Copyright© AE&M all rights reserved. DOI: 10.1590/2359-3997000000221 Accepted onMay/27/2016 Received onFeb/20/2016 [email protected] 80030-110 –Curitiba,PR,Brasil Av. Agostinho Leão Jr, 285 Moreira Carolina A. Correspondence to: 3 2 1 Pró-Renal, Curitiba,PR,Brasil Histomorfometria Óssea,Fundação Paraná (UFPR),Curitiba,PR,Brasil Interna daUniversidade Federal do (UFPR), Curitiba,PR,Brasil Universidade Federal doParaná doParanáMetabologia (SEMPR), 532 H INTRODUCTION acts in order to maintain serum levelsofcalciumand to maintainserum acts inorder causes.Physiologically,genetic orirradiative PTH called post-surgical HP;orbyautoimmune,infiltrative, then being or ), total (as region oftheanterior cervical surgical procedures may beinducedbydamagetotheglandsduring bytheparathyroids lacking. ThelowerPTHproduction the diseaseitselfanddataaboutitsepidemiologyare inhabitants intheUSA(3).InBrazil,studiesabout of37casesper100,000 with anestimatedprevalence disease, condition calledpseudo-HP)(1,2).HPisarare toPTHinitstarget tissues (a glands orbyresistance (PTH)bytheparathyroid hormone of theparathyroid original article LaboratórioP. R.O., Divisãode deMedicina Departamento deEndocrinologiae Serviço caused either by deficient or absent production caused eitherbydeficientorabsentproduction (HP)isametabolicdisorder ypoparathyroidism methods: doses ofcalciumandvitaminD,onlaboratorytestsrenalultrasonography (USG). and complications etiology, laboratory features : and Maicon PianaLopes Objectives: ABSTRACT Rodrigo Kulchetscki¹,Rodrigo Victor Borsani¹, Savi Larissa mg/kg/d) than in those without calcification (1.8mg/kg/d) (p < 0.05). mg/kg/d) Urinary calciumexcretionin24hwas significantlyhigherinpatientswithkidneycalcification(3.3 correlation betweenserum andurinarylevelsofcalciumthepresencecalcification was found. No amount ofcalciumandvitaminDdosesamongpatientswithkidneycalcificationsothers. USG, and10 (25%)presentedwithkidneycalcifications. There was nosignificantdifference inthe levels ofphosphatedecreasedduringthesameperiod(p<0.001). Outofthe55patients,40had andserum andlastvisits(p< 0.001 andp<0.05,respectively); creatinine increasedbetweenthefirst disease of 11.2 years. The most frequent etiology was post-surgical. Levels of serum and patients were identified, 42 females and 13 males; meanfive age of 44.5 and average time of the patients and determine the prevalence and predictors forrenalabnormalities. patients anddeterminetheprevalencepredictors Hypoparathyroidism; renalcomplication;calcification;;pseudohypoparathyroidism Keywords Endocrinol Metab. 2016;60(6):532-6 of urinarycalciumexcretionshouldbeaimedforinthemanagementhypoparathyroidism. range, was associatedwithdevelopmentofcalcification. Thesefindingssuggestthatlowerrates were prevalentinthiscohort, andhigherurinarycalciumexcretion,evenifstillwithinthenormal serum creatininedemonstratesanimpairmentofrenalfunctionduringfollow-up. Kidneycalcifications hypocalcemia andhyperphosphatemia suggestaneffectiveness ofthetreatment,andincreasein Carolina A.Moreira Data from medical records of five different Datafrommedicalrecordsoffive visitswereobtained,focusingontherapeutic To identifyaclinicalprofileandlaboratoryfindingsofcohort of hypoparathyroidism 1,2,3 1 , Breno S. Kliemann interval on the ECG. All of these are consequences ontheECG.Allof theseare interval disturbances suchasanenlargement oftheQT cardiac and Chvostek signs,,convulsion, hyperreflexia, ,HP includefatigue,, Trousseau and (5,6). The main manifestations of tubularcells(1,3,4). inrenal secretion and phosphate PTH stimulates calcium reabsorption Inaddition, calcium absorptionandboneresorption. for important ofvitaminDandtherefore active form ofcalcitriol,whichisthe enzyme forproduction – an essential hydroxylase stimulation of the 1α-renal theskeleton,and ofcalciumandphosphatefrom release with action includesstimulationofboneremodeling Its mechanism of and 2.5 to 4.5mg/dL, respectively). range(8.8 to 10.4mg/dL phosphate withinthe normal HP isclinicallycharacterizedbyhypocalcemiaand 1 , Bini IleanaBorsato 1 , Victoria Z. C. Borba Conclusions: Arch Metab. Endocrinol 2016;60/6 1 ,

The reduction of Materials and Results: 1,2 ,

Fifty- Arch Arch Arch Metab. Endocrinol 2016;60/6 analyzed to identify the presence of such calcifications ofsuchcalcifications analyzed toidentify thepresence and cranial tomography (CT), when available, were collected andanalyzed. Renal ultrasonography (USG) were (calcium, ,and/or ) at diagnosis,durationofdisease, anddosesoftreatment suchasage,gender,Clinical features HPetiology, age Data collection thisanalyses. alsoexcludedfrom were failure duelong-standingrenal secondary were cause oftheparathyroid is definedastransientHP(14).Patientswhomthe diseasedurationoflessthan6months,which were thehospitaldatabase.Theexclusioncriterions through onHumanBeings. local EthicsCommitteeinResearch ofthe do Paraná(SEMPR).Thisstudyhastheapproval Endocrinologia eMetabologiadaUniversidadeFederal de Clinic oftheDivisionEndocrinologyatServiço study. patientsoftheBone Datahavecomefrom analytical,andobservational This isaretrospective, Selection ofpatients MATERIALS ANDMETHODS abnormalities. forrenal well asthepredictors as the prevalence and to determine hypoparathyroidism andlaboratorialfindingsof patientswith profile (12). failure andrenal nephrolithiasis, may leadtonephrocalcinosis, hypercalciuria is oftenseeninthesepatients.Chronic highand hypercalciuria usuallyvery and vitaminDare thedosesofcalcium intheurine.Furthermore, excreted thesupplementedcalciumisrapidly is notrepaired, tubulesfavoringcalciumreabsorption PTH intherenal have beenlinkedtoHP(9).Infact,astheactivityof (9-11).Recently,and cholecalciferol complications renal of calciumandvitaminDanalogues,suchascalcitriol Rather, it consists of supplementation with high doses consist ofadministrationthedefectivehormone. inmostcountries,doesnot diseases whosetreatment, among others(7,8). ;andalopecia, symptoms suchasdepression; soft tissuecalcification,asinbasalganglia;psychiatric hypocalcemia (2,5). Otherdescribedmanifestations are caused by extracellular of the muscle hyperexcitability An active search for patients with HP was performed forpatientswithHPwasperformed An activesearch to identify aclinical The aims of this study are HP is one of the few endocrine hyposecretory as dosesofcalciumandvitaminD. aswell features theirclinicaland laboratory regarding witheachother compared calcification –andwere –withand without renal divided intotwogroups the lastvisit. availablefor those patientswithweightandcreatinine filtration rate(eGFR)of the estimatedglomerular alsocalculated. patients atthefivetimepointswere usedbythe carbonate, calcitriol,andcholecalciferol with therange(minimumandmaximum)ofcalcium 2000, LosAngeles,CA,USA).Themeandosesalong bychemiluminescence(DPC,Immulite determined Bayer, LevelsofiPTHwere Leverkusen,Germany). equipment(ADVIA1650, spectrophotometric usingautomated used, andanalysiswasperformed kitswere standard andcreatinine calcium, phosphorus of total serum (5 time points). For the measurement visits intermediary of eachpatient,aswellonthree collectedbasedonthefirstandlastvisit were excretion calcium andPTHaswell24-hoururinary creatinine, totalcalcium,phosphate, deviation (SD)ofserum and basalgangliainthebrain.Themeanstandard inthekidneys andnephrocalcinosis as nephrolitiasis females and 13 (23.6%) males, with a mean age of 44.5 females and 13 (23.6%) males, with a mean age of 44.5 in Table identified:42(76.4%) 1.Fifty-fivepatientswere presented Main clinicalcharacteristicsof thepatientsare RESULTS IBMSPSSStatisticsv.20.0.the computationalsoftware analyzedusing as statisticallysignificant.Thedatawere Results withvaluesofp<0.05havebeenconsidered and Fisher’sexacttestforthequalitativevariables. Whitney testwasusedforthequantitativevariables, t-test forindependentsamplesornonparametricMann- calcification,Student’s withandwithoutrenal groups Fortheanalysisbetween results. with thelaboratory estimatedtotesttheassociationofdiseaseduration were coefficients correlation qualitative variables. Spearman’s forquantitative and asappropriate was performed testand/orbinomial or nonparametricWilcoxon samples analyzed.Student’st-testfor paired visit were variables, respectively. ofthefirstandlast Theresults or bymeanandSDforqualitativequantitative andpercentage describedasfrequency Data were Statistical analysis Patients who had renal USG results available were availablewere USGresults Patients whohadrenal (15)wasusedtocalculate formula Cockroft-Gault Hypoparathyroidism andpseudohypoparathyroidism 533

Copyright© AE&M all rights reserved. Copyright© AE&M all rights reserved. 534 Data arepresentedasN (percent)forthesubgroups. Data arepresentedasmean±SD(range)forage atonsetanddurationofhypoparathyiroidism. Table 1. Demographicsofpatientcohort phosphate (R = with the serum positive correlation patients,alongwitha different time ofdiseaseacross calcium and between serum was observed correlation (6.14 ±2.1to4.891.0;p<0,001).Aninverse phosphatefellsignificantly in thesamewaythatserum to thelastvisit(6.87±1.658.621.3;p<0.001) thefirst significantlyfrom calciumrose values ofserum The totheUSGresults. 1,according shown inFigure calciumineachofthefivemomentsare 24-h urinary and calcium,phosphateand creatinine, values ofserum calcification (3.3vs1.8mg/kg/d,p<0.05).Mean calcificationthan in thosewithout in patientswithrenal in 24 h was higher calcium excretion adjusted urinary ofcalcificationwasfound.However,presence weight- levelsofcalciumandthe andurinary between serum Nocorrelation andnephrocalcinosis. nephrolithiasis suchas USGand10(25%)hadabnormalities normal 30(75%)hada USG,whereas submitted torenal mean weeklydoseof35,000UI(range:7,000-70,000). ina takingcholecalciferol (range: 0.25-2),and75%were wer with ameandoseof1,232mg(range500-2,150),80% taking calcium supplements of the patients were percent duration ofdiseasewas11.2±7.5years.Ninety-two ± 7.4yearsforthosewithothercauses-HP. Themean surgical HP, 15±5.2yearsforpseudo-HP, and12.1 totheetiologies:40.4±16.6yearsforpost- according 32.9 ±19years.Theaverageageatdiagnosisvaried 5to76years,beingonaverage at diagnosisvariedfrom (16.4%) hadautoimmuneHP. Theageofthepatients (74.5%) patients,while5(9.1%)hadpseudo-HPand9 ± 19.3years.Post-surgical HPwastheetiologyin41 Hypoparathyroidism andpseudohypoparathyroidism Etiology Duration ofhypoparathyroidism hypoparathyroidism Age oftheonset Gender Age (years) Pseudohypoparathyroidism Autoimune Postsurgical Male Female Out ofthe55patients,40(72.7%)hadbeen e receiving daily calcitriol in a mean dose of 0.67 ucg daily calcitriol in a mean dose of 0.67 ucg e receiving 32.9 ±19.0(5-76) 11.2 ±7.5(1-32) 44.5 ±19.3 41 (74.5%) 13 (23.6%) 42 (76.4%) 9 (16.4%) 5 (9.1%) N =55 varied from 13.8 to 223 mL/min/1.73 m varied from filtrationrate(eGFR) for males)(16).Theglomerular calcium >250mg/24hforfemalesand300 for theothers,PTHwas7.8±11pg/mL. patients withpseudo-HPwas130±146pg/mL;and statistical significance(p=0.04).ThemeanofPTHfor during thisperiod(0.81±0.17–1.10.45),alsowith calcium. PTH,or24-hurinary levels ofcreatinine, wasfoundbetweendiseasedurationand No correlation -0.32, p=0.033andR+0.38,0.013,respectively). renal calcification. Figure 1. Follow-upoflaboratorialfindingsaccording tothepresenceof

Urinary Calcium (mg/24h) Serum Creatinine (mg/dL) Serum Phosphate (mg/dL) Serum Calcium (mg/dL) wasfoundin15patients(urinary Hypercalciuria valuesincreased Considering allpatients,creatinine 100 150 200 250 300 0.6 0.7 0.8 0.9 1.1 1.2 3.5 4.5 5.5 6.5 6.5 7.5 8.5 9.5 50 10 1 3 4 5 6 7 6 7 8 9 0 1 1 1 1 2 2 2 2 With calci cations Without calci cations With calci cations Without calci cations With calci cations Without calci cations Without calci cations With calci cations Follow-up Follow-up Follow-up Follow-up Arch Metab. Endocrinol 2016;60/6 3 3 3 3 4 4 4 4 2 , and its mean 5 5 5 5 caused byotheretiologies. had post-surgical HP, 1hadpseudo-HP, and2hadHP thesepatientswithBCG,2 calcification (BGC).From while5(45%)hadbasalganglia in theirrecords, kidneydiseaseatleaststageII. chronic Stage 3: GFR30-59; Stage 4: 15-29;Stage5: <15ordialysis. Arch Metab. Endocrinol 2016;60/6 be appropriate for HP patients. Indeed, lower levels of for HPpatients. Indeed,lower levels of be appropriate range)mightnot calcium (normal mg/kg/d ofurinary calcification, suggestingthataupperlimitof4.0 renal seeninpatients with were calciumexcretion of urinary withinthetarget range.However,were higher levels calciumlevels andurinary even thoughmeanserum number ofpatients in agreat present were impairment renal function the target range.Kidneycalcificationand andthecalciumlevelwaswithin not havehypercalciuria numberofpatients;however,in agreat ourpatientsdid present were renal functionimpairment calcification and ofpatients.Kidney complicationinthiscohort of renal wasthepresence The mostsignificantclinicalfeature (5,19,20). withtheliterature disease (12,18),agreeing the etiology post-surgicalof the being the most frequent offemales,with age atdiagnosisandahighproportion wasawiderangeof there complications. Inthiscohort findings, dosesofcalciumandvitaminD, centerdescribingtheetiologies,laboratory reference (HP)patients followed ata hypoparathyroidism on This isapioneerstudyinourcountry DISCUSSION Figure 2. Distributionofpatientsaccordingtheirrenalfailurestage. * Stage1: glomerular filtrationrate(GFR)>90mL/min/1.73m was 92.9±36.2mL/min/1.73m lower than 90 mL/min/1.73 m 2). Hence, 21 (46.7%) showedan eGFR V (Figure in stageIII,1(2.2%)IV, and1(2.2%)instage Outcomes QualityInitiative(KDIGO)(17),4(8.9%) kidneydiseaseasstatedinKidneyDisease of chronic functionwasin15(33.3%)patientsstageII renal

Number of patients Eleven patients(20%)hadacranialCTevaluation 10 15 20 25 30 0 5 0 2 Stage* 3 2 and would present a and would present 2 . Consequently, the 2 4 ; Stage2: GFR60-80; 5 population mayachieve12.5% (24).Somestudies ofBGCinthegeneralthat theestimatedprevalence 12% up to 74%. However,from it should be noted variedsignificantly demonstrated intheHPcohorts established asapossibleoutcomeofHP. Itsprevalence (22,23). in theliterature qualityoflife,anissuethathasbeendiscussed improve may thistreatment complications.Furthermore, renal the incidence of and consequently decrease excretion calcium urinary mayreduce of calcium,andtherefore tohighloads ofcalcemiawithouttheexposure control mayleadto some countries(11,22).Thisnewtreatment Recently, in PTH1-84hasbeenusedinHPtreatment longlifetreatment. disease,andrequires HP isachronic goals, maintaining patients without symptoms, since However, it is a challenge to achieve these therapeutic (5,13). and nephrocalcinosis to diagnose nephrolitiases ultrasound aswellrenal outhypercalciuria, for ruling of 24-hour urine calcium is encouraging measurement (1,5).Inaddition, theannual is recommended ranges theupperlimitof normal phosphate around thelowerlimitandserum calciumaround of serum ranges for86%ofthetime(9). calciumwithinthe recommended patients keptserum eventhoughtheir ofeGFRimpairment, prevalence age. Similarly, Mitchellandcols.foundahigher function duringthefollow-up,despitetheiryounger asignificantworsening ofkidney patients wentthrough However, duringthetreatment. our and phosphorus calcium variabilityintheserum ofthegreat be theresult asothers,or could similardosesoftreatment receiving may havetodevelopingthesecalcifications,evenwhen could demonstrateahighersusceptibilitysomepatients This abnormalities. D supplementation andlaboratory was identifiedsuchasthedosesofcalciumandvitamin study,the present complication of renal no predictor and hyperphosphatemia (21). In hypercalcemia relative of beingthedegree the mostsignificantpredictors withHP, inchildren of 38%nephrocalcinosis with aprevalence (9).Levyandcols.reported impairment of renal the duration ofthe disease and the presence to our study, between they demonstrated a correlation calcificationwas31%(9).Incontrast ofrenal prevalence the whereas of 120patientswithhypoparathyroidism inacohort thesefindingspreviously cols. reported complications.Mitchelland renal toprevent in order calciumshouldbethegoalforthesepatients urinary Basal gangliacalcification(BGC)hasbeen toavoidthesecomplications,maintenance In order Hypoparathyroidism andpseudohypoparathyroidism 535

Copyright© AE&M all rights reserved. Copyright© AE&M all rights reserved. 536 5. 4. 3. 2. 1. REFERENCES was reported. relevant tothisarticle nopotentialconflictofinterest Disclosure: aimed forinthesepatients. shouldbe calciumexcretion lower ratesofurinary recommended. In addition, for calcifications is highly complete kidneyfunctionevaluation,andthesearch Since HPismostcommonlyalife-longdisease, was associated with development of calcification. range, evenifstillwithinthenormal calcium excretion, ofkidneycalcifications.Higherurinary the presence levelsand creatinine inserum did notavoidanincrease levels. However, and phosphate serum the treatment ofcalcium ledtolaboratorialcontrol that thetreatment the SouthofBrazil.Inthiscasuistic,itwasobserved hospitalofCuritiba,in care followed upinatertiary patients withBGC. forHPintwooutofourfiveetiology responsible (7),thiswasthemade earlyinpost-operativecare causing thiscomplication,becausethediagnosisis Although post-surgical HPisdescribedasrarely ofBGC(9). (52%)withthepresence percentage (26%) ofpatientswithcranialCT, alongwithahigh study,aforementioned alsofoundasmallpercentage those withCTexams.Mitchellandcols.,inthesame ofourpatientswithBGC(45%)amongpercentage symptomatology,neurological leadingtothehigh presented inpatientswhoalready been performed at thediagnosis,andthuscranialCTs mayhave a silentoutcomeofthediseaseandcouldbeseen Contrasting withkidneycalcifications,BGCisnot with thepersistenthighphosphatelevels(9,12,24). specificallyhave shownBGCtobeassociatedmore Hypoparathyroidism andpseudohypoparathyroidism

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