Influence of educational level on test and treatment for incident hypothyroidism.

OBJECTIVE: The incidence of hypothyroidism is not expected to differ by socioeconomic factors. However, the decision to test and initiate treatment may differ. We aimed to examine whether educational level influences the probability of thyroid stimulation hormone (TSH)-measurement and initiation of levothyroxine treatment. DESIGN: Citizens in the greater Copenhagen Area during 2001-2015 were included. Individual-level data on educational level, diagnoses, GP-contact, TSH-measurement and medication were derived from administrative and healthcare registers. The relative risks (RR) between educational levels of annual TSH-measurement and treatment initiation following a TSH-measurement were analysed in Poisson regression models with generalized estimation equations. RESULTS: A TSH-measurement was performed in 19% of 9,390,052 person years. The probability of TSH-measurement was higher with short (RR 1.16 [95% CI 1.15-1.16]) and medium (RR 1.11 [95% CI 1.06-1.12]) compared with long education. Treatment was initiated after 0.8% of 2,049,888 TSH-measurements. For TSH < 5 mIU/L, RR for treatment initiation ranged between 0.47 (95%CI 0.39-0.57) and 0.78 (95%CI 0.67-0.91) for short and medium compared with long education. For TSH 5-10 mIU/L, there was no statistically significant difference. For TSH > 10 mIU/L, RR was 1.07 (95% CI 1.02-1.12) for short and 1.08 (95% CI 1.03-1.13) for medium compared with long education. CONCLUSION: The probability of TSH-measurement was higher with shorter education, and the probability of treatment initiation with TSH > 10 mIU/L was marginally higher with short-medium education compared with long education. However, the probability of treatment initiation with TSH < 5 mIU/L, that is treatment incongruous with guidelines, was substantially higher in persons with long education.

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).

Changes in Prescription Routines for Treating Hypothyroidism Between 2001 and 2015: An Observational Study of 929,684 Primary Care Patients in Copenhagen.

Background: Increased public attention toward health and quality-of-life issues has led to more intensified screening for various medical conditions, including hypothyroidism. A falling serum thyrotropin (s-TSH) at initiation of levothyroxine (LT4) treatment has been reported in the United Kingdom between 2001 and 2009, indicating a falling TSH threshold, which may lead to less benefit from therapy and possibly overtreatment. The aim of this study was to investigate changes in s-TSH threshold used by general practitioners to initiate LT4 therapy between 2001 and 2015 in Copenhagen. Methods: Retrospective analysis was conducted of all s-TSH measurements between 2001 and 2015 performed at the general practitioners' joint laboratory merged with The Danish Register of Medicinal Products Statistics and The Danish National Patient Registry. For each year, both the median s-TSH at therapy initiation and the estimated treatment threshold were calculated from all s-TSH measurements performed in that year, representing the s-TSH level where the estimated probability of starting LT4 therapy was 50%. Results: A total of 929,684 individuals with 2,975,277 s-TSH measurements were included in the calculations. The size and composition of the study population remained virtually unchanged. During the study period, the number of performed s-TSH measurements increased from 110,886 to 292,911 (164%), and the number of patients initiating LT4 therapy increased from 786 to 1825 (132%), though this was comparably unchanged from 2010 to 2015. The median s-TSH at therapy initiation decreased from 10 mIU/L (interquartile range 5.2-29.7 mIU/L) in 2001 to 6.8 mIU/L (interquartile range 5.1-11 mIU/L) in 2015, while the estimated treatment threshold decreased from 28.3 mIU/L [confidence interval 21.0-40.2 mIU/L] in 2001 to 14.2 mIU/L [confidence interval 12.0-18.0 mIU/L] in 2007. In 2015, 25% of patients started LT4 therapy with s-TSH ≤5 mIU/L, and during the entire period, 50% of patients started therapy with a single s-TSH measurement >5 mIU/L. Conclusions: This study performed on a sizeable primary care population demonstrates a considerable fall in the threshold for initiating LT4 therapy in hypothyroid patients. This increases the risk of futile treatment as well as overtreatment.

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.

[Beer discrimination among users of Studenterklubben: a randomized double-blinded trial]. / Øldifferentiering blandt brugere af Studenterklubben.

INTRODUCTION: Studenterklubben has been serving beer from Tuborg breweries for Danish medical students throughout the years. A discussion of changing supplier raised concerns about the students' ability to discriminate between Grøn Tuborg and Ceres Royal Pilsner. MATERIAL AND METHODS: Two hypotheses were developed: 1) the participants would rate the beers equally and 2) the participants would be unable to identify the Grøn Tuborg. A randomised double-blinded trial was conducted to test the hypotheses. Fifty-seven participants completed the trial. The participants rated the two randomised beers on a Numeric Rating Scale (NRS) 1-10 and tried to identify the Grøn Tuborg. RESULTS: The participants rated the Grøn Tuborg (NRS 6.18 SD 1.9) better than Ceres Royal Pilsner (NRS 5.23; SD 1.9), which was significant (p = 0.008). 68% identified Grøn Tuborg correctly which differed significantly (p = 0.004) from the developed hypothesis. The group preferring Grøn Tuborg was significantly better at identifying the correct beer (p < 0.0001). CONCLUSION: The participants were considered to be representative of the general users of Studenterklubben. It required several supermarkets to buy the required amount of Ceres Royal Pilsner, which might have influenced the participant's general shopping pattern and knowledge about Ceres Royal Pilsner, as well as having lead to different dates of production. This might have influenced the taste of Ceres Royal Pilsner. The guests of Studenterklubben are able to identify Grøn Tuborg. The guests prefer the taste of Grøn Tuborg over Ceres Royal Pilsner.