BACKGROUND
Hypothyroidism, a condition that results in an underactive thyroid, is very common. Overt hypothyroidism occurs when both the TSH level is high and the FT4 levels is low. Subclinical hypothyroidism occurs when the TSH is increased but the FT4 level is normal. Treatment of hypothyroidism is thyroid hormone replacement, usually in the form of levothyroxine.

Symptoms of hypothyroidism may include being tired, slow, sluggish, gaining weight, cold, dry skin and constipation. None of these symptoms are specific to hypothyroidism. In the vast majority of patients with overt hypothyroidism, symptoms either improve or resolve when thyroid hormone levels are returned to the normal range with thyroid hormone therapy. In patients with subclinical hypothyroidism, results are not as clear. Indeed, in both overt and subclinical hypothyroidism, some patients might still have some symptoms despite thyroid levels being normalized. This study analyzed how many have new or persistent symptoms after the use of levothyroxine to treat hypothyroidism.

THE FULL ARTICLE TITLE
Hidalgo J et al 2023 Real practice assessment of persistent symptoms after initiation of levothyroxine. Endocr Pract. Epub 2023 Oct 30:S1530-891(23)00730-9. PMID: 37913925.

SUMMARY OF THE STUDY
The study analyzed random 500 patient charts between January 2017 and December 2019 at a single center (Mayo Clinic in Rochester, Minnesota, U.S.A). Included patients’ charts had at least one follow up note after levothyroxine initiation and up to 3 more with labs and documented symptoms. Results showed 356 patients, 66.6% being female, white (92.3%), and having obesity (71.9%).

Several other disorders were commonly noted in 72.7%, with depression being the leading one common in 35.3% of all. At the initial visit, almost half of the patients (47.7%) had symptoms consistent with hypothyroidism, with fatigue being the most common. More than half of those patients were started on levothyroxine therapy for subclinical hypothyroidism. The average initial dose of levothyroxine prescribed was 50 mcg. Despite starting patients on levothyroxine, around 40% of the patients still had laboratory numbers indicating subclinical hypothyroidism, even during the follow-up period.

During the first, second, and third follow-up encounters, 26.7% (42 of 157), 27.3% (29 of 106), and 28% (16 of 57) of patients experienced persistent or new symptoms of hypothyroidism, despite normalized TSH values. Fatigue remained the most common symptoms, followed by weight gain. The treating physician chose to increase the levothyroxine dose in about 20% of patients, referred to an endocrinologist in 2.2% of patients at the first follow-up visit (and in 17.6% by the third encounter), and suggested other strategies (e.g., rheumatology referral, psychological or nutrition counseling) in 6.7% of patients at the first and second encounter and in 11.8% at the third evaluation.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
This study suggests that ~1 in 4 patients with hypothyroidism on levothyroxine still reports symptoms, despite normal TSH levels. Whether these symptoms were due to hypothyroidism or to other disorders is unclear. Although the authors did not identify causes for it, this study shows the need to better understand the issue in order to help with solutions for our patients and to not overlook their symptoms.

— Joanna Miragaya, MD

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