Endokrinološka obrada dojenčeta s retencijom testisa i hipospadijom
DOI:
https://doi.org/10.13112/pc.1205Ključne riječi:
Hipospadija; Kriptorhizam; Poremećaji diferencijacije spola; Endokrinologija; Patologija, molekularnaSažetak
Hypospadias and cryptorchidism are common congenital anomalies of the male reproductive system, which, when occurring together, particularly in more severe forms, may indicate a disorder of sex development (DSD). Endocrinological evaluation of these infants is crucial for distinguishing isolated anatomical variants from manifestations of complex endocrine or genetic disorders that require specific diagnostic and therapeutic approaches. Male sex differentiation is a complex process dependent on the coordinated activity of numerous genes and hormones during critical periods of embryonic development. Defects at any stage of this process may result in hypospadias, cryptorchidism, or their combination. Initial assessment includes a detailed clinical examination with an objective evaluation of the degree of external genitalia masculinization, ideally using standardized scoring systems. Particular attention is required for high-risk clinical signs such as bilaterally nonpalpable gonads, severe proximal hypospadias, micropenis, or genital hyperpigmentation.
Hormonal evaluation should be temporally optimized to utilize the diagnostic window of "minipuberty" during the first 3-6 months of life, when gonadotropins and sex hormones are physiologically elevated. Basal hormonal assessment includes measurement of LH, FSH, testosterone, AMH, and inhibin B, while in cases of suspected specific steroidogenesis disorders, dihydrotestosterone, androstenedione, and 17-hydroxyprogesterone are measured. Outside the minipuberty period, stimulation tests are required. Karyotyping and molecular analysis are fundamental diagnostic procedures, and the application of NGS DSD panels and whole-exome sequencing enables etiological diagnosis in a significant proportion of cases. Imaging studies, primarily pelvic ultrasound, are used to assess the presence and position of gonads and identify internal genital structures.
A multidisciplinary approach, including pediatric endocrinologists, urologists, clinical geneticists, and psychologists, is essential from the earliest stage of evaluation. Decisions regarding sex assignment must be individualized and based on diagnosis, prognosis of sexual function, and fertility potential. Long-term follow-up must be conducted in specialized centers with specially trained multidisciplinary teams, extend into adulthood, and include monitoring of reproductive function, psychosexual development, and the risk of gonadal malignancy.
Reference
1. Ahmed SF, Achermann JC, Arlt W, Balen A, Conway G, Edwards Z, et al. UK guidance on the initial evaluation of an infant or an adolescent with a suspected disorder of sex development (revised 2015). Clin Endocrinol (Oxf). 2016;84:771-88.
2. Lee PA, Nordenström A, Houk CP, Ahmed SF, Auchus R, Baratz A, et al. Global disorders of sex development update since 2006: perceptions, approach and care. Horm Res Paediatr. 2016;85:158-80.
3. van der Horst HJ, de Wall LL. Hypospadias, all there is to know. Eur J Pediatr. 2017;176:435-41.
4. Radmayr C, Dogan HS, Hoebeke P, Kočvara R, Nijman R, Silay S, et al. Management of undescended testes: European Association of Urology/European Society for Paediatric Urology guidelines. J Pediatr Urol. 2016;12:335-43.
5. Baxter RM, Vilain E. Translational genetics for diagnosis of human disorders of sex development. Annu Rev Genomics Hum Genet. 2013;14:371-92.
6. Imperato-McGinley J, Zhu YS. Androgens and male physiology: the syndrome of 5α-reductase-2 deficiency. Mol Cell Endocrinol. 2002;198:51-9.
7. Rey RA, Grinspon RP. Normal male sexual differentiation and aetiology of disorders of sex development. Best Pract Res Clin Endocrinol Metab. 2011;25:221-38.
8. Hutson JM, Southwell BR, Li R, Lie G, Ismail K, Harisis G, et al. The regulation of testicular descent and the effects of cryptorchidism. Endocr Rev. 2013;34:725-52.
9. Virtanen HE, Toppari J. Epidemiology and pathogenesis of cryptorchidism. Hum Reprod Update. 2008;14:49-58.
10. Ahmed SF, Khwaja O, Hughes IA. The role of a clinical score in the assessment of ambiguous genitalia. BJU Int. 2000;85:120-4.
11. Tuladhar A, Davis J, Cunnath A, Zacharin M. Establishing normal values for penile length in Caucasian children: a prospective study. J Paediatr Child Health. 2020;56:1092-7.
12. Grinspon RP, Rey RA. Anti-Müllerian hormone and Sertoli cell function in paediatric male hypogonadism. Horm Res Paediatr. 2010;73:81-92.
13. Becker M, Hesse V. Minipuberty: why does it happen? Horm Res Paediatr. 2020;93:76-84.
14. Bergadá I, Milani C, Bedecarrás P, Andreone L, Ropelato MG, Gottlieb S, et al. 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;91:4092-8.
15. Speiser PW, Arlt W, Auchus RJ, Baskin LS, Conway GS, Merke DP, et al. Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103:4043-88.
16. Eggers S, Sadedin S, van den Bergen JA, Robevska G, Ohnesorg T, Hewitt J, et al. Disorders of sex development: insights from targeted gene sequencing of a large international patient cohort. Genome Biol. 2016;17:243.
17. Baetens D, Verdin H, De Baere E, Cools M. Update on the genetics of differences of sex development (DSD). Best Pract Res Clin Endocrinol Metab. 2019;33:101271.
18. Dessens AB, Slijper FM, Drop SL. Gender dysphoria and gender change in chromosomal females with congenital adrenal hyperplasia. Arch Sex Behav. 2005;34:389-97.
19. Pasterski V, Mastroyannopoulou K, Wright D, Zucker KJ, Hughes IA. Predictors of posttraumatic stress in parents of children diagnosed with a disorder of sex development. Arch Sex Behav. 2014;43:369-75.
20. Cools M, Drop SL, Wolffenbuttel KP, Oosterhuis JW, Looijenga LH. Germ cell tumors in the intersex gonad: old paths, new directions, moving frontiers. Endocr Rev. 2006;27:468-84.
21. Mouriquand PD, Gorduza DB, Gay CL, Meyer-Bahlburg HF, Baker L, Baskin LS, et al. Surgery in disorders of sex development (DSD) with a gender issue: if (why), when and how? J Pediatr Urol. 2016;12:139-49.
22. Wood HM, Elder JS. Cryptorchidism and testicular cancer: separating fact from fiction. J Urol. 2009;181:452-61.
23. Hughes IA, Houk C, Ahmed SF, Lee PA; LWPES Consensus Group; ESPE Consensus Group. Consensus statement on management of intersex disorders. Arch Dis Child. 2006;91:554-63.
24. Miller WL, Auchus RJ. The molecular biology, biochemistry and physiology of human steroidogenesis and its disorders. Endocr Rev. 2011;32:81-151.
25. Mendonca BB, Gomes NL, Costa EM, Inacio M, Martin RM, Nishi MY, et al. 46,XY disorder of sex development (DSD) due to 17β-hydroxysteroid dehydrogenase type 3 deficiency. J Steroid Biochem Mol Biol. 2017;165:79-85.
26. Kalfa N, Paris F, Philibert P, Orsini M, Broussous S, Fauconnet-Servant N, et al. Is hypospadias associated with prenatal exposure to endocrine disruptors? A French collaborative controlled study of a cohort of 300 consecutive children without genetic defect. Eur Urol. 2015;68:1023-30.
27. Houk CP, Lee PA. Approach to assigning gender in 46,XX congenital adrenal hyperplasia with male external genitalia: replacing dogmatism with pragmatism. J Clin Endocrinol Metab. 2010;95:4501-8.
28. Damgaard IN, Jensen TK; Nordic Cryptorchidism Study Group. Risk factors for congenital cryptorchidism in a prospective birth cohort study. PLoS One. 2008;3:e3051.
29. Kollin C, Stukenborg JB, Nurmio M, Sundqvist E, Gustafsson T, Söder O, 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;97:4588-95.
30. Tüttelmann F, Ruckert C, Röpke A. Disorders of spermatogenesis. Med Genet 2018;30:12-20.
31. Meyer-Bahlburg HF, Dolezal C, Baker SW, New MI. Sexual orientation in women with classical or non-classical congenital adrenal hyperplasia as a function of degree of prenatal androgen excess. Arch Sex Behav. 2008;37:85-99.
32. Pleskacova J, Hersmus R, Oosterhuis JW, Setyawati BA, Faradz SM, Cools M, et al. Tumor risk in disorders of sex development. Sex Dev. 2010;4:259-69.
33. Dieckmann KP, Pichlmeier U. Clinical epidemiology of testicular germ cell tumors. World J Urol. 2004;22:2-14.
Preuzimanja
Objavljeno
Broj časopisa
Rubrika
Licenca
Autorska prava (c) 2026 Katja Dumić Kubat, Duje Braovac
Ovo djelo je licencirano pod licencom Creative Commons Attribution 4.0 Međunarodna licenca.
By publishing in Paediatria Croatica, authors retain the copyright to their work and grant others the right to use, reproduce, and share their research articles in accordance with the Creative Commons Attribution License (CC BY 4.0), which allows others to distribute and build upon the work as long as they credit the author for the original creation.
