

36.

Robertson DM, Sullivan J, Watson M, Cahir N. Inhibin forms in human plasma. J Endocrinol. 1995;144(2):261–9. http://www.ncbi.nlm.nih.gov/pubmed/7706979. Accessed 28 Mar 2017CrossRefPubMed

37.

Crofton PM, Evans AEM, Groome NP, Taylor MRH, Holland CV, Kelnar CJH. Inhibin B in boys from birth to adulthood: relationship with age, pubertal stage, FSH and testosterone. Clin Endocrinol (Oxf). 2002;56(2):215–21. http://www.ncbi.nlm.nih.gov/pubmed/11874413. Accessed 17 Apr 2017CrossRef

38.

Radicioni AF, Anzuini A, De Marco E, Nofroni I, Castracane VD, Lenzi A. Changes in serum inhibin B during normal male puberty. Eur J Endocrinol. 2005;152(3):403–9. https://doi.org/10.1530/eje.1.01855.CrossRefPubMed

39.

Young J, Couzinet B, Chanson P, Brailly S, Loumaye E, Schaison G. Effects of human recombinant luteinizing hormone and follicle-stimulating hormone in patients with acquired hypogonadotropic hypogonadism: study of Sertoli and Leydig cell secretions and interactions. J Clin Endocrinol Metab. 2000;85(9):3239–44. https://doi.org/10.1210/jcem.85.9.6811.CrossRefPubMed

40.

Christiansen P, Anderson AM, Skakkebæk NE, Juul A. Serum inhibin B, FSH, LH and testosterone levels before and after human chorionic gonadotropin stimulation in prepubertal boys with cryptorchidism. Eur J Endocrinol. 2002;147(1):95–101.CrossRefPubMed

41.

Cortes D, Thorup J, Hogdall E, Norgaard-Pedersen B, Petersen BL, Hogdall C. The relation of germ cells per tubule in testes, serum inhibin B and FSH in cryptorchid boys. Pediatr Surg Int. 2007;23(2):163–9. https://doi.org/10.1007/s00383-006-1839-9.CrossRefPubMed

42.

Longui CA, Amhold IJP, Mendonca BB, DOsvaldo AF, Bloise W. Serum inhibin levels before and after gonadotropin stimulation in cryptorchid boys under age 4 years. J Pediatr Endocrinol Metab. 1998;11(6):687–92.CrossRefPubMed

43.

Raivio T, Dunkel L. Inverse relationship between serum inhibin B and FSH levels in prepubertal boys with cryptorchidism. Pediatr Res. 1999;46(5):496–500. https://doi.org/10.1203/00006450-199911000-00002.CrossRefPubMed

44.

Pierik FH, Deddens JA, Burdorf A, Keizer-Schrama SMPFDM, De JFH, Weber RFA. The hypothalamus-pituitary-testis axis in boys during the first six months of life: a comparison of cryptorchidism and hypospadias cases with controls. Int J Androl. 2009;32(5):453–61. https://doi.org/10.1111/j.1365-2605.2008.00877.x.CrossRefPubMed

45.

Chada M, Průsa R, Bronský J, et al. Inhibin B, follicle stimulating hormone, luteinizing hormone and testosterone during childhood and puberty in males: changes in serum concentrations in relation to age and stage of puberty. Physiol Res. 2003;52(1):45–51. http://www.ncbi.nlm.nih.gov/pubmed/12625806. Accessed 13 Sept 2017PubMed

46.

Ramaswamy S, Marshall GR, McNeilly AS, Plant TM. Dynamics of the follicle-stimulating hormone (FSH)-inhibin B feedback loop and its role in regulating spermatogenesis in the adult male rhesus monkey ( Macaca mulatta ) as revealed by unilateral Orchidectomy ¹. Endocrinol. 2000;141(1):18–27. https://doi.org/10.1210/endo.141.1.7276.CrossRef

47.

Thorup J, Petersen BL, Kvist K, Cortes D. Bilateral vanished testes diagnosed with a single blood sample showing very high gonadotropins (follicle-stimulating hormone and luteinizing hormone) and very low inhibin B. Scand J Urol Nephrol. 2011;45(6):425–31. https://doi.org/10.3109/00365599.2011.609833.CrossRefPubMed

48.

Thorup J, Kvist K, Clasen-Linde E, Hutson JM, Cortes D. Serum inhibin B values in boys with unilateral vanished testis or unilateral cryptorchidism. J Urol. 2015;193(5):1632–6. https://doi.org/10.1016/j.juro.2014.10.110.CrossRefPubMed

49.

Zivkovic D, Hadziselimovic F. Development of Sertoli cells during mini-puberty in normal and cryptorchid testes. Urol Int. 2009;82(1):89–91. https://doi.org/10.1159/000176032.CrossRefPubMed

50.

Hamdi SM, Almont T, Galinier P, Mieusset R, Thonneau P. Altered secretion of Sertoli cells hormones in 2-year-old prepubertal cryptorchid boys: a cross-sectional study. Androl. 2017;5(4):783–9. https://doi.org/10.1111/andr.12373.CrossRef

51.

Cortes D, Clasen-Linde E, Hutson JM, Li R, Thorup J. The Sertoli cell hormones inhibin-B and anti M??Llerian hormone have different patterns of secretion in prepubertal cryptorchid boys. J Pediatr Surg. 2016;51(3):475–80. https://doi.org/10.1016/j.jpedsurg.2015.08.059.CrossRefPubMed

52.

Verkauskas G, Malcius D, Eidukaite A, et al. Prospective study of histological and endocrine parameters of gonadal function in boys with cryptorchidism. J Pediatr Urol. 2016;12(4):238.e1–6. https://doi.org/10.1016/j.jpurol.2016.05.007.CrossRef

53.

Main KM, Toppari J, Suomi AM, et al. Larger testes and higher inhibin B levels in Finnish than in Danish newborn boys. J Clin Endocrinol Metab. 2006;91(7):2732–7. https://doi.org/10.1210/jc.2005-2443.CrossRefPubMed

54.

IRKILATA H, YILDIRIM I, ONGURU O, AYDUR E, MUSABAK U, DAYANC M. The influence of Orchiopexy on serum inhibin B level: relationship with histology. J Urol. 2004;172(6):2402–5. https://doi.org/10.1097/01.ju.0000145223.75776.cd.CrossRef

55.

Chemes HE. Infancy is not a quiescent period of testicular development. Int J Androl. 2001;24(1):2–7. http://www.ncbi.nlm.nih.gov/pubmed/11168644. Accessed 13 Sept 2017CrossRefPubMed

56.

Irkilata HC, Dayanc M, Kibar Y, et al. Effect of scrotal incision orchiopexy on serum inhibin B levels and comparison with classic inguinal orchiopexy. Urol. 2008;72(3):525–9. https://doi.org/10.1016/j.urology.2008.03.063.CrossRefPubMed

57.

Thorup J, Petersen BL, Kvist K, Cortes D. Bilateral undescended testes classified according to preoperative and postoperative status of gonadotropins and inhibin B in relation to testicular histopathology at bilateral orchiopexy in infant boys. J Urol. 2012;188(4 SUPPL):1436–42. https://doi.org/10.1016/j.juro.2012.02.2551.CrossRefPubMed

Title: Inhibin B in healthy and cryptorchid boys
Authors: Susanna Esposito
Marta Cofini
Donato Rigante
Alberto Leonardi
Laura Lucchetti
Clelia Cipolla
Lucia Lanciotti
Laura Penta
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: Italian Journal of Pediatrics / Issue 1/2018
Electronic ISSN: 1824-7288
DOI: https://doi.org/10.1186/s13052-018-0523-8

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Inhibin B in healthy and cryptorchid boys

Abstract

Background

Discussion

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Discussion

Conclusion

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