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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. [ABSTRACT FROM AUTHOR]

Background: Insulinomas are rare insulin-secreting neuroendocrine neoplasms of the pancreas. First-line treatment is the surgical removal of the tumor, however, the localization with standard imaging techniques is often challenging. With the help of selective intraarterial calcium stimulation the insulinoma's localization can be narrowed down to one third of the pancreas which the selected artery supplies. Objective: We aimed to prove the usefulness of the calcium stimulation test in case of 9 patients treated between 2006 and 2021 diagnosed with endogenous hyperinsulinemic hypoglycemia confirmed by fasting test, where conventional imaging methods, like transabdominal ultrasound, CT or MRI failed to detect the source of hyperinsulinemia. Methods: We performed selective intraarterial calcium stimulation with angiography with calcium gluconate injected to the main supporting arteries of the pancreas (splenic, superior mesenteric and gastroduodenal arteries); blood samples were obtained from the right hepatic vein before, and 30, 60 and 120 seconds after calcium administration. Results: With selective angiography we found a significant elevation of insulin levels taken from the right hepatic vein in five of the nine cases. On histopathology, the lesions were between 1-2 cm, in one case malignancy was also confirmed. In four patients we found a significant rise of insulin levels obtained from all catheterized sites, which confirmed the diagnosis of nesidioblastosis. In three cases no surgery was performed, and the symptoms relieved with medical treatment. Conclusions: Selective intraarterial calcium stimulation remains an important tool in localization of the source of insulin excess, especially in cases where other diagnostic modalities fail. [ABSTRACT FROM AUTHOR]

Objective: Preoperative diagnosis for follicular thyroid cancer (FTC) remains challenging. The purpose of this study was to explore the maximum intensity projection (MIP) features, which can be utilized for reconstructing and characterizing the structure of microvascular in tissue, associated with FTC, and to explore the independent risk factors for FTC in combination with multimodal ultrasonography and blood indicators. Methods: This single-center, prospective, single-blind, observational study included patients with suspected follicular thyroid carcinoma based on preoperative ultrasonography findings. All patients underwent routine ultrasonography, contrast-enhanced ultrasonography (CEUS), and correlated blood indexes tests. Offline MIP reconstruction of the CEUS images was performed. The tumor was histologically diagnosed postoperatively. Multivariable logistics regression was utilized for analyzing MIP characteristics combined with multimodal ultrasonography and preoperative blood indicators to identify independent risk factors for FTC. Results: In this study, 61 thyroid nodules were finally included according to the atretic criteria. (1) Compared with traditional color profile ultrasonography and CEUS, MIP technology can provide more information regarding microvascular characteristics inside thyroid tumors. The short, rod-like, crossed, curved and firework-like features of MIP images revealed statistically significant differences between the benign and malignant groups. (2) Multivariable logistic regression analysis indicated that the firework-like MIP characteristics of microvascular, thyroglobulin (Tg) level and vessel intensity (VI) value were independent risk factors for malignancy. Conclusion: (1) MIP technology has potential applications in the differential diagnosis of follicular thyroid carcinoma from benign lesions. (2) Firework MIP microvascular characteristics, Tg values and VI values can serve as parameters for the differential diagnosis of follicular thyroid carcinoma from benign lesions. This study provides a novel approach idea for preoperative multimodal differentiation of follicular thyroid carcinoma from benign lesions. [ABSTRACT FROM AUTHOR]

Background: Micronutrients play pivotal roles in modulating various aspects of the immune response. However, the existing literature on the association between micronutrients and autoimmune thyroiditis (AIT) remains limited and contentious. To address this gap, we conducted Mendelian randomization (MR) to investigate potential links between genetically predicted concentrations of six micronutrients (Copper (Cu), Iron (Ir), Calcium (Ca), Vitamin D (VD), Vitamin C (VC), Zinc (Zn)) and the risk of AIT. Method: Utilizing summary statistics from genome-wide association studies (GWAS) in individuals of European descent, we employed MR methodologies to elucidate the interplay between micronutrients and AIT. Three distinct MR techniques were employed: Inverse Variance Weighted (IVW), MR-Egger regression, and Weighted Median Estimator (WME). Additionally, we evaluated outcome heterogeneity using Cochran’s Q statistic and assessed pleiotropy using the MR-Egger intercept. Result: IVW analysis revealed no substantial evidence supporting a significant impact of genetically predicted micronutrient concentrations on AIT risk (Cu: OR = 0.918, P = 0.875; Ir: OR = 0.653, P = 0.264; Ca: OR = 0.964, P = 0.906; VD: OR = 0.717, P = 0.378; VC: OR = 0.986, P = 0.875; Zn: OR = 0.789, P = 0.539). Cochran’s Q test for IVW indicated no notable heterogeneity. Moreover, the MREgger intercept method suggested the presence of horizontal pleiotropy between serum VC levels and AIT (MR-Egger intercept = −0.037, p = 0.026), while no such pleiotropy was observed for other micronutrients. Conclusion: Our MR analysis does not support a causal relationship between genetically predicted concentrations of six micronutrients (Cu, Ir, Ca, VD, VC, and Zn) and the risk of AIT. [ABSTRACT FROM AUTHOR]

Contrast-enhanced ultrasonography (CEUS) has been established as a diagnostic tool for assessing microvascularization, essential for understanding angiogenesis in neoplastic development. Aim: This study assesses the effectiveness of CEUS as a supplementary tool to TIRADS in enhancing the ultrasound-based diagnosis of thyroid cancer. Methods and Materials: Over one year, 157 nodules in 133 patients, with predominantly solid thyroid nodules, were examined using ultrasound and CEUS and underwent thyroidectomy, allowing for a comparison of ultrasound findings with pathological reports. Results: Thyroid cancer was identified in 31.21% (49/157) of cases. Significant CEUS high-risk features included inhomogeneous enhancement, enhancement defects, and complete hypoenhancement (AUC 0.818, 0.767, 0.864 respectively). Nodules exhibiting any of these features were classified as high-risk in CEUS. The diagnostic performance of TIRADS improved when combined with CEUS, with AUC increasing from 0.707 to 0.840 and improved sensitivity. Conclusion: The integration of CEUS with TIRADS significantly enhances the diagnostic accuracy and specificity in identifying thyroid cancer. This combination proves to be a more effective method for risk stratification and diagnosis, highlighting the value of CEUS as an adjunctive tool in thyroid cancer evaluation. [ABSTRACT FROM AUTHOR]

In hypothyroid patients needing large doses of levothyroxine (L-T4) (>1.7-2 mg/kg/day) to reach euthyroidism, lactose intolerance (LI) needs to be excluded, owing to the high prevalence in the population. If LI is present, a lactose-free diet decreases the rate of L-T4 malabsorption. However, an increased requirement of L-T4 is described in patients with LI, which can be beneficially treated using lactose-free L-T4 formulation. The lactose-free liquid L-T4 formulation is able to circumvent LI malabsorption leading to the normalization of thyroid-stimulating hormone (TSH) in patients with subclinical hypothyroidism and long-term stable TSH levels. [ABSTRACT FROM AUTHOR]

Background: Hypothyroidism is treated with daily levothyroxine (LT4). In recent years, soft gel caps of LT4 (LT4-C) have been commercialized, and their performance has been optimized. Since guidelines recommend dose LT4 according to the tablet preparation efficacy, the present study was undertaken to obtain data about the daily requirement, normalized per body weight, of LT4-C. Methods: Patients undergoing LT4-C after total thyroidectomy and radioiodine treatment for differentiated thyroid carcinoma were selected. There was no specific indication of suppression of TSH (i.e., <0.5 or <0.1 mIU/L). Patients were required to maintain a stable LT4 dose during the study period. Patients with interfering factors were excluded from this study. Results: Thirty patients were enrolled (18 females and 12 males; median age, 50 years; median body weight, 71 kg; median LT4-C dose, 1.71 μg/kg/day). The analysis of patient age did not reveal any differences. The LT4-C dose correlated with free-T4 p = 0.03), but not with TSH (p = 0.42) and free-T3 (p = 0.13). TSH was <1.0 mIU/L in 90% of the cases. The LT4-C dose-TSH response effect was analysed by probit regression model: the probability to achieve TSH <1.0 mIU/l was 99% with a dose of 1.84 (95%CI 1.57-2.12) μg/kg/day, 75% with a dose of 1.38 μg/kg/day (95%CI 1.17-1.59), and 50% with a dose of 1.20 (95%CI 0.96-1.43). At ROC curve analysis, the most accurate cut-off of LT4-C dose to achieve TSH <1.0 mIU/l was 1.53 ug/kg/day with 70% sensitivity and 100% specificity. Conclusions: Athyreotic patients can be initially treated with an LT4-C dose lower than previously stated. Therefore, further prospective studies are warranted. [ABSTRACT FROM AUTHOR]

Introduction: Adult growth hormone deficiency (AGHD) is associated with a high prevalence of metabolic syndrome (MS), which contributes to the unfavorable cardiovascular risk profile in these patients. Insulin like growth factor-1 (IGF-1) is a widely used biomarker, however it does not always reflect the cardiometabolic risk and has a poor relationship with clinical efficacy endpoints. Consequently, there is an unmet need for biomarkers to monitor responses to GH-replacement. Afamin is a hormone-like glycoprotein, expressed in the liver. Higher afamin levels are strongly associated with MS and insulin resistance (IR). Although both MS and IR are very common in AGHD, afamin has not been investigated in these patients. Purpose: To investigate afamin as a potential biomarker in patients with AGHD. Materials and methods: Participants included 20 AGHD patients (11 GHsubstituted and 9 GH-unsubstituted) and 37 healthy controls. Subjects underwent routine laboratory examinations, anthropometric measurements, body composition analysis using multi-frequency bioelectrical impedance analysis (InBody720) and measurement of serum afamin concentrations. In GH-substituted subjects, GH-substitution was withdrawn for 2 months. Measurements were carried out right before GH-withdrawal, at the end of the 2-month withdrawal period, and 1 month after reinstituting GH-replacement therapy (GHRT). Results: GH-unsubstituted patients demonstrated higher afamin levels compared to controls (p=0.03). Afamin positively correlated with skeletal muscle mass, bone mineral content, total body water, extracellular- and intracellular water content, insulin (all, p<0.01), HOMA-IR (p=0.01) and Cpeptide (p=0.03) levels in AGHD but not in healthy controls. In GH-substituted patients 2-month of GH-withdrawal caused significant changes in body composition, including decreased fat-free mass, skeletal muscle mass, total body water, and intracellular water content (all, p<0.01); but these changes almost fully recovered 1 month after reinstituting GHRT. Unexpectedly, afamin levels decreased after GH-withdrawal (p=0.03) and increased with reinstitution (p<0.01). Changes of afamin levels during GH-withdrawal positively correlated with changes of HOMA-IR (r=0.80; p<0.01) and changes of insulin (r=0.71; p=0.02). Conclusion: Higher afamin levels in unsubstituted AGHD patients might indicate severe metabolic dysregulation. Significant changes accompanying GHwithdrawal and reinstitution, along with strong correlations with measures of IR, suggest that afamin could be a promising biomarker to monitor GHRTassociated changes of insulin sensitivity. [ABSTRACT FROM AUTHOR]

Primary cilia (PC) are non-motile and microtube-based organelles protruding from the surface of almost all thyroid follicle cells. They maintain homeostasis in thyrocytes and loss of PC can result in diverse thyroid diseases. The dysfunction of structure and function of PC are found in many patients with common thyroid diseases. The alterations are associated with the cause, development, and recovery of the diseases and are regulated by PCmediated signals. Restoring normal PC structure and function in thyrocytes is a promising therapeutic strategy to treat thyroid diseases. This review explores the function of PC in normal thyroid glands. It summarizes the pathology caused by PC alterations in thyroid cancer (TC), autoimmune thyroid diseases (AITD), hypothyroidism, and thyroid nodules (TN) to provide comprehensive references for further study. [ABSTRACT FROM AUTHOR]

Approximately 10%–15% of subjects with hypothyroidism on L-thyroxine (LT4) alone have persistent symptoms affecting their quality of life (QoL). Although the cause is unclear, there is evidence that “tissue T3 lack” may be responsible. If so, combining liothyronine (LT3) with LT4 would be helpful. However, randomized controlled trials (RCT), have not established greater efficacy for the LT3 + LT4 combination in these subjects than for LT4 alone. While the trial design may have been responsible, the use of unphysiological, short-acting LT3 preparations and non-thyroid-specific patient-reported outcome measures (PROMs) may have contributed. We recommend attention to the following aspects of trial design for future RCTs of LT3 + LT4 compared to LT4 alone: (a) Subject selection—(i) measurable symptoms (disadvantages should be recognized); (ii) using a validated thyroid specific PROM such as ThyPRO39 or the Composite scale derived from it; (iii) those taking over 1.2 mg/day or 100 mg/day (for pragmatic reasons) of LT4 defining a population likely without intrinsic thyroid activity who depend on exogenous LT4; (iv) recruiting a preponderance of subjects with autoimmune thyroiditis increasing generalisability; and (v) those with a high symptom load with a greater response to combination therapy e.g. those with the deiodinase 2 polymorphism. (b) The use of physiological LT3 preparations producing pharmacokinetic similarities to T3 profiles in unaffected subjects: two long-acting LT3 preparations are currently available and must be tested in phase 2b/3 RCTs. (c) The superiority of a crossover design in limiting numbers and costs while maintaining statistical power and ensuring that all subjects experienced the investigative medication. [ABSTRACT FROM AUTHOR]

Objective: To determine the impact of thyroid eye disease (TED) on patients in various stages of the disease. Background: TED is a debilitating and potentially sight-threatening inflammatory autoimmune disease that is frequently misdiagnosed. Challenging quality-of-life (QoL) issues can persist long after the active phase of disease has subsided. Methods: A 62-question survey was designed as a hypothesis-generating instrument to identify key issues confronting patients ≥18 years old with physician-diagnosed TED. Questions focused primarily on physical and emotional status, and QoL experiences in the 2 months prior to the survey. Data for individual questions are presented as summary statistics. Correlations between questions were determined using X² analyses. Results: The 443 respondents were 18 to >80 years old; >90% female, and >80% from the United States. Time since TED diagnosis ranged from <1 year to >10 years. Participants provided >500 free-form responses describing experiences of living with TED. Physical signs/symptoms were experienced by 307/443 (69%) patients. Of those responding to the QoL questions (N = 394), 53 (13%) reported symptoms improving, 73 (19%) reported symptoms worsening, and 255 (65%) reported no change in the 2 months prior to the survey. The most bothersome signs/symptoms were dry/gritty eyes, light sensitivity, bulging eyes, and pressure or pain behind the eyes. Respondents <60 years were significantly (p < 0.0001) more likely to report symptomatic TED than older patients. Of 394 respondents, 179 (45%) reported feeling depressed and/or anxious, 174 (44%) reported concern about their appearance, and 73 (19%) avoided public situations; 192 (49%) reported declines in confidence or feelings of general well-being, and 78 (20%) reported an inability to achieve goals. Activities limited by TED included reading, driving, and socializing. The proportion of respondents experiencing these negative QoL measures was higher when patients reported experiencing >5 symptoms, had been diagnosed within the last 5 years, or were <60 years of age. [ABSTRACT FROM AUTHOR]

The most frequent extrathyroidal Graves' disease manifestation is Graves' orbitopathy (GO). The treatment of GO is determined by its severity and activity. There is currently no reliable, impartial method for assessing it clinically or distinguishing fibrosis from active inflammatory disorders. Today, imaging methods including orbital ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI) are frequently employed to show pathological abnormalities in the ocular adnexa of GO patients. In addition, a not widely accepted technique -- 99mTc-DTPA SPECT -- has some potential to evaluate retrobulbar inflammation in GO patients. However, FDG-PET/CT is possibly superior to other imaging modalities in detecting inflammation in GO and it may be useful in assessing disease activity in case of clinical or serological uncertainty. It might also act as an early indicator of GO development and its aggravation before irreversible tissue alterations take place and may be used in the differential diagnosis of inflammatory disorders of the orbit. However, before FDG-PET/CT could be applied in daily clinical practice, the methodology of GO activity assessment with defined cut-off values for radionuclide concentration -- standardized units of value (SUV) have to be established and validated. In addition, the limitations of this technique have to be recognized. [ABSTRACT FROM AUTHOR]

Background: Subclinical hypothyroidism (SCH) is a common endocrine problem with prevalence estimates between 4% and 20%. Symptoms are often non-specific but can substantially affect well-being leading to repeated medical consultations. The effect of thyroid hormone replacement therapy (THRT) in patients with SCH remains uncertain. Current guidelines, limited by the lack of high-quality evidence, have been controversial with limited adherence in clinical practice. Methods: Three-round modified Delphi method to establish consensus regarding diagnosis and treatment of individuals with SCH with and without affective disorder or anxiety, conducted with clinicians from three specialties, general practice, endocrinology and psychiatry, and two countries, Sweden and the United Kingdom. Results: Sixty clinicians, 20 per specialty, were recruited. Fifty-three (88%) participants completed all three rounds. The participants reached consensus on five of the 26 practice statements that (a) repeated testing was required for the diagnosis of subclinical hypothyroidism, (b) antibody screening should usually occur, and (c and d) antibody screening would strengthen the indication for thyroid hormone replacement therapy in both individuals with or without affective disorder or anxiety. The participants disagreed with (e) a requirement of a TSH threshold = 20 mIU/L for thyroid hormone replacement therapy start. Psychiatrists and GPs but not endocrinologists, agreed that there was a frequent discrepancy between laboratory results and clinical symptoms, and disagreed that testing for thyroid dysfunction was overused in patients presenting with depression or anxiety, or fatigue. Conclusions: In many aspects, attitudes toward diagnosing and treating SCH remain diverse. The inability of our Delphi panel to achieve consensus on most items and the disagreement with a TSH = 20 mIU/L threshold for treatment suggest that the concept of SCH may need rethinking with a better understanding of the hypothalamic-pituitary-thyroid physiology. Given that the scientific evidence is currently not conclusive, guidelines in this area should not be taken as definitive. [ABSTRACT FROM AUTHOR]

Purpose: Endothelial dysfunction, which was associated with chronic hypothyroidism, was an early event in atherosclerosis. Whether short-term hypothyroidism following thyroxine withdrawal during radioiodine (RAI) therapy was associated with endothelial dysfunction in patients with differentiated thyroid cancer (DTC) was unclear. Aim of the study was to assess whether short-term hypothyroidism could impair endothelial function and the accompanied metabolic changes in the whole process of RAI therapy. Methods: We recruited fifty-one patients who underwent total thyroidectomy surgery and would accept RAI therapy for DTC. We analyzed thyroid function, endothelial function and serum lipids levels of the patients at three time points: the day before thyroxine withdrawal(P1), the day before 131I administration(P2) and 4-6 weeks after RAI therapy(P3). A high-resolution ultrasound named flow-mediated dilation (FMD) was used to measure endothelial function of the patients. Results: We analyzed the changes of FMD, thyroid function and lipids at three time points. FMD(P2) decreased significantly compared to FMD(P1) (P1vsP2, 8.05 ± 1.55vs 7.26 ± 1.50, p<0.001). There was no significant difference between FMD (P3) and FMD(P1) after restoring TSH (thyroid stimulating hormone) suppression therapy (P1 vs P3, 8.05 ± 1.55 vs 7.79 ± 1.38, p=0.146). Among all parameters, the change of low-density lipoprotein (DLDL) was the only factor correlated negatively with the change of FMD (DFMD) throughout the RAI therapy process (P1-2, r=-0.326, p=0.020; P2-3, r=-0.306, p=0.029). Conclusion: Endothelial function was transiently impaired in DTC patients at short-term hypothyroidism state during the RAI therapy, and immediately returned to the initial state after restoring TSH suppression therapy. [ABSTRACT FROM AUTHOR]

Background: Advanced glycation end products (AGEs) are heterogenous group of irreversible chemical moieties originated from non-enzymatic glycation and oxidation of proteins, nucleic acids, and lipids. The engagement of AGEs with their chief cellular receptor (RAGE) activates a myriad of signaling pathways contributing to the progression of chronic diseases like autoimmune thyroiditis, type 2 diabetes mellitus and its complications. Soluble RAGE (sRAGE) prevents AGE-RAGE interaction in a competitive manner. Objective: We investigated the association between serum AGE, sRAGE and thyroid function in 73 Hashimoto thyroiditis patients (HT) on levothyroxine substitution, and in 83 age, BMI and gender-matched healthy controls. Methods: The serum AGEs levels were determined by autofluorescence on a multi-mode microplate reader, and the serum sRAGE levels by ELISA method. Results: Mean AGE level was lower (10.71 vs 11.45 AU/µg protein; p=0.046), while mean sRAGE level was higher (923 vs 755 pg/mL; p<0.0005) in the serum of HT patients than the controls. AGE correlated with age, while sRAGE correlated negatively with BMI in both groups. We found negative correlation between AGE and fT3 levels (r=-0.32; p=0.006) and sRAGE and TSH levels (r=-0.27; p=0.022) in HT patients, while we failed to find association between AGE, sRAGE and parameters of thyroid function in the control group. Median AGE/sRAGE ratio was lower in HT patients than in controls (2.4, IQR 1.9 -- 3.1 vs 3.3, IQR 2.3 -- 4.1 AU/pg; p < 0.001). In HT patients, the AGE/sRAGE ratio correlated positively with BMI and correlated negatively with fT3. Conclusion: According to our results in HT patients lower TSH and higher fT3 levels within the reference range is accompanied by a favorable AGE/RAGE balance. Further investigations are needed to confirm these results. [ABSTRACT FROM AUTHOR]

Common symptoms of overt hypothyroidism are non-specific and include fatigue, lethargy, and dry skin. Although the diagnosis is considered to be straightforward, no single symptom can be used to identify patients with overt hypothyroidism, while many patients with subclinical hypothyroidism are asymptomatic. A large population-based study on the spectrum of symptoms in subclinical hypothyroidism showed similar rates of thyroid disease-related symptoms compared with euthyroid subjects, while the TSH concentration had no impact on symptom score. Together, these findings make it challenging to attribute symptoms to their underlying cause. This is also true in the case of unexplained persistent symptoms in levothyroxine-treated patients. Although generally considered a life-long replacement therapy, successful thyroid hormone discontinuation resulting in euthyroidism has been reported in approximately one third of patients. Thus, we overtreat patients with (subclinical) hypothyroidism, highlighting the importance of reliable diagnostic criteria. The diagnostic process, including the implementation of robust TSH and FT4 reference intervals, is especially challenging in specific situations including aging, pregnancy, non-thyroidal illness, and central hypothyroidism. There is a clear need for improved adherence to current guidelines from scientific societies and for willingness to manage symptoms without a clear pathological correlate, especially in the case of mild TSH elevations. This review will highlight recent literature on this topic and offers some practice points. [ABSTRACT FROM AUTHOR]

Sheehan syndrome (SS) caused by postpartum hemorrhage leads to partial or complete pituitary hormone deficiency. In addition to lipid and glucose abnormalities, patients with SS have increased body fat, insulin resistance (IR), coagulation abnormalities, increased leptin concentration, low-grade inflammation, and endothelial dysfunction that predispose them to cardiovascular diseases. Untreated growth hormone (GH) deficiency, hypogonadism, and excess glucocorticoid use are considered risk factors for these abnormalities. Compared to other hypopituitary subjects, patients with SS are younger and have a longer duration of disease and severe GH deficiency. Replacement with GH in addition to standard hormone replacement improves their cardiometabolic profile. [ABSTRACT FROM AUTHOR]

Background: This is the first study, that aimed: a) to compare immune response, namely the kinetics of neutralizing antibodies (Nabs), after vaccination with BNT162b2 mRNA vaccine (Comirnaty, Pfizer/BioNTech) between patients with autoimmune thyroiditis and controls, and b) to investigate changes in thyroid function in healthy subjects with no history of thyroid dysfunction before and after vaccination with BNT162b2 mRNA vaccine (Comirnaty, Pfizer/BioNTech). Methods: The entire study consisted of two sub-studies. In the first sub-study, NAbs levels after BNT162b2 mRNA vaccination were compared between 56 patients with autoimmune thyroiditis and 56 age and gender-matched healthy controls from the day of the first dose until a period of up to three months after the second dose. In the second sub-study, thyroid hormones (T3, T4, TSH) and thyroid auto-antibodies levels (anti-TG, anti-TPO) of 72 healthy subjects with no history of thyroid disease were examined before (D1) and one month after completion of the second dose (D50). Results: Among patients with autoimmune thyroiditis, the median neutralizing inhibition on D22, immediately before second dose, was 62.5%. One month later (D50), values increased to 96.7%, while three months after the second dose NAbs titers remained almost the same (94.5%). In the healthy group, median NAbs levels at D22 were 53.6%. On D50 the median inhibition values increased to 95.1%, while after three months they were 89.2%. The statistical analysis did not show significant differences between two groups (p-values 0.164, 0.390, 0.105 for D22, D50 and three months). Regarding changes in thyroid function, the mean value for T4 before vaccination was 89.797 nmol/L and one month after the second dose was 89.11 nmol/L (p-value=0.649). On D1 the mean T3 value was 1.464 nmol/L, which dropped to 1.389 nmol/L on D50 (p-value = 0.004). For TSH, mean levels were 2.064 mIU/ml on D1 and fell to 1.840 mIU/ml one month after the second dose (p-value=0.037). Despite decrease, all thyroid hormone levels remained within the normal range. No changes were found for anti-TPO or anti-TG. Conclusions: This study provided evidence that patients with autoimmune thyroiditis present similar immunological response to COVID-19 BNT162b2 mRNA vaccine (Comirnaty, Pfizer/BioNTech) with healthy subjects, while vaccination may affect thyroid function. [ABSTRACT FROM AUTHOR]

Background: The standard treatment of hypothyroidism is levothyroxine (LT-4). However, there are several controversies regarding treatment of hypothyroid patients. Aim: To investigate the Swedish endocrinologists' use of thyroid hormones in hypothyroid and euthyroid individuals. Methods: Physician members of the Swedish Endocrine Society (SEF) were invited by e-mail to participate in an online survey investigating this topic. Results: Out of the eligible 411 members, 116 (28.2%) responded. The majority (98.9%) stated that L-T4 is the treatment of choice. However, around 50% also prescribed liothyronine (L-T3) or a combination of L-T4+L-T3 in their practice. Combination therapy was mostly (78.5%) used in patients with persistent hypothyroid symptoms despite biochemical euthyroidism on L-T4 treatment. Most respondents prescribed L-T4 tablets and did not expect any major changes with alternative formulations such as soft-gel capsules or liquid formulations in situations influencing the bioavailability of L-T4. In euthyroid patients, 49.5% replied that treatment with thyroid hormones was never indicated, while 47.3% would consider L-T4 for euthyroid infertile women with high thyroid peroxidase (TPO) antibody levels. Conclusion: The treatment of choice for hypothyroidism in Sweden is L-T4 tablets. Combination therapy with L-T4+L-T3 tablets was considered for patients with persistent symptoms despite biochemical euthyroidism. Soft-gel capsules and liquid solutions of L-T4 were infrequently prescribed. Swedish endocrinologists' deviation from endocrine society guidelines merits further study. [ABSTRACT FROM AUTHOR]

Arterial hypertension represents a major global health concern; more than one fourth of the population is affected by high blood pressure. Albeit the underlying cause of the disease remains unclear in the vast majority of the cases, ~10% are of secondary origin. Endocrine disorders are common illnesses and some of them may lead to elevated blood pressure, among which thyroid diseases are of high prevalence and often overlooked, especially in mild cases. Overt and subclinical hyper- and hypothyroidism can both lead to (mostly mild) hypertension; however, the underlying mechanisms are only partially understood. The results of clinical studies are often controversial. During the past decades, some genetic mutations in the hypothalamus-pituitary-thyroid axis with cardiovascular consequences were revealed. Atherosclerotic changes resulting from lipid abnormalities due to thyroid dysfunction also affect the vasculature and can cause elevated blood pressure. The review gives a synopsis of our knowledge how thyroid hormone metabolism and functional thyroid diseases affect the cardiovascular system, their negative impact and causative role in the development of hypertension. [ABSTRACT FROM AUTHOR]

The interplay between thyroid hormone action and the immune system has been established in physiological and pathological settings. However, their connection is complex and still not completely understood. The thyroid hormones (THs), 3,3′,5,5′ tetraiodo-L-thyroxine (T4) and 3,3′,5-triiodo-L-thyronine (T3) play essential roles in both the innate and adaptive immune responses. Despite much research having been carried out on this topic, the available data are sometimes difficult to interpret or even contradictory. Innate immune cells act as the first line of defense, mainly involving granulocytes and natural killer cells. In turn, antigen presenting cells, macrophages and dendritic cells capture, process and present antigens (self and foreign) to naïve T lymphocytes in secondary lymphoid tissues for the development of adaptive immunity. Here, we review the cellular and molecular mechanisms involved in T4 and T3 effects on innate immune cells. An overview of the state-of-the-art of TH transport across the target cell membrane, TH metabolism inside these cells, and the genomic and non-genomic mechanisms involved in the action of THs in the different innate immune cell subsets is included. The present knowledge of TH effects as well as the thyroid status on innate immunity helps to understand the complex adaptive responses achieved with profound implications in immunopathology, which include inflammation, cancer and autoimmunity, at the crossroads of the immune and endocrine systems. [ABSTRACT FROM AUTHOR]

Thyroid stimulating hormone (TSH), a glycoprotein hormone produced by the anterior pituitary, controls the production of thyroxine (T4) and triiodothyronine (T3) in the thyroid. TSH is also known to be produced by the cells of the immune system; however, the physiological importance of that to the organism is unclear. We identified an alternatively-spliced form of TSHβ that is present in both humans and mice. The TSHβ splice variant (TSHβv), although produced at low levels by the pituitary, is the primary form made by hematopoietic cells in the bone marrow, and by peripheral leukocytes. Recent studies have linked TSHβv functionally to a number of health-related conditions, including enhanced host responses to infection and protection against osteoporosis. However, TSHβv also has been associated with autoimmune thyroiditis in humans. Yet to be identified is the process by which the TSHβv isoform is produced. Here, a set of genetic steps is laid out through which human TSHβv is generated using splicing events that result in a novel transcript in which exon 2 is deleted, exon 3 is retained, and the 3′ end of intron 2 codes for a signal peptide of the TSHβv polypeptide. [ABSTRACT FROM AUTHOR]

Background: Protective effects of vitamin D have been reported in autoimmune and malignant thyroid diseases, though little is known about the underlying mechanism. Sirtuin 1 histon deacethylase (SIRT1) links the vitamin D pathway with regulation of transcription factor FOXO3a, a key player in cell cycle regulation and apoptosis. Aim of the present study was to investigate common single nucleotide polymorphisms (SNP's) in FOXO3a gene in respect to thyroid diseases, as well as to evaluate the hypothesis of Sirtuin1-FOXO3a interaction being a mediator of anti-proliferative vitamin D effects. Methods: The SNP's FOXO3a rs4946936/rs4945816/rs9400239 were genotyped in 257 patients with differentiated thyroid carcinoma (DTC), 139 patients with Hashimoto thyroiditis (HT) and 463 healthy controls (HC). Moreover, T-helper cells of HC and papillary thyroid cancer cell line BCPAP were incubated with 1,25(OH)2D3 and/or SIRT1 inhibitor Ex-527 in order to elucidate SIRT1- dependent vitamin D effects on cell proliferation and FOXO3a gene expression in vitro. Results: Patients with DTC tended to carry more often allele C in FOXO3a rs4946936 in comparison to HC (pcorrected = pc = 0.08). FOXO3a rs9400239T and rs4945816C was more frequent in HT in comparison to HC (pc = 0.02 and pc = 0.01, respectively). In both DTC and HT, we could not find a correlation of FOXO3a SNP's with vitamin D status. However, on in vitro level, 1,25(OH)2D3 showed an anti-proliferative effect in both T-helper cells and BCPAP, that was blocked by SIRT1 inhibition (T-helper cells: p = 0.0059, BCPAP: p = 0.04) and accompanied by elevated FOXO3a gene expression in T-helper cells (p = 0.05). Conclusions: FOXO3a rs9400239T and rs4945816C may constitute risk factors for HT, independent of the vitamin D status.This indicates the implication of FOXO3a in pathogenesis of autoimmune thyroid diseases. The dependency of anti-proliferative vitamin D effects on SIRT1 activity further suggests a key role of vitamin D-SIRT1-FOXO3a axis for protective vitamin D effects. [ABSTRACT FROM AUTHOR]