In the United States, the prevalence of hypothyroidism is approximately 5%,1 and it is more common in women than men.2 The clinical presentation of hypothyroidism is heterogeneous and may vary based on the patient’s age, gender, and disease duration.3 Common symptoms of hypothyroidism include fatigue, weight gain, cold intolerance, constipation, dry skin, hair loss, irregular menstrual cycles, depression, memory loss, and muscle weakness.4 However, not all patients experience the same symptoms; some may have mild or no symptoms.5

The primary treatment for hypothyroidism is levothyroxine (LT4), which aims to restore thyroid function and alleviate symptoms.6 However, despite achieving normal thyroid stimulating hormone (TSH) levels with LT4 treatment, approximately 10% to 15% of patients experience persistent symptoms. These ongoing symptoms can significantly impact their quality of life, satisfaction with care, and the patient-clinician relationship.5

Various factors contribute to or partially explain the burden of symptoms in these patients7 .This includes the presence of coexisting nonthyroid conditions that contribute to the symptoms, unmet expectations for well-being and health status, and variations in tissue-specific availability of thyroid hormone, regardless of serum TSH and FT4 levels.

Despite the increasing focus on addressing persistent hypothyroid symptoms after LT4 treatment, many aspects of this condition remain unclear.8 Important questions include the frequency and most common types of symptoms, how clinicians typically respond to this challenge,9 and which patients are at a higher risk of experiencing persistent hypothyroid symptoms. Gaining a better understanding of the burden of hypothyroidism symptoms during LT4 treatment could help identify at-risk subgroups, prognostic factors, and potential interventions.

To address this issue, as a first step, we conducted an exploratory study using a retrospective analysis of a cohort of patients who had started LT4 therapy for the first time. Our study aimed to evaluate the frequency of patients with persistent and new hypothyroidism symptoms during the follow-up period, investigate the association between symptoms and thyroid function categories, and document the management response from clinicians when presented with patients experiencing persistent or new symptoms in the face of normal TSH values.