Predictors of Improvement in Quality of Life When Treating Hypothyroidism.

BACKGROUND: Primary hypothyroidism is characterized by reduced quality of life (QoL). Although thyrotropin (TSH) is utilized as the primary indicator of thyroid disease and treatment adequacy, no simple correlation between QoL and TSH has been shown. This study aimed to investigate changes in clinically relevant predictors during initiation of levothyroxine (L-T4) therapy and their ability to predict improvement in QoL. METHOD: Quality of life was measured in patients with newly diagnosed hypothyroidism, during the initial 12 months of L-T4 therapy, by the thyroid-related patient-reported outcome questionnaire, ThyPRO-39. The main outcome measures were the Composite QoL scale and the Tiredness and Emotional Susceptibility subscales (0-100, higher scores worse). Clinical variables (resting energy expenditure (REE), body composition, thyroid function, L-T4 dose, and cognitive function tests) were evaluated as predictors of improvement in QoL by univariate and multiple regression analysis. RESULTS: Thirty-seven hypothyroid patients with a baseline median TSH of 30 mU/l and a median QoL score of 29 were included. After twelve months of L-T4 treatment, the ThyPRO-39 QoL score had significantly improved to a median score of 14, while REE per kg fat-free mass (FFM) increased significantly from a mean of 26.5 to 28.7 kcal/day/kg (p < 0.001). Change in ThyPRO-39 was not associated with a change in REE/FFM (unstandardized coefficient (USC): 0.09 with confidence interval (CI): -1.93 to 2.11, p=0.93) but was positively predicted by baseline body mass index (BMI) (USC: 1.54 with CI: 0.59 to 2.49, (p=0.002), without association with weight loss (USC: 0.33 with CI: -1.21 to 1.27, p=0.96). CONCLUSION: Improvement in QoL as measured by ThyPRO-39 after initiation of L-T4 therapy for hypothyroidism was not associated with changes in REE. High baseline BMI, but not weight loss during therapy, was associated with improvement in QoL. This trail is registered with www.Clinicaltrials.gov (registration no. https://clinicaltrials.gov/ct2/show/NCT02891668).

Levothyroxine/Liothyronine Combination Therapy and Quality of Life: Is It All about Weight Loss?

OBJECTIVES: According to one hypothesis, the popularity of levothyroxine (L-T4)/liothyronine (L-T3) 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-T4 monotherapy to L-T4/L-T3 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-T4 monotherapy (without other explanations for the symptoms) were switched from L-T4 monotherapy to L-T4/ L-T3 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-T4 monotherapy to L-T4/L-T3 combination therapy showed a substantial improvement in QoL measured by the ThyPRO-39. This improvement could not be explained by weight loss.

Neither Baseline nor Changes in Serum Triiodothyronine during Levothyroxine/Liothyronine Combination Therapy Predict a Positive Response to This Treatment Modality in Hypothyroid Patients with Persistent Symptoms.

BACKGROUND: Despite biochemical euthyroidism, some levothyroxine (L-T4)-treated hypothyroid patients report persisting symptoms and some of these patients are tentatively treated with a combination of L-T4 and liothyronine (L-T3). 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-T3) at baseline or during combination therapy can be used as an indicator of a positive effect from L-T4/L-T3 combination therapy. MATERIALS AND METHODS: Observational retrospective study of patients (n = 42) with persisting symptoms of hypothyroidism despite L-T4 therapy who had normal TSH levels and did not have any comorbidities that could explain their symptoms. All were then treated with L-T4/L-T3 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-T3 and in free T3 estimates. Further, logistic regression showed no correlation between S-T3 and free T3 estimates and responder/nonresponder status. CONCLUSION: Our data indicate that serum T3 measurements are not suitable to predict which patient will benefit from L-T4/L-T3 combination therapy, and treatment response cannot be followed by repeated T3 measurements either.

Treating Hypothyroidism with Thyroxine/Triiodothyronine Combination Therapy in Denmark: Following Guidelines or Following Trends?

BACKGROUND: Five to ten percent of patients with hypothyroidism describe persistent symptoms despite being biochemically well regulated on levothyroxine (L-T4). Thyroxine (T4)/triiodothyronine (T3) combination therapy [L-T4/liothyronine (L-T3) 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 T4/T3 combination therapy as compared to L-T4 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 T4/T3 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-T3 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 T4/T3 combination therapy are not always followed in Denmark and many patients adjust their medication themselves and may therefore be at risk of overtreatment.

The dose of levothyroxine in pregnant women with hypothyroidism should be increased by 20-30% in the first trimester.

INTRODUCTION: Severe hypothyroidism in pregnancy is associated with maternal and foetal complications, and in less severe cases impaired neuropsychological foetal development is seen. The aim of the present study was to evaluate the efficiency of the clinical control suggested in the guidelines. METHODS: This was a retrospective study of 93 consecutive pregnant women with hypothyroidism who were followed at Herlev Hospital in 2012. The thyroid function was evaluated upon confirmation of pregnancy and thereafter every fourth week. The aim of the treatment was a concentration of serum thyroid-stimulating hormone (S-TSH) less than 2.5 mU/l. RESULTS: The frequency of an S-TSH of more than 4.1 mU/l was 39%. In 27% of all patients, a single measurement was made of a slight increase in S-TSH during the pregnancy, and only 12% had several increased S-TSH measurements exceeding 4.1 mU/l. Furthermore, 62% had a minimum of one S-TSH measurement above 2.5 mU/l. The pregnant women with increased S-TSH levels in the beginning of their pregnancy had a tendency to be overtreated later in their pregnancy. CONCLUSION: Although a careful follow-up was performed, we found a high number of patients with a single occurrence of S-TSH outside of the recommended range during their first trimester. The high S-TSH values were registered during the first weeks of the pregnancy, but hereafter corrected, and the number of pregnancy complications recorded did not seem to differ from the number of complications in patients with a normal thyroid function. We recommend increased attention and monitoring of fertile women with hypothyroidism who are planning pregnancy. FUNDING: not relevant. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02094079.