Objectives: According to one hypothesis, the popularity of levothyroxine (L-T<sub>4</sub>)/liothyronine (L-T<sub>3</sub>) combination therapy relates to weight loss. The purpose of this study was to detect a possible correlation between thyroid-related quality of life (QoL) and weight loss in hypothyroid patients switched from L-T<sub>4</sub> monotherapy to L-T<sub>4</sub>/L-T<sub>3</sub> combination therapy. Methods: In an open-label cohort study, all hypothyroid patients referred to the University Hospital endocrine clinic due to persistent symptoms despite adequate L-T<sub>4</sub> monotherapy (without other explanations for the symptoms) were switched from L-T<sub>4</sub> monotherapy to L-T<sub>4</sub>/ L-T<sub>3</sub> combination therapy at a ratio of approximately 17/1. At baseline and after 3 months of treatment we measured: QoL by the Thyroid Patient-Reported Outcome (ThyPRO-39) questionnaire, thyroid hormones, body weight, body composition by a DEXA-scan, and cognitive function by evaluating participants’ reaction time as well as working memory by the California Computerized Assessment Package (CalCAP®). QoL was re-evaluated after 12 months. Results: Twenty-three patients participated (91% women, median age 47 years). The ThyPRO-39 composite score decreased from a median of 54 (quartiles: 34, 74) to 15 (11, 28) after 3 months (p < 0.0001), and 20 (14, 26) after 12 months, indicating a better QoL. There was no change in body weight, and no correlations between QoL and weight. There was a slight improvement in cognitive function, whereas body composition, heart rate, and serum TSH did not change. Conclusion: Our study on hypothyroid patients switched from L-T<sub>4</sub> monotherapy to L-T<sub>4</sub>/L-T<sub>3</sub> combination therapy showed a substantial improvement in QoL measured by the ThyPRO-39. This improvement could not be explained by weight loss.
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- Author: Jeppe Lerche la Cour x
Luba Freja Michaelsson, Jeppe Lerche la Cour, Bjarke Borregaard Medici, Torquil Watt, Jens Faber, and Birte Nygaard
Bjarke Borregaard Medici, Jeppe Lerche la Cour, Luba Freja Michaelsson, Jens Oscar Faber, and Birte Nygaard
Background: Despite biochemical euthyroidism, some levothyroxine (L-T<sub>4</sub>)-treated hypothyroid patients report persisting symptoms and some of these patients are tentatively treated with a combination of L-T<sub>4</sub> and liothyronine (L-T<sub>3</sub>). Combination therapy and the appropriate choice of blood tests to monitor treatment are highly debated among specialists and patients. Aim: To evaluate whether measuring serum triiodothyronine (S-T<sub>3</sub>) at baseline or during combination therapy can be used as an indicator of a positive effect from L-T<sub>4</sub>/L-T<sub>3</sub> combination therapy. Materials and Methods: Observational retrospective study of patients (n = 42) with persisting symptoms of hypothyroidism despite L-T<sub>4</sub> therapy who had normal TSH levels and did not have any comorbidities that could explain their symptoms. All were then treated with L-T<sub>4</sub>/L-T<sub>3</sub> combination therapy at a dose ratio of 17/1 according to European Thyroid Association guidelines. Based on patient-reported outcome, they were divided into responders and nonresponders. Results: Five patients were lost to follow-up and thus excluded. At the 3-month follow-up, 11 were classified as nonresponders and 26 as responders. At 12 months these figures had changed to 13 (35%) and 24 (65%), respectively. When comparing responders versus nonresponders, no differences were seen at baseline or during follow-up in S-T<sub>3</sub> and in free T<sub>3</sub> estimates. Further, logistic regression showed no correlation between S-T<sub>3</sub> and free T<sub>3</sub> estimates and responder/nonresponder status. Conclusion: Our data indicate that serum T<sub>3</sub> measurements are not suitable to predict which patient will benefit from L-T<sub>4</sub>/L-T<sub>3</sub> combination therapy, and treatment response cannot be followed by repeated T<sub>3</sub> measurements either.
Jeppe Lerche la Cour, Line Tang Møllehave, Bjarke Røssner Medici, Christian Zinck Jensen, Anne Ahrendt Bjerregaard, and Birte Nygaard
High compared with low educational level increases the odds of starting levothyroxine (L-T4) with a normal thyroid-stimulating hormone – the mechanism is most likely patient request. The use of liothyronine (L-T3) and desiccated thyroid extract (DTE) is also speculated to be initiated at patients’ request. Therefore, the primary aim of this study was to evaluate if educational level influences treatment with L-T3 and DTE.
Material and methods
In this register-based cross-sectional study, we included all Danish citizens ≥30 years with redeemed prescription of L-T4, L-T3, or DTE during 2017–2020. We defined educational levels as short, medium, and long (<10 years, 10–12 years, and above 12 years, respectively). The association between educational level and treatment with LT3 or DTE vs only LT4 was analyzed in logistic regression models adjusted for age and sex.
We included 154,360 individuals using thyroid medication of whom 3829 were treated with L-T3 (2.48%) and 430 with DTE (0.28%). The usage was highest among women (3.15%) and the age group 40–49 (5.6%). Longer education compared with short increased the odds of being treated with DTE or L-T3 (medium education odds ratio (OR) 1.61 (95% CI 1.50–1.8) and long education OR 1.95 (95% CI 1.79–2.13)). Test for trend: OR: 1.37 (95% CI 1.31–1.42). Adjustment for other covariates did not affect the results substantially.
Persons with a longer compared to a shorter education are more often treated with either DTE or L-T3, and the usage of these drugs is limited to less than 3% of thyroid hormone users.
Luba Freja Michaelsson, Bjarke Borregaard Medici, Jeppe Lerche la Cour, Christian Selmer, Michael Røder, Hans Perrild, Nils Knudsen, Jens Faber, and Birte Nygaard
Background: Five to ten percent of patients with hypothyroidism describe persistent symptoms despite being biochemically well regulated on levothyroxine (L-T<sub>4</sub>). Thyroxine (T<sub>4</sub>)/triiodothyronine (T<sub>3</sub>) combination therapy [L-T<sub>4</sub>/liothyronine (L-T<sub>3</sub>) or desiccated thyroid] are still regarded as experimental with no evidence of superior effect on persistent symptoms according to meta-analyses. However, some randomized controlled trials have demonstrated patients' preference for T<sub>4</sub>/T<sub>3</sub> combination therapy as compared to L-T<sub>4</sub> monotherapy. In 2013, attention to combination therapy increased in Denmark after a patient published a book describing her experiences with hypothyroidism and treatment. Objective: To investigate current Danish trends in the use of T<sub>4</sub>/T<sub>3</sub> combination therapy. Methods: We used an Internet-based questionnaire, distributed as a link via two Danish patient fora. Further, information was obtained from the Division of Pharmacies and Reimbursement at the Danish Health and Medicines Authority and from the only pharmacy in Denmark producing desiccated thyroid and L-T<sub>3</sub> tablets. Results: A total of 384 patients answered the questionnaire, and 293 responders were included. Sixty-nine percent of the responders had six or more symptoms, and 84% reported a treatment effect. Forty-four percent of the responders received their prescriptions from general practitioners; 50% received desiccated thyroid and 28% reported that they adjust their dose themselves. Responders followed by general practitioners more frequently received desiccated thyroid and adjusted their dose themselves. Conclusions: Increased media focus has changed the prescription pattern of thyroid hormones; European guidelines on T<sub>4</sub>/T<sub>3</sub> combination therapy are not always followed in Denmark and many patients adjust their medication themselves and may therefore be at risk of overtreatment.