Journal of Endocrinology and Metabolism, ISSN 1923-2861 print, 1923-287X online, Open Access
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Volume 12, Number 1, February 2022, pages 1-9

Pleuropericardial Compromise Associated With Graves’ Disease: A Systematic Review


Figure 1.
Figure 1. Flow diagram of screening and selection of articles adapted from the PRISMA. PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses; ATD: antithyroid drug.


Table 1. Clinical and Cytochemical Features of Patients With Pleural or Pericardial Effusion Associated With Thyroid Disease
ReferenceAge/sexImmunological signsCardiac tamponadeSerosaCharacteristics of the effusionEffusion’s management (diagnosis, biopsy, drainage)GD treatmentAdditional treatmentFollow-upOutcomes
M: male; F: female; GD: Graves’ disease; NS: does not specify; NR: does not refer; -: does not apply; Pe: pericarditis; Pl: pleurisy; RAI: radioiodine therapy.
Airel et al, 2013 [39]24/MBilateral orbitopathy, lid lagNoPeNRNR-Atenolol, methimazoleYesNRPrednisone3 monthsHypothyroidism, mild regression of orbitopathy
Bui et al, 2016 [43]76/MNoYesNRHematic, exudateLeft-sided, transudatePericardiocentesis, thoracentesisMethimazoleNRNRHeparin, corticoids, aspirin, diltiazem5 monthsAsymptomatic
Clarke et al, 2002 [44]35/FLid lagYesPeYes/NSYes, bilateral/NSPericardiocentesisCarbimazole, propranololYesNRNR18 monthsEuthyroid, no effusions
Clarke et al, 2002 [44]47/FNRNoPeYes/NSNRNRPropranolol, carbimazoleNRNRHeparin12 monthsAsymptomatic
Cullen et al, 2017 [45]17/MBilateral orbitopathy, lid lagNoPeNoNR-Methimazole, propranololNRNRLorazepam1 monthNo recurrence, proptosis persisted
Gondal et al, 2020 [46]24/MThyroid enlargementNoPeYes/NSNRNRCarbimazole, propranololNRNRIbuprofen, omeprazole3 monthsEuthyroid, clinically and biochemically
Gupta et al, 2015 [47]40/MNRNoPeNRNR-Propylthiouracil, labetololNRNRIbuprofen10 daysFollow-up was recommended
Hosseini et al, 2019 [48]69/FNRYesNRExudateLeft-sided/NSPericardiocentesisNRNRNRParacetamol4 weeksPericardial effusion (re-hospitalized)
Inami et al, 2014 [49]69/FNRNoPeNoNR-Methimazole, β antagonistNRNRIbuprofen, colchicine4 weeksEuthyroid state
Khalid et al, 2011 [7]68/FNRNoPe, PlYes/NSYes/exudatePleural biopsyCarbimazole, propranololNRNRNR6 monthsEuthyroid state
Koo et al, 2012 [50]42/MNRNoPeYes/NSNRNRMethimazoleNRNRIbuprofen, colchicine3 monthsNo recurrence
Kortekaas et al, 2014 [51]44/MNoNRPeNRNRDashThiamazole, metoprololNRNRCarbasalate calcium, colchicineOutpatient follow-up was scheduled
Nakata et al, 2005 [40]43/MNRNoNoHematic, exudateNRPericardiocentesisMethimazole, iodine (drug)NRNRNR1 monthNo recurrence
Rodriguez et al, 2006 [41]68/MNoNoPlNRYes, right-sided/exudateDiagnostic thoracentesis, pleural biopsyNRYesNRNR12 monthsAsymptomatic
Teague et al, 2009 [42]42/FEdemaYesPeHematic, exudateYes/NSPericardiocentesisCarbimazole and propranololNRNRDiureticsNS“She remained well”


Table 2. Diagnostic Features of Pleuropericardial Compromise (PPC)
ReferenceDiagnosis of PPC
Clinical symptomsImaging compatible with PPCECG compatible with pericarditis
Pe: pericarditis; ECG: electrocardiogram; CT: computed tomography; ECO: echocardiography; MRI: magnetic resonance imaging; Pe-Ef: Pericardial effusion; Pl-Ef: Pleural effusion; NR: does not refer.
Airel et al, 2013 [39]Pe: substernal, pleuritic chest pain relieved in the upright positionNRPR segment depression, and diffuse ST segment elevation
Bui et al, 2016 [43]NRECO: Pe-Ef; chest X-ray: Pl-EfNR
Clarke et al, 2002 [44]NRNRNR
Clarke et al, 2002 [44]NRECO: Pe-EfNR
Cullen et al, 2017 [45]Pe: pain improved sitting upright and leaning forwardNRDiffuse ST-segment elevation
Gondal et al, 2020 [46]Pe: sharp chest pain, increased by breathing, improved by leaning forwardECO: small global pericardial effusionDiffuse ST elevation and PR depression in limb leads
Gupta et al, 2015 [47]Substernal, pleuritic chest pain; improved on leaning forward; mild dyspnea; friction rubECO: Pe-EfPR depressions and downsloping TP-segments, except in leads aVR and V1
Hosseini et al, 2019 [48]Cardiac tamponade: jugular vein distension, pulses paradoxes, and muffled heart soundsECO: Pe-Ef; chest X-ray: Pl-EfNR
Inami et al, 2014 [49]Retrosternal chest pain which increased with deep breathing and position changeECO: normal; CT: thickened pericardiumDiffuse ST-segment elevation in all leads except aVR and V1.
Khalid et al, 2011 [7]Loud pericardial rub and raised jugular venous pressureECO: Pe-Ef; chest X-ray: Pl-EfNR
Koo et al, 2012 [50]Pain increased with deep breathing and position changeECO: Pe-Ef; MRI: thickened pericardium and Pe-EfDiffuse concave ST-segment elevation in all leads except aVR and V1
Kortekaas et al, 2014 [51]Sharp retrosternal pain; precordial friction rub chest painECO: no Pe-EfConcave ST-segment elevation in all leads except aVR and aVL
Nakata et al, 2005 [40]Does not refer symptoms of pericarditisECO; chest X-ray; CT: Pe-EfNR
Rodriguez et al, 2006 [41]Pl-EfChest X-ray and CT (Pl-Ef)Atrial fibrillation
Teague et al, 2009 [42]Pl-EfECO: Pe-Ef; chest X-ray: Pl-EfDoes not refer


Table 3. Quality Assessment of Included Papers
StudySelectionAscertainmentCausalityReportingTotal score
a. Does the patient(s) represent(s) the whole experience of the investigator (center) or is the selection method unclear to the extent that other patients with similar presentation may not have been reported?b. Was the exposure adequately ascertained?c. Was the outcome adequately ascertained?d. Were other alternative causes that may explain the observation ruled out?e. Was follow-up long enough for prognosis outcomes to occur?f. Is the case described with sufficient details to allow other investigators to replicate the research or to allow practitioners make inferences related to their own practice?
Airel et al, 2013 [39]YesYesYesNoNoYes4
Bui et al, 2016 [43]YesYesYesYesNoYes5
Clarke et al, 2002 [44]NoYesYesYesYesNo4
Clarke et al, 2002 [44]NoYesYesYesYesNo4
Cullen et al, 2017 [45]NoYesYesNoNoYes3
Gondal et al, 2020 [46]NoYesYesYesNoYes4
Gupta et al, 2015 [47]YesYesNoNoNoYes3
Hosseini et al, 2019 [48]YesYesYesYesNoYes5
Inami et al, 2014 [49]NoYesYesYesNoYes4
Khalid et al, 2011 [7]NoYesYesYesYesYes5
Koo et al, 2012 [50]YesYesYesYesNoYes5
Kortekaas et al, 2014 [51]NoYesNoYesNoYes3
Nakata et al, 2005 [40]NoYesYesYesNoYes4
Rodriguez et al, 2006 [41]YesYesYesYesYesYes6
Teague et al, 2009 [42]YesYesNoNoNoYes3