Levothyroxine adherence in primary hypothyroidism: clinical impact, measurement challenges, and opportunities for personalized care

Primary hypothyroidism, most commonly caused by Hashimoto’s thyroiditis, is a highly prevalent chronic condition typically managed with lifelong levothyroxine therapy. Although treatment is generally straightforward, a substantial proportion of patients do not achieve stable biochemical control or continue to report persistent symptoms. Suboptimal adherence may contribute to these challenges, but should be distinguished from other causes of treatment instability, including administration-related factors, drug and food interactions, and gastrointestinal malabsorption. This narrative review examines current evidence on the prevalence, determinants, clinical consequences and assessment of suboptimal adherence to levothyroxine therapy in primary hypothyroidism. Reported adherence estimates vary substantially according to the populations studied, definitions used and methods of assessment, while biochemical instability alone should not be regarded as evidence of non-adherence. Patient-, treatment- and healthcare system-related factors may all influence medication-taking behaviour. Practical strategies to identify and address suboptimal adherence include patient-centred discussion, education, simplification of administration where appropriate, and targeted use of alternative dosing strategies or formulations. Integrating adherence assessment into routine clinical care may help identify modifiable contributors to unstable treatment and support more individualized levothyroxine management.