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www.bjorl.org

Brazilian

Journal

of

OTORHINOLARYNGOLOGY

ORIGINAL

ARTICLE

Hypoparathyroidism:

what

is

the

best

calcium

carbonate

supplementation

intake

form?

Loraine

Gollino

a

,

Maria

Fernanda

Giovanetti

Biagioni

a

,

Nathalia

Regina

Sabatini

a

,

José

Vicente

Tagliarini

b

,

José

Eduardo

Corrente

c

,

Sérgio

Alberto

Rupp

de

Paiva

a

,

Gláucia

Maria

Ferreira

da

Silva

Mazeto

a,∗

aUniversidadeEstadualPaulista‘‘JúliodeMesquitaFilho’’(Unesp),FaculdadedeMedicinadeBotucatu,Departamentode

MedicinaInterna,Botucatu,SP,Brazil

bUniversidadeEstadualPaulista‘‘JúliodeMesquitaFilho’’(Unesp),FaculdadedeMedicinadeBotucatu,Departamentode

Oftalmologia,OtorrinolaringologiaeCirurgiadeCabec¸aePescoc¸o,Botucatu,SP,Brazil

cUniversidadeEstadualPaulista‘‘JúliodeMesquitaFilho’’(Unesp),InstitutodeBiociência,DepartamentodeBioestatística,

SãoPaulo,SP,Brazil

Received16August2017;accepted21October2017 Availableonline15November2017

KEYWORDS

Calcium;

Calciumcarbonate; Hypoparathyroidism; Phosphorus;

Thyroidectomy

Abstract

Introduction:Inhypoparathyroidism,calciumsupplementationusingcalciumcarbonateis nec-essaryforthehypocalcemiacontrol.Thebestcalciumcarbonateintakeformisunknown,beit associatedwithfeeding,juiceorinfasting.

Objective: Theobjectivewastoevaluatethecalcium,phosphorusandcalcium×phosphorus productserumlevelsofhypoparathyroidismwomenaftertotalthyroidectomy,followingcalcium carbonateintakeinthreedifferentforms.

Methods:A crossoverstudywascarriedoutwithpatientspresentingdefinitive hypoparathy-roidism, assessedindifferentsituations(fasting,withwater,orangejuice,breakfastwitha one-weekwashout).Throughthereviewofclinicaldatarecordsoftertiaryhospitalpatients from1994to2010,12adultwomen(18-50yearsold)wereidentifiedanddiagnosedwith defini-tivepost-thyroidectomyhypoparathyroidism.Thelaboratoryresultsofcalciumandphosphorus serum levelsdosedbefore andevery 30minwereassessed,for5h,aftercalciumcarbonate intake(elementarycalcium500mg).

Pleasecitethisarticleas:GollinoL,BiagioniMF,SabatiniNR,TagliariniJV,CorrenteJE,PaivaSA,etal.Hypoparatyroidism:whatisthe

bestcalciumcarbonatesupplementationintakeform?BrazJOtorhinolaryngol.2019;85:63---70.

Correspondingauthor.

E-mail:gmazeto@fmb.unesp.br(G.M.Mazeto).

PeerReviewundertheresponsibilityofAssociac¸ãoBrasileiradeOtorrinolaringologiaeCirurgiaCérvico-Facial.

https://doi.org/10.1016/j.bjorl.2017.10.010

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Results:Themaximumpeakaveragevaluesforcalcium,phosphorusandcalcium×phosphorus product were 8.63mg/dL (water), 8.77mg/dL (orange juice) and 8.95mg/dL (breakfast); 4.04mg/dL (water), 4.03mg/dL (orange juice) and 4.12mg/dL (breakfast); 34.3mg2/dL2

(water),35.8mg2/dL2(orangejuice)and34.5mg2/dL2(breakfast),respectively,andthearea

underthecurve 2433mg/dLmin(water),2577mg/dLmin(orangejuice)and2506mg/dLmin (breakfast), 1203mg/dLmin (water), 1052mg/dLmin (orange juice) and 1128mg/dLmin (breakfast),respectively.Therewasnosignificantdifferenceamongthethreedifferenttests (p>0.05).

Conclusion:Thecalcium,phosphorusandcalcium×phosphorusproductserumlevelsevolved inasimilarfashioninthethreecalciumcarbonateintakeforms.

© 2017 Associac¸˜ao Brasileira de Otorrinolaringologia e Cirurgia C´ervico-Facial. Published by Elsevier Editora Ltda. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).

PALAVRAS-CHAVE

Cálcio;

Carbonatodecálcio; Hipoparatireoidismo; Fósforo;

Tireoidectomia

Hipoparatireoidismo:qualéamelhorformadeingestãodesuplementodecarbonato decálcio?

Resumo

Introduc¸ão:No hipoparatireoidismo, asuplementac¸ão decálcio comcarbonato de cálcio é necessáriaparaocontroledahipocalcemia.Amelhorformadeingestãodecarbonatodecálcio aindaédesconhecida,sejaconcomitantecomalimentac¸ão,nosucoouemjejum.

Objetivo:Avaliarosníveisséricosdecálcio,fósforoeprodutocálcio-fósforoemmulherespós tireoidectomiaporhipoparatireoidismo,apósaingestãodecarbonatodecálcioemtrêsformas diferentes.

Método: Foirealizado um estudocruzadoem pacientescomhipoparatireoidismo definitivo, avaliados em diferentes situac¸ões (em jejum, comágua, suco de laranja,café da manhã, após washout de uma semana). A revisão dos prontuários dos pacientes de um hospital terciário de 1994a 2010identificou 12 mulheres adultas (18-50 anos),diagnosticadas com hipoparatireoidismodefinitivopós-tireoidectomia.Osresultadoslaboratoriaisdosníveis séri-cosdecálcioefósforoforammensuradosanteseacada30minutosdurante5horas,apósa ingestãodecarbonatodecálcio(cálcioelementar500mg).

Resultados: Os valores de pico máximo médio de cálcio, fósforo e produto cálcio-fósforo foram 8,63mg/dL (água), 8,77mg/dL (suco de laranja) e 8,95mg/dL (café da manhã); 4,04mg/dL(água),4,03mg/dL(sucodelaranja)e4,12mg/dL(cafédamanhã);34,3mg2/dL2

(água), 35,8mg2/dL2 (suco de laranja) e 34,5mg2/dL2 (café da manhã), respectivamente,

e a área sob a curva foi 2.433mg/dL.min. (água), 2.577mg/dL.min. (suco de laranja) e 2.506mg/dL.min. (café da manhã), 1.203mg/dL.min. (água), 1.052mg/dL.min. (suco de laranja)e1.128mg/dL.min.(cafédamanhã),respectivamente.Nãohouvediferenc¸a signif-icanteentreostrêsdiferentestestes(p>0,05).

Conclusão:Osníveis séricosde cálcio,fósforo eprodutocálcio-fósforo evoluíram deforma semelhantenastrêsformasdeingestãodecarbonatodecálcio.

© 2017 Associac¸˜ao Brasileira de Otorrinolaringologia e Cirurgia C´ervico-Facial. Publicado por Elsevier Editora Ltda. Este ´e um artigo Open Access sob uma licenc¸a CC BY (http:// creativecommons.org/licenses/by/4.0/).

Introduction

Hypoparathyroidism(HypoPT)stemsfromdysfunctional pro-ductionand/orsecretionofactiveparathormone(PTH)by theparathyroidglands.1HypoPThasmanycauses,andthe

most frequent are parathyroidectomy and thyroidectomy surgeries.2Aftertotalthyroidectomy,theincidenceof

post-operative HypoPT ranges from 0.5% to 6.6%.2 However,

incidences ashigh as 20% have been reported3---6

depend-ingonsurgeryextensionandcomplexity,whicharegreater inmalignant neoplasms, suchas thyroidcancer, the main indicationfortotalthyroidectomy.7---9Inthesecases,central

compartmentneckdissectionisariskfactorforpermanent hypoparathyroidism.10

PermanentHypoPT aftertotalthyroidectomy is charac-terizedby persistenthypocalcemia andlowor inappropri-atelynormallevelsofPTHfor morethansixmonthsafter surgery.11Itstreatmentinvolvesthesupplementprotocolof

calciumandvitaminD1tocontroltheclinicalmanifestations

ofhypocalcemia,tomaintaincalcium(Ca)andphosphorus (P) levels, and adequate Ca×P product.12 For this

treat-ment andin manyother situationswhere Ca replacement isindicated,calciumcarbonate(CaCO3)istheCasaltmost

(3)

elemental Ca13 and better absorption in the normal or

acidic pH of the stomach.2,14,15 Normal individuals should

takeCaCO3withmealsoraparticularfoodtoincreasethe

bioavailabilityofthemineral.16 Yet,forHypoPT,where Ca

supplement isassociated withqualityoflife maintenance andpatientsurvival,nostudieshaveassessedtheinfluence of CaCO3 intake protocol on certain parameters, such as

calcemia and phosphatemia. Moreover, in normal individ-ualscalcemiaisrigorouslycontrolledbyafeedbacksystem that involves many factors,especiallyPTH.1,17,18 This

sys-temmaintains serum Calevels constant,evenwhen a Ca overloadoccurs,whichimpairsassessingthetemporaleffect ofCaCO3intake.Inthissense,HypoPTpatientscouldbea

goodmodel forassessing therealimpactof CaCO3 intake

protocolsoncalcemiaandphosphatemia.

Thus,thepresentstudyinvestigatedhowtheserum lev-elsofCa,P,andCa×Pvaryovertimeafterthreedifferent protocolsofCaCO3intakebywomenwithpermanentHypoPT

secondarytototalthyroidectomy.

Methods

Subjectandmethods

Thisisacrossoverstudythatassessedthreedifferentintake protocols with a washout period of one week between assessments.Allpatientsweresubmittedtothethreeintake protocols.

Patients

Thesamplesizewascalculatedtocomplywiththecrossover design, considering a 10% difference between treatment means and a coefficient of variation of 10%.19 According

tothis analysis, the sample shouldhave at least 12 indi-viduals. Data were collected from patients submitted to totalthyroidectomysecondarytodifferentiatedthyroid car-cinoma (DTC)between 1994 and2010 atthe Hospital das Clínicas,FaculdadedeMedicinadeBotucatu-UNESP.Twelve females aged18---50 years wereselected. These patients, whodidnothaveothercomorbidities,hadbeendiagnosed withpermanentHypoPT,definedasthepresenceof persis-tenthypocalcemiaandloworinappropriatelynormalserum PTHlevelsforatleastoneyearaftertotalthyroidectomy.4

Theywereregularlyfollowedataoutpatientclinic.

Ethics,consentandpermissions

This study wasapproved by the Research Ethics Commit-tee of the institution, under protocol number 4332-2012, in accordancewiththeHelsinki Declaration of 1975,with approvementof ClinicalTrial Registration (Number: 4332-2012)andallparticipantssignedaninformedconsentform toparticipateinthestudy.

Datacollection

Testswere conductedto assessthe serumlevels ofCa, P andof the Ca×Pproductover timeafter threedifferent CaCO3 supplementationprotocols:afteran overnightfast,

takenwith200mLofwater;afteranovernightfast,taken with200mLoforangejuiceSuFresh®(WowIndústria Comér-cio,Cac¸apava,Brazil);andtakenwith200mLofwaterright afterbreakfast(breadroll withmargarineandsweetened coffee).TheCaCO3dosewas1282mg(Oscal

®

,Sanofi Aven-tis,Suzano,Brazil),equivalentto500mgofelementalCa, whichisthedosehabituallyprescribedforHypoPTpatients, whotake1---3gofelementalCaperday,2averaging1.5g/day

divided intotwo or threedoses. The orderof the proto-colswasvariedbyraffletominimizethepossibilityofone influencingtheother.

ThebaselineserumlevelsofCa,P,magnesium(Mg), alka-line phosphatase (ALP), total proteins and fractions, PTH and25-hydroxyvitaminDbeforeCaCO3administrationwere

measured regardless before each protocol. After CaCO3

administration,theserumlevelsofCaandPweremeasured every30minfor5h(11samplesperparticipant).

Statisticalanalyses

The serum Ca and P levels were expressed as mean and standard deviation. Independent samples were analyzed by analysis of variance (ANOVA), followed by the mul-tiple comparison Tukey test for symmetric distribution, adjustinggenerallinear modelswithGamma distribution, followed by the multiple comparison Wald test for asym-metricdata.Pearson’scorrelationwasperformedbetween theCaareaunderthecurve(AUC)andtheserumlevelsof 25-hydroxyvitaminD,andbetweentheCaAUCandtheage ofthewomen.Allanalyseswereperformedbythe statisti-calapplicationsSASforWindows® version9.3andSigmaStat 3.5.Thesignificancelevelwassetat5%.

Table1 Generalcharacteristicsand effectivetreatment for chronic hypocalcemia of 12 patients with permanent hypoparathyroidism due tototal thyroidectomyfor differ-entiatedthyroidcarcinoma.

Generalcharacteristics n=12

Age(years)a 43.3±7.3

Caucasionb 11(91.7%)

Educationattainment: secondarydegreeof secondaryschoolb

4(33.2%)

Variousworkersb 7(58.3%)

Timeafterthyroidectomy (years)a

8.60±5.4

CaCO3supplementuseb 12(100%)

CaCO3supplementdose

(mg/day)a

2141±1193

Elementalcalciumintake (mg/day)a

856±477

Calcitriolsupplementuseb 10(83.3%)

Calcitriolsupplementdose (␮g/day)a

0.38±0.18

a Valuesexpressedasmean±SD. b n(%);n,numberofpatients;CaCO

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Table2 Baselinebiochemicalandhormonalserumlevels.

Serum CaCO3supplementation p-value

Water Juice Breakfast

Calcium(mg/dL) 8.54±3.32 8.54±3.32 8.73±3.32 0.809 Phosphorus(mg/dL) 3.8±0.69 3.74±0.72 4±0.65 0.640 Magnesium(mg/dL) 1.93±0.17 1.88±0.13 1.92±0.17 0.693 Totalprotein(g/dL) 6.84±0.58 6.89±0.55 7.05±0.76 0.716 Albumin(g/dL) 3.93±0.38 3.98±0.24 3.98±0.38 0.939 Globulin(g/dL) 2.91±0.34 3.25±1.00 3.08±0.48 0.482 Alkalinephosphatase(U/L) 72.58±12.2 74±15.8 71.33±12.7 0.840 25-hydroxyvitaminD(ng/mL) 32.19±10.2 33.36±11.6 32.87±9.56 0.964 PTH(pg/mL) 12.36±8.66 14.01±9.63 12.46±8.04 0.876 TSH(␮LU/mL)a 1.21±2.88 0.92±2.01 0.9±2.36 0.896

FT4(ng/mL) 1.34±0.28 1.35±0.31 1.33±0.38 0.990

Valuesexpressedasmean±SD.Statisticaltests:ANOVAfollowedbyTukey.

aAdjustmentindistributionrange(asymmetricdata);significance,p<0.05.

CaCO3,calciumcarbonate;FT4,freethyroxine;TSH,thyrotropin;PTH,parathyroidhormone.

Referencevalues:calcium8.4---10.2mg/dL; phosphorus2.5---4.5mg/dL;magnesium1.6---2.3mg/dL;totalprotein6.3---8.2g/dL; albu-min3.5---5g/dL;globulin1.4---3.2g/dL;alkaline phosphatase35---104U/L;25-hydroxyvitaminD 30---60ng/mL;PTH 11---65pg/mL;TSH 0.4---4␮LU/mL;FT40.8---1.8ng/mL.

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Water Juice Breakfast

Figure1 Evolutionoftheserumcalciumaftercalciumcarbonatesupplementationaccordingtothedifferentintakeforms.A,

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0 30 60 90 120 150 180 210 240 270 300

Time (minutes)

Water Juice Breakfast

Figure2 Evolutionofserumphosphorusaftercalciumcarbonatesupplementationaccordingtothedifferentintakeforms.A,

meansandstandarderrors;B,CandD,serumphosphorusscatterplotsinfastingwithwater,withorangejuiceandafterbreakfast, respectively.

Results

Cohortdescription

Femaleshadameanageof43yearsandmostwerewhite. Theaveragetimebetweenthyroidectomyandthetestswas 8.6years.AllpatientsweretreatedwithCaCO3,withamean

elementalCaintakeof856mg,andmostalsotookcalcitriol (Table1).

Temporalvariationofserumcalcium,phosphorus,

andCa×P

Themeanbaselinehormoneandbiochemicallevelsdidnot differsignificantly(p>0.05)inthethreeCaCO3intake

pro-tocols (Table 2). Calcemia and phosphatemia had similar curvesregardless of CaCO3 intake protocol. The mean Ca

levels were below the lower limit of normality, and the meanPlevelswereinthereferencerange(Figs.1and2). TheCa×Pproductremainedbelow55mg2/dL2atalltimes,

anditstemporalvariationwassimilarinthethreeprotocols (Fig.3).

Themeansofthepeak,time-to-peak,andAUCforserum CaandPandCa×PproductdidnotdifferbyCaCO3intake

protocol(Table3),evenafteradjustingtheCaCO3,

elemen-talCa,andcalcitrioldoses(datanotshown).

The age [r=0.063 (water), r=−0.14 (juice), r=0.08 (breakfast)] and the serum concentrations of 25-hydroxyvitaminD[r=0.18(water),r=0.28(juice),r=0.20 (breakfast)]didnotcorrelate(p>0.05)withtheCaAUC.

Discussion

HypoPT maybea consequence of totalthyroidectomy,3,20

which is the most frequent treatment for DTC,21 a

neo-plasmwhoseincidencehasincreasedconsiderablyinthelast years.22,23PatientswithpermanentHypoPTrequirelifelong

treatmentwithCasaltstocontrolcalcemia,phosphatemia, andtheCa×Pproduct.2,12,24CaCO

3isthemostcommonsalt

usedfor this purposebecause of itshigher elemental Ca percentage13 withgoodabsorption.14 Studiesthatassessed

calcemia, phosphatemia, and Ca×P product in different CaCO3intakeprotocols,inHypoPTpatientsafter

thyroidec-tomy,werenotfound.

ThisstudycomparedthreedifferentprotocolsofCaCO3

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of healthy women did not vary over time after CaCO3

supplementation.25Ontheotherhand,Caserumofwomen

with polycystic ovary syndrome increased significantly.26

However,comparisonof thestudy results withindividuals with normal PTH secretion is inappropriate. Additionally, although the therapeutic objectives seem to have been achieved,individualanalysisof thethreeintakeprotocols showedthatroughly41%ofserumCavalueswerebelowthe lowerlimitofnormality.Hypocalcemiamayhaveunknown healthrepercussions.

The calcemiapeaks rangedfrom8.6to8.9mg/dL,and thetimes-to-peakrangedfrom152to202min,withanAUC of2433---2577mg/dLminregardlessof CaCO3intake

proto-col.Thepeaksremainedinthelowerhalfofnormality,which isdesirableinHypoPTpatientsbecauseserumCainthese patientsshouldremainlow,despitetheadverseeffectsof hypocalcemia.12 These values differ from those reported

byTondapu andcontributors27 whostudied CaCO

3

supple-mentation in patients submitted to the bariatric surgery Roux-en-Yandfoundapeakof9.2mg/dL,time-to-peakof 126min,andAUCof3240mg/dLmin.The differentresults arejustifiedbythefactthatbothcalcemiaandAUCrelyon PTHaction,whichwasnormalinthesamplestudied.27PTH

controlscalcemiarigorously,asshownbyacrossoverstudy ofhealthywomenthatcomparedCaCO3andplacebointakes

anddidnotfinddifferencesintheCapeakandAUC.25

Even-tually,theageandvitaminDsufficiencyofthepatientscould have influencedthe resultsobtained. However,no signifi-cantassociationswerefoundbetweentheseparametersand CaAUC.

The study time-to-peak means were higher than those reported elsewhere,27 which may also stem from low

PTH. Still, Wang and contributors28 assessed healthy

pre-menopausalwomenandfoundaCatime-to-peakof240min, higher than the study time-to-peak. On the other hand, Hellerandcontributors29 assessedhealthypostmenopausal

womenandfoundatime-to-peakof174min,similartothe studytime-to-peak.

Thephosphatemiaofnormalindividualshasacircadian rhythm,withanadirataround10inthemorningandapeak at around 2 in the afternoon, generally ranging from2.4 to3.6mg/dL.30 Phosphatemia is affected by food intake.

Valderas andcontributors31 assessed phosphatemia for 3h

afterastandardmealandfoundmeanphosphatemiavalues ranging from 3.1 to 3.5mg/dL. At eight in the morning, timeof the first blood collection, the participants’ phos-phatemia ranged from 2.7 to 5.7mg/dL. The last blood samples were collected at one o’clock in the afternoon, whennormalindividualshaveadiscreteelevationofserum phosphorus.30 Phosphatemia peak, time-to-peak,and AUC

weresimilarinallthreeCaCO3intakeprotocols,regardless

offoodintake.Themeanpeakvaluesrangedfrom4.03to 4.12mg/dL,time-to-peakrangedfrom135to167min,and AUCranged from1052 to1203mg/dL.min.Althoughmean phosphatemiawaswithinthereferencerange,roughly10% oftheparticipantshadPlevelsbeyondtherecommended limits, especially above, which may negatively impact their metabolic control. In HypoPT hyperphosphatemia is almost as harmful as hypocalcemia. Hyperphosphatemia is associated with lower bone resorption32 and

calcifi-cation of the basal ganglia33 and coronary artery.34,35

In normal individuals hyperphosphatemia decreases

40

30

20

10

0

0 30 60 90 120 150 180 210 240 270 300 Time (minutes)

Water Juice Breakfast

Ca x P product (mg

2/dL.min 2)

Figure 3 Evolution of the values of calcium×phosphorus

product(Ca×P)expressedasmeanstandarderror,after cal-cium carbonate supplementation according to the different intakeforms.

calcemia, which stimulates PTH secretion and conse-quently, increases calcemia. Thus, in HypoPT patients hyperphosphatemia worsens hypocalcemia even more because of PTH deficiency.36 Phosphatemia must be

rig-orously monitored to avoid significant fluctuations, since hypophosphatemiamayalsohave negativeeffects,asit is associated,forexample,withhigherchildhoodmortality.37

Interestingly,becauseofhypocalcemia,CaCO3mayalsobe

usedforcontrollinghyperphosphatemia.38

In HypoPT the Ca×P product should stay below 55mg2/dL2,39 toavoidprecipitation ofCa---Pcomplexes in

soft tissues, such as basal ganglia, lens, and kidneys,11

andvascularcalcification,33,40,41especiallyinthecoronary

arteries.35 In additiontoorganic processes,

neuropsychol-ogical disordershavebeen associatedwithchangesin the Ca×Pproduct.42 InuntreatedHypoPT calcemiadecreases

andphosphatemiaincreases,sotheCa×Pproductshould not change. In fact, this product did not change in rats submittedtoparathyroidectomy.32Nonetheless,whenthese

patients take Ca supplements to correct hypocalcemia, Ca×Pproductmayincrease.Inthepresentstudy,allCa×P productvalueswerebelowtherecommendedupperlimit, andthemeanCa×Pproductvaluesweresimilarinthethree CaCO3intakeprotocols.

Thisstudyhassomelimitations,suchasthesmallsample size.Nevertheless,thesamplesizewascalculated statisti-cally basedonthe study design.Another limitationis the relativelylowCadoseused(500mgofelementalCa),which mayhavecontributedtothesimilartemporalvariationsof thestudyparametersinthethreeCaCO3 intakeprotocols.

Still,otherstudiesthatusedthesamedoseobserved signifi-cantchanges,withanincreaseincalcemia.26,29,43Moreover,

thestudydosewouldbetherecommendeddoseforHypoPT patients,giventhattherecommended1---3gdoseof elemen-talCaperdayisdividedintotwoorthreedoses.2Asamatter

offact,oncethemaximumintestinalsolubilityofCaCO3is

reached,higherdoseswouldnotbeabsorbed.44Another

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Table3 Maximumpeak,time topeak andarea underthecurve ofserum calcium,phosphorusand areaunder thecurve calcium×phosphorusproduct.

Serum CaCO3supplementation p-value

Water Juice Breakfast

Calcium Maximumpeak(mg/dL) 8.63±0.87 8.77±0.55 8.95±0.38 0.477 Timetopeak(min) 202.5±85.9 182.5±57.8 152.5±94.5 0.326 AUC(mg/dLmin) 2433±239 2577±214 2506±121 0.226 Maximumpeak(mg/dL) 4.04±0.76 4.03±0.69 4.12±0.66 0.945 Phosphorus Timetopeak(min) 142±92.1 135±99.0 167±107 0.706 AUC(mg/dLmin) 1203±173 1052±119 1128±320 0.981 Ca×Pproduct Maximumpeak(mg2/dL2) 34.3±6.55 35.8±7.34 34.5±6.41 0.827

Timetopeak(min) 180±85.9 187±85.9 192±100 0.944 AUC(mg2/dLmin2) 9038±1645 8846±1365 9094±1095 0.900

Valuesexpressedasmean±SD.

Statisticaltests:ANOVAfollowedbyTukey;significance:p<0.05.

AUC,areaunderthecurve;CaCO3,calciumcarbonate;Ca×Pproduct,productcalcium×phosphorus.

the limitations, the present study is the first to assess thetemporalvariationofcalcemiaandphosphatemiaafter CaCO3 supplementation in HypoPT patients. Furthermore,

thisendocrinedisordermaybeamodelfortheassessmentof CaCO3perse,withouttheinfluenceofPTHonthetemporal

variationsofcalcemiaandphosphatemia.Sinceourfindings suggestthatbetterCaabsorptioninHypoPTpatientsdoes notrequiretakingthesaltaftermeals,perhapsthis conclu-sioncouldbeextrapolatedtootherconditionsthatrequire Casupplementation.

Conclusion

The temporal variations of calcemia, phosphatemia, and theCa×Pproductinwomenwithpermanent hypoparathy-roidism secondary to total thyroidectomy are similar regardless of theCaCO3 supplementation protocol (water,

juice or breakfast). Therefore, considering only calcemia andphosphatemia,thesepatientsmaytakeCaCO3afteran

overnightfastwithwaterororangejuice,orafterbreakfast.

Funding

This work wassupported by the National Council for Sci-entific and Technological Development (CNPq --- Conselho NacionaldeDesenvolvimentoCientíficoeTecnológico),no. 130424/2013-7,andhadnoinfluenceonthedesignof the study,oronthecollection,analysis,andinterpretationof data,oronthewritingthemanuscript.

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

Acknowledgements

We thank the CNPq for the masters’ scholarship (Loraine Gollino), as well as Marcia Tonin Rigotto Carneiro, Ana PaolaPilotOliveiraandDanielaGonc¸alvesfromtheClinical ResearchUnit(UPECLIN)fromtheFaculdadedeMedicinade

Botucatu,UniversidadeEstadualPaulista---Unesp.Wealso thankthedoctorMariaSaleteSartorifortheimmeasurable supportfortheexecutionofthissurvey.

References

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Imagem

Table 1 General characteristics and effective treatment for chronic hypocalcemia of 12 patients with permanent hypoparathyroidism due to total thyroidectomy for  differ-entiated thyroid carcinoma.
Figure 1 Evolution of the serum calcium after calcium carbonate supplementation according to the different intake forms
Figure 2 Evolution of serum phosphorus after calcium carbonate supplementation according to the different intake forms
Figure 3 Evolution of the values of calcium × phosphorus product (Ca × P) expressed as mean standard error, after  cal-cium carbonate supplementation according to the different intake forms.
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