Use of levothyroxine for euthyroid, thyroid antibody positive women with infertility: Analyses of aggregate data from a survey of European thyroid specialists (Treatment of Hypothyroidism in Europe by Specialists: An International Survey).

OBJECTIVES: The use of levothyroxine (LT4) treatment aiming to improve fertility in euthyroid women with positive thyroid peroxidase antibodies (TPOAb) is not supported by the available evidence. The aim of the study was to document the use of LT4 by European thyroid specialists in such patients. DESIGN: The data presented derive from Treatment of Hypothyroidism in Europe by Specialists, an International Survey (THESIS), a questionnaire conducted between 2019 and 2021 to document the management of hypothyroidism by European thyroid specialists. Here, we report the aggregate results on the use of LT4 in infertile, euthyroid women with positive TPOAb. RESULTS: A total of 2316/5406 (42.8%) respondents stated that LT4 may be indicated in TPOAb positive euthyroid women with infertility. The proportion of those replying positively to this question varied widely across different countries (median 39.4, range 22.9%-83.7%). In multivariate analyses males (OR: 0.8; CI: 0.7-0.9) and respondents >60 years (OR: 0.7; 0.6-0.8) were the least inclined to consider LT4 for this indication. Conversely, respondents managing many thyroid patients ("weekly" [OR: 1.4; CI: 1.0-1.9], "daily" [OR: 1.8; CI: 1.3-2.4]) and practicing in Eastern Europe (OR: 1.5; CI: 1.3-1.9) were most likely to consider LT4. CONCLUSIONS: A remarkably high number of respondents surveyed between 2019 and 2021, would consider LT4 treatment in TPOAb positive euthyroid women with infertility. This view varied widely across countries and correlated with sex, age and workload, potentially influencing patient management. These results raise concerns about potential risks of overtreatment.

Patients' Persistent Symptoms, Clinician Demographics, and Geo-Economic Factors Are Associated with Choice of Therapy for Hypothyroidism by European Thyroid Specialists: The "THESIS" Collaboration.

Background: Hypothyroidism is common, however, aspects of its treatment remain controversial. Our survey aimed at documenting treatment choices of European thyroid specialists and exploring how patients' persistent symptoms, clinician demographics, and geo-economic factors relate to treatment choices. Methods: Seventeen thousand two hundred forty-seven thyroid specialists from 28 countries were invited to participate in an online questionnaire survey. The survey included respondent demographic data and treatment choices for hypothyroid patients with persistent symptoms. Geo-economic data for each country were included in the analyses. Results: The response rate was 32.9% (6058 respondents out of 17,247 invitees). Levothyroxine (LT4) was the initial treatment preferred by the majority (98.3%). Persistent symptoms despite normal serum thyrotropin (TSH) while receiving LT4 treatment were reported to affect up to 10.0% of patients by 75.4% of respondents, while 28.4% reported an increasing such trend in the past 5 years. The principal explanations offered for patients' persistent symptoms were psychosocial factors (77.1%), comorbidities (69.2%), and unrealistic patient expectations (61.0%). Combination treatment with LT4+liothyronine (LT3) was chosen by 40.0% of respondents for patients who complained of persistent symptoms despite a normal TSH. This option was selected more frequently by female thyroid specialists, with high-volume practice, working in countries with high gross national income per capita. Conclusions: The perception of patients' dissatisfaction reported by physicians seems lower than that described by hypothyroid patients in previous surveys. LT4+LT3 treatment is used frequently by thyroid specialists in Europe for persistent hypothyroid-like symptoms even if they generally attribute such symptoms to nonendocrine causes and despite the evidence of nonsuperiority of the combined over the LT4 therapy. Pressure by dissatisfied patients on their physicians for LT3-containing treatments is a likely explanation. The association of the therapeutic choices with the clinician demographic characteristics and geo-economic factors in Europe is a novel information and requires further investigation.

Prevalence of morphometric vertebral fractures in patients with type 1 diabetes.

OBJECTIVE: Several studies showed low bone mineral density (BMD) and elevated risk of symptomatic fractures in patients with type 1 diabetes (T1D). To our knowledge, there has been no investigation on the prevalence of asymptomatic vertebral fractures (VFx) in T1D. In the current study, we assessed BMD and the prevalence of VFx in T1D. RESEARCH DESIGN AND METHODS: We evaluated 82 T1D patients (26 males and 56 females, aged 31.1 ± 8.6 years, BMI 23.5 ± 3.3 kg/m(2), disease duration 12.8 ± 8.3 years) and 82 controls (22 females and 60 males, aged 32.9 ± 5.8 years, BMI 23.9 ± 4.8 kg/m(2)). Spinal and femoral BMD (as Z-score, Z-LS and Z-FN, respectively) and the prevalence of VFx were evaluated by dual X-ray absorptiometry. RESULTS: T1D patients had lower Z-LS and Z-FN than controls (-0.55 ± 1.3 vs. 0.35 ± 1.0, P < 0.0001, and -0.64 ± 1.1 vs. 0.29 ± 0.9, P < 0.0001, respectively) and a higher prevalence of VFx (24.4 vs. 6.1%, P = 0.002). Age, diabetes duration, age at diabetes manifestation, glycosylated hemoglobin, Z-LS, Z-FN, and the prevalence of chronic complications were similar for patients with and without VFx. In the logistic regression analysis, the presence of VFx was associated with the presence of T1D but not with lumbar spine BMD. Whereas moderate or severe VFx was associated with low lumbar spine BMD in the whole combined group of T1D patients and controls, there was no association between moderate or severe VFx and lumbar spine BMD in the T1D group. CONCLUSIONS: T1D patients have low BMD and elevated prevalence of asymptomatic VFx, which is associated with the presence of T1D independently of BMD.

Low bone mineral density and its predictors in type 1 diabetic patients evaluated by the classic statistics and artificial neural network analysis.

OBJECTIVE: To investigate factors associated with bone mineral density (BMD) in type 1 diabetes by classic statistic and artificial neural networks. RESEARCH DESIGN AND METHODS: A total of 175 eugonadal type 1 diabetic patients (age 32.8 ± 8.4 years) and 151 age- and BMI-matched control subjects (age 32.6 ± 4.5 years) were studied. In all subjects, BMI and BMD (as Z score) at the lumbar spine (LS-BMD) and femur (F-BMD) were measured. Daily insulin dose (DID), age at diagnosis, presence of complications, creatinine clearance (ClCr), and HbA(1c) were determined. RESULTS: LS- and F-BMD levels were lower in patients (-0.11 ± 1.2 and -0.32 ± 1.4, respectively) than in control subjects (0.59 ± 1, P < 0.0001, and 0.63 ± 1, P < 0.0001, respectively). LS-BMD was independently associated with BMI and DID, whereas F-BMD was associated with BMI and ClCr. The cutoffs for predicting low BMD were as follows: BMI <23.5 kg/m(2), DID >0.67 units/kg, and ClCr <88.8 mL/min. The presence of all of these risk factors had a positive predictive value, and their absence had a negative predictive value for low BMD of 62.9 and 84.2%, respectively. Data were also analyzed using the TWIST system in combination with supervised artificial neural networks and a semantic connectivity map. The TWIST system selected 11 and 12 variables for F-BMD and LS-BMD prediction, which discriminated between high and low BMD with 67 and 66% accuracy, respectively. The connectivity map showed that low BMD at both sites was indirectly connected with HbA(1c) through chronic diabetes complications. CONCLUSIONS: In type 1 diabetes, low BMD is associated with low BMI and low ClCr and high DID. Chronic complications negatively influence BMD.