Clinical insights into levothyroxine overdose: A systematic review

Abstract

BACKGROUND

Levothyroxine (LTX) is one of the most commonly used medications due to the high prevalence of hypothyroidism in various age groups. Overdose (OD) with LTX, intentional or unintentional, is rare but can have clinically significant and even life-threatening consequences. Data on clinical outcomes of patients with LTX OD are limited, and guidelines on its management are suboptimal.

AIM

To compile all available data on the clinical characteristics, management, and outcomes of patients with LTX OD.

METHODS

A systematic literature search was conducted to identify English-language articles through PubMed, Scopus, and EMBASE that reported primary patient data on LTX OD in all age groups. All analyses were performed using STATA-18.

RESULTS

Forty-nine studies, comprising 95 individual cases and six larger retrospective studies (n = 11513), were analyzed. The median age of patients in case reports was 20 years (3.5-42), with a female preponderance (66.1%). The median ingested dose of LTX was 4250 μg (1250-10000), with a median time to presentation of 4.5 hours (1.5–24). Tachycardia (38.9%), confusion (23.2%), and fever (18.9%) were the most frequent symptoms. Severe complications included atrial fibrillation (5.3%), and one death was reported. Patients with intentional LTX OD were significantly older (median 35.5 vs 3.5 years, P < 0.001) and had higher diastolic blood pressure (P = 0.003), while non-intentional OD cases had higher heart rates (P = 0.02). Among the 11513 patients from larger studies, more than 90% experienced minimal or no symptoms, particularly in pediatric cohorts. Rarely severe outcomes, such as coma and cardiac failure, were observed in adults with high-dose ingestions, requiring interventions such as beta-blockers, corticosteroids, and plasmapheresis.

CONCLUSION

This study provides the first comprehensive dataset on LTX OD. Patients with non-suicidal/accidental LTX OD mainly belong to the pediatric age group, while those with suicidal intent belong to the older age group. Despite the risk of toxicity with ingestion of high doses of LTX, mortality is extremely rare.

Keywords: Levothyroxine; Overdose; Toxicity; Thyroid; Suicide; Thyroxine

Core Tip: This systematic review presents the most comprehensive data synthesis on levothyroxine (LTX) overdose (OD) across all age groups. It highlights key clinical patterns that distinguish unintentional pediatric OD from intentional adult OD, with the latter exhibiting more prominent symptom severity. Despite wide dose variability, mortality was rare. Most cases were managed conservatively. Extracorporeal modalities were employed in cases that were severe and refractory. This systematic review highlights the need for treatment protocols and prevention strategies for LTX toxicity, providing valuable insights for clinicians managing thyroid hormone toxicity.