www.bjorl.org
Brazilian
Journal
of
OTORHINOLARYNGOLOGY
ORIGINAL
ARTICLE
Hypoparathyroidism:
what
is
the
best
calcium
carbonate
supplementation
intake
form?
夽
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).
夽 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
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
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
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---4LU/mL;FT40.8---1.8ng/mL.
A
C
D
B
1210
8
6
4
2
0
0 30 60 90 120 150 180 210 240 270 300
Ser
um calcium (mg/dL)
12
10
8
6
4
2
0
Ser
um calcium (mg/dL)
Time (minutes)
0 30 60 90 120 150 180 210 240 270 300
12
10
8
6
4
2
0
0 30 60 90 120 150 180 210 240 270 300
Ser
um calcium (mg/dL)
Time (minutes)
12
10
8
6
4
2
0
0 30 60 90 120 150 180 210 240 270 300
Ser
um calcium (mg/dL)
Time (minutes) Time (minutes)
Water Juice Breakfast
Figure1 Evolutionoftheserumcalciumaftercalciumcarbonatesupplementationaccordingtothedifferentintakeforms.A,
A
C
D
B
6
5
4
3
2
1
0
6
5
4
3
2
1
0 0
Ser
um phosphor
us (mg/dL)
Ser
um phosphor
us (mg/dL)
Ser
um phosphor
us (mg/dL)
Ser
um phosphor
us (mg/dL)
6
5
4
3
2
1
0 5
4
3
2
1
0
30 60 90 120 150 180 210 240 270 300
Time (minutes)
0 30 60 90 120 150 180 210 240 270 300
Time (minutes)
0 30 60 90 120 150 180 210 240 270 300
Time (minutes)
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
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
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.
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