Abstract
Objective: To assess the sensitivity and specificity of anti-Mullerian hormone (AMH) and inhibin B for diagnosis of 46,XY disorders of sex development (DSD).
Patients and methods: The study included 43 patients of 46,XY DSD and compared them with 43 healthy, male, age matched controls. All patients underwent karyotyping, assessment of testosterone, dihydrotestosterone (DHT) and Δ4-androstendione (Δ4A) basal and after human chorionic gonadotropin (HCG) testing. Basal dehydroepiandrosterone (DHEA) was measured. Ultrasonograghy was also done and some cases underwent laparoscopy or gonadal biopsies. Basal AMH and inhibin B were measured in both cases and controls.
Results: The mean age of patients was 5.16±4.24 years. There were significant correlations between basal AMH and HCG stimulated testosterone and DHT (r=0.64; p<0.001 and r=0.52; p<0.001, respectively). Also, significant positive correlations were found between inhibin B and HCG as well as stimulated testosterone and DHT (r=0.62; p<0.001 and r=0.44; p=0.003, respectively). A highly significant correlation was found between AMH and inhibin B (r=0.78; p<0.001). The sensitivity of AMH was (96.6%), specificity (60.7%), NPV (89.5%) and PPV (83.6%). Best cut-off value was (27.11 IU/mL) while overall accuracy was (85%). The sensitivity of inhibin B was (96.6%), specificity (67.9%), NPV (90.5%), PPV (86.2%), and best cut-off value was (41.9 IU/mL) with an overall accuracy (87%).
Conclusion: AMH and inhibin B are valuable, and reliable noninvasive parameters for the detection of functioning testicular tissues in prepubertal patients.
References
1. Hersmus R, Stoop H, White SJ, Drop SL, Oosterhuis JW, et al. Delayed recognition of disorders of sex development (DSD): a missed opportunity for early diagnosis of malignant germ cell tumors. Int J Endocrinol 2012; Article ID 671209, doi:10.1155/2012/671209.10.1155/2012/671209Search in Google Scholar PubMed PubMed Central
2. Pelayo BF, Carabano AI, Sanz SF, Laorden IE. Ambiguous genitalia. Rev Pediatr Aten Primaria 2011;13:419–33.10.4321/S1139-76322011000300009Search in Google Scholar
3. Mendonca BB, Domenice S, Arnhold IJ, Costa EM. 46, XY disorders of sex development (DSD). Clin Endocrinol (Oxf) 2009;70:173–87.Search in Google Scholar
4. Rey R. How to evaluate gonadal function in the cryptorchid boy; Lessons from new testicular markers. J Pediatr Endocrinol Metab 2003;16:357–64.10.1515/JPEM.2003.16.3.357Search in Google Scholar
5. Huang S, Tou J. Comment on “Serum AMH concentration as a marker evaluating gonadal function in boys operated on for unilateral cryptorchidism between 1st and 4th year of life”. Endocrine 2012;41:544–5.10.1007/s12020-012-9601-7Search in Google Scholar PubMed
6. Aksglaede L, Sørensen K, Boas M, Mouritsen A, Hagen CP, 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;95:5357–64.10.1210/jc.2010-1207Search in Google Scholar PubMed
7. Grinspon RP, Loreti N, Braslavsky D, Bedecarrás P, Ambao V, et al. Sertoli cell markers in the diagnosis of paediatric male hypogonadism. J Pediatr Endocrinol Metab 2012;25:3–11.10.1515/jpem-2011-0453Search in Google Scholar PubMed
8. Adamopoulos DA, Koukkou EG. Value of FSH and inhibin-B measurements in the diagnosis of azoospermia – A clinician’s overview. Int J Androl 2010;33:109–113.10.1111/j.1365-2605.2009.00980.xSearch in Google Scholar PubMed
9. Ahmed SF, Achermann JC, Arlt W, Balen A, Conway G, et al. UK Guidance on the initial evaluation of an infant or an adolescent with a suspected disorder of sex development. Clin Endocrinol (Oxf) 2011;75:12–26.10.1111/j.1365-2265.2011.04076.xSearch in Google Scholar PubMed PubMed Central
10. Cinaz P, Yeşilkaya E, Onganlar YH, Boyraz M, Bideci A, et al. Penile anthropometry of normal prepubertal boys in Turkey. Acta Paediatr 2012;101:33–6.10.1111/j.1651-2227.2011.02386.xSearch in Google Scholar PubMed
11. Zorc JJ, Alpern ER, Brown LW, Loomes KM, Marino BS, et al. Schwartz’s Clinical handbook of pediatrics. 2012;148–153.Search in Google Scholar
12. Grinspon RP, Rey RA. New perspectives in the diagnosis of pediatric male hypogonadism: the importance of AMH as a Sertoli cell marker. Arq Bras Endocrinol Metabol 2011;55: 512–19.10.1590/S0004-27302011000800003Search in Google Scholar PubMed
13. La Marca A, Broekmans FJ, Volpe A, Fauser BC, Macklon N. Anti-Mullerian hormone (AMH): what do we still need to know? Hum Reprod 2009;24:2264–75.10.1093/humrep/dep210Search in Google Scholar PubMed
14. Crofton PM, Evans AE, Groome NP, Taylor MR, Holland CV, et al. Inhibin B in boys from birth to adulthood: relationship with age, pubertal stage, FSH and testosterone. Clin Endocrinol (Oxf) 2002;56:215–21.10.1046/j.0300-0664.2001.01448.xSearch in Google Scholar PubMed
15. Ohnuma K, Kaneko H, Noguchi J, Kikuchi K, Ozawa M, et al. Production of inhibin A and inhibin B in boars: changes in testicular and circulating levels of dimeric inhibins and characterization of inhibin forms during testis growth. Domest Anim Endocrinol 2007;33:410–21.10.1016/j.domaniend.2006.08.004Search in Google Scholar PubMed
16. Lee PA, Gollenberg AL, Hediger ML, Himes JH, Zhang Z, et al. Luteinizing hormone, testosterone and inhibin B levels in the peripubertal period and racial/ethnic differences among boys aged 6–11 years: analyses from NHANES III, 1988–1994. Clin Endocrinol (Oxf) 2010;73:744–51.10.1111/j.1365-2265.2010.03866.xSearch in Google Scholar PubMed PubMed Central
17. Szarras-Czapnik M, Gajewska M, Ksiazyk J, Janas R, Ginalska-Malinowska M. Anti-Müllerian hormone (AMH) measurements in the assessment of testicular function in prepubertal boys and in sexual differentiation disorders. Endokrynol Diabetol Chor Przemiany Materii Wieku Rozw 2006;12:195–199.Search in Google Scholar
18. Kubini K, Zachmann M, Albers N, Hiort O, Bettendorf M, et al. Basal Inhibin B and the testosterone response to human chorionic gonadotropin correlate in prepubertal boys. J Clin Endocrinol Metab 2000;85:134–8.10.1210/jc.85.1.134Search in Google Scholar
19. 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;45:425–31.10.3109/00365599.2011.609833Search in Google Scholar PubMed
20. Brauner R, Neve M, Allali S, Trivin C, Lottmann H, et al. Clinical, biological and genetic analysis of anorchia in 26 boys. PLoS One 2011;6:23292. doi:10.1371/journal.pone.0023292.10.1371/journal.pone.0023292Search in Google Scholar PubMed PubMed Central
21. Gaudino R, Cavarzere P, Camilot M, Teofoli F, Zampieri N, et al. Prepubertal serum inhibin B in cryptorchid infants and in monorchid boys with compensatory testicular hypertrophy. Fertil Steril 2008;90:2217–21.10.1016/j.fertnstert.2007.10.017Search in Google Scholar PubMed
22. Lahlou N, Roger M. Inhibin B in pubertal development and pubertal disorders. Semin Reprod Med 2004;22:165–175.10.1055/s-2004-831892Search in Google Scholar PubMed
23. Adan L, Lechevalier P, Couto-Silva AC, Boissan M, Trivin C, et al. Plasma inhibin B and antimüllerian hormone concentrations in boys: discriminating between congenital hypogonadotropic hypogonadism and constitutional pubertal delay. Med Sci Monit 2010;16:511–17.Search in Google Scholar
24. Lee MM, Donahoe PK, Silverman BL, Hasegawa T, Hasegawa Y, et al. Measurements of serum müllerian inhibiting substance in the evaluation of children with nonpalpable gonads. N Engl J Med 1997;336:1480–86.10.1056/NEJM199705223362102Search in Google Scholar PubMed
25. Misra M, MacLaughlin DT, Donahoe PK, Lee MM. The role of Müllerian inhibiting substance in the evaluation of phenotypic female patients with mild degrees of virilization. J Clin Endocrinol Metab 2003;88:787–92.10.1210/jc.2002-020889Search in Google Scholar PubMed
26. Coutant R, Biette-Demeneix E, Bouvattier C, Bouhours-Nouet N, Gatelais F, et al. Baseline inhibin B and anti-Mullerian hormone measurements for diagnosis of hypogonadotropic hypogonadism (HH) in boys with delayed puberty. J Clin Endocrinol Metab 2010;95:5225–32.10.1210/jc.2010-1535Search in Google Scholar PubMed
27. Nagata Y, Fujita K, Banzai J, Kojima Y, Kasima K, et al. Seminal plasma inhibin-B level is a useful predictor of the success of conventional testicular sperm extraction in patients with non-obstructive azoospermia. J Obstet Gynaecol Res 2005;31:384–8.10.1111/j.1447-0756.2005.00306.xSearch in Google Scholar PubMed
28. Goulis DG, Polychronou P, Mikos T, Grimbizis G, Gerou S, et al. Serum inhibin-B and follicle stimulating hormone as predictors of the presence of sperm in testicular fine needle aspirate in men with azoospermia. Hormones (Athens) 2008;7:140–7.10.1007/BF03401505Search in Google Scholar PubMed
29. Misra M, MacLaughlin DT, Donahoe PK, Lee MM. Measurement of Mullerian inhibiting substance facilitates management of boys with microphallus and cryptorchidism. J Clin Endocrinol Metab 2002;87:3598–3602.10.1210/jcem.87.8.8742Search in Google Scholar PubMed
©2014 by De Gruyter
