March 19, 2020
2 min read

Slow metabolism persists despite levothyroxine therapy in hypothyroidism with obesity

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Gianluca Perseghin
Gianluca Perseghin

Women with obesity and primary hypothyroidism prescribed levothyroxine continued to have a lower resting energy expenditure, a measurement of whole-body metabolism, when compared with similar women who were euthyroid, according to findings published in The Journal of Clinical Endocrinology & Metabolism.

“The results of our study are in agreement with a line of thinking that suggests levothyroxine therapy may not be able to correct the entire set of symptoms and metabolic defects associated with hypothyroidism,” Emanuele Muraca, MD, of Policlinico di Monza, Universita delgi Studi dell'Insubria, Italy, told Healio. “In particular, the findings show that whole-body energy metabolism, which is known to be impaired in overt hypothyroidism, measured using indirect calorimetry, was not fully normalized in women with obesity and long-lasting hypothyroidism taking the right dose of levothyroxine in comparison with women who are obese without hypothyroidism.”

In an observational, retrospective study, Perseghin and colleagues analyzed data from a cohort of women with obesity but without diabetes and normal thyroid-stimulating hormone levels (range, 0.4-4 mUI/L) who attended a standard protocol for bariatric surgery between January 2013 and July 2019. The protocol included an assessment of resting energy expenditure using indirect calorimetry after an overnight fast, and body composition measurement using body impedance assessment. Researchers stratified participants into two groups — women with primary hypothyroidism prescribed levothyroxine therapy (n = 85) and women with normal thyroid function (n = 564). Primary outcomes were resting energy expenditure and body composition measurements.

The proportion of women who had undergone previous bariatric surgery (91.7% laparoscopic adjustable gastric banding) was similar for euthyroid women (33.3%) and women with hypothyroidism (34.1%).

Muraca Infographic
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Researchers found that resting energy expenditure was reduced among women with hypothyroidism in the levothyroxine group vs. controls (mean, 28.59 vs. 29.91 kcal/kg of free fat mass), with results persisting after adjustment for age, BMI, body composition and level of physical activity (P = .008).

The between-group difference was attenuated only after adjusting for insulin resistance, according to researchers.

“A portion of patients with hypothyroidism may remain with truly unmet needs in spite of proper therapy,” Gianluca Perseghin, MD, a full professor of endocrinology in the department of medicine and surgery at Università degli Studi di Milano Bicocca at Policlinico di Monza, Italy, told Healio. “One possibility is that achieving appropriate circulating levels of triiodothyronine using oral administration of levothyroxine may be a difficult task in these patients, especially when the effect is to be measured on metabolic variables. It is also possible that our finding could be related to the nonphysiological oral route of administration of levothyroxine, implying a major role of the intestine and the liver, yet to be clarified, in the homeostasis of thyroid hormones.”


Perseghin said the findings demonstrate that different patient groups with thyroid dysfunction may require different therapeutic approaches.

Perseghin said it is crucial to better understand thyroid hormone physiology and genetic variations in deiodinases, TSH receptors and thyroid hormone transporters.

“They are all important rate-limiting steps implicated in thyroid hormone metabolism and in the mechanisms of adaptation of peripheral tissues to the oral rather than physiologic administration of thyroid hormones,” Perseghin said. “Preparations of thyroid hormones with a physiologic extended-release profile, in particular T3, may also be one of our options for therapy in the future.” – by Regina Schaffer

For more information:

Gianluca Perseghin, MD, can be reached at the Department of Medicine and Surgery, Università degli Studi di Milano Bicocca and Department of Medicine and Rehabilitation, Policlinico di Monza, Via Modigliani 10, 20900 Monza, MB, Italy; email:; Twitter: @Gianluperse.

Disclosures: The authors report no relevant financial disclosures.