Improved levothyroxine treatment observed in adults with obesity
An analysis of a cohort of adults with morbid obesity and primary hypothyroidism demonstrated that most were adequately treated with levothyroxine replacement therapy, with younger age and lower BMI predicting increased risk for overtreatment, according to findings from a cross-sectional study.
“Results highlight a peculiar role for obesity on [levothyroxine] requirements, with nearly 75% of participants showing [thyroid-stimulating hormone] levels within the euthyroid range,” Chiara Mele, MD, PhD, of the department of translational medicine at the University of Piemonte Orientale in Novara, Italy, and colleagues wrote. “Among those with abnormal TSH, the rate of [levothyroxine] under-replacement predominated as compared to that of over-replacement, namely 17.2% vs. 7.5% of cases. The reason for this outcome remains unclear. Current general recommendations toward specialized management of obesity increase the chance of stricter follow-ups, thus that our finding could simply be the result of improved obesity management.”
Mele and colleagues analyzed data from 691 consecutive patients with morbid obesity and primary hypothyroidism prescribed stable levothyroxine therapy, admitted between 2011 and 2014 (mean age, 59 years; 87.6% women), as well as 691 BMI-, age- and sex-matched euthyroid adults (controls). Researchers assessed thyroid function, lipid profile, body composition and energy expenditure via indirect calorimetry; levothyroxine users were stratified by low, euthyroid and high TSH levels (< 0.27 mU/L, 0.27-4.2 mU/L and > 4.2 mU/L). Researchers conducted regression analyses to identify predictors of levothyroxine dose and the effect of variables on the risk of undertreatment and overtreatment. Primary outcomes included rates of overtreatment and undertreatment among levothyroxine users and factors associated with levothyroxine adequacy; secondary outcomes included metabolic profile differences between levothyroxine users and controls.
Within the cohort, 75.8% of levothyroxine users and 77.6% of controls had a BMI greater than 40 kg/m². Among levothyroxine users, 519 were considered to be adequately treated, 119 were undertreated and 52 were overtreated (median daily dose, 100 µg). TSH was low in 7.5% of levothyroxine users, high in 17.2% of users and normal in 75.2% of users. Among patients with low TSH, 13.4% had high free thyroxine levels; 12.6% of patients with high TSH had low free T4 levels, according to researchers.
In a regression analysis model adjusted for age, sex, cause of hypothyroidism, diabetes status, percentage of fat mass and percentage of free fat mass, researchers found that daily levothyroxine dose was best predicted by free fat mass (P < .0001), total thyroidectomy (P < .0001) and sex (P < .05). In multinomial logistic regression analyses, the researchers found that the risk for levothyroxine over-replacement increased with younger age (OR = 0.96; 95% CI, 0.94-0.99), higher levothyroxine dose (OR = 2.98; 95% CI, 1.44-6.14) and lower BMI (OR = 0.93; 95% CI, 0.88-0.99).
The risk for under-replacement was associated only with male sex (OR = 2.37; 95% CI, 1.1-5.11), according to researchers.
“While our results imply that a limited proportion of [levothyroxine] users is overtreated among obese patients referring to an obesity clinic, current data also support the recommendation that TSH target during [levothyroxine] replacement should be age-adjusted, and [levothyroxine] adequacy should be especially monitored in elderly obese individuals to avoid the detrimental effect of overtreatment,” the researchers wrote. – by Regina Schaffer
Disclosures: The authors report no relevant financial disclosures.