Obese Women With Hypothyroidism Treated with Levothyroxine Have Reduced Resting Energy Expenditure

Abstract

Clinical ThyroidologyVol. 32, No. 5 HypothyroidismFree AccessObese Women With Hypothyroidism Treated with Levothyroxine Have Reduced Resting Energy ExpenditureMary H. SamuelsMary H. SamuelsDivision of Endocrinology, Diabetes, and Clinical Nutrition, Department of Medicine; Oregon Health & Science University, Portland, Oregon, U.S.A.Search for more papers by this authorPublished Online:6 May 2020https://doi.org/10.1089/ct.2020;32.218-220AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail Review of: Muraca E, Ciardullo S, Oltolini A, Zerbini F, Bianconi E, Perra S, Villa M, Cannistraci R, Castoldi G, Pizzi P, Manzoni G, Lattuada G, Perseghin G 2020 Resting Energy Expenditure in Obese Women with Primary Hypothyroidism and Appropriate Levothyroxine Replacement Therapy. J Clin Endocrinol Metab. Apr 1;105.SUMMARYBackgroundThyroid hormone is a major regulator of resting energy expenditure (REE), and overt thyroid disease leads to significant alterations of this metabolic measurement (1). A previous report suggested that reductions in REE may persist in treated hypothyroid patients, despite normal serum thyroid stimulating hormone (TSH) levels (2), but this has not been extensively studied. The current study investigated this question in a large group of obese women with hypothyroidism attending a bariatric surgery clinic (3).MethodsThis retrospective observational study enrolled 649 obese women (body mass index [BMI] >30 kg/m2) attending a bariatric surgery clinic in Monza, Italy. Of the cohort, 564 were euthyroid with no history of thyroid disease, while 85 has a past history of hypothyroidism and were currently treated with levothyroxine (L-T4). Both groups had serum TSH levels within the laboratory reference range (0.4-4.0 mU/L). Men were excluded due to confounding effects of gender on energy expenditure and the small number of men attending the clinic. None of the enrolled subjects had diabetes or other chronic illnesses or were taking medications known to affect energy expenditure. Body composition was measured by bioimpedence analysis (BIA), REE was measured by indirect calorimetry, and eating behavior and physical activity were assessed by validated questionnaires during a single visit to the clinic.ResultsThe mean age of the participants was 44 years in the euthyroid group and 49 years in the L-T4 treated group (p < 0.001). Mean BMI was 40.7 kg/m2 in the euthyroid group and 39.7 kg/m2 in the L-T4 treated group (p=not significant [NS]). Mean TSH levels were 2.03 mU/L in the euthyroid group and 1.97 in the L-T4 treated group (p=NS). The L-T4 treated group had slightly higher levels of physical activity and lower levels of insulin resistance by the Homeostatic Model Assessment of Insulin Resistance (HOMA2-IR) calculation. The mean L-T4 dose in the L-T4 treated group was 0.99 mcg/kg/day.The mean REE was 6% lower in the L-T4 treated group compared to the euthyroid group (1494 vs. 1593 kcal/day, p < 0.001). Corrected for lean body mass, the REE was 4% lower in the L-T4 treated group compared to the euthyroid group (28.6 vs. 29.9 kcal/kg fat free mass/day, p = 0.002). The REE results were not affected after adjusting for age, BMI, waist circumference, or level of physical activity, but were attenuated after further adjusting for insulin resistance by HOMA2-IR. There was no correlation between REE and TSH in the entire cohort, or between REE and L-T4 dose in the L-T4 treated group. When the L-T4 group was divided into low-normal vs. high-normal TSH (0.4-2.5 vs. 2.5-4.0 mU/L), REE remained lower than the euthyroid group in both L-T4 treated subgroups. There were no differences between the two groups in BMI or body composition by BIA.ConclusionsObese L-T4 treated hypothyroid women with normal TSH levels have slightly but significantly lower REE than obese control euthyroid women. This phenomenon may be related to insulin resistance. Despite these metabolic differences, body mass and composition are similar in obese L-T4 treated and euthyroid women.COMMENTARYThyroid hormone plays a critical role in determining REE by stimulating thermogenesis (1). Alterations in REE occur in both hyper- and hypothyroidism, but studies have not consistently shown correlations between variations of serum thyroid function within the reference range and REE in euthyroid subjects (4,5). Only one study has investigated REE in L-T4 treated hypothyroid patients, with some indication that their REE may not normalize despite normal TSH levels (2). Finally, changes in REE have not translated to consistent effects on weight or body composition in this population (2).The current study (3) reports that obese L-T4 treated hypothyroid women with normal TSH levels had a 4% lower REE corrected for lean body mass, compared to obese euthyroid women. This result is identical to a smaller study in non-obese L-T4 treated women (2). Despite this, body mass and composition were not different between the two groups in either study. REE is the main component of total energy expenditure, and even small alterations in REE would be expected to lead to changes in body mass and/or composition over time. Other components of energy intake or expenditure may adjust to maintain body mass; in this regard, it is interesting that physical activity in the current study was higher in the L-T4 treated women.The mechanism for lowered REE in L-T4 treated subjects is not clear. The authors postulate that first-pass exposure to elevated levels of T4 in the liver may alter insulin sensitivity and lead to unspecified peripheral effects, but this is speculative. Another possibility is that lower intracellular triiodothyronine (T3) levels may be present in L-T4 treated patients, decreasing REE. Many L-T4 treated hypothyroid patients have serum free T3 (fT3) levels below the reference range, and positive correlations have been reported between serum fT3 levels and REE in these patients (6). Unfortunately, serum free thyroxine (fT4) or fT3 levels were not available in the current study.There are other aspects of the current study that limit its generalizability. Only women were studied. They were quite obese, with a mean BMI of 40 kg/m2. One third of subjects in both groups had undergone bariatric surgery, which may alter energy balance. There was no documentation of past diagnoses of hypothyroidism, and it is possible that some euthyroid women were treated with L-T4. The mean L-T4 dose was 0.99 mcg/kg/day, suggesting that many subjects had some residual endogenous thyroid function.The current results are intriguing, and further research is needed to elucidate the mechanisms underlying this observation. However, the clinical relevance of this finding is unclear, as most patients are concerned about their weight, not their REE. Results from the current study, combined with other observational and intervention studies, have not found consistent effects of thyroid function, increased L-T4 doses, or combined L-T4/L-T3 therapy on weight in L-T4 treated patients (7,8). Therefore, current recommendations for weight control in L-T4 treated patients should be no different than those in euthyroid patients.