Nov. 30, 2023
Levothyroxine is one of the most commonly prescribed drugs in the United States, with approximately 7% of the population estimated to have an active prescription. Over time, prescriptions of levothyroxine have increased in contrast to the prevalence of overt hypothyroidism, which has been stable. Therefore, this increase in prescriptions is not fully explained by the incidence and treatment of thyroid cancer. Levothyroxine also is prescribed in subclinical hypothyroidism, which affects up to 15% of the population. Recent evidence suggests little to no benefit of levothyroxine treatment in patients with subclinical hypothyroidism, particularly among patients older than 65 years of age. Levothyroxine treatment is associated with changes to daily habits as well as added health cost to the patient, and it is therefore important to understand if the prescription for levothyroxine is necessary.
Juan P. Brito Campana, M.B.B.S., an endocrinologist at Mayo Clinic in Rochester, Minnesota, performed a retrospective chart review across three large academic centers in the United States that looked at factors driving levothyroxine prescription. The results of this study were published in The Journal of Clinical Endocrinology & Metabolism in 2023.
"We included all adult patients who received their first outpatient levothyroxine prescription at the University of Arkansas and the University of Florida Gainesville, as well as a cohort of patients from Mayo Clinic in Rochester, Minnesota, between January 2017 and December 2020," Dr. Brito says.
The data collection included social demographic data, the date and dose of the first levothyroxine prescription, factors — including symptoms — that influenced the initiation of levothyroxine, and the reason for the prescription. Researchers also extracted thyroid function testing and antibody testing preceding the initial levothyroxine prescription.
Patients were then classified into the categories of overt hypothyroidism, mild subclinical hypothyroidism (TSH < 10 mIU/L and normal free T4), moderate to severe subclinical hypothyroidism (TSH ≥ 10 mIU/L and normal free T4), normal thyroid function and other. Based on the most recent American Thyroid Association guidelines and research team consensus, the researchers further classified each case into categories of appropriate, indeterminate and nonevidence based. The TSH cutoff was 7 mIU/L instead of 10 mIU/L due to differences in expert recommendations.
A total of 977 patients were screened. The mean age was 55 years, and the majority of the patients were female (69%) and white (84%), with BMI in the overweight or obese category (43%). The most common comorbidities were depression (19%) and dyslipidemia (15%), and the most common symptoms were fatigue (22%) and cold intolerance (6%). Interestingly, the majority (56%) of patients had no symptoms. Median TSH prior to initiation of levothyroxine was 7.1 mIU/L.
Based on the classification plan, approximately half (54%) of levothyroxine prescriptions were considered nonevidence based, and about 12% were indeterminate. In a bivariate analysis, patients receiving nonevidence-based levothyroxine prescriptions were more likely to be female; receive the prescription from a primary care clinician than other specialist; and have at least one symptom compared with no symptoms. The most common clinical indication preceding a nonevidence-based levothyroxine prescription was a TSH value of less than 10 mIU/L without confirmation or T4 value determination.
Limitations of this study include studying patients only treated in tertiary care centers, which does not represent most of the population receiving levothyroxine. This was a retrospective study limited by selection and ascertainment bias, and the reasons for levothyroxine prescription were based on available electronic medical health records, which may not have captured all documentation including outside laboratory records.
Dr. Brito concludes: "This study highlights the prevalence of nonevidence-based levothyroxine prescription as well as differences in prescription practices between primary care professionals and endocrinologists or other specialists. This may point to the need for better dissemination of thyroid-related guidelines to our clinician colleagues who prescribe levothyroxine most often. Additional research to replicate these findings and explore prescriber and patient perspectives on levothyroxine would be important to better understand this area."
For more information
Ayala IN, et al. Appropriateness of levothyroxine prescription: A multicenter retrospective study. The Journal of Clinical Endocrinology & Metabolism. 2023.
Refer a patient to Mayo Clinic.