Levothyroxine Replacement Therapy and Overuse: A Timely Diagnostic Approach

Levothyroxine (LT4) is one of the most prescribed drugs worldwide. Once started, approximately 90% of patients continue treatment long term. However, accumulating evidence suggests that many patients, for whom the indication for its administration is not adequately established and the diagnosis is not well documented, are overusing it. This study aimed to evaluate the necessity for and determine potential prognostic factors of long-term LT4 supplementation.

A prospective clinical cohort follow-up study was carried out. In 291 subjects (84% females) aged 48 ± 16 years on LT4 replacement therapy without a solid diagnosis of hypothyroidism being provided, the treatment was paused. At the beginning and after six to eight weeks of treatment discontinuation, thyrotropin (TSH) and free thyroxine levels were assessed, and thyroid ultrasound was performed. A TSH value of ≥4.5 IU/mL was considered as underlying hypothyroidism.

Among the 291 individuals, 114 became hypothyroid (group A), while 177 subjects remained euthyroid off LT4 (group B; 39.2% vs. 60.8%, p < 0.001). The groups were comparable regarding sex, family history, age, body mass index, duration of treatment, basal TSH and free thyroxine values, thyroid volume, and presence of thyroid autoantibodies. However, diffuse inhomogeneous echogenicity on ultrasound examination was significantly higher (p < 0.001) in group A.

These findings suggest considerable overuse of thyroxine therapy. The results underline the initial need to establish the diagnosis firmly before treatment initiation and to undertake periodic evaluation of all patients on chronic LT4 treatment as to the necessity for treatment continuation. In all patients on long-term LT4 therapy in whom the diagnosis has not been definitively established, it appears rational to introduce a six- to eight-week period of LT4 replacement therapy discontinuation, preceded and followed by TSH tests, as the first-line approach-a procedure that could be implemented as part of a common strategy among the scientific community to decrease current LT4 overuse.