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.

Characteristics of specialists treating hypothyroid patients: the "THESIS" collaborative.

Introduction: Thyroid specialists influence how hypothyroid patients are treated, including patients managed in primary care. Given that physician characteristics influence patient care, this study aimed to explore thyroid specialist profiles and associations with geo-economic factors. Methods: Thyroid specialists from 28 countries were invited to respond to a questionnaire, Treatment of Hypothyroidism in Europe by Specialists: an International Survey (THESIS). Geographic regions were defined according to the United Nations Statistics Division. The national economic status was estimated using World Bank data on the gross national income per capita (GNI per capita). Results: 5,695 valid responses were received (response rate 33·0%). The mean age was 49 years, and 65·0% were female. The proportion of female respondents was lowest in Northern (45·6%) and highest in Eastern Europe (77·2%) (p <0·001). Respondent work volume, university affiliation and private practice differed significantly between countries (p<0·001). Age and GNI per capita were correlated inversely with the proportion of female respondents (p<0·01). GNI per capita was inversely related to the proportion of respondents working exclusively in private practice (p<0·011) and the proportion of respondents who treated >100 patients annually (p<0·01). Discussion: THESIS has demonstrated differences in characteristics of thyroid specialists at national and regional levels, strongly associated with GNI per capita. Hypothyroid patients in middle-income countries are more likely to encounter female thyroid specialists working in private practice, with a high workload, compared to high-income countries. Whether these differences influence the quality of care and patient satisfaction is unknown, but merits further study.

[Graves' disease in HIV patient receiving antiretroviral therapy].

The article focuses on the clinical case of Graves’ disease in a patient with HIV infection who is receiving antiretroviral therapy. The number of HIV-infected patients has increased significantly in recent decades all over the world. The currently used highly active antiretroviral therapy can significantly improve the prognosis for these patients. However, its use is associated with a number of complications, in particular the development of immune reconstitution syndrome, under which the development of such autoimmune diseases as Graves’ disease, polymyositis and Guillain-Barre syndrome may occur. Therefore, we would like to draw the attention of doctors to the possibility of such a complication in patients receiving antiretroviral therapy. Timely diagnosis and treatment of thyroid disorders will help to avoid the complications associated with an excess or deficit of thyroid hormones.

A registry for patients with chronic hypoparathyroidism in Russian adults.

Hypoparathyroidism and pseudohypoparathyroidism are rare endocrine disorders, characterized by low serum calcium due to inappropriate parathyroid hormone (PTH) levels or resistance to its action. There is little epidemiological information regarding chronic hypoparathyroidism in Russia. This study aims to build a registry database of Russian patients with chronic hypoparathyroidism who were referred for hospital treatment in order to conduct initial analysis of clinical presentations and hospital management. The Italian registry model was taken to be able to integrate our data in the future. Two hundred patients with hypoparathyroidism (n = 194) and pseudohypoparathyroidism (n = 6) were enrolled over 2 years (2017-2019). The most frequent cause of hypoparathyroidism was neck surgery (82.5%, mostly females), followed by idiopathic hypoparathyroidism (10%), syndromic forms of genetic hypoparathyroidism (4.5%) and forms of defective PTH action (3%). Calcium supplements and alfacalcidol were prescribed in most cases. However, a minority of patients (n = 6) needed to receive teriparatide as the only way to maintain calcium levels and to prevent symptoms of hypocalcemia. Consequently, substitution treatment with parathyroid hormone should be available in certain cases of hypoparathyroidism. This database will be useful to estimate the potential requirement for recombinant PTH in Russia and standards for clinical and therapeutic approaches.

2012 ETA Guidelines: The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism.

BACKGROUND: Data suggest symptoms of hypothyroidism persist in 5-10% of levothyroxine (L-T4)-treated hypothyroid patients with normal serum thyrotrophin (TSH). The use of L-T4 + liothyronine (L-T3) combination therapy in such patients is controversial. The ETA nominated a task force to review the topic and formulate guidelines in this area. METHODS: Task force members developed a list of relevant topics. Recommendations on each topic are based on a systematic literature search, discussions within the task force, and comments from the European Thyroid Association (ETA) membership at large. RESULTS: SUGGESTED EXPLANATIONS FOR PERSISTING SYMPTOMS INCLUDE: awareness of a chronic disease, presence of associated autoimmune diseases, thyroid autoimmunity per se, and inadequacy of L-T4 treatment to restore physiological thyroxine (T4) and triiodothyronine (T3) concentrations in serum and tissues. There is insufficient evidence that L-T4 + L-T3 combination therapy is better than L-T4 monotherapy, and it is recommended that L-T4 monotherapy remains the standard treatment of hypothyroidism. L-T4 + L-T3 combination therapy might be considered as an experimental approach in compliant L-T4-treated hypothyroid patients who have persistent complaints despite serum TSH values within the reference range, provided they have previously received support to deal with the chronic nature of their disease, and associated autoimmune diseases have been excluded. Treatment should only be instituted by accredited internists/endocrinologists, and discontinued if no improvement is experienced after 3 months. It is suggested to start combination therapy in an L-T4/L-T3 dose ratio between 13:1 and 20:1 by weight (L-T4 once daily, and the daily L-T3 dose in two doses). Currently available combined preparations all have an L-T4/L-T3 dose ratio of less than 13:1, and are not recommended. Close monitoring is indicated, aiming not only to normalize serum TSH and free T4 but also normal serum free T4/free T3 ratios. Suggestions are made for further research. CONCLUSION: L-T4 + L-T3 combination therapy should be considered solely as an experimental treatment modality. The present guidelines are offered to enhance its safety and to counter its indiscriminate use.

Levothyroxine replacement therapy in patients with subclinical hypothyroidism and coronary artery disease.

OBJECTIVE: To assess the potential benefits and risks associated with levothyroxine (LT4) therapy in patients with subclinical hypothyroidism (SH) and concomitant coronary artery disease (CAD). METHODS: We enrolled 33 patients (4 male and 29 female subjects) with SH and CAD in this study. The study cohort consisted of 2 groups: 19 patients who were randomly assigned to receive LT4 therapy, titrated to maintain a normal serum thyrotropin level (main group), and 14 patients who did not receive any LT4 replacement therapy (control group). Variables of the lipid profile and left ventricular diastolic function were measured and 24-hour electrocardiographic monitoring was performed before randomization and at 6-month follow-up. Medical therapy for the CAD remained unchanged throughout the 6-month study period. RESULTS: In the main group, no statistically significant differences were found in the lipids, variables of left ventricular diastolic function, and heart rate pattern between the hypothyroid and euthyroid states. Individual analysis revealed, however, that LT4 therapy was beneficial in terms of lipid abnormalities in those patients with lower body mass index, shorter history of CAD, and higher cholesterol levels at baseline. In the control group, we noted statistically significant prolongation of early filling deceleration time after 6 months, which indicated less flexibility of the left ventricular myocardium and diastolic myocardial dysfunction with long-term SH. In reference to adverse effects of LT4 therapy, 5 of the 19 patients had an increased rate of ventricular premature beats. These 5 patients were significantly older and initially had more supraventricular and ventricular premature beats than the rest of the main group. No ST depressions were recorded during LT4 therapy. CONCLUSION: In patients with SH and CAD, LT4 therapy can be beneficial in diminishing lipid abnormalities in those with lower body mass index, briefer duration of CAD, and higher levels of cholesterol at baseline. Patients in our study who experienced adverse effects of LT4 treatment were older and had more supraventricular premature beats at baseline in comparison with the other patients.

TSH and thyroid hormones concentrations in patients with hypothyroidism receiving replacement therapy with L-thyroxine alone or in combination with L-triiodothyronine.

The aim of this study was to evaluate parameters of thyroid function in patients with primary hypothyroidism receiving either monotherapy with L-T4 or combination L-T4+L-T3. Fifty-eight women with primary hypothyroidism receiving L-T4 were enrolled in the study. The patients were randomised into two groups: Group 1 (n=42) patients continued monotherapy with L-T4, and Group 2 (n=16) patients were switched to combined therapy with L-T4+L-T3 (25 microg L-T4 was replaced with 12.5 microg L-T3). The final examination was carried out 6 months thereafter. There was also a third group of 20 healthy women (control group). Under monotherapy with L-T4, serum FT4 levels were higher (p < 0.05) and FT3 lower (p < 0.05) than in the control group, while the monotherapy subgroup of patients with low-normal TSH had serum FT4 levels higher than in the control group (p < 0.05). Serum FT4 under combined therapy was significantly lower than in both control and monotherapy groups. FT3 levels did not differ between the two groups of combined and monotherapy subjects; the highest FT3 levels were in the control group. L-T4 replacement therapy is associated with non-physiologically high FT4 and low FT3 levels. Therapy with L-T3 once a day does not simulate the normal production of T3 by the thyroid.