Stopping Levothyroxine Therapy in Subclinical Hypothyroidism, Perhaps We Could Start a Trend

Abstract

Introduction: Subclinical hypothyroidism (SCH) is diagnosed based on elevated thyrotropin (TSH) and normal thyroxine (FT4) levels. Previous guidelines recommended treatment of SCH with levothyroxine (LT4) when TSH is > 10 uIU/mL or if TSH <10 uIU/mL with symptoms suggestive of hypothyroidism, positive thyroperoxidase antibodies (TPO Ab) or evidence/risk factors of cardiovascular disease. There has been an increasing practice of LT4 prescription for SCH, which contributes to making LT4 the second most prescribed drug in the US. Case: This case reviews the course of a patient with SCH treated with LT4. A 68 year old woman with medical history of hyperlipidemia, osteoporosis, and non-toxic multinodular goiter was diagnosed with SCH due to Hashimoto’s thyroiditis based on TSH 9.59 uIU/mL (0.34 - 5.60), FT4 0.66 ng/dL (0.58 - 1.64), and +TPO Ab. The patient had similar thyroid function tests (TFT) 1 year ago. She reported symptoms of hair loss, dry skin, and fatigue. She decided to undergo a trial of LT4 50 mcg daily. Two months later, her TSH had normalized and she reported slight improvement of fatigue. After one year on LT4, the patient reported symptoms of anxiety and heat intolerance and decided to stop LT4. Laboratory work up revealed TSH 0.22 uIU/mL and FT4 1.03 ng/dL consistent with exogenous hyperthyroidism. At the time of her follow up, the patient had been off LT4 for about 3 weeks. She continued to have ongoing fatigue, but reported resolution of the hyperthyroid symptoms. She was advised to stay off LT4 and to have yearly TFT. Discussion This case illustrates that not only LT4 treatment for SCH did not result in apparent improvement of hypothyroid-related symptoms, but also caused iatrogenic hyperthyroidism. A recent meta-analysis of 21 randomized clinical trials including 2192 patients with SCH found that LT4 therapy is not significantly associated with improvement in general quality of life or thyroid-related symptoms. Additionally, there is evidence of potential harm associated with LT4 and added burden of lifelong management. In 2019, a new guideline panel issued a strong recommendation against thyroid hormones in adults with SCH. Patients who are already on LT4 therapy for SCH may benefit from LT4 deprescribing. Clinicians need to discuss with their patients if LT4 discontinuation is a reasonable consideration. Studies at low risk of bias assessing patient important outcomes after LT4 discontinuation are required imminently.