Acta Medica Okayama
Volume
56,
Issue3 2002
Article7
J UNE 2002
An unusual cause of hypercalcemia in polycythemia vera: parathyroid adenoma.
Ozay Tiryakioglu
∗Pinar Kadioglu
†Seniz Ongoren
‡Ozer Acbay
∗∗Burhan Ferhanoglu
††Sadi Gundogdu
‡‡Ustun Korugan
§∗University of Isatanbul,
†Istanbul University,
‡University of Isatanbul,
∗∗University of Isatanbul,
††University of Isatanbul,
‡‡University of Isatanbul,
§Istanbul University, Turkey,
Copyright c1999 OKAYAMA UNIVERSITY MEDICAL SCHOOL. All rights reserved.
Ozay Tiryakioglu, Pinar Kadioglu, Seniz Ongoren, Ozer Acbay, Burhan Ferhanoglu, Sadi Gundogdu, and Ustun Korugan
Abstract
In this paper we describe a patient with polycythemia vera (PV), who presented with hy- percalcemia due to a parathyroid adenoma. In November 1999, the patient was admitted to our hospital with meteorism and constipation. Her physical examination revealed plethora and hepatosplenomegaly. Laboratory data revealed hyperparathyroidism in addition to PV: Rbc 8 x 10(6)/mm3, Hct 63.7%, serum calcium 13.4 mg/dl, serum phosphorus 1.2 mg/dl, albumin 4.25 mg/dl, and alkaline phophatase activity 433 U/l. Intact Parathyroid Hormone level (iPTH) was 376 pg/ml (n.v.12-72 pg/ml). Twenty-four hour urinary calcium excretion was higher than normal (900 mg). A parathyroid adenoma was detected with Tc-99m sesta-MIBI scanning under the left lobe of the thyroid gland and an ultrasonographic examination of the neck also supported the di- agnosis. The patient was recommended for surgery. The histopathological examination confirmed the diagnosis. Postoperatively, iPTH dropped to 53.4 pg/ml at the 15 th minute and to 33.5 pg/ml at the first hour. The calcium level was 7.5 mg/dl one hour after the operation. Five days later, Hct was 40.8%. This case represents a rare association between PV and primary hyperparathyroidism, and may provide evidence for a causal link between PTH and polycythemia vera in our patient. In conclusion, this case indicates that the differential diagnosis of hypercalcemia and polycythemia vera should also include the possibility of a parathyroid tumor in addition to malignancy.
KEYWORDS:hyperparathyroidism, intact PTH, scintigraphy and myelodie hyperplasia
∗PMID: 12108588 [PubMed - indexed for MEDLINE]
Copyright (C) OKAYAMA UNIVERSITY MEDICAL SCHOOL
AnUnusualCauseofHyper cal cemi ai nPol ycyt hemi aVer a:
Par at hyr oi dAdenoma
̈zayTiO ryakioglu ,PınarKadıoglu,
e
enizÖngoren,ÖzerAçbay, BurhanFerhanoglu,SadiGundogdu,andÜstunKorugan
DepartmentofInternalMedicine,Divisionof Endocrinology,and Hematology, Cerrahp
a
aMedicalFaculty,UniversityofIstanbul,34303,Cerrahp
a a,Turkey
Inthispaperwedescribeapatientwithpolycythemiavera(PV),whopresentedwithhypercalcemia duetoaparathyroidadenoma.InNovember1999,thepatientwasadmittedtoourhospitalwith meteorism andconstipation.Herphysicalexaminationrevealedplethoraandhepatosplenomegaly.
Laboratorydatarevealedhyperparathyroidism inadditiontoPV:Rbc8×10/mm ,Hct63.7 , serum calcium 13.4mg/dl,serum phosphorus1.2mg/dl,albumin 4.25mg/dl,andalkalinepho- phataseactivity433U/l.IntactParathyroidHormonelevel(iPTH)was376pg/ml(n.v.12‑72pg/ml). Twenty-fourhoururinarycalcium excretion washigherthan normal(900mg).A parathyroid adenomawasdetectedwithTc-99m sesta-MIBIscanningundertheleftlobeofthethyroidglandand an ultrasonographicexamination oftheneck also supported thediagnosis. Thepatientwas recommendedforsurgery.Thehistopathologicalexaminationconfirmedthediagnosis.Postoper- atively,iPTH droppedto53.4pg/mlatthe15thminuteandto33.5pg/mlatthefirsthour.The calcium levelwas7.5mg/dlonehouraftertheoperation.Fivedayslater,Hctwas40.8 .Thiscase representsarar
e
association between PV andprimaryhyperparathyroidism,andmayprovide evidenceforacausallinkbetweenPTH andpolycythemiaverainourpatient.Inconclusion,this caseindicatesth
i
tthedierentialdiagnosisofhypercalcemiaandpolycythemi
w
verashouldalso includethepossibilityofaparathyroidtumorinadditiontomalignancy.
Keywords:hyperparathyroidism,intactPTH,scintigraphyandmyeloidhyperplasia
H
yasppercoallycceymithaieminmyaveerloaiprsuolifesruaatillvytedhisoourgdhettrssobucherelatedtomalignancy.Theco-incidenceofpolycythemia veraandrenalcellcarcinomaiswellknown［1］.In addition,othercarcinomas,suchashepatocellularcar- cinoma［2］, ph
o ochromocytomas［3］, and ovarian
carcinomas［4］,mayco-occurwithpolycythemiavera, butan association between hyperparathyroidism and
polycythemiaverahasrarelybeenreported. Th
h
spaperdescribesapatientwithpolycythemiavera presenting
e
ith hypercalcemia due to a parathyroid adenoma.
CaseReport
A58-year-oldwomanwasdiagnosedwithp
h
lycythe- miaverainJanuary1995accordingtothecriteriaofthe Polycyth
h
miaVeraStudyGroup［5］.Therewereno endocrinologicalorhematologicaldisordersin
n
erfamilial t
istory.Onerphysicalexamiationahepaomegaloyf2 S
s s
ReceivedApril11,2001;acceptedJanuary10,2002.
Correspondingauthor.Phone:＋90‑212‑6647622;Fax:＋90‑212‑2111345 E-mail:droztr＠yahoo.com (̈.TiO ryakioglu)
http://www.lib.okayama-u.ac.jp/www/acta/
ActaMed.Okayama,2002 Vol.56,No.3,pp.167‑170
Ca s eRe p o r t
Copyrightｃ2002byOkayamaUniversityMedicalSchool.
1 Tiryakioglu et al.: An unusual cause of hypercalcemia in polycythemia vera:
Produced by The Berkeley Electronic Press, 2002
cm,andasplenomegalyof5cmwasdetected.Herblood counts were Red Blood Cell(Rbc)7.4×10/mm, Hematocrit(Hct)58 ,Whitebloodcell(Wbc)12.800/ mm (7 band neutrophil, 83 neutrophil, 8 lymphocyte, 2 monocyte), platelet170.000/mm, erythrocyte mass:49.4ml/kg (normal value:20‑30 ml/kg),arterialoxygensaturation96 ,serum calcium 9.2mg/dl(n.v.8.5‑11.9mg/dl),serumphosphorus1.8 mg/dl(n.v.1.6‑6.8mg/dl),albumin4.45g/dl,alkaline phosphataseactivity250U/l(n.v.98‑279U/l),and intactParathyroidHormonelevel(iPTH)58pg/ml(n.v. 12‑72pg/ml). The disease was controlled by phlebotomies(500ml/daywith30daysinterval)until November 1998, when she developed progressive splenomegaly and thrombocytopenia(platelet:75.000/ mm).ThebonemarrowbiopsyshowedgradeIIreticular fiberincrement,focalmegaloblasticchanges,andery- throidandmyeloidhyperplasia.Laboratorydataalso includednormalserumcalcium(8.8mg/dl)andphospho- rus(1.8mg/dl)inthisperiod.
InNovember1999,thepatientwasagainadmittedto ourhospital, with meteorism and constipation. Her physicalexaminationrevealedplethora,hepatomegaly(2 cm),splenomegaly(14cm),andcrepitationsintheleft lowerlungfieldonchestauscultation.Sheshowedno signsofosmoticdehydrationinherphysicalexamination. Laboratory data included:Rbc 8×10/mm, Hct 63.7 , aleukocytecountof7.900/mm, platelet 81.000/mm,serum calcium 13.4mg/dl,serum phos- phorus1.2mg/dl,albumin4.25g/dl,andalkalinephos- phataseactivity433U/l.iPTH levelwas376pg/ml (n.v.12‑72pg/ml,DPC,LA,USA).Twenty-four hoururinarycalcium excretionwashigherthannormal (900mg)(n.v.100‑250mg).Serumbilirubinlevelswere bothnormal［totalbilirubin0.8mg/dl(n.v.),indirect bilirubin 0.4mg/dl(n.v.)］. On hertelecardiography, cardio-thoracicindexwas0.5andtheleftatrium was dilated.OnECG,theQTintervalwasshortened(0.3 sec)(N:0.35‑0.44sec)andtherewasabi-phasicPwave indicatingaleftatrialhyperthropy.Nephrocalcinosiswas absentontherenalsonogram.
Shewasphlebotomized(500ml/dayforatotalof 1.5l)andtreatedforhypercalcemiawithsalinediuresis, methylprednisolone(80mg/day,iv)andcalcitonin(200 μg/day,sec).Thecalcium levelwasinsu ciently controlledandthepatientwasdevelopingconfusion.In response,asingledoseofpamidronatedisodium(15mg, iv)wasgivenonthethirddayofadmission.Theconfu-
siondisappearedonthefirstdayandthecalcium value returnedto10.3mg/dlonthethirddayafterpamidronate. Thesalinediuresisandglucocorticoidtreatmentswere stopped.
A parathyroidadenomawasdetectedwithTc-99m sesta-MIBIscanningundertheleftlobeofthethyroid gland(Fig.1).Anultrasonographicexaminationofthe necksupportedthediagnosis.Totalbodybonescanning with Tc-99m sesta-MIBI showed the parathyroid adenomaalong with increased bonemarrow activity, whichisseeninmyeloproliferativedisorders.
Thepatientwasdiagnosedtowithhyperparathyroid- ismduetoparathyroidadenomaandunderwentsurgeryin December1999.Intraoperativeexplorationoftheneck andmediastinumrevealedanodularlesionintheleftlobe atthelocationnotedonparathyroidultrasonographyand scintigraphy.Thehistopathologicalexaminationofthis noduleshowedaparathyroidadenoma.Postoperatively, PTHdroppedto53.4pg/dlatthe15thminandto33.5 pg/mlatfirsthour.Calcium levelwas7.5mg/dl1h aftertheoperation,and5dayslaterRbccountwas5.5× 10/mm,Hb12.5g/dl,Hct40.8 ,Wbccount9.1× 10/mm andplatelet110×10/mm,althoughonly150 mlbloodwaslostpostoperativelythroughthedrain.As showninFig.2,adramaticdecreaseinHct(from63.7 to40.8 )andincalciumlevels(from13.4mg/dlto7.5 mg/dl)wasobservedaftercalcium-loweringtreatmentand parathyroidsurgery,andnoadditionalphlebotomywas neededfor4months.Therewasnoincreaseinbilirubin levels(Totalbilirubin0.9mg/dl,indirectbilirubin0.5 mg/dl).Thedevelopinghungrybonesyndromewas
Tiryakiogluetal. ActaMed.Okayama Vol.56,No.3 168
Fig.1 Tc-99m sesta-MIBIscintigraphyofthe neckshowsa parathyroidadenomaundertheleftlobeofthethyroidgland.
treatedwithoralcalcium replacement(2.940mgcalcium lactategluconate＋300mgcalciumcarbonate)and1‑25 dihydroxycholecalciferol(0.5μg/day).
Thepatientwasdischarged10daysaftertheoperation withoutanycomplications.Shereceivedphlebotomies (500ml/dayata60dayinterval)forthefollowing2years withoutanysubsequentproblems.
Discussion
This case represents a rare association between polycythemiaveraandparathyroidadenoma.Anassocia- tionbetweenthese2entitieswasfirstdescribedbyBerlin in1949［6］.Sincethen,4additionalpatientswith hyperparathyroidism andpolycythemiaverahavebeen reported［7‑10］.Intheselatercases,remissionofthe hypercalcemiaandpolycythemiaverawasobservedafter resectionofaparathyroidadenoma.Inthepresentcase, theneedforphlebotomywasalsoincreasedduringthe hypercalcemicperiod.Recently,Pizzolittoetal.report- edinacohortstudy thatastrong and statistically significantdirectassociationwasfoundbetweenpara- thyroidadenomaandPV［11］.Ourcasereportis anotherexampleofthisrareassociation.
AbimodaleectofPTHonerythropoiesishasbeen
reportedintheliterature［12］.Levietal.andZevinet al.showedthatalow levelofPTH increasesheme synthesis［13,14］.Ontheotherhand,Meytesetal. showedthathighlevelsofPTH causeapronounced decreaseofhemesynthesis［15］.Thisinhibitionwas however,onlyfoundwithahighlevelofPTHtypicalof advanced uremia. Another tie between parathyroid tumorsandhematopoiesiswassuggestedbyMarxetal. in1989［16］.Theauthorsreportedthatanincreasein theintranuclearionizedcalcium concentrationmightlead tothetranscriptionofaregionofchromosome11,which isassociatedwiththeoncogenesinhematologicaldis- orders.Yelamartyetal.［17］alsoreportedthatinthe presenceofionizedhypercalcemiasuchasthatseenin parathyroidcancer,theproductionofagrowthfactorthat causes hematopoietic stem cellproliferation may be producedorstimulated.
Thiscasereportmayprovideevidenceofacausallink betweenPTHorhypercalcemiaandpolycythemiaverain ourpatient.Althoughphlebotomiesandsurgerymaylead tosomedegreesofbloodloss,irondeficiencyalonefails toaccountforthemaintenanceoflow Hctlevelsafter resectionofparathyroidadenomainthispatient.Onthe otherhand,thisimmediatereductionofHctmaybedue tohepatosplenomegaly,althoughwedidnotdetectany
PolycythemiaVeraandParathyroidAdenoma June2002
Fig.2 Eectsofmedicaltherapyandparathyroidsurgeryonpatientʼscalcium andhematocritlevels.
169
3 Tiryakioglu et al.: An unusual cause of hypercalcemia in polycythemia vera:
Produced by The Berkeley Electronic Press, 2002
increaseinserum bilirubinlevelsduringthepre-or postoperativeperiod.Afterappliedtherapiesforacute hypercalcemiasuchasivinfusionofmethylprednisolone andpamidronate,thepresentationofpolycythemiavera improvedbutwecouldnotdeterminewhethercalciumor parathormonehadinfluenceditscourse.However,this improvementsuggeststhatthecalcium-PTH axisis importantfortheactivationoferythropoiesis,andalso demonstratesanassociationofpolcythemiaveraand parathyroidadenoma.
Inconclusion,thecause-eectrelationshipbetween PTHandmyeloproliferativedisordersisnotyetcomplete- lyunderstood.Thiscaseemphasizesthatinvivoandin vitrostudiesarenecessarytoinvestigatetheeectof calcium-PTHaxisonbonemarrowanderythropoiesis.
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