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Introduction

Hypertension in pregnancy is a commoncondition, and pre-eclampsia is the mostcommonprobleminprimigravidae.Severecasesofpre-eclampsiamaybesymptomaticandcausesignificantmaternalandfetalcomplicationsthatrequire delivery of the fetus and placenta as anultimatetreatment. Pheochromocytoma is a catecholamine-secreting tumour that is rare during pregnancy,with the prevalence of 1 in 54 000 pregnancies(1). Recognising pheochromocytoma antenatallyis difficult because it may mimic pre-eclampsiaandotherproblemsduringpregnancy.Therefore,the management of pheochromocytoma is agreat challenge to healthcare providers. Failureto diagnose the disease and delays in providingnecessarytreatmentsmaycausefatalityandlife-threatening situations for the mother and thefetus(2).However,pheochromocytomaiscurablebyremovingthetumour.Theabilitytoaccuratelyidentifypheochromocytomaduringtheantenatalperiodwithtimelyandappropriatemanagement

Case Report

Submitted: 2Mar2011Accepted: 26Apr2011

reducesmaternalmortalityandfetalloss(1,3,4).In the current report, we discussed a case ofpheochromocytoma that was diagnosed duringpregnancyandthecomplexityofitsmanagement.

Case Report

A29-year-oldMalaywoman(gravida2,para0+1)presentedat21weeksofamenorrhea(POA)withuncontrolledhypertensionandproteinuria.She was newly diagnosed with gestationaldiabetesmellituswithnopriormedicalillnesses.Sheremainedasymptomaticbuthadepisodesofpalpitations.Herbloodpressure (BP)was labilewith episodes of tachycardia during admission.Thefirstimpressionofthiscasewasapregnancywith pre-eclampsia. However, the differentialdiagnosis of pheochromocytoma was suspectedbasedon theevidenceof labileBPanddifficult-to-controlhypertensionthatwasassociatedwithtachycardia. Further physical examinations revealed apale woman with BP ranging 100–203 mmHg(systolicBP)and73–120mmHg(diastolicBP)with

Pheochromocytoma and Pregnancy: A Difficult and Dangerous OrdealMohamed Ismail Nor AzliN1, Abd Rahman rAhANA1, Abd Wahab NorAsyikiN2, Muhammad rohAizAk3, Nor Azmi kAmAruddiN2

1 DepartmentofObstetricsandGynaecology,FacultyofMedicine,UniversitiKebangsaanMalaysia,JalanYaacobLatiff,56000Cheras,KualaLumpur,Malaysia

2 DepartmentofMedicine,FacultyofMedicine,UniversitiKebangsaanMalaysia,JalanYaacobLatiff,56000Cheras,KualaLumpur,Malaysia

3 DepartmentofSurgery,FacultyofMedicine,UniversitiKebangsaanMalaysia,JalanYaacobLatiff,56000Cheras,KualaLumpur,Malaysia

Abstract Pheochromocytomaduringpregnancyispotentiallydisastroustothemotherandfetus.Itsambiguouspresentationisoftenmistakenforpre-eclampsia,althoughitmayimitateotherproblemsduringpregnancy.Earlydiagnosisandtimely,appropriatemanagementreducespossiblematernalandfetalcomplications.Weidentifiedacaseofpheochromocytomaduringpregnancy;theconditionwasinitiallydiagnosedaspre-eclampsiacomplicatedwithgestationaldiabetes.Surgicalinterventionvialeftadrenalectomywassuccessfullyperformedinthesecondtrimester.Aftersurgery,allofthepatient’smedicalproblemsnearlysubsidedandshedidnotrequirefurthertreatment.However,herfetusdisplayedrestrictedintrauterinegrowth,andthepatienteventuallyhadprematuredeliveryviaacaesareansection.Amultidisciplinaryteamtoidentifyandtreatpheochromocytomaismandatorytoensureoptimalconditionsfortumourremovalandtoanticipateanypossiblecatastrophicevents.

Keywords: gestational diabetes, gynaecologic oncology, hypertension, pheochromocytoma, pregnancy,proteinuria

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episodes of tachycardia. Her weight and heightwere 37 kg and 161 cm, respectively. No goitrewasdetected.Herpregnancywasgrosslynormal,andultrasoundscanparameterscorrespondedtothe estimated dates (approximately 20weeks ofgestation). She developed acute renal failure withworseningcomplicationsthatwereassociatedwithgestational diabetes requiring insulin treatment.Thehighestserumcreatininelevelwas148µmol/L,andtherenalfailurewaseventuallyresolvedwithrehydration.Althoughherhaemoglobinlevelwas7g/dL,therewasnoevidenceofoccultbleeding.Left ventricular hypertrophy with diastolicdysfunction was evident from echocardiogram.Her thyroid function tests were normal. The24-hour urine catecholamine test revealedelevations of noradrenaline at 1075 µg (normalrange 12.1–85.5 µg) and adrenaline at 196 µg(normalrange1.7–22.4µg).TheabdominalMRIconfirmed thepresenceof a left adrenal tumourthatwas4.9×5.7×7.5cm(Figure1). A multidisciplinary team consisting ofobstetricians, endocrinologists, endocrinesurgeons, and anaesthetists was involved intreatmentmanagement.Controllingthepatient’sBP was difficult because the BP remainedlabile. The treatment consisted of numerousantihypertensives, such as prazosin (20 mgonce daily), labetalol (300 mg thrice daily),metoprolol (200mgtwicedaily),bisoprolol (10mgtwicedaily),andfelodipine(10mgoncedaily).Magnesium sulphate and phenoxybenzamine at40mgoncedailywereusedtoprepareforsurgery.Fluid replacement and blood transfusions wereprovidedduringthemanagementofthepatient’slabile BP and resulted in recurrent pulmonaryoedemathatrequiredadmissiontotheintensivecareunit. The patient’s condition was acceptable at24 weeks POA to perform an open leftadrenalectomy.Whileanaesthesiawasprovided,her BP surged to 340/230 mmHg, which wassuccessfully controlled by infusing glyceryltrinitrate and sodium nitroprusside. After theremoval of the tumour (Figure 2), the lowestrecordedBPwas70/40mmHg.Thepatientwasnormotensive after 2 hours of noradrenalineinfusion. Post-operatively, the patient’s BP wascontrolledwithlowdosesofanantihypertensiveagent,withnormalisationofurinecatecholaminelevels. The patient and her fetus were in goodhealth,althoughthefetusexperiencedintrauterinerestricted growth, which was most likelyattributed to all of the patient’s complications.

Figure 1: Sagittal section of T2-weightedmagneticresonanceimageshowingtheleftadrenalpheochromocytomaandafetus.

Figure 2: A section of the dissected leftpheochromocytoma (70 × 40 ×20mm).

Case Report |Pheochromocytomainpregnancy

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Herpregnancywasmonitoredthroughoutpatientantenatal visits. After the surgery, she gained11 kg. Her hypertension and diabetes hadimproved and required no medication. In the27weeksPOA,thegrowthofherfetuswasbelowthe5thcentile.TheDopplerstudyoftheumbilicalarteryflowwasnormaluntil37weeksPOA.Then,an emergency caesarean section due to fetaldistresswasperformed. The surgerywas successful and a baby boywasdelivered,weighing1.86kg.Theneonatologyreviewwas satisfactory.Herpost-partumperiodwas uneventful, with normal results for themodifiedglucosetolerancetest.Discussion

The classical presentation ofpheochromocytoma with paroxysmalhypertension, headaches, sweating, andpalpitation (5,6) may not be simultaneouslypresent, especially during pregnancy.Therefore, the initial diagnosis of hypertensionduring pregnancy is frequently attributed topre-eclampsia rather than pheochromocytoma(5,7).Ourpatientpresentedwithhypertensionandproteinuriaat21weeksPOA.Atthistime,wemadethemost appropriate diagnosis, especially for apseudo-primigravida.Excessweightandincreasedweight gain during pregnancy predisposedwomen to pre-eclampsia, although suddenweightgainisrarelyseeninpheochromocytoma(5). This patient was underweight at thestart of her pregnancy. However, her weightincreased after the adrenalectomy. Weight lossin pheochromocytoma is due to catecholamine-induced hypermetabolism, which might be thereasonforthepatient’slowweightbeforesurgeryand subsequent weight gain after surgery withnormalisationofcatecholaminelevels(6). In addition to hypertension, alteredrenal function and proteinuria are causedby catecholamine-mediated renovascularabnormalities, which is common inpheochromocytoma (7). Some of the reportedcasesmaydisplayhyperglycaemiaandhadbeentreatedasgestationaldiabetes(5,7,8),whichwasevident in this case. Episodic hyperglycaemiais most likely due to the effect of adrenaline-secreting pheochromocytoma. These dataexplainedtheinitialmisdiagnosisofthispatient.Pheochromocytoma was suspected when theBP became labile and difficult to control, withepisodic tachycardia. Pheochromocytoma-associatedsyndromes,suchasmedullarythyroidcarcinoma, are currently being investigated in

thispatient,althoughshedidnothaveanygoitre.Further investigation for medullary thyroidcarcinoma was not undertaken when she wasinitiallyadmittedbecauseherconditionwasnotstableandshewaspregnant. Pregnancyitselfwouldrevealtheunderlyingpheochromocytomathroughtheenlarginguterus,changesofintra-abdominalpressureduringfetalmovements,compressionofthegrowingtumourby pregnancy, stressful conditions related todeliveryandanaesthesiathatcouldhaveresultedin the release of catecholamines. The suspicionof pheochromocytoma in pregnancy, which wasindicatedbylabileBPanddifficultyincontrollinghypertension, can direct the appropriateinvestigation to lead to an early diagnosis (7,8).Meanwhile, pulmonary oedema (6)may furthercomplicate the management of this delicatehypertensive problem. The detection of high24-hour urine catecholamine levels (2,9) andthe imagingof theadrenalmassusingmagneticresonance imaging (MRI), which is safe for thefetus as it requires no radiation, were used todiagnosepheochromocytoma in thispatientandwerethetoolsthatwereconsistentwithpreviousreports (2,5). Conversely, the ultrasound scanwas reported tohavepoor sensitivity, especiallyduringthe3rdtrimester(2). Because the disease was diagnosed at22weeksofgestationinthispatient,thefetuswasstill developing. The fetal growthwas restrictedto lower than the 5th centile until 37 weeks.Similar cases of intrauterine restriction (8,10)havebeenreportedandmaybeexplainedbytheexcessiveproductionofcatecholamines.Althoughcatecholamines do not cross the placenta, theutero-placental insufficiency can occur throughmaternal vessels with the paroxysmal reductionandincrementinbloodpressurethatmayworsenintrauterinehypoxia. The timing of the surgery is controversialand requires consideration on an individualbasis. Surgery is less preferred during the1st trimester due to the higher incidence ofmiscarriages.Adrenalectomyisrecommendedfor2nd-trimester cases. In the 3rd trimester, thesurgery is delayed or often performed duringcaesarean section (6). General anaesthesiais preferred and recommended becausemost of the anaesthetic gases are safe forfetuses, except for halothane and desflurane(5). Although this is a definitive treatment,medical preparation is essential and can beachieved by using alpha-blockers (prazosin andphenoxybenzamine), beta-blockers, and otherdrugs,suchasmagnesiumsulphate.Magnesium

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sulphate is beneficial in the managementof pre-eclampsia and pheochromocytoma.In pre-eclampsia, magnesium sulphatereduces the BP and acts to prevent eclampsia.In pheochromocytoma, magnesium sulphateinhibits catecholamine release fromthe tumour,blocks peripheral catecholamine receptors, andisadirectvasodilator(7).Almosteveryreportofpheochromocytoma in pregnancy has diligentlystressed the importance of correctly balancingvasodilatation and vasoconstriction to optimisethemother’s conditionandprevent fetaldemise(5). Methyldopa, which is frequently used forhypertensionduringpregnancy,mayworsenthesymptomsofpheochromocytoma(5). Diabetes, hypertension, and proteinuria inourpatientwerealmostcompletelyresolvedaftertheadrenalectomyandaresimilar to theresultsthat have been previously described (5,7). Theultimateaimwastopreventahypertensivecrisis(7) that is predictably disastrous to the motherand fetus. Utero-placental insufficiency affectedthegrowthoffetusinthiscase.However,thefetuscontinuedgrowingatthe5thcentile.Acaesareansectionwasperformedduetofetaldistress. In conclusion, the commitment of amultidisciplinary team is of utmost importance,and individual patient consideration is essentialduring the management of this dangerouscondition.

Authors’ Contribution

Conception and design, collection, assembly,analysis,and interpretationof thedata,draftingofthearticle:MINAProvision of patient, critical revision and finalapproval of the article:MINA,ARR,AWN,MR,NAK

Correspondence

DrNorAzlinMohamedIsmailBSc(StAndrews),MBChB(Glasgow),MOG(UKM)DepartmentofObstetricsandGynaecologyFacultyofMedicineUniversitiKebangsaanMalaysiaJalanYaacobLatiff56000CherasKualaLumpur,MalaysiaTel:+603-91455949Fax:+603-91456672Email:azlinm@ppukm.ukm.my

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