Copyright© AE&M all rights reserved. Kahramanmaras, Turkey Department ofInternalMedicine, University, FacultyofMedicine, Kahramanmaras, Turkey Department ofFamily Medicine, University, FacultyofMedicine, Kahramanmaras, Turkey Department ofBiochemistry, University, FacultyofMedicine, Kahramanmaras, Turkey Endocrinology andMetabolism, Medicine, Departmentof Imam University, Facultyof 482 (LH),folliclestimulat to thatluteinizing hormone hCG isuniquetobut alpha-subunitisidentical (TSH).Thebetasubunit of stimulating hormone roid similaritytothy thathasstructural hormone protein these patients(2). usedin are andgonadotropins includes testosterone fertility. (ART) treatment that replacement Androgen andtesticulardevelopmentthatallowfuture puberty or youngadultmalesincludetheinductionofnormal fects (1).ThegoalsoftherapyforIHHinadolescent de tohypothalamicorpituitary secondary otropins) I INTRODUCTION DOI: 10.1590/2359-3997000000096 Accepted onJuly/1/2015 Received onJune/19/2015 [email protected] 46100 –Kahramanmaras, Turkiye Sütçü I- Avs Kayseri Yolu 10 km Ayten Oguz Correspondence to: 4 3 2 1 (low testosterone and low or normal levelsofgonad andlowornormal (low testosterone original article Kahramanmaras SutcuImam Kahramanmaras SutcuImam Kahramanmaras SutcuImam Kahramanmaras Sutcu ar KampüsüKahramanmarasÇ Ç Human chorionic gonadotropin (hCG)isaglyco Human chorionicgonadotropin may present as an isolated hormonal deficiency asanisolatedhormonal may present hypogonadism(IHH) solated hypogonadotropic mam Üniversitesi Body mass index, TSH, fT we comparedthepatientgroupwithcontrolgroup,therewas nosignificantdifference forage, Ahmet Celik treatment (ART). among maleswithisolatedhypogonadotropic hypogonadism androgenreplacement (IHH)whotake 6 monthsafter treatment. Patient group was comparedwith control groupaswell. increase thyroid volume? gonadotropine treatment Should humanchorionic Ayten Oguz up inhCG-treatedpatients. cially inhCG-treatedpatients. Therefore, wesuggestthatthyroid volume changes shouldbefollowed p =0.09,respectively). tosterone levelswith TSH, fT tion tests[thyroid stimulatinghormone(TSH),freethyroxine (fT Objective: ABSTRACT Thyroid volume;thyroidstimulatinghormone;humanchorionicgonadotropin Keywords difference intermsof TSH, but fT treated patients(n=25).Patient groupwas comparedintermsoftotaltestosterone,thyroid func was totestosterone-treatedpatients(n=19) divided andhumanchorionic gonadotropine(hCG)- 2014 and40healthy malecontrolwithameanage27.77 (18-55) wereinvolved tostudy. Patient group diagnosed inEndocrinologyandMetabolismDepartment betweenSeptember 2013 andSeptember after testosteronetreatment (p>0.05). There was nostatisticallysignificantcorrelation betweentes among hCG-treatedpatients(p=0.001) buttherewas nodifference forthyroid volume beforeand we comparedtestosterone-treatedpatientsandhCG-treatedpatients;thyroid volume was higher after treatment,whenthe patientgroupwas comparedbeforeandafter treatment(p<0.05). When Our aimwas toinvestigate thethyroid functiontestsandthyroid volume differences 1 2 , TuzunDilek , NumanGuvenc Materials andmethods: Conclusion: 4 and thyroid volume between two groups before treatment. There was no Arch EndocrinolMetab. 2015;59(6):482-6 4 - - - - - 1 and thyroid volume (r=0.09,p0.32;r0.14, p=0.11; r=0.15, , Murat Sahin 4 , testosteronelevelsandthyroid volume weresignificantlyhigher ity aswell,and thishomologysuggests thebasisfor similar showstructural ogy butalsotheirreceptors homol notonly structural that hCGandTSHshare cells (8).Manyinvestigationshavedetectedthyroid ratadenylate cyclase, and DNA synthesis in cultured assay (4).Additionally, hCGstimulatesiodideuptake, 0.5µUTSHintheMousebio lent toapproximately activityequiva Unite hCGhasintrinsicthyrotrophic studies showedthathCGisthemolarTSHand1 (4,5).Thesebeen foundinseveralhCGpreparations bioassay (7). Subsequently, activity has thyrotrophic of hCGwasfirstdemonstratedbyBurger inamouse preparation activityofacommercial roid-stimulating assays inmice,rats,chicksandmen(4-6).Thethy activityinbio hasthyroid-stimulating gonadotropin ing hor Our studyshowedthat ART increasesthethyroid volume espe 3 , ElifInanc Forty-four malewithIHHameanage33.2(18-54), mone (FSH)andTSH(3).Humanchorionic 1 , NeseBulbul 4 , Kamile Gul 1 4 , )] andthyroid volume, beforeand
1 Arch Metab. Endocrinol 2015;59/6 Results: When ------
control group as well. aswell. group control evaluatedbetweenpatientand These parameterswere and 6monthsaftertreatment. volume,before thyroid Arch Metab. Endocrinol 2015;59/6 (i.e. low or non-elevated levels), the absence of any (i.e. lowornon-elevated levels),theabsence ofany LH TT levels (< 250 ng/dL),insufficient low serum and dysfunction/infertility) libido anderectile reduced nadism (e.g.incompleteordelayedsexual development, tohypogo ofclinicalsymptomsrelated as thepresence hypogonadismwasdefined Isolated hypogonadotropic Inclusion criteria (fT thyroxine functiontests[TSH,free thyroid (TT), of body mass index (BMI), total testosterone interms wascompared (n=25).Patientgroup group (n=19)and HCG withtestosterone two goups;treated involvedtostudy.were wasdividedinto Patientgroup withameanage27.77(18-55) group) (control control ber 2013andSeptember201440healthymale mild iodinedeficientcityin Turkey) betweenSeptem inKahramanmaras(a gy andMetabolismDepartment age 33.2(18-54)thatwasdiagnosedinEndocrinolo withamean malewithIHH(patientgroup) Forty-four Subjects andstudyprotocol University. the ethicscommitteeofKahramanmarasSutcuImam includedinthestudy.were by Thestudywasapproved nic atKahramanmarasSutcuImamUniversityHospital admittedtoEndocrinologyandMetabolismCli were who Male patientswithIHHandhealthymalecontrols MATERIALS ANDMETHODS volumeinmaleswithIHH. tests andthyroid function thethyroid and ART (especiallyhCG)effect we aimedtoinvestigatewhetherbothhypogonadism hypogonadism.So evaluated onlypatientswithprimary (TRH).Butmoststudies hormone rotropin-releasing tothy (14)TSHresponse (13)orunaltered decreased (12), administration maybeassociatedwithincreased pogonadism. Severalstudiesalsoshowedthatandrogen of ART functiontestsamongmaleswithhy onthyroid volume)(11).thyroid TSHconcentrations)andanatomically(increased rum stimulation,bothfunctionally(lowerse with thyroid associated highhCGconcentrationsare Therefore, (9,10). ofhCGwiththeTSHreceptor the reactivity There are several conflicting results about the effect results aboutthe effect several conflicting are There 4 )] and )] and ------and pathological findings on a pituitary magnetic reso magnetic and pathologicalfindingsonapituitary hypofunction other anteriorand/orposteriorpituitary Cortisol (5-23 µg/dL). Hormone analyses were car analyseswere (5-23µg/dL).Hormone Cortisol not includedinthestudy. Patientswithsystemicillnes radioactive iodine were operation or received thyroid including iodine7daysago,andthosewhounderwent drugs within atleast3days,thosewholastreceived gical examinationwithaniodinatedcontrastmedium radiolo excluded. Moreover, patients who underwent andsulfonamides were perchlorate, lithium, interferon, rapy, drugs, somatostatin,anti-thyroid bromocriptine, the suppression L-thyroxin ditis), andthosereceiving (factitia, subacute thyroi to’s disease, thyrotoxicosis Hashima orhypothyroid euthyroid hypothyroidism, or secondary primary those with hyperthyroidism, gland, thyroid affecting any drugs sease or receiving di of thyroid known history Patients withpreviously Exclusion criteria nance image(1). grey scale measurements were performed bythesame performed were scalemeasurements grey heterogeneity.lity suchasanodule or parenchymal All wasanyabnorma and itwasinvestigatedwhether there ultrasonography apreliminary underwent participants Each and6monthafterthetreatment. before formed ultrasonography(US)wasper Conventional thyroid Conventional thyroidultrasonography kits. Coulter CA,USA)commercial Los Angeles,CA,USA,orUniCelDxI800,Beckman Corporation, say (Immulite2000,DiagnosticProducts ried outusingchemiluminescenceenzymeimmunoas TSH (0.4-4.2 µIU/mL), fT (3–14.7 ng/mL), TT (280-1100 ng/dL), prolactin FSH (1.42–15.4mIU/ml),LH(1.24–7.8mIU/mL), asfollow valueswere reference monal parameters.Normal variation,especiallyforhor becauseofdiurnal ferences fasttoavoiddif 08.00–09.00 hoursafteranovernight between Blood sampleswascollectedinthemorning Biochemical analyses king adiagnosisofIHH. ma excludedbefore mia andintracranialmasses,were nadism, suchaspanhypopituitarism,hyperprolactinae hypogo causesofhypogonadotropic levels. Secondary andtestosterone themetabolismof testosterone affect medicationsorasthesecould usedcertain sive exercise, excluded,inadditiontothosewho tookexces ses were HCG treatment andthyroid volume 4 (0.8-2.7 ng/dL) and (0.8-2.7 ng/dL) and 483 ------
Copyright© AE&M all rights reserved. Copyright© AE&M all rights reserved. thyroxine; GH: growthhormone; TV: thyroidvolume. 484 BMI: bodymassindex; TT: totaltestosterone; TSH: thyroidstimulatinghormone; fT Table 2. Total testosteronelevels, thyroidfunctiontestsandvolume changesbeforeandaftertreatmentinpatientgroup IHH: ısolatedhypogonadotropichypogonadism;BMI: bodymassındex;FSH: folliclestimulatinghormone;LH: luteinizinghormone; TT: totaltestosterone; TSH: thyroidstimulatinghormone;fT Table 1. Thebaselinecharacteristicsandthyroidfunctiontests, totaltestosteronelevels, thyroidvolumeofthemalepatientswithIHHandcontrols 0.05 wasdefinedasstatisticallysignificant. test.P< tions wasevaluatedwithpearsoncorrelation betweenvaria relationship deviation.Direct standard asthemean± expressed bution, andthevariableswere distri withanormal inaccordance variables thatwere independentvariables and dependent used tocompare was usedforstatisticalanalysis.TheStudent’st-test (ver.The SPSS for Windows 11.0.; Chicago, IL, USA) Statistical evaluation of thevolumeslobesexceptforisthmus. length (15).Total asthesum volume was determined volume(mL)=π/6xwidthdepth the formula, Volumemeasured. of each lobe was calculated using and length(inlongitudinalplane)ofeachlobewere dimensions.Depth,width(intransverseplane), three glandwasscannedin acoustic material. The thyroid with theskinwascovered the neckinhyperextension, waslyinginsupinepositionwith While theparticipant WI, USA) using a linear transducer of 12 MHz width. System, GeneralElectricMedicalSystems,Milwaukee, endocrinologist withthesameUSdevice(LogicP5 HCG treatment andthyroid volume TV (mL) GH (ng/mL) Cortisol (mcg/dL) Prolactin (ng/mL) TV (mL) BMI (kg/m Parameters BMI (kg/m Age (year) Parameters fT TSH (mIU/mL) TT (ng/dL) TT (ng/dL) LH (mIU/mL) FSH (mIU/mL) fT TSH (mIU/mL) 4 4 (ng/dL) (ng/dL) 2 2 ) ) Before treatmentn=44 Patient group(n=44) 98.65 ±69.70 98.65 ±69.69 19.23 ±1.14 32.47 ±9.30 27.33 ±6.61 1.16 ±0.19 8.62 ±1.46 1.86 ±0.55 7.64 ±3.39 1.16 ±0.19 8.76 ±1.13 27.3 ±3.90 1.45 ±0.75 1.44 ±1.24 1.82 ±1.68 1.41 ±0.79 4 : freethyroxine; TV: thyroidvolume. - - respectively) were significantly higher after treatment significantly higheraftertreatment were respectively) andafter treatment, mL and9.02±0,99mL;before but fT (p>0.05), andaftertreatment to TSHlevels,before according wasnosignificantdifference there group, summarizedintable2.Inpatient were patient group in andaftertreatment, volumechanges,before thyroid (p<0.05). significantly lowerinpatientgroup (p<0.05),butTTlevelswere patientgroup treatment ofage,BMI,TSH,fT interms significant difference wasno summarizedintable1.There are group trol volumeofthemalepatientwithIHHandcon thyroid functiontests,TTlevels, ne characteristicsandthyroid involvedtothestudy. were male controls Thebaseli malepatientswithIHHand40healthy Forty-four RESULTS volume was significantly higher after treatment (8.28± volume wassignificantlyhigheraftertreatment ment type(Table thyroid group, 3).InhCG-treated (p =0.001). and thyroid volume between control group andpre group volumebetweencontrol and thyroid Total functiontestsand levels,thyroid testosterone We tothetreat alsoanalyzedthepatientsaccording After treatmentn=44 Control group(n=40) 4 434.83 ±138.64 460.52 ±90.36 , TT levels and thyroid volume(8.76 ± 1.13 , TTlevelsandthyroid 19.36 ±1.22 28.77 ±9.68 1.10 ±0.14 8.78 ±0.81 2.04 ±0.75 7.85 ±2.77 1.34 ±0.49 9.02 ±0.99 27.1 ±5.10 26.5 ±7.06 1.39 ±0.56 3.71 ±1.50 1.70 ±0.94 5.1 ±2.21 Arch Metab. Endocrinol 2015;59/6 < 0.001 < 0.001 < 0.001 < 0.001 0.128 0.558 0.261 0.623 0.772 0.024 0.001 0.078 0.620 0.605 0.627 0.133 p p 4 : free - - - - 4
Arch Metab. Endocrinol 2015;59/6 respectively). respectively). 0.09, p=0.32;r0.14,0.11;0.15, TT: totaltestosterone;HCG: humanchorionicgonadotropin;BMI: bodymass index; TSH: thyroidstimulatinghormone;fT Table 3. Bodymassindex, totaltestosteronelevels, thyroidfunctiontestsandvolume changesaccordingtothetreatmenttype Additionally, effect. small thyroid-stimulating Burman a hCG indosesof100,000and150,000IUproduced the supraphysiologicaldoses.Inthisstudy, commercial in men that wasunderhCGtreatment in euthyroid T4,T3, or TSH nosignificantchangesinserum were Sowersandcols.(17),found that there male controls. toTRHsimilar tothoseofthe dism hadTSHresponses therapy. Inthisstudy, themalepatientswithhypogona T4 during hCG in serum showed a transient reduction hypogonadal maleandfemalepatients.Malepatients in onTSHsecretion andandrogens ofestrogens effect tients (14,16-18).Spitzandcols.(16),evaluatedthe volumeamonghypogonadalmalepa tions andthyroid func andhCGonthyroid ofsexhormones the effects waslimited dataabout to inthesepatients(2).There havebeenused treatment) orgonadotropin tosterone (tes treatment replacement disease.Androgen treatable but hypogonadism is a rare Isolated hypogonadotropic DISCUSSION between TTlevelsandTSH,fT wasnosignificantcorrelation (n=40)there group trol (p>0.05). andaftertreatment before ferent fT tosterone, significanthigherfT was aborderline but there (p>0.05), andaftertreatment before compared group toTSHlevelsinhCG-treated according difference mL, wasnosignificant (p>0.05).There respectively) (9.39±0.95mLand9.470.88 and aftertreatment volumewassimilarbefore thyroid with testosterone, treated (p=0.001),butingroup ment, respectively) andaftertreat 1.04 mLand8.68±0.95mL,before * The statisticalcomparison ofpreandpost-treatmentinthegrouptreated withtestosterone;** The statisticalcomparison ofpreandpost-treatmentinthegrouptreated withHCG. after treatment (p = 0.057). In group treated withtes treated (p=0.057).Ingroup after treatment FT BMI (kg/m TSH (mIU/mL) TT (ng/dL) TV (mL) Parameters 4 (ng/dL) When weanalysedbothpatient(n=44)andcon 2 ) 4 and TSH levels were notsignificantlydif andTSHlevelswere 133.04 ±72.87 Pre-treatment 1.65 ±0.88 9.39 ±0.95 1.21 ±0.19 28.9 ±5.1 TT group n =19 4 , thyroid volume (r= , thyroid 446.10 ±155.24 Post-treatment 28.46 ±4.03 1.41 ±0.45 9.47 ±0.88 1.31 ±0.31 TT group n =19 4 levels Pre-treatment 72.52 ±55.43 1.30 ±0.60 8.28 ±1.04 1.12 ±0.18 HCG group 27.5 ±6.6 ------n =25 (before treatment). After ART, treatment). (before TSHlevels didn’t chan andmalepatientswithIHH between healthycontrols patients with the Klinefelter’s syndrome. On the con patients with the Klinefelter’s syndrome. parametersinthe onanyofthyroid no significanteffect had treatment and cols.(14),showedthattestosterone hCG. In group treated withhCG,fT treated hCG. Ingroup activityof maybeduetothyrotrophic that thisincrease withhCG,sowespeculated treated was duetogroup ge significantly butfT nadism. Inourstudy, TSHandfT hypogo toTRHinthemenwithprimary responses TSH withdecreased administration hasbeenreported trary, Morley and cols. (18), mentioned that androgen roid-stimulating activityofhCGaswell. roid-stimulating (p =0.001).We thinkthatthischangewasduetothy wasasignificantincrease withhCG there treated group butin group intestosterone-treated ume difference vol wasnothyroid analysisthere 0.05). Insubgroup (p< inpatientgroup volume significantlyincreased thyroid But after treatment treatment). IHH (before andmale patientswith similar betweenhealthycontrol volume was cells(19-21).Inourstudythyroid thyroid of and even growth secretion, 3,5,3’-triodothyronine able tostimulateiodineuptake,generationofcAMP, activity,has aweakintrinsicthyroid-stimulating being level(8).Invitro,hCG atthereceptor cross-reactive family, hormone lated glycoprotein potentially theyare human TSH belong to the biochemically closely re activity.rotropic and Humanchorionicgonodotropine TSHlevelssuggestthat hCGhasthy and suppressed hCGlevels mors. Thesecases,considerablyincreased been reported in many patients with trophoblastic tu inmanypatientswithtrophoblastic been reported after treatment. and this maybethecauseofsimilarTSHlevelsbefore rangeand butstillwithinthenormal after treatment subgroup analysiswedetectedthatthisfT subgroup Hyperthyroidism or increased thyroid functionhave thyroid orincreased Hyperthyroidism 426.26 ±127.23 Post-treatment 27.97 ±9.12 1.37 ±0.63 8.68 ±0.95 1.36 ±0.60 HCG group 4 : freethyroxine; TV: thyroidvolume. n =25 4 levels increased significantly. levelsincreased In < 0.001 HCG treatment andthyroid volume 0.296 0.374 0.834 0.227 p* 4 levels were similar similar levelswere 4 levels increased levelsincreased < 0.001 0.540 0.001 0.915 0.057 4 p** increase increase 485 ------
Copyright© AE&M all rights reserved. Copyright© AE&M all rights reserved. 486 8. 7. 6. 5. 4. 3. 2. 1. REFERENCES was reported. relevant tothisarticle nopotentialconflictofinterest Disclosure: volumeinmaleswith IHH. changes ofthyroid toexplain the required studiesare with hCG.More volume changes shouldbefollowed in patients treated wesuggestthatthyroid withhCG.Therefore, treated volume especially in patients ART the thyroid increases of ART inmaleswithIHH.Ourstudyshowedthat function volumeandthyroid ing changesonthyroid iodine status. wasduetoage,BMIand volumedifference thyroid Sowedon’tthinkthatthis a mildiodinedeficientarea. is andthisregion region pants wastheMediterranean Thelocationofthepartici group. tient andcontrol to BMI and age in pa according significant difference iodide(24).Inourstudy,median urinary wasno there tothe volumewasinverselyrelated thyroid plete area, (23).Inadditionto,inaniodinere or bodysurface dependent to age to increase volume is reported roid volume(22).Thy caninfluencethyroid area surface dine supply, age,sex, weight,height,BMI,andbody HCG treatment andthyroid volume
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