Evaluation and treatment for ovotesticular disorder of sex development (OT-DSD) - experience based on a Chinese series
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1 o et l. BC Urology (2017) 17:21 DI /s RESEARCH ARICLE pen Access Evlution nd tretment for ovotesticulr disorder of sex development (DSD) experience bsed on Chinese series Yu o 1, Shoji Chen 1, Ru Wng 2, Xuejun Wng 1, Dorui Qin 1 nd Yunmn ng 1* Abstrct Bckground: he im of this study is to review nd present the clinicl fetures nd process of evlution nd tretment for DSD in single center in recent yers in Chin. ethods: Sixteen ptients with DSD during the pst 4 yers underwent the evlution nd tretment in single center. he clinicl chrcteristics nd outcomes of surgery were nlyzed. Results: he surgicl ge rnged from 17 months to 66 months with men ge of 20 months, nd the men followup ws 30 months (4 months to 56 months). he presenttion in 11 ptients ws mbiguous genitli, nd the rest 5 ptients were suspected to hve DSD in preopertive exmintion before hypospdis repir. he kryotypes were 46, XX in 11 ptients, 46, XX/46, XY in 3, 46, XX/47, XXY in 1, nd 46, XY in 1. Initil rered sex ws mle in 14 ptients, femle in 1, nd undetermined in 1. After surgery, genders were ressigned in 3 ptients, while 15 ptients were rised s mle with testiculr tissue left. nly 1 ptient with ovrin tissue left ws rised s femle. Repir ws completed in 11 mles nd 1 femle, nd stge I urethroplsty ws done in 4 mles. further surgery to remove the gonds ws needed for inconsonnce of gender ssignment. gondl tumors were detected. Conclusions: DSD is rre nd complex deformity with few systemtic reports in Chin. It s importnt to estblish regulr lgorithm for evlution nd tretment of DSD. Keywords: votestis, Hypospdis, Urethroplsty, Disorder of sex development Bckground he nomenclture ovotesticulr disorder of sex development (DSD) hs replced the obsolete one, true hermphroditism, since 2006 [1]. It is defined by the presence of testiculr tissue with welldeveloped seminiferous tubules nd ovrin tissue with primordil follicles in the sme individul. hese tissues my be coexistent in the sme gond (ovotestis) or independently the ovry on one side nd the testicle on the other). he incidence is rre, ccounting for nerly 3 to 10% of DSD cses [2]. he externl genitli show vrible phenotypes, rnging from norml mle to norml femle presenttion. However, mbiguous genitli is the most common mnifesttion s noted in 90% of the cses [3]. * Correspondence: toil112@163.com 1 Deprtment of Peditric Surgery of Children s edicl Center, Sichun Acdemy of edicl Sciences & Sichun Provincil People s Hospitl, Chengdu, Chin Full list of uthor informtion is vilble t the end of the rticle he deformed genitli compromises psychosocil s well s physiologicl helth of the ptients nd their fmilies. In Chin, dt re in gret need on the clinicl fetures, ssessing modlities, surgicl procedures nd outcomes, nd the prognosis in the involved ptients. We shre the fetures of DSD in our recent series. ethods From September 2011 to December 2015, 16 ptients with DSD were evluted nd treted in our hospitl. As shown in Fig. 1, the procedure for dignosis nd mngement of DSD ws step by step, s first collection of clinicl dt, second chromosoml nd endocrinl ssessment, third multidisciplinry tem (D) consulttion, then surgicl & histopthologicl confirmtion of gonds nture with gender ssignment, gond(s) removl nd genitl plstic surgery in ccordnce he Author(s) pen Access his rticle is distributed under the terms of the Cretive Commons Attribution 4.0 Interntionl License ( which permits unrestricted use, distribution, nd reproduction in ny medium, provided you give pproprite credit to the originl uthor(s) nd the source, provide link to the Cretive Commons license, nd indicte if chnges were mde. he Cretive Commons Public Domin Dediction wiver ( pplies to the dt mde vilble in this rticle, unless otherwise stted.
2 o et l. BC Urology (2017) 17:21 Pge 2 of 7 Fig. 1 he procedure for dignosis nd mngement of DSD ptients in our hospitl with ssigned gender. he finl dignosis depended on gondl histopthology. Clinicl dt included ge, rering gender, medicl history, physicl exmintion, imging nd screening of ssocited nomlies. Prder grding of the externl genitli nd plption of gonds re of essentil importnce in physicl exmintion. Although the dignostic ccurcy of the internl genitl orgns ws unstisfctory vi ultrsonogrphy nd RI [4, 5], we still used these imging modlities to chrcterize urogenitl system before surgery. Kryotype nlysis ws detected from the peripherl blood in ll ptients. Although the dignosis depended on histopthologicl findings, we utilized biochemicl exmintion nd humn chorionicgondotropin (HCG) test to distinguish DSD from other DSDs before surgery. Before HCG test, serum testosterone (), luteinizing hormone (LH), follicle stimultion hormone (FSH), ntimüllerin hormone (AH), InhibinB, 17hydroxyprogesterone (17HP), ndrostenedione, nd sex hormone binding globulin (SHBG) were detected. Consecutive HCG injection, dose of 100 units/kg/dy, ws indicted for 3 dys. At the 4th dy,, LH, FSH, ndrostenedione, SHBG, nd dihydrotestosterone (DH) were detected gin. he concentrtion fter HCG stimultion of higher thn 200 ng/dl ws defined s norml response, 100 to 200 ng/dl s borderline response, lower thn 100 ng/dl s poor response. Ptient s dt were submitted to D, including peditric endocrinologist, ndrologist, gynecologist, peditric urologist, geneticists, pthologist, psychologist, nd medicl ethics committee, for consulttion. hen the prents were involved in the discussion of possible gender ssignment. Surgery included 3 prts. A cystoscopy with 3Fr ctheter ws used to mesure the length of urogenitl sinus, wterfilled vgin nd the distnce from the bldder neck to the vgin metus, s well s to identify the existence of cervicl orifice t the end of the vgin. he second step ws gondl detection, biopsy nd selected removl. Lproscopy ws pplied to confirm the components of intrperitonel gonds nd internl genitl ducts combining with puncturl biopsy or excisionl biopsy. Prents would mke finl decision of gender ssignment bsed on the results of explortion before gond removl during the opertion. ccsionlly, üllerin duct structures were removed vi lproscopy. n the bsis of dominnt gonds nd the consensus of gender ssignment, only one type of gond ws reserved, nd the other ws resected. he third step ws genitoplsty. Clitoroplsty, vginoplsty, nd lbioplsty were crried out in femle gender. According to the length of urogenitl sinus, we used prtil urogenitl mobiliztion (PU) or flp vginoplsty for vginoplsty. rthoplsty, urethroplsty nd scrotoplsty were crried out in mle gender. Plte reconstruction with twostge tubulriztion urethroplsty [6] nd Duckett urethroplstyurethrostomy by stges [7] were the twostge techniques we routinely used in severe hypospdis repirs (Fig. 2). ne month fter surgery, for ptient ressigned s femle, humn menopusl gondotropins (HG) test [8] with dily intrmusculr dose of 150 IU on 3 consecutive dys ws indicted to verify no residury testicle tissue. While for ptients ressigned s mle, HCG test ws crried out to confirm no residury ovrin tissue. All the ptients were followed up t 1, 3, 6, 12 months fter surgery nd every yer therefter. All procedures used in the study confirmed to the tenets of the Declrtion of Helsinki. he Ethics Committee of Sichun Acdemy of edicl Sciences & Sichun Provincil People s Hospitl pproved the protocols used. All prticipnts hve known to prticipte in the study. Written informed consents were obtined from ll prticipnts. Results As shown in ble 1, the ge rnged from 17 months to 66 months with men ge of 20 months, nd the men followup ws 30 months (4 months to 56 months). Eleven ptients cme to our hospitl for mbiguous
3 o et l. BC Urology (2017) 17:21 Pge 3 of 7 Fig. 2 he ppernce fter the first stge of twostge techniques we routinely used in urethroplsty. Plte reconstruction with twostge tubulriztionurethroplsty. After the first stge, the new metus is in the shft of the phllus. b Ducketturethroplstyurethrostomy by stges. After the first stge, the urethroplsty is finished except fistul genitli nd 5 ptients were referred to our institution for hypospdis repir. relevnt fmily history or ssocited nomlies were noted. According to Prder clssifiction, stge to V were recorded with stge ccounting for 62.5% (10 out of 16). üllerin remnnts were detected in 8 ptients before surgery vi ultrsonogrphy or RI. With HCG stimultion, norml response ws noted in 13 ptients, nd the rest 3 ptients showed borderline response. Followup in puberty is importnt for the 3 borderline response ptients. he other endocrinl indexes were norml or meningless for considering other DSD. In this group of ptients, the kryotypes were 46, XX in 11 ptients (68.75%), 46, XX/46, XY in 3 (18.75%), rre kryotype 46, XX/47, XXY in 1 (6.25%) nd 46, XY in 1 (6.25%). he most common gond ws ovotestis (68.75%), followed with ovries (18.75%), nd the lest common ws testis (12.5%). votestis ws esily noticed in the scrotum (50%), subsequently in the inguinl cnl (36.4%), then in the bdominl cvity (13.6%). All the 6 ble 1 he chrcteristic of these DSD ptients Kryotype Prder R post L gonnd R gond L duct R duct UVB (cm) grde imging HCG Position issue Position issue (ng/dl) ,XY /5/4 S 3 /46,XY /5/4.5 4 IV /6/ /4.5/3.5 F /6.5/ /6.5/5 U Uterus Gender Compliction ssignment 3.5/4.5/2.5 8 /46,XY /5.5/4.5 9 /47,XXY /4.5/ /5/4 11 /46,XY /5.5/ /6/ /5.5/5.5 F /5/ /5/3.5 F 16 V /4/3.5 R üllerin remnnt, L Left, R Right, UVB Length of urogenitl sinus/ wterfilled vgin/ the loction of the vginl confluence to the bldder neck, uinl cn, ominl cvity, otum, votestis, vry, esticle, Fllopin tube, deferens, le, F Femle, U Undetermined sex, F Fistul, S Urethrl stricture, Didn t finished the second stge
4 o et l. BC Urology (2017) 17:21 Pge 4 of 7 ovries were discovered in the bdominl cvity. hree testes were found in the scrotum nd the other one in the inguinl cnl. Adjcent to the ovotestis, internl genitl duct ws verified s vs deferens on 6 lterlities vi biopsy nd s fllopin tube in 16. Bilterl ovotestis ws the most frequent pttern of the gonds s seen in 7 ptients. An ovotestis on one side nd n ovry on the other side ws noted in 5 ptients, while n ovotestis on one side nd testis on the other side ws noted in 3 ptients. In only 1 ptient testis on one side nd n ovry on the other ws noted. he vgin ws found out in 16 ptients with cystoscopy. At the end of the vgin, cervicl orifice ws noted in 14 ptients. he men length of urogenitl sinus (U), i.e., the length from confluence of the vgin nd the urethr to the urethrl metus ws 2.7 cm. he men length of wterfilled vgin (V) ws 5.3 cm. he men distnce from the vginl confluence to the bldder neck (B) ws 4.1 cm.in the ble 1, we use the bbrevition UVB to describe the three distnce. During surgery, gondl gender ws determined vi frozen section biopsy. In ll the ptients, the frozen pthologicl outcomes fell into nticipted possibilities of preopertive D consulttion. Gender ssignment ws then decided ccordingly. Initil rered sex ws mle in 14 ptients, femle in 1, nd undetermined in 1. he gender ws ressigned in 1 ptient who ws primrily rered s mle, 1 s femle, nd the previously undetermined 1 ws ssigned s mle. All the gonds nd djcent ducts in bdominl cvity were subjected to bipolr puncturl biopsy vi lproscopy. All the ovotestes presented in bipolr fshion. Stged urethroplsty ws indicted in ll the ptients ssigned s mle. Plte reconstruction with twostge tubulriztion urethroplsty (PRU) ws used in 10 ptients. Stge urethroplsty ws chieved in 8 ptients with urethrocutneous fistul noted in 1 nd urethrl stricture in 1 s postopertive complictions. wo ptients just finished the first stge without compliction. Duckett urethroplstyurethrotomy by stges ws dopted in 5 ptients. hree ptients finished the fistul repir nd 2 ptients just finished the first stge of Duckett urethroplsty with fistul left. complictions were found in the 5 cses (ble 1). üllerin ducts were removed in 4 ptients nd left intct in 11. Clitoroplsty nd prtil urogenitl mobiliztion (PU) were crried out in only 1 ptient who ws ssigned s femle. complictions were noticed in this ptient during the followup. Histopthology ws used s gold stndrd of finl dignosis. All the immedite outcomes of frozen section during opertion were ccordnt with tht of prffin section fter opertion (Fig. 3). he testiculr tissues presented numerous solid seminiferous tubules filled with immture Sertoli cells nd few primitive germ cells. he testiculr interstitium contined undifferentited spindle cells tht were immture Leydig cells. In the ovrin tissue, numerous primordil follicles nd few primry nd ntrl follicles were found in the outer cortex. In the first month of the followup, HCG/HG test ws completed with no evidence of residul inconsonnt gond. gondl tumors were noted during the followup. Discussion Ethicists nd ptient support groups dvocted tht the genitl surgery should not be wrrnted until the ptient ws ble to understnd the informed consent, insted of repir in infncy period [9]. However, s the ppernce of bisexsul phenotype nd continuous nxiety of prents cll for the mngement, it is rtionl nd in degree mndtory to initite the evlution t n erly ge. Ambiguous or undermsculinized genitli of DSD is esy to detect, while decision mking is difficult when the genitl ppernce seems to be norml femle or otherwise norml hypospdic mle [10]. Physicl exmintion for the gonds is importnt. In 5 ptients out of this series, DSD ws suspected s tough nodule djcent to the testicle or bipolr symmetricl texture of the testicle ws Fig. 3 votestis in DSD. he ovrin comprtment hs numerous primordil nd growing follicles contining primry oocytes within the ovrin corticl strom. b he testiculr comprtment shows solid tubules filled with immture Sertoli cells nd germ cells. he testiculr interstitium contins immture Leydig cells
5 o et l. BC Urology (2017) 17:21 Pge 5 of 7 plpted in physicl exmintion for hypospdis preopertive evlution. he Imging only reveled 8 ptients with internl genitl ducts, however, the vgin ws found out in ll the 16 ptients with cystoscopy. Imging modlities to chrcterize urogenitl system before surgery is lso inccurte. he kryotype showed geogrphic vrition. It ws interesting tht our dt showed similr pttern of kryotype in this Chinese series s tht reported in Europe nd rth Americ, in contrst to tht in Jpn [11]. In Jpn the 46, XY kryotype is more common thn tht in other countries [12]. he mosicism of Klinefelter syndrome with /47,XXY in DSD is very rre with less thn 10 cses reported worldwide [13]. ur ptient 9 is 2 yers nd 5 months old with this kryotype. His mnifesttion s listed in ble 1 showed no difference to tht with other kryotypes of DSD. hough sexdetermining region on the Y chromosome (SRY) is n importnt gene in testiculr development, the impliction of SRY presence in DSD remins indeterminte. SRY detection is not indicted in our institution s routine. votestis is the most common gond in DSD s reported in most rticles [13, 14]. Wiersm nd Rmdil [14] evluted the gonds from 111 ptients with DSD in South Afric. hey proposed three distinct ptterns of gond, nmely the dmixed pttern tht ws centrl core contining strom nd mixture of ovrin nd testiculr tissue (50%), the comprtmentlized pttern tht ws ovrin tissue in upper pole with lower pole of testiculr tissue encpsulted by mntle of ovrin tissue (39%), nd the bipolr pttern tht ws strict polr distribution of testiculr nd ovrin tissue (11%). In our ptients, most ovotestes were of bipolr type, which ws end to end fshion (Fig. 4). vrin tissue locted on the upper pole, ws cerinous, rigid, nd smller thn testiculr tissue. n the contrry, the testiculr tissue locted on the lower pole, ws buff, softer nd lrger thn ovrin tissue. Demrction ws significnt between the two prts. he demrction between ovrin tissue nd testiculr tissue in the 16th ptient ws not obvious on gross view (Fig. 4b). While the different texture mde it evident to distinguish the boundry. his might be the type ssigned s comprtmentlized by Wiersm nd Rmdil, except for tht ovrin tissue ws not found out in the mntle with microscopy. In DSD, either testiculr prt of ovotestis or isolted testis presents mldeveloped microscopic fetures. n the contrry, either ovrin prt of ovotestis or isolted ovry presents welldeveloped microstructures. In microscopy, the presence of numerous primordil follicles contining primry oocytes with or without mturing follicles is considered well developed ovrin tissue, which mking definitive dignosis of DSD. enstrution is expected in 50% cses bsed on welldeveloped ovrin tissue [15]. he negtive feedbck effect of ovrin steroids suppressing gondotropins results in tubulr trophy, poor germ cell development, Leydig cell hyperplsi, nd sclerosis tht finlly cuses infertility of the testiculr tissue. As the individul gets older, the dmge on the testicle in ovotesitulr ptient would deteriorte [15]. his is nother reson why we indicte gender ssignment, especilly for those who with mle dominnce, in infncy. If the pthologists hve misgivings bout the nture of the gonds in the frozen section, the next step should be postponed witing the outcomes of hemtoxylineosin stining. Being the most common form of DSD, ovotestis should be screened out during preopertive physicl exmintion ccording to the typicl morphologicl fetures. Internl genitl ducts djcent to the ovotestis re usully difficult to identify with nked eyes, nd frozen biopsy is wrrnted in surgery. n the bsis of PVE clssifiction system [16], we designed UVB mesurement to ssess the loction of vgin confluence nd the length of urogenitl sinus nd vgin. he criticl fctor in the vginoplsty is not the length of the common sinus but rther the distnce from the bldder neck to the loction of vgin confluence. he former index is very useful in the surgicl plnning Fig. 4 Intropertive findings of ovotestes. vrin portion (blck rrow) is firm nd yellow in n upper pole, wheres testiculr portion (green rrow) is soft nd pink in lower pole. here is distinct line of demrction between the two portions. b he demrction between the two portions is not obvious in the 16th ptient
6 o et l. BC Urology (2017) 17:21 Pge 6 of 7 of vginoplsty. Prtil urogenitl mobiliztion (PU) or flp vginoplsty is indicted bsed on these evlutions. ur multidisciplinry tem nd the fmilies took prt in the gender ssignment. Prder grding, kryotype, nture nd function of gonds, vlues of UVB, presence of üllerin ducts, psychologicl ssessment nd living environment re criticl fctors involved in the gender ssignment. However it is difficult when the decision from the D nd tht from the prents re conflicting. According to Chinese trdition tht the boys crry on the fmily lines, most conservtive fmilies prefer mle to femle in DSD fter thorough evlution, s well s worry bout the ctstrophic effect of gender ressignment on the whole fmily. Even with Prder genitli, possibility of fertility for femle ssignment, which led the D suggesting femle more pproprite, most prents still insist on mle s finl gender. he D would try to fully inform the prents with professionl evlution, but the finl decision is mde by the prents. All the three fmilies ccepted gender ressignment chose to move to remote plce for new life. Lproscopy is widely utilized in the explortion of gonds nd resection of üllerin ducts. Resection of üllerin duct derivtives s routine severl yers go is not recommended in ptients without ny symptom nowdys. However, Frikullh reported 3 to 8% incidence of mlignncy in üllerin remnnts [17]. Informing the prents with this incidence of mlignncy, we were surprised tht removl of the müllerin ducts ws required in ll the ltest 4 symptomtic ptients for the risk of mlignncy. f course, if the gender couldn t be decided during the opertion or the finl gender ws femle, he üllerin remnnts must be retined. Bipolr nd multisite puncturl biopsy of gonds in bdominl cvity with lproscopy is minimlly invsive nd these gondl biopsies re enough to chieve histopthologicl evlution for dignosis. Repir of severe hypospdis is chllenging nd the compliction rte is lwys high. During the recent yers in our institution, plte reconstruction with twostge tubulriztion urethroplsty [6] nd Duckett urethroplstyurethrotomy by stges [7] re the min twostge techniques we routinely indicte in primry severe hypospdis repir. he complictions of the two technique in primry severe hypospdis repir in our hospitl re 16.7 nd 9.43%, respectively [6, 7]. Both the two techniques re suitble for urethroplsty in DSD. he low incidence of Y chromosome in kryotype nd young ge of the ptients induced no gondl tumor to be detected. he incidence of gondl tumors is pproximtely 3% in 46, XY nd 46, XX/46, XY DSD, though rre in 46, XX DSD. Both gondoblstom nd dysgerminom hve been described [18]. HG/ HCG test is n importnt content in the followup. he residul gond inconsistent with rering sex will result in bisexul phenotype in puberty. Conclusions DSD is rre nd complex mlformtion with lots of typicl fetures. Stndrdized procedure of evlution nd tretment for DSD is very importnt. D consulttion might gurntee the high efficiency nd ccurcy in evlution nd tretment. Chinese prents prefer mle to femle when they fce to the gender ressignment. Abbrevitions 17HP: 17hydroxyprogesterone; AH: Antimüllerin hormone; DH: Dihydrotestosterone; DSD: Disorder of sex development; FSH: Follicle stimultion hormone; HCG: Humn chorionic gondotropin; HG: Humn menopusl gondotropins; LH: Luteinizing hormone; D: ultidisciplinry tem; RI: gnetic Resonnce Imging; DSD: votesticulr disorder of sex development; PU: Prtil urogenitl mobiliztion; SHBG: Sex hormone binding globulin; : Serum testosterone Acknowledgements We cknowledge the ptients nd fmilies. We thnk o Liu, Yue jio Chen, Ji yun Yng nd Jing Fu for mking this study possible. Funding his study ws supported by grnts from the Youth Foundtion of Sichun Provincil People s Hospitl ( ). he funders hd no role in study design, dt collection nd nlysis, decision to publish, or preprtion of the mnuscript. Avilbility of dt nd mterils All dt nd mterils cn be obtined by mil of the corresponding uthor. Authors contributions Y crried out the study nd drfted the mnuscript. SJC, Y designed nd coordinted the study. RW helped in the lbortory work. RW, XJW,DRQ performed the dt collection nd sttistics. All uthors red nd pproved the finl mnuscript. Competing interests he uthors declre tht they hve no competing interests. Consent for publiction Written informed consent ws obtined from the gurdins of ll children enrolled for publiction of the ccompnying imges. A copy of the consent is vilble for review by the editors of this journl. Ethics pprovl nd consent to prticipte his study hs been pproved by the Ethics Committee of Sichun Acdemy of edicl Sciences & Sichun Provincil People s Hospitl. All gurdins hve known to prticipte in the study nd hve given consent for the use of their child s informtion. Written informed consents were obtined from ll gurdins. Publisher s te Springer Nture remins neutrl with regrd to jurisdictionl clims in published mps nd institutionl ffilitions. Author detils 1 Deprtment of Peditric Surgery of Children s edicl Center, Sichun Acdemy of edicl Sciences & Sichun Provincil People s Hospitl, Chengdu, Chin. 2 Deprtment of Burn nd Plstic Surgery, West Chin Hospitl of Sichun University, Chengdu, Chin.
7 o et l. BC Urology (2017) 17:21 Pge 7 of 7 Received: 6 September 2016 Accepted: 20 rch 2017 References 1. Lee PA, Houk CP, Ahmed SF, Hughes IA, Interntionl Consensus Conference on Intersex orgnized by the Lwson Wilkins Peditric Endocrine S, the Europen Society for Peditric E. Consensus sttement on mngement of intersex disorders. Interntionl Consensus Conference on Intersex. Peditrics. 2006;118:e Krstic ZD, Smoljnic Z, Vuknic D, Vrinc D, Jnjic G. rue hermphroditism: 10 yers experience. Peditr Surg Int. 2000;16: Sultn C, Pris F, Jendel C, Lumbroso S, Glifer RB. Ambiguous genitli in the newborn. Semin Reprod ed. 2002;20: Bisws K, Kpoor A, Krk AK, Kriplni A, Gupt DK, Kucheri K, et l. Imging in intersex disorders. J Peditr Endocrinol etb. 2004;17: Steven, oole S, Lm JP, ckinly GA, Cscio S. Lproscopy versus ultrsonogrphy for the evlution of ullerin structures in children with complex disorders of sex development. Peditr Surg Int. 2012;28: Yunmn, Shoji C, Yu, Xuejun W, o L. Plte reconstruction nd tubulriztion urethroplsty in the repir of complicted hypospdis. Chin J Peditr Surg. 2015;36: Yunmn, Xuejun W, Yu, Shoji C, o L, Yuejio C. Duckett urethroplstyurethrotomy for stged hypospdis repir. Chin J Reprtive Reconstr Surg. 2016;30: Steinmetz L, Roch N, Longui CA, Dmini D, Dichtchekenin V, Setin N, et l. Inhibin A production fter gondotropin stimulus: new method to detect ovrin tissue in ovotesticulr disorder of sex development. Horm Res. 2009;71: D Alberton F. Disclosing disorders of sex development nd opening the doors. Sex Dev. 2010;4: Kropp BP, Keting A, oshng, Duckett JW. rue hermphroditism nd norml mle genitli: n unusul presenttion. Urology. 1995;46: Krob G, Brun A, Kuhnle U. rue hermphroditism: geogrphicl distribution, clinicl findings, chromosomes nd gondl histology. Eur J Peditr. 1994;153: tsui F, Shimd K, tsumoto F, Itesko, Nr K, Id S, et l. Longterm outcome of ovotesticulr disorder of sex development: single center experience. Int J Urol. 2011;18: Pul GB, Ribeiro Andrde JG, GurgnFilho G, Sewybricker LE, irnd L, cielguerr A, et l. votesticulr disorder of sex development with unusul kryotype: ptient report. J Peditr Endocrinol etb. 2015;28: Wiersm R, Rmdil PK. he gonds of 111 South Africn ptients with ovotesticulr disorder of sex differentition. J Peditr Surg. 2009;44: vn Niekerk WA, Retief AE. he gonds of humn true hermphrodites. Hum Genet. 1981;58: Rink RC, Adms C, isseri R. A new clssifiction for genitl mbiguity nd urogenitl sinus nomlies. BJU Int. 2005;95: Frikullh J, Ehtishm S, Nppo S, Ptel L, Hennyke S. Persistent ullerin duct syndrome: lessons lerned from mnging series of eight ptients over 10yer period nd review of literture regrding mlignnt risk from the ullerin remnnts. BJU Int. 2012;110:E Verp S, Simpson JL. Abnorml sexul differentition nd neoplsi. Cncer Genet Cytogenet. 1987;25: Submit your next mnuscript to Bioed Centrl nd we will help you t every step: We ccept presubmission inquiries ur selector tool helps you to find the most relevnt journl We provide round the clock customer support Convenient online submission horough peer review Inclusion in Pubed nd ll mjor indexing services ximum visibility for your reserch Submit your mnuscript t
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