A pediatric case of reversible dilated cardiomyopathy caused by autoimmune hypothyroidism

Chanyoung Chung; Hyoung Doo Lee; Hyang-Ok Woo; Joung-Hee Byun; Heirim Lee; Hoon Ko

doi:10.22470/pemj.2025.01501

Abstract

Dilated cardiomyopathy is the most common form of cardiomyopathy in children and often leads to irreversible myocardial dysfunction. To improve the prognosis, it is critical to identify rare but reversible causes. We report a 12-year-old girl referred to the emergency department for dyspnea on exertion and generalized edema that lasted for 1 month. She gained 20 kg over the past 3 years, which had gone uninvestigated. Transthoracic echocardiography demonstrated left ventricular dysfunction with pericardial effusion. Thyroid function tests revealed concentrations of free T4 and thyroid-stimulating hormone of 0.12 ng/dL (reference value, 0.93–1.7) and 86.9 µIU/mL (0.3–4.2), respectively, with anti-thyroid peroxidase and anti-thyroglobulin antibodies elevated, confirming the presence of autoimmune hypothyroidism. We initiated heart failure management alongside levothyroxine replacement therapy. After 5 months of treatment, a follow-up echocardiography showed improved left ventricular and thyroid function.

Introduction

Dilated cardiomyopathy (DCM) is the most common form of cardiomyopathy in children, accounting for approximately 50% of all pediatric cardiomyopathies (1). The disease entity is typically characterized by ventricular chamber enlargement accompanied by impaired systolic function of the left ventricle (LV), which frequently progresses to symptomatic heart failure (HF). The etiology is most commonly idiopathic (2). Among identifiable causes, myocarditis is most frequent (46%), followed by neuromuscular disorders (26%) (2,3). Hypothyroidism-induced DCM is a rare but potentially reversible condition. Hypothyroidism has been associated with both systolic and diastolic dysfunction as well as various extracardiac manifestations.

Therefore, it is essential to recognize and treat reversible causes, such as hypothyroidism, as the uncommon causes could alter the clinical courses and outcomes of the disease. We report an adolescent girl with a reversible case of DCM secondary to autoimmune hypothyroidism, highlighting the importance of early recognition, appropriate hormonal therapy, and comprehensive HF management. Informed consent for publication of this case report was obtained from the patient and her legal guardian.

Case

A 12-year-old girl was referred to our emergency department (ED) with a 1-month history of exertional dyspnea and generalized edema at presentation. She had no recent history of upper respiratory infection or fever, or exposure to psychiatric medications or cardiotoxic agents. Her past medical history was remarkable for a 20-kg weight gain over the past 3 years that had not been medically addressed. She had no history of perinatal complications or developmental delays, with no abnormalities in both liquid chromatography-tandem mass spectrometry and fluorescence immunoassay performed on day 3 of her life. She had no family history of cardiomyopathy or arrhythmia.

The initial vital signs were as follows: blood pressure, 87/55 mmHg; heart rate, 107 beats/minute; respiratory rate, 30 breaths/minute; temperature, 36.4 °C; and oxygen saturation, 95% on room air. At the time of presentation, her height and weight were 150 cm (10-25 percentile) and 102 kg (>97 percentile), respectively.

Initial laboratory findings were as follows: white blood cells, 15,650/mm³; hemoglobin, 14.9 g/dL; creatine kinase, 258 U/L; aspartate aminotransferase, 62 U/L; alanine aminotransferase, 72 U/L; myoglobin, 30.1 ng/mL; creatine kinase-myocardial band, 8.1 ng/mL; troponin-T, 53 ng/mL; B-type natriuretic peptide (BNP), 2,559 pg/mL; sodium, 133.7 mmol/L; C-reactive protein, 0.12 mg/dL; blood urea nitrogen, 25.4 mg/dL; creatinine, 1.39 mg/dL; urine sodium, 11.3 mmol/L; and urine creatinine, 126.3 mg/dL. Given the presence of generalized edema and the need to evaluate for acute kidney injury or chronic kidney disease, we calculated creatinine clearance using the Cockcroft-Gault equation and fractional excretion of sodium, resulting in values of 50 mL/min/1.73 m² and 0.1%, respectively. These values were consistent with decreased renal perfusion rather than intrinsic renal lesions.

The initial chest radiography showed cardiomegaly (Figure 1). A portable transthoracic echocardiography (TTE) performed at the ED demonstrated an ejection fraction of LV (LVEF) of 33% on motion mode, an enlarged LV internal dimension in systolic phase (52 mm; Z-score 3.38) (4), and an elevated left atrial volume index of 39 mL/m² with a moderate pericardial effusion (maximum depth, 17 mm), all consistent with DCM complicated by HF (Figures 2, 3). The ratio of early transmitral peak velocity to septal early diastolic mitral annulus velocity (E/e') was 16, indicating elevated LV filling pressure. A contrast-enhanced chest computed tomography showed no evidence of coronary artery anomalies.

Autoimmune evaluations for myocarditis or systemic lupus erythematosus showed a concentration of anti-double-stranded DNA antibodies within normal limits and a weakly positive fluorescent antinuclear antibody test (1:40, speckled pattern), which was deemed clinically irrelevant. A next-generation sequencing panel for hereditary cardiomyopathy identified a variant of uncertain significance in the VCL gene, which was considered non-pathogenic given the lack of family history. Metabolic evaluation for obesity revealed mild hypercholesterolemia (total cholesterol, 251 mg/dL and low-density lipoprotein, 178 mg/dL), but was otherwise unremarkable for cortisol or hemoglobin A1c concentration.

However, thyroid function tests performed on day 1 to investigate secondary causes of DCM showed concentrations of free T4, 0.12 ng/dL (reference value, 0.93-1.7) and thyroid-stimulating hormone (TSH), 86.9 µIU/mL (0.3-4.2). These findings indicate severe hypothyroidism. Concentrations of both anti-thyroid peroxidase and anti-thyroglobulin antibodies were elevated, while those of TSH receptor antibodies were normal. Thyroid Doppler ultrasonography performed on day 20 demonstrated heterogeneous echogenicity consistent with thyroiditis. She was admitted to the pediatric intensive care unit and required endotracheal intubation and mechanical ventilation for HF. Management was initiated with inotropes (dopamine, dobutamine, milrinone, and digoxin), diuretics (furosemide and spironolactone), losartan, carvedilol, and levothyroxine (150 µg once daily).

On day 4, the patient was successfully extubated and switched to oxygenation via a nasal prong, with dopamine discontinued. Follow-up tests showed a creatinine concentration of 0.79 mg/dL with a creatinine clearance of 191 mL/minute/1.73 m² (Cockcroft-Gault). She was transferred to the general ward on day 9. By day 55, TTE showed a 38% LVEF; consequently, dobutamine and milrinone were discontinued. She was maintained on oral HF medications and levothyroxine. The temporal trend of TSH, free T4, BNP, and LVEF during the hospitalization is plotted in Figure 4. On day 119, a follow-up TTE showed a 52% LVEF. On day 121, diuretics, digoxin, and carvedilol were discontinued, leaving her taking only losartan and levothyroxine.

On day 151, a follow-up repeat motion mode of TTE demonstrated further improvement in cardiac function as follows: LVEF, 56%; left atrial volume index, ≤34 mL/m² (reference value, ≤34); and E/e′ ratio, 8. Thyroid hormone concentrations returned to within normal ranges, while her weight changed from 102 kg on day 1 to 67 kg, corresponding to a body mass index change from 45.3 kg/m² to 29.8 kg/m² with losartan discontinued. On day 152, she was discharged uneventfully. This prolonged hospital stay was related to obesity-related gait and joint problems, as well as obstructive sleep apnea, independent of the cardiac and hypothyroidism issues. Over a 2-year follow-up period, she remained clinically stable on thyroxine monotherapy without recurrence of DCM.

The diagnosis of DCM due to autoimmune hypothyroidism was confirmed by the absence of other identifiable etiologies and a favorable clinical response to thyroid hormone replacement therapy.

Discussion

In pediatric patients with HF, it is essential to evaluate for congenital cardiac anomalies, particularly coronary artery anomalies, alongside a comprehensive assessment of cardiac function (5). Furthermore, HF should be treated simultaneously with the diagnostic workup (6).

Thyroid hormone plays a pivotal role in regulating myocardial contractility and hemodynamics. Hypothyroidism can induce DCM through mechanisms including bradycardia, decreased myocardial contractility, or increased systemic vascular resistance (7). Thyroid hormone replacement therapy is critical in reversing these impairments by improving myocardial oxygen consumption efficiency and enhancing cardiac output (8).

In this case, we diagnosed DCM due to autoimmune hypothyroidism with HF. The patient’s obesity and pericardial effusion on TTE were clinical clues for hypothyroid-induced HF. Following the initiation of levothyroxine therapy, the cardiac function progressively improved, allowing for the tapering of HF medications. Notably, her massive weight loss (35 kg) was considered the resolution of fluid retention and myxedema. In addition to the abovementioned clues, key highlights in her clinical course were the autoimmune thyroid etiology confirmed by the antibody testing and Doppler ultrasonographic findings, long-term sustained recovery following levothyroxine therapy, and absence of other identifiable causes of DCM or HF. These findings support the central role of hypothyroidism in this case.

A similar adult case of DCM with HF caused by hypothyroidism showed an improvement after thyroid hormone replacement therapy (9). In the cited case, LV dilatation and systolic function improved, and the adult patient’s body mass index returned to the normal range within 3 months.

In pediatric patients presenting to EDs with DCM with HF, it is essential to evaluate thoroughly for underlying or secondary causes, including endocrine diseases, in order to guide appropriate management and optimize outcomes.