Background and Aim: Hypothyroidism is a common clinical condition resulting from insufficient thyroid hormone levels. If left untreated, it can lead to serious complications affecting various organs. Given its prevalence, therapeutic challenges, and the impact of clinical manifestations on patients’ quality of life, a comprehensive and up-to-date review of the scientific literature is essential. Such a review may contribute to improve clinical decision- making.
Methods: In this narrative review, studies published up to the end of 2024 were identified through keyword searches including Hypothyroidism, Diagnosis, Treatment, Levothyroxine, and Liothyronine in databases such as Google Scholar, PubMed, and Web of Science. Clinical studies, review articles, original research, and clinical guidelines focusing on the etiology, diagnosis, and treatment of hypothyroidism were included. Duplicate publications and articles outside the scope of the topic were excluded. Ultimately, 105 articles most relevant to the study objectives were selected for review.
Results: Hypothyroidism is classified as primary, central, or peripheral based on the site of dysfunction. The biochemical diagnosis of primary hypothyroidism is based on persistent elevation of serum thyroid-stimulating hormone (TSH) along with low free thyroxine (fT4) levels (overt hypothyroidism) or normal fT4 levels (subclinical hypothyroidism). The full replacement dose of levothyroxine (LT4) in adults is approximately 1.6 µg/kg/day. The LT4 dosage is adjusted by measuring serum TSH levels 4-8 weeks after initiation of treatment. Monotherapy with liothyronine (LT3) is not recommended due to its short serum half- life and significant hormonal fluctuations. Despite normalization of TSH and fT4 levels, a considerable proportion of patients treated with LT4 continue to experience persistent symptoms that negatively affect their quality of life. Elevated serum T4 levels and relatively low T3 levels may contribute to these persistent symptoms in some patients.
Conclusion: Levothyroxine remains the standard treatment for hypothyroidism; however, persistent symptoms in some patients highlight the limitations of LT4 monotherapy. Although combination therapy with LT4 and liothyronine has been proposed as a potential alternative, conclusive evidence from clinical trials is still lacking, and further
well- designed studies are needed.