Hypothyroid Pericardial Effusion

Hypothyroid pericardial effusion is a pericardial effusion caused by thyroid hormone deficiency. The fluid accumulates slowly and, unlike most other causes, tamponade is rare. It resolves with thyroid hormone replacement.

Pericardial effusion occurs in about 30% of patients with overt hypothyroidism and in up to 80% of those with severe disease (myxoedema). It is uncommon in mild or subclinical hypothyroidism.

Causes of hypothyroidism are autoimmune thyroiditis (Hashimoto), post-thyroidectomy or post-radioiodine hypothyroidism, neck radiotherapy, drugs (amiodarone, lithium, immune checkpoint inhibitors, tyrosine kinase inhibitors), and central hypothyroidism. Iodine deficiency remains a cause in some regions.

Severity ranges from a small incidental effusion to a large effusion with symptoms. Myxoedema coma is the most severe form and a medical emergency.

Pathophysiology.

Thyroid hormone deficiency increases capillary permeability, which allows protein and fluid to leak into the pericardial space. Lymphatic drainage falls, and sodium and water retention follows low cardiac output and renal effects.

The fluid is protein rich and contains high cholesterol and glycosaminoglycans (mucopolysaccharides), giving a straw coloured or gold paint appearance.

Effusion accumulates over months, so the pericardium stretches and tolerates large volumes. Tamponade occurs when the effusion accumulates quickly or coexists with pericarditis or heart disease.

Low cardiac output, bradycardia, raised systemic vascular resistance, reduced contractility and dyslipidaemia also occur in hypothyroidism.

Many patients have no cardiac symptoms. Others have dyspnoea, fatigue, chest heaviness, peripheral oedema and orthopnoea. Hypothyroid features: cold intolerance, weight gain, constipation, dry skin, hair loss, hoarse voice, slow relaxing reflexes, bradycardia, delayed ankle jerk relaxation, carpal tunnel syndrome, menstrual disturbance, and puffy facies.

Heart sounds are muffled, and the apex beat is hard to palpate. Pericardial rubs and pulsus paradoxus are uncommon. Pleural effusion and ascites may coexist. Tamponade shows hypotension, raised jugular venous pressure, and pulsus paradoxus.

• Thyroid function: TSH markedly raised (usually over 20 mU/L in effusion) with low free thyroxine in primary hypothyroidism; low or inappropriately normal TSH with low free thyroxine in central hypothyroidism. Anti-thyroid peroxidase antibodies for autoimmune cause.
• Echocardiography: size of effusion (small under 10 mm, moderate 10 to 20 mm, large over 20 mm in diastole), signs of tamponade physiology, and ventricular function. Cardiac MRI or CT if loculated.
• ECG: sinus bradycardia, low voltage, flat or inverted T waves, and prolonged QT interval.
• Other tests: creatine kinase (often raised), cholesterol (raised), sodium (low), full blood count (anaemia), creatinine, liver tests, glucose, cortisol (exclude coexisting adrenal insufficiency, especially in autoimmune polyendocrine disease).
• Pericardiocentesis only for tamponade or diagnostic uncertainty. Fluid is usually an exudate with a high cholesterol content.
• Exclude other causes: tuberculous, malignant, uraemic, viral, autoimmune pericarditis, heart failure and nephrotic syndrome.

Differential diagnosis.

• Idiopathic, viral and autoimmune pericarditis, and tuberculous pericarditis.
• Malignant effusion and radiation pericarditis.
• Uraemic pericarditis and heart failure with effusion.
• Dilated cardiomyopathy, nephrotic syndrome and cirrhosis.

Thyroid hormone replacement (the main treatment).

• Levothyroxine, young adults without cardiac disease: 1.6 microgram/kg orally once daily (adjust by weight; usual 75 to 150 microgram daily), taken on an empty stomach 30 to 60 minutes before breakfast, separated by 4 hours from iron, calcium, antacids and sucralfate.
• Older adults, coronary disease or heart failure: start 12.5 to 25 microgram orally once daily and increase by 12.5 to 25 microgram every 4 to 6 weeks, to the dose that normalises TSH. Rapid replacement can provoke angina, arrhythmia or infarction. Monitor ECG and symptoms after each increase. Maximum is individualised by TSH (usually 1.6 microgram/kg daily).
• Check TSH and free thyroxine 6 to 8 weeks after any dose change, then every 6 to 12 months once stable. Adjust for weight change, interacting drugs (rifampicin, phenytoin, carbamazepine), and pregnancy.
• No renal or hepatic dose adjustment except cautious starting doses in the frail.

Myxoedema coma (emergency).

• Intensive care with airway and ventilatory support, warming (passive), and treatment of precipitants (infection, drugs, cold exposure).
• Hydrocortisone 100 mg intravenously every 8 hours until adrenal insufficiency is excluded (give before levothyroxine).
• Levothyroxine 200 to 400 microgram intravenously as a loading dose (lower end, 200 microgram, for older adults and those with coronary disease), then 1.6 microgram/kg daily intravenously at 75% of the oral dose (usually 50 to 100 microgram daily) until oral therapy is possible. Liothyronine 5 to 20 microgram intravenously as a loading dose, then 2.5 to 10 microgram every 8 hours (lower doses in older adults and cardiac disease), is added in some centres; use with continuous ECG monitoring.
• Treat hyponatraemia with fluid restriction, hypoglycaemia with dextrose, and avoid sedatives and opioids. Active rewarming only if temperature is under 30 degrees Celsius.

Effusion.

• Most effusions resolve over weeks to months (usually 3 to 12 months) with replacement alone. Drainage is not needed for asymptomatic or minimally symptomatic effusions.
• Pericardiocentesis (under echocardiographic control, subcostal or apical approach) for tamponade or when the diagnosis is uncertain. Leave a pigtail drain until output falls under 25 mL in 24 hours. Recurrence after drainage is uncommon once euthyroid.
• Diuretics are of limited use and risk hypotension and renal impairment when preload is critical. Avoid NSAIDs, colchicine and corticosteroids for pericardial effusion alone (they add nothing in this setting), except for coexisting pericarditis.

Associated problems. Treat dyslipidaemia after thyroid hormone replacement (lipids improve with replacement). Avoid statins until TSH is controlled because of the risk of myopathy.

Monitoring. Echocardiography at 4 to 6 weeks, 3 months and 6 months, and every 3 to 6 months until the effusion resolves. TSH and free thyroxine at 6 to 8 weeks, with ECG and heart rate review. Weight, blood pressure and symptoms at each visit. Creatinine, sodium and creatine kinase at 4 to 6 weeks.

Referral and escalation. Refer to endocrinology for all new overt hypothyroidism with effusion. Urgent referral and admission for tamponade, myxoedema coma, altered consciousness, hypothermia, hypotension, bradycardia or hyponatraemia (sodium under 120 mmol/L). Refer for drainage when tamponade physiology develops.

Special groups.

• Pregnancy: increase the levothyroxine dose by about 25 to 30% as soon as pregnancy is confirmed; check TSH every 4 weeks until midpregnancy, then at least once at 30 weeks; target TSH under 2.5 mU/L.
• Children: congenital hypothyroidism needs levothyroxine 10 to 15 microgram/kg daily from the first days of life, with specialist paediatric endocrinology care.
• Older adults: low starting doses and slow titration; assess for coronary disease.
• Kidney or liver impairment: pericardial effusion from uraemia or liver disease may coexist; separate causes of effusion are sought.
• Region specific: iodine deficiency and autoimmune thyroid disease should be considered; tuberculosis and HIV pericarditis should be excluded where prevalent.