Myxedema Heart and Pseudotamponade

Chelsey Baldwin; Jonathan D. Newman; Franco Vallejo; Valerie Peck; Loren Wissner Greene; Ira J Goldberg


J Endo Soc. 2021;5(1) 

In This Article


We present 3 cases of myxedema pericardial effusion that highlight the hemodynamic stability of hypothyroid patients with large pericardial effusions with significant echocardiographic findings. All 3 patients had biochemical and clinical evidence of severe hypothyroidism. Our first case demonstrates that patients with large pericardial effusions due to hypothyroidism can be managed conservatively with thyroid hormone replacement despite echocardiographic findings of chamber compromise and abnormal diastology. Our second case supports the use of pericardiocentesis when the underlying etiology for the effusion cannot be reasonably limited to hypothyroidism. It should be noted, however, that prolonged pericardial drainage may increase the risk of nosocomial infections. Our final case exhibits a rare complication—to our knowledge, the first reported case—of a large effusion due to hypothyroidism causing compression of the left mainstem bronchus. The patient presented with airway obstruction, and only after cross sectional imaging was it apparent that the large pericardial effusion caused bronchial compression. A single therapeutic pericardiocentesis and concomitant thyroid replacement was sufficient for symptomatic relief. This case demonstrates the need for therapeutic evacuation of a large effusion due to hypothyroidism when there are extenuating circumstances.

Patients with pericardial effusions due to hypothyroidism typically present with complains of dyspnea (61.1%),[4] cough (25%),[4] and/or chest pain (13.9%)[4] in the setting of clinical and biochemical features of severe hypothyroidism including lethargy, facial swelling, dry skin with nonpitting edema, delayed relaxation of deep tendon reflexes, low thyroxine levels, and abnormal TSH levels (elevated in primary hypothyroidism and low or inappropriately normal in secondary or tertiary hypothyroidism). Elevation of TSH greater than 30 mU/L was seen in all 3 of our cases and 95% in other series.[4] The most common causes of severe hypothyroidism in our case series was medication noncompliance or undiagnosed hypothyroidism in patients with prolonged absence from medical attention.

Initial evaluation of patients presenting with dyspnea, a common symptom of severe hypothyroidism with pericardial effusion, typically includes a chest X-ray and ECG. Each of our patients had an enlarged cardiac silhouette. Concurrent pulmonary effusion due to serositis may be seen. Consolidations of the pulmonary parenchyma would be unexpected without a concurrent disease process. ECG changes associated with severe hypothyroidism include low voltage, sinus bradycardia, flattened T, or inverted T waves, prolonged QTc predisposing patient to risk of development of torsade de pointes ventricular tachycardia, and, rarely, AV block.[4,16] Of note, only 1 of our patients was bradycardic, and none were tachycardic as might be expected with large pericardial effusions limiting chamber filling. The abnormalities of the chest X ray and ECG require evaluation for pericardial effusion by echocardiogram based on current guidelines.[17]

Pericardial effusions associated with severe hypothyroidism is not an uncommon finding;[9–11] however, it is rarely associated with clinical signs of tamponade. The frequency of tamponade physiology associated with myxedema pericardial effusions is greatly impacted by how the clinician defines tamponade. The diagnosis of cardiac tamponade is a clinical diagnosis made in the setting of hypotension, jugular distention, and tachycardia, often with pulsus paradoxus. None of our patients fit these clinical criteria.

We describe echocardiographic features of large pericardial effusions in the setting of severe hypothyroidism without tamponade physiology. Evaluation of effusion with echocardiography is recommended by European Society of Cardiology.[17] Findings associated with tamponade include IVC plethora due to increased right atrial pressure, RA and RV diastolic collapse, and respiratory variation of diastolic flow across the mitral value. However, these findings lack specificity and sensitivity. Right ventricular diastolic collapse can be seen with hypovolemic states and large pleural effusions, and right ventricular diastolic collapse may be absent in tamponade in patients with high pulmonary pressures. Respiratory variation of mitral valve inflow may occur in obstructive pulmonary disease, pulmonary embolism, and right ventricular infarction.[15] In 2010, Wang et al reported that 50% of their patients with pericardial effusion associated with hypothyroidism had echocardiographic evidence of cardiac tamponade.[4] However, only 22% of patients in the 2010 Wang et al study meet the traditional clinical definition of tamponade of exhibiting pulsus paradoxus or unstable hemodynamics. All of our patients demonstrated echocardiographic signs of tamponade, but none had clinical evidence of tamponade physiology. Two of our patients underwent pericardiocentesis for diagnosis or management of noncardiac complications, and the third was successfully treated without invasive interventions.

Slow accumulation of fluid in the pericardial space allows for a rightward shift of the pressure-volume curve allowing for large volumes of fluid to collect prior to reaching limit of pericardial stretch, at which point a steep rise in pericardial pressure results in cardiac chamber collapse.[15,18] While larger volumes of fluid can be compensated for longer in disease processes with slow accumulation (ie, myxedema associated effusion), the pressure-volume curve will at some volume exhibit a steep rise in pressure leading to tamponade physiology. However, myxedema-associated pericardial effusion appears to have a prolonged period of time when echocardiographic evidence of tamponade may be present without clinical features of tamponade, as exemplified by our case series, and can be reversed with thyroid hormone replacement alone, as demonstrated in Case 1. We hypothesize accumulation of large volume effusion results in a rise in oncotic pressure within the pericardial space, which balances with osmotic pressure developed by capillary protein leak, protecting these patients from accumulation of fluid beyond the maximal stretch of the pericardium at which point cardiovascular compromise is expected (Figure 4).

Figure 4.

Pericardial effusion management in a hypothyroid patient. ŧ Echocardiographic findings of IVC plethora due to increased right atrial pressure and RA and RV diastolic collapse; respiratory variation of diastolic flow across the mitral valve may be present in the absence of hemodynamic compromise consistent with pseudotamponade. ˠ Findings on ECG consistent with myxedema heart include low voltage, flattened or inverted T waves, relative bradycardia, prolongation of QTc, and ±electrical alternans. *Initial dose of levothyroxine dependent on clinical severity of hypothyroidism and history/suspicion of cardiac comorbidities.

There are no available specific clinical guidelines to direct the evaluation and treatment of myxedema associated pericardial effusion. We suggest once the diagnosis of hypothyroidism is determined to be the most likely etiology of pericardial effusion, hemodynamic stability should be carefully confirmed by physical exam, including use of maneuvers to elicit pulses paradoxus, if present. Echocardiography may demonstrate echocardiographic features with large pericardial effusions not associated with hemodynamic instability that resolve with thyroid hormone replacement alone, leading us to suggest these findings are consistent with "pseudotamponade."

Thyroid hormone replacement, in the form of levothyroxine, reverses the progression of fluid accumulation and prevents cardiac collapse. Pericardial effusions due to severe hypothyroidism will begin to resolve even prior to biochemical and clinical euthyroidism. Complete resolution of the effusion occurs within 8 to 26 weeks[4,19] without invasive management. The American Thyroid Association (ATA) recommends that the initial levothyroxine doses be given intravenously until the patient demonstrates clinical improvement.[20] Even very low doses of levothyroxine can correct capillary permeability;[19] therefore, initial doses can be more conservative than estimates for full replacement by body weight (1.6 μg/kg/day) as suggested by ATA for patients with myxedema coma. Often clinicians reduce the dose by 25% when dosing intravenously due to improved bioavailability; further dose reductions should be considered in patients with history of or suspected history of untreated coronary artery disease.[20,21] An initial bolus of levothyroxine should be reserved for the most severe presentations of hypothyroidism. In Case 3, a bolus of 200 mcg of IV levothyroxine was given as this patient necessitated ICU admission for altered mental status and hypercapnic respiratory failure in setting of low normal body temperature, concerning for myxedema coma. Therefore, we felt early aggressive intervention was indicated based on our clinical suspicion, despite known cardiac risks of tachycardia, arrhythmia, and myocardial infarction.[20] Also, the doses of levothyroxine at discharge were higher than ATA prediction for full replacement in Case 1 and Case 2, with discharge doses of levothyroxine of 2.3 mcg/kg and 2.8 mcg/kg, respectively. Our doses were guided by serial laboratory tests to demonstrate normalization of fT4 and trend of TSH improvement. Levothyroxine resistance demonstrated in these patients can be due to concurrent medication use altering gastric pH or levothyroxine absorption, alterations of gut flora, concurrent autoimmune disease affecting the gut, and noncompliance with fasting after administration of levothyroxine tablet.[22] In Case 1, the patient was started on proton pump inhibitor for gastric protection in the setting of dual antiplatelet therapy use for stroke, which made have led to poor dissolution and therefore bioavailability of levothyroxine tablet. In Case 2, the patient's phenotype of polyautoimmunity could be consistent with concurrent gastrointestinal conditions impairing levothyroxine absorption. Autoimmune atrophic gastritis and celiac disease have been associated with concurrent thyroid autoimmunity[23,24] and may provide an explanation for the requirement of higher doses of levothyroxine. Additionally, this patient required antibiotics that may have altered gut flora resulting in impaired levothyroxine absorption.[22] Given the possibility of changes to medication regimen and gut flora post discharge, follow-up is imperative to avoid over treatment and work-up concomitant conditions.

In addition to levothyroxine, clinicians should consider a stress dose of glucocorticoid prior to levothyroxine if unable to rule out concurrent adrenal insufficiency.[20] The use of concurrent intravenous liothyronine is reserved for patients with myxedema coma and those without clinical improvement with levothyroxine monotherapy.

In some cases, the etiology of pericardial effusion is unclear. While laboratory testing consistent with severe hypothyroidism in the absence of typical beta-adrenergic driven tachycardia (HR less than 90 bpm) is highly suggestive of hypothyroidism as the underlying cause of the pericardial effusion, it may be necessary to rule out concurrent disease processes. In Case 2, known rheumatologic disease raised the concern for possible alternative explanation of effusion. Similar diagnostic confusion may be present in patients with concurrent trauma, sepsis, renal failure, or malignancy. The majority of patients who develop clinical cardiac compromise in the form of tamponade due to myxedema associated pericardial effusion will have precipitating factor-like infection or trauma.[4] Therefore, a diagnostic pericardiocentesis may be helpful when there is diagnostic uncertainty. European Society of Cardiology guidelines for diagnosis and management of pericardial disease suggest that if a specific etiology of pericarditis and effusion is suspected or high risk features (such as fever, subacute onset, large pericardial effusion, cardiac tamponade, or lack of response to one week of anti-inflammatory therapy) are present, diagnostic pericardiocentesis is indicated. Pericardiocentesis or surgical intervention is also required when the clinical diagnosis of tamponade is made, again reflecting the importance of the defining tamponade clinically to avoid unnecessary intervention.

A volume of 50 to 100 mL of pericardial fluid is satisfactory for diagnostic testing. Also, aspiration of relatively small volume may result in a decline in pericardial pressure in patients with tamponade physiology.[15]

There are no specific clinical guidelines to direct the evaluation and treatment of myxedema associated pericardial effusion. We extrapolate from the 2015 European Society of Cardiology guidelines for evaluation and management of pericardial disease and the 2014 ATA guidelines for hypothyroidism, along with experiences reported in the literature supported by our 3 additional cases to suggest a method for the appropriate management of myxedema associated pericardial effusion (Figure 4). In summary, patients found to have large pericardial effusion and stable hemodynamics investigation for etiology should include TSH and fT4. Laboratory evidence and clinical syndrome consistent with severe hypothyroidism in the context of a large pericardial effusion with relative bradycardia is highly consistent with myxedema associated pericardial effusion. TSH receptor blocking antibodies are used by some clinicians in patients with hypothyroidism as a mechanistic indicator of atrophic hypothyroidism, which may be associated with severe clinical presentations of hypothyroidism.[25] These antibodies were not obtained in our patients due to the clinically apparent severity of their conditions and lack of readily available quick turn-around cell-based bioassays to prove functional inhibition of TSH receptor. Echocardiography is essential for the diagnosis of pericardial effusions; however, it may demonstrate echocardiographic findings associated with tamponade physiology without impending cardiovascular compromise, consistent with "pseudotamponade." Therefore, the diagnosis of tamponade should be reserved for patients demonstrating clinical features of tamponade, pulsus paradoxus, and hemodynamic compromise. Patients with myxedema or severe hypothyroidism may be protected against clinical manifestations of tamponade through the slow accumulation of pericardial fluid. Hypothyroidism associated pericardial effusions rarely accumulate fluid beyond maximal extension of the pericardium, protecting the patient from clinical features of tamponade. Because pericardial effusions of hypothyroidism will resolve with levothyroxine, monotherapy pericardiocentesis should be reserved for cases of diagnostic confusion and rare cases of cardiovascular compromise or compromise of adjacent vital structures. Clinical evidence of tamponade physiology in the setting of myxedema associated pericardial effusion may support investigation for other underlying causes of pericardial effusion.