Copyright© ABE&M todos os direitos reservados. Faculdade deMedicina,Portugal Portugal; Universidade doPorto, S.Centro Hospitalar João, Porto, Diabetes andMetabolism, Accepted onMay/23/2013 Received onNov/1/2012 [email protected] 4200-319 –Porto, Portugal Alameda Prof. HernâniMonteiro Universidade doPorto Faculdade deMedicina, SãoJoão,Centro Hospitalar Diabetes andMetabolism, Department ofEndocrinology, Selma B. Souto Correspondence to: 2 1 S. João, Porto, Portugal and Obstetric,CentroHospitalar 68 V INTRODUCTION symptoms after surgical treatment (7). (7). symptoms aftersurgical treatment behavior, of andreversion withanexcellentprognosis Leydigcelltumorsusuallyhaveabenign Virilizing state, andsomepatientsalso have vaginalbleeding(6,7). Occasionally, thesetumorsmayexhibitahyperestrogenic atrophy, (2-5). libido,clitoromegalia) increased virilization (hirsutism,acne,deepvoice,mammary statewithsignsof ofahyperandrogenic the presence cell tumor. Themajorityofthecasesisdiagnosedin atypeofsteroid for 0.1%ofallovariantumors,andare all ovarianneoplasms(1,2).Leydigcelltumorsaccount to belessthan 5% of reported after menopause,and are case report DepartmentofGynecology Department ofEndocrinology, hyperandrogenism, are most frequently found found most frequently are hyperandrogenism, causeof arare irilizing ovariantumorsare severe hyperandrogenism post-menopausal patientwith Ovarian Leydig celltumorina Selma B. Souto pós-menopausa comhiperandrogenismo grave Tumor ovariano decélulasLeydig empaciente em de androgêniosvoltaram aonormal,eossinaisdevirilizaçãoregrediram. -histoquímica confirmaram o diagnóstico de tumor de células de Leydig. Após a cirurgia, os níveis feita umahisterectomiatotalesalpingooforectomiabilateral.Osexameshistopatológicosaimuno mostrou umnódulosólidonoovário esquerdoenenhumaevidênciadealteraçãonasadrenais.Foi evidências detumorovariano, masatomografiaaxialcomputadorizadadaregiãopélvico-abdominal de gonadotrofinasparaumamulherempós-menopausa.Oultrassomtransvaginalnãoapresentou inadequadamente baixostestosterona sérica, delta 4-androstenediona e estradiol, além de níveis de virilizaçãoeocorrência desangramentovaginal. de As análisesclínicasmostraramaltosníveis testosterona. Relatamos aquiocasodeumamulher81anosidadecomsinaisprogressivos de cas. Maisde75%dospacientesapresentamsinaisvirilizaçãodevidoàproduçãoexcessiva Tumores ovarianos decélulasLeydig sãoneoplasias rarasdecélulasovarianas esteroidogêni SUMÁRIO regression ofthesignsvirilization. the diagnosisofLeydig celltumor. After surgery, androgenlevelsreturnedtonormal,andtherewas teral salpingoophorectomy were performed. Histopathology and immunohistochemistry confirmed ovarian solidnodule,andnoevidenceofalterationintheadrenalglands. Total hysterectomy andbila ovarian tumor, butpelvicandabdominalcomputerized axialtomography imagingrevealedaleft of gonadotrophinsforapost-menopausalwoman. Transvaginal ultrasoundshowednoevidenceof vels ofserumtestosterone,delta4-androstenedioneandestradiol,alsoinappropriatelowlevels signsofvirilization,andpresentingvaginalbleeding.Clinicalanalysesrevealedhighle progressive of virilizationduetooverproduction oftestosterone. We report acaseofan8-year-old womanwith arerareovarianLeydig steroidcellneoplasms.Morethan75%ofpatientsshowsigns celltumors SUMMARY 2014;58(1):68-70 1 , Pedro V. Baptista no features of Cushing syndrome. ofCushingsyndrome. no features was140/80mmHg.Shehad masses. Bloodpressure enlargement oftheclitorisandnopalpableadnexal an deep voice. Gynecological examination revealed alopecia,and scale),androgenetic Ferriman-Gallwey 15, signs of virilization with hirsutism (score revealed wasnotnoteworthy.history Physical examination 10mg/day.therapy withatorvastatin Familyclinical andwasunder dyslipidemia, anddementialsyndrome, infertility, ofprimary Shehadhistory year before. one alopecia,anddeepvoice,starting androgenetic totherapidonsetofvirilization,withhirsutism, referred year.vaginal bleedingfortheprevious Her family acaseof81-year-old womenwith The authorsreport CASE REPORT Arq BrasEndocrinolMetab. 2014;58(1):68-70 2 , DanielC. Braga 1 , Davide Carvalho Arq Bras Metab. Endocrinol 2014;58/1 Arq BrasEndocrinolMetab. 1 - - - - not regress. not regress. did scale),howeverclitoromegaly Ferriman-Gallwey 3, significantly (score improved of hyperandrogenism levels(Tableto normal 1), andoneyear later, the signs One monthaftersurgery, levelshad dropped androgen aLeydigcelltumor oftheovary.Histology revealed discussedwiththepatientand herfamily.previously as performed, were bilateral salpingoophorectomy and Hysterectomy normal. chest X-rayandEKGwere and tumormarker(CA125,CA19.9, 1).Serum (Figure theovariansolidnodule(29.5x22.8mm) confirmed and image (MRI) was also performed resonance ascites orlymphnodeenlargement. Pelvicmagnetic detected, namely,No otherpathologicfindingswere glands. ofthe adrenal normality morfodimensional ovarian solid nodule with 30 mm in diameter, and computerized axialtomography(CT)showedaleft in thepouchofDouglas.Thepelvicandabdominal fluid visualization ofadnexalmasses,withoutanyfree nodule, withoutendometrial hyperplasia, no fibroid range(Table withinthenormal were 1). (24hr-UFC) cortisol free twenty-four hoursurinary and (17-OHP)andprolactin 17-hidroxyprogesterone (DHEA-S), levels ofdehydroepiandrosterone-sulfate menopausal woman,withhighlevelsofestradiol.Serum lowforapost- inappropriately (FSH)were hormone (LH)and folliclestimulating of luteinizinghormone levels concentrations.Serum delta 4-androstenedione and testosterone totalserum with markedlyincreased Arq Bras Metab. Endocrinol 2014;58/1 hormone; FSH: folliclestimulatinghormone; 24hr-UFC: twenty-four-hour freecortisol. urinary DHEA-S: dehydroepiandrosterone-sulfate;17-OHP: 17-hidroxyprogesterone;LH: luteinizing one monthaftersurgery Table 1. Clinicalanalyticalparametersdeterminedbeforesurgery, and Free testosterone 17-OHP Delta 4-androstenedione DHEA-S Total testosterone FSH LH Estradiol Prolactin 24hr-UFC Transvaginal ultrasound showed an intramural hyperandrogenism, Endocrine evaluationrevealed -FP) levels were within the normal range, and within the normal α-FP) levels were Before > 10.0 1.181 141.0 16.38 15.08 .55.3 1.28 12.8 29.5 740 After 1.90 73.9 25 < 0.015-0.155ng/dL 25.8-150.3 mIU/mL Reference values 10.4-64.6 mIU/mL 0.30-2.99 ng/mL 0.11-1.20 ng/mL < 5-54.7pg/mL 12.0-154 μg/dL 1.2-29.9 ng/mL 36-137 ug/24h 11-78 ng/dL DISCUSSION ovary. Figure 1.PelvicMRIrevealedasolidnoduleof29.5x22.8mmintheleft examination isoperator-dependent. Inourpatient,the tumor (5);however, theaccuracyofultrasound sensitive methodforthe detection ofanovarian onultrasound,andisodense onCT(4,9). to theuterus becauseitisisoechoic by radiologicalimaging,inpart toidentifyit (2,6,8).Itmaybedifficult ovary normal less than5cmofdiameter–justslightlybiggera hyperplasia andvaginalbleeding. in endometrial resulting oftestosterone, aromatization (5).Highestradiollevelsmaybedueto source adrenal of DHEA-Shigherthan600mg/dLmaysuggestan tumor, values of an androgen-producing and serum levelsabove200ng/dLshouldraise thesuspicion serum cause.Testosterone outanadrenal DHEA-S ruled level of serum of a virilizing neoplasm, while normal thepresence (740ng/dL)confirmed testosterone notdiagnosedforyears. virilizing tumorsare ones(5).Many ofovarian common thanadrenal more the menopause,ovariancausesofvirilizationare tumor. androgen-producing ovarian oradrenal After toexcludean inorder isalso required, androgens masses orclitoromegaly. ofserum Themeasurement ofadnexal examination, toevaluatethepresence gynecological acareful it isessentialtoperform virilizing tumor. Inawomanwithsignsofvirilization, signsofvirilizationraisedsuspicion ofa progressing state with rapidly In our case, the hyperandrogenic Nevertheless, transvaginalultrasound isthemost Nevertheless, usuallysmall,measuring Leydig celltumorsare levelsoftotal case,thehighserum In thepresent Ovarian tumorandhyperandrogenism 69

Copyright© ABE&M todos os direitos reservados. Copyright© ABE&M todos os direitos reservados. 70 was reported. relevant tothisarticle nopotentialconflictofinterest Disclosure: ofclinicalhyperandrogenism. and improvement values, levelstonormal androgen ofserum was areturn final diagnosisofLeydigcelltumor. Asexpected,there causes(10). aftertheexclusionofadrenal be considered should levels, an oophorectomy elevated testosterone with successratesaslow26-45%(5). andovarianveinsisdifficult, catheterization ofadrenal and ovariansampling(5).However, simultaneous adenomashouldundergo combinedadrenal adrenal orwithasmall radiological images,inconclusiveresults tumorin which apatientwithoutovarianoradrenal in management ofpost-menopausalhyperandrogenism analgorithmfor the diagnosisand and cols.proposed 7%,Alpañés in patientsover70yearsofagereaches mass offindinganunsuspectedadrenal the probability (5).Consideringthefactthat ofexcessandrogen source the toconfirm ovarian venoussamplingwasperformed an ovarianetiology. by CTandMRIenabletheattributionofcauseto despite being 3 cm in diameter. Radiological imaging tumor was not visualized in the transvaginal ultrasound Ovarian tumorandhyperandrogenism In our patient, surgical intervention enabledthe In ourpatient,surgical intervention In post-menopausalwomenwithvirilizationand In afewcasesofpost-menopausalvirilization,an 10. 9. 8. 7. 6. 5. 4. 3. 2. 1. REFERENCES women: report oftwocases.GynecolEndocrinol.2013;29(3):213-5 . Leydig cellhyperplasia andLeydig celltumourinpostmenopausal Hofland M,CosynsS,DeSutter P, Bourgain C, B. Velkeniers characteristics. UltrasoundObstetGynecol.1997;10(4):282-8. Timor-Tritsch sonographic IE.Ovarian steroid celltumors: Monteagudo A, HellerD,HusamiN,Levine RU, McCaffrey R, Freedmen’s Hospital.JNatlMed Assoc. 1964;56 (1):66-70. Hill WE, ClarkJFJ. Functional atenyearstudyat ovarian tumors: J. 2009;2:7521. tumor ina40yearoldSouth Indianfemale:acasereport. Cases Salim L. S,ShanthaGPS,Sudhakar Virilizing ovarian steroidcell Assoc. 1976;68(1):34-8. Iloabachie oftheovary. G.Masculinizingtumors JNatlMed Aimakhu VE, Adeleye JA, Hendrickse M,de Von Hendrickse JP, Endocrinol Metab.2012;97(8):2584-8. Morreale HF. Managementofpostmenopausalvirilization.JClin Alpañés M,González-CasbasJM,Sánchez J, PiánH,Escobar- case report. EurJRadiol. 1998;26(3):269-73. oftheovary: clinical,ultrasonic,andMRIdiagnosis--a cell tumors Wang PH,ChaoHT, Lee RC,LaiCR,Lee WL, Kwok CF, et al.Steroid 2012;120(4):205-9. with polycysticovary syndrome.ExpClinEndocrinol Diabetes. Rachon D.Differential diagnosisofhyperandrogenism in women 2005;21(4):238-41. severe hyperandrogenism andvirilization.GynecolEndocrinol. Ovarian Leydig celltumorinaperi-menopausalwomanwith Nardo LG, Ray DW, Laing I, Williams C, McVey RJ, Seif MW. Pathologe. 2003;24(4):314-22. Stegner HE,Loning T. oftheovary]. tumors [Endocrine-active Arq Bras Metab. Endocrinol 2014;58/1