The Endocrine Society

The Endocrine Society

March 22, 2018
3 min read

Levothyroxine therapy associated with lower quality of life in hypothyroidism

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Hanneke Wouters
Hanneke Wouters

CHICAGO — Adults with hypothyroidism prescribed levothyroxine were more likely to experience lower health-related quality of life and increased comorbidities when compared with similar adults not prescribed thyroid hormone therapy, according to study data presented here.

“Hypothyroidism is a common endocrine disorder, and substitution therapy with levothyroxine is the standard of care,” Hanneke Wouters, BSc, of University Medical Center Groningen, Netherlands, said during an oral abstract presentation at the Endocrine Society Annual Meeting. “Unfortunately, about 10% of the individuals using this drug continue to experience symptoms and a disturbed wellbeing and a disturbed quality of life, despite the fact that their [thyroid-stimulating hormone] level is within the normal range, so they are euthyroid.”

Wouters and colleagues analyzed data from 34,400 adults with thyroid function measurements participating in the population-based Dutch Lifelines cohort. Participants self-reported medical history and medication use and completed the RAND-36 short form health survey, with domains on physical functioning, social functioning, physical and emotional role limitations, mental health, vitality, bodily pain and general health (scores ranged from 0-100 in each domain). Researchers assessed mean scores for each domain and the percentage of participants who scored below a predetermined, sex-specific cutoff value. Comorbidities were defined as medication use other than levothyroxine and oral contraceptives, or a medical history of diseases for which medication is not always prescribed, such as migraines. Logistic regression analysis was used to assess the association between levothyroxine use health-related quality-of-life scores and comorbidities.

Within the cohort, 995 adults (2.8% of total cohort) were prescribed levothyroxine. Compared with the population not prescribed levothyroxine, these patients were more likely to be women (89.4% vs. 57.9%), older (mean age, 51 years vs. 45 years), have higher BMI (mean, 27.2 kg/m² vs. 26.1 kg/m²) and use more medications (range, 0-4 vs. 0-2). Patients prescribed levothyroxine were also more likely to have a comorbidity vs. those not prescribed the drug (80.6% vs. 66%).

Among those prescribed levothyroxine, 60% had a normal thyroid-stimulating hormone level (0.4-4 mU/L), 13.4% had TSH defined as suppressed (< 0.4 mU/L) and 26.6% had elevated TSH (at least 4 mU/L), Wouters said. Among patients not using levothyroxine, 89% had normal TSH measurements, she said.

“Since we had these large differences in main characteristics, we decided to match our euthyroid [levothyroxine] users 1:5 with peers from the general population for these variables,” Wouters said.

In comparing the euthyroid levothyroxine users (n = 573) with matched adults not using levothyroxine (n = 2,859), researchers observed that TSH levels between the two groups were similar (mean, 1.9 mU/L vs. 2.1 mU/L); however, mean FT4 for the euthyroid levothyroxine group was higher (18.5 vs. 15.6 pmol/L) whereas mean FT3 level was lower (4.6 vs. 5.1 pmol/L), Wouters said.


Researchers found that patients prescribed levothyroxine had lower scores in all health-related quality-of-life domains, apart from emotional functioning, when compared with patients not on levothyroxine therapy (P < .001 for all). There were no between-group differences in health-related quality of life among patients prescribed levothyroxine therapy when stratified by TSH level or by levels of FT3 and FT4, Wouters said.

Wouters noted that among adults prescribed levothyroxine therapy, only 25 men did not have a comorbidity. When assessing women prescribed levothyroxine, researchers found that the presence of at least one comorbidity was more likely to influence health-related quality of life vs. women not prescribed levothyroxine, particularly in the physical functioning and general health domains, Wouters said. Compared with adults not prescribed levothyroxine, those prescribed levothyroxine were more likely to have hypertension (34.9%), anemia (26%) and hypercholesterolemia (23.7%) after adjustment for age and BMI. Diabetes and multiple sclerosis were also more likely in patients prescribed levothyroxine therapy; however, there were no between-group differences for other autoimmune diseases, Wouters said.

“Patients using [levothyroxine] therapy replacement for hypothyroidism had an impaired quality of life,” Wouters said. “Quality of life is impacted independent of the actual level of thyroid hormone ... and comorbidity is not only more frequently present in women using [levothyroxine], it also has more impact on quality of life.”

Addressing questions after the presentation, Wouters said that since only levothyroxine therapy — and not thyroid hormone levels — was independently predictive of health-related quality of life, the relationship between levothyroxine use and quality of life may be bidirectional, adding that the drug’s use could serve as a marker for patients who have more medical interactions. – by Regina Schaffer


Wouters H. OR34-1. Presented at: The Endocrine Society Annual Meeting; March 17-20, 2018; Chicago.

Disclosures: Wouters reports no relevant financial disclosures.