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.

A survey on the psychological impact and access to health care of thyroid patients during the first SARS-COV-2 lockdown.

OBJECTIVE: Information on the impact of SARS-COV-2 on the daily life of thyroid patients during lockdown is sparse. The main objective was explorative, focusing on how SARS-COV-2 affected thyroid patients. DESIGN: Cross-sectional, questionnaire-based, using an online platform. PATIENTS: Patients >18 years with a history of thyroid disease. MEASUREMENTS: Demographic data, psychological impact of SARS-COV-2, medical care during the pandemic. RESULTS: Valid responses were received from 609 responders. The median age was 50 years, 94% were female and 98.5% were UK residents. The commonest diagnosis was primary hypothyroidism (52.2%). Negative psychological effects following the lockdown were reported by 45.6%-58.7%. Cancellations of appointments with thyroid specialists were reported by 43.8%, although cancellations of thyroid investigations and treatments were relatively infrequent (12.9%-14.1%). Overall satisfaction rates for thyroid services were low (satisfaction score 40.1-42.8 out of 100), but nearly 80% were satisfied with remote consultations. Responder ratings of online information sources about SARS-COV-2 and thyroid diseases were lowest for government sites. Unmet needs during lockdown were: more remote access to thyroid specialists, more online information in 'plain English', and psychological support. In multivariate analyses, younger age, female gender, history of depression, hyperthyroidism, not having contracted SARS-COV-2 and multiple comorbidities were risk factors for a negative psychological impact of lockdown. CONCLUSIONS: This survey identified a significant negative impact of SARS-COV-2 and lockdown on psychological wellbeing, particularly in some groups of patients defined by demographic factors, history of hyperthyroidism and comorbidities. Low satisfaction with healthcare services among thyroid patients was noted, but remote consultations were rated favourably.

Postradioiodine Graves' management: The PRAGMA study.

OBJECTIVE: Thyroid status in the months following radioiodine (RI) treatment for Graves' disease can be unstable. Our objective was to quantify frequency of abnormal thyroid function post-RI and compare effectiveness of common management strategies. DESIGN: Retrospective, multicentre and observational study. PATIENTS: Adult patients with Graves' disease treated with RI with 12 months' follow-up. MEASUREMENTS: Euthyroidism was defined as both serum thyrotropin (thyroid-stimulating hormone [TSH]) and free thyroxine (FT4) within their reference ranges or, when only one was available, it was within its reference range; hypothyroidism as TSH ≥ 10 mU/L, or subnormal FT4 regardless of TSH; hyperthyroidism as TSH below and FT4 above their reference ranges; dysthyroidism as the sum of hypo- and hyperthyroidism; subclinical hypothyroidism as normal FT4 and TSH between the upper limit of normal and <10 mU/L; and subclinical hyperthyroidism as low TSH and normal FT4. RESULTS: Of 812 patients studied post-RI, hypothyroidism occurred in 80.7% and hyperthyroidism in 48.6% of patients. Three principal post-RI management strategies were employed: (a) antithyroid drugs alone, (b) levothyroxine alone, and (c) combination of the two. Differences among these were small. Adherence to national guidelines regarding monitoring thyroid function in the first 6 months was low (21.4%-28.7%). No negative outcomes (new-onset/exacerbation of Graves' orbitopathy, weight gain, and cardiovascular events) were associated with dysthyroidism. There were significant differences in demographics, clinical practice, and thyroid status postradioiodine between centres. CONCLUSIONS: Dysthyroidism in the 12 months post-RI was common. Differences between post-RI strategies were small, suggesting these interventions alone are unlikely to address the high frequency of dysthyroidism.

Patient satisfaction and quality of life in hypothyroidism: An online survey by the british thyroid foundation.

OBJECTIVE: Dissatisfaction with treatment and impaired quality of life (QOL) are reported among people with treated hypothyroidism. We aimed to gain insight into this. DESIGN AND PATIENTS: We conducted an online survey of individuals with self-reported hypothyroidism. RESULTS: Nine hundred sixty-nine responses were analysed. Dissatisfaction with treatment was common (77.6%), and overall QOL scores were low. Patient satisfaction did not correlate with type of thyroid hormone treatment, but treatment with combination levothyroxine (L-T4) and liothyronine (L-T3) or with desiccated thyroid extract (DTE) was associated with significantly better reported QOL than L-T4 or L-T3 monotherapies (P < .001); however, multivariate analysis inclusive of other clinical parameters failed to confirm an association between type of thyroid hormone treatment and QOL or satisfaction. Multivariate analysis showed positive correlations between satisfaction and age (P = .026), male gender (P = .011), being under the care of a thyroid specialist (P < .001), family doctor (GP) prescribing DTE or L-T4 + L-T3 or L-T3 (P < .001) and being well informed about hypothyroidism (P < .001); negative correlations were observed between satisfaction and negative experiences with L-T4 (P < .001) and expectations for more support from the GP (P < .001), for L-T4 to resolve all symptoms (P = .004), and to be referred to a thyroid specialist (P < .001). For QOL, positive correlations were with male gender (P = .011) and duration of hypothyroidism (P = .002); negative correlations were with age (P = .027), visiting the GP more than 3 times before diagnosis (P < .001), sourcing DTE or L-T3 independently (P = .014), negative experiences with L-T4 (P = .013), having expectations for L-T4 to resolve all symptoms (P < .001) and of more support from the GP (P = .006). CONCLUSIONS: Multiple parameters including prior healthcare experiences and expectations influence satisfaction with hypothyroidism treatment and QOL. Focusing on enhancing the patient experience and clarifying expectations at diagnosis may improve satisfaction and QOL.

Comparison of efficacy and safety of parenteral versus parenteral and oral glucocorticoid therapy in Graves' orbitopathy.

BACKGROUND/AIMS: The most effective and safe treatment protocol for Graves' orbitopathy (GO) needs to be further assessed. The aim of the present study was to evaluate the efficacy, safety and outcome of parenteral versus parenteral and oral glucocorticoid (GC) protocols in euthyroid patients with untreated and active moderate to severe GO. METHODS: This was a retrospective observational study in 140 patients comparing intravenous GC pulses only (IVGC group, 74 patients, 51 ± 11 years) with historical controls of combined oral and intravenous GC therapy (CombGC group, 66 patients, 49 ± 10 years, P = ns). IVGC therapy included infusions of 500 mg of methylprednisolone weekly for the first six weeks, followed by infusions of 250 mg weekly for the remaining six weeks (cumulative dose 4.5 g). CombGC therapy included 500 mg of methylprednisolone in 500 mL of saline solution for two alternative days, followed by oral prednisone tapering dose repeated each month for the next 5 months (cumulative dose 10.2 g). RESULTS: The overall success of the treatment was 43/66 (65%) in the CombGC group and 37/73 (51%, P = .071) in the IVGC group. Deterioration of GO developed in four (6%) patients during CombGC therapy and in nine (12%, P = .214) patients during IVGC therapy. After 6 months, relapse of GO was observed in 10/37 (26%) in the IVGC group, whereas none of the patients in CombGC had a relapse (P < .001). There were significantly more side effects in the CombGC versus IVGC group (49/66, 74% vs 28/74, 38%, P < .001). CONCLUSIONS: Our data suggest that CombGC therapy was more efficient with significantly less relapse rate, but with more side effects in comparison to IVGC therapy.

Etanercept in the treatment of Graves' ophthalmopathy with primary hypothyroidism and rheumatoid arthritis.

Graves' ophthalmopathy (GO) is an autoimmune disease affecting ocular and orbital tissues. Overproduction of tumor necrosis factor α (TNF-α) in rheumatoid arthritis (RA) and GO has destructive consequences. The subject of this paper is a case of a female patient initially diagnosed with primary hypothyroidism substitution with levothyroxine, and subsequent diagnosis of RA with insufficient therapeutic efficacy of a standard medication. Three years later, the patient presented symptoms and signs of GO. Etanercept was administrated for RA, and after four months, an improvement of the eye symptoms and reduced exophthalmos were observed and confirmed using visual methods. Graves' ophthalmopathy association with primary hypothyroidism is uncommon. The treatment of RA using etanercept led to clinical improvement of GO symptoms, which indicates that RA and GO may share similar pathogenic features. The paper suggests that etanercept may suppress the symptoms and clinical signs of GO. However, controlled trials are needed to further evaluate the effect of TNF-α inhibitors, particularly etanercept, and to compare its side effects with the current options for medical treatment.

Environmental and take-home lead exposure in children living in the vicinity of a lead battery smelter in Serbia.

Blood lead levels (BLLs) have been falling steadily worldwide due to restricted use of lead (Pb) and its compounds. although they remain above preindustrial Pb levels. Elevated BLL can still be found in children living near secondary Pb smelters that represent around 50% of Pb production. There have been no studies on Pb exposure in children living in Serbia ever since the 1980s. The aim of this study was to evaluate the BLLs in children living in two villages in Serbia (Zajaca, the location of a secondary lead smelter, and Paskovac, 5 km away), identify the primary determinants of children's BLLs, and investigate the impact of BLLs on children's health symptoms and school achievement. The study was conducted in 2011 on 127 children, aged 1-18 years, whose BLLs were measured using inductively coupled argon plasma mass spectrometry (ICP-MS). The median BLL in children was 12 µg/dl, with a significantly higher value of 17.5 µg/dl in Zajaca, compared to 7.6 µg/dl in Paskovac. Only 1 out of 75 and 12 out of 52 children from Zajaca and Paskovac, respectively, had BLLs below the CDC recommended 5 µg/dl level. Living near the smelter resulted in 19 times, and having a father who works in the plant 4 times higher odds of elevated BLLs. No significant effects of elevated BLLs health symptoms were seen in this study. BLLs of children living near a battery recycling plant in Serbia, an upper-middle income European country, were in the range and even higher than those of children living in developing countries. For the first time, the contribution of environmental and take-home lead exposure was quantified using mixed-effect modeling, and our results indicate a contribution of 25-40% of the take-home lead exposure to the BLLs of children living in the vicinity of a secondary lead smelter.

Variability of HOMA and QUICKI insulin sensitivity indices.

Assessment of insulin sensitivity based on a single measurement of insulin and glucose, is both easy to understand and simple to perform. The tests most often used are HOMA and QUICKI. The aim of this study was to assess the biological variability of estimates of insulin sensitivity using HOMA and QUICKI indices. After a 12-h fast, blood was sampled for insulin and glucose determination. Sampling lasted for 90 min with an intersample interval of 2 min. A total of 56 subjects were included in the study, and in nine subjects sampling was done before and after weight reduction, so total number of analyzed series was 65. To compute the reference value of the insulin sensitivity index, averages of all 46 insulin and glucose samples were used. We also computed point estimates (single value estimates) of the insulin sensitivity index based on the different number of insulin/glucose samples (1-45 consecutive samples). To compute the variability of point estimates a bootstrapping procedure was used using 1000 resamples for each series and for each number of samples used to average insulin and glucose. Using a single insulin/glucose sample HOMA variability was 26.18 ± 4.31%, and QUICKI variability was 3.30 ± 0.54%. For 10 samples variability was 11.99 ± 2.22% and 1.62 ± 0.31% respectively. Biological variability of insulin sensitivity indices is significant, and it can be reduced by increasing the number of samples. Oscillations of insulin concentration in plasma are the major cause of variability of insulin sensitivity indices.

The Value of Multidetector Computed Tomography of Orbits in Globe Protrusion in Comparison to Hertel Exophthalmometry

The use of multidetector computed tomography (MDCT) is an integral part of contemporary diagnostics of Graves' orbitopathy. The aim of this study was to assess proptosis measurement by MDCT and to compare it to the current standard, Hertel exophthalmometry. A cross-sectional study was conducted at the Clinical Centre of Serbia and included 91 patients (19 male and 72 female) with verified Graves' orbitopathy. Globe protrusion measured by MDCT (globe protrusion, GPR) was correlated to Hertel measured protrusion (HR). There was no constant or any systematic bias between the two methods. GPR significantly correlated with the best-corrected visual acuity, while HR did not. Age, body mass index and duration of the disease did not influence proptosis measurement by either method. Proptosis was significantly larger in males. According to our results, GPR compared to HR provides better assessment of the protrusion in Graves' disease. GPR measurement is simple and should always be part of the radiological assessment of orbits in Graves' disease.

Indirect estimation of reference intervals for thyroid parameters.

BACKGROUND: The aim of this work was to determine indirect reference intervals from patients' results obtained during routine laboratory work. This could be an accurate alternative to the laborious and expensive job of producing reference intervals for populations according to international recommendations. METHODS: All the results for thyrotropin (TSH), total and free thyroxine, and triiodothyronine (T4, fT4, T3, and fT3) stored in our laboratory information system between 2008 and 2011 were included in this study. We used logarithmic transformation of the raw data to exclude outliers. After visual observation of the data distribution, we estimated non-parametric reference intervals. A standard normal deviation test was performed to test the significance of differences between subgroups. RESULTS: There was no significant difference in the serum levels of the analyzed thyroid parameters, so we calculated combined reference values. However, we found a significant difference in TSH values between ambulatory and hospitalized patients, but only in 2011. Indirect reference values for TSH, T4, fT4, T3 and fT3 were 0.42 - 3.67 mIU/L, 66.0 - 136.10 nmol/L, 10.20 - 18.40 pmol/L, 1.10 - 2.39 nmol/L, and 3.17 - 5.59 pmol/L, respectively. CONCLUSIONS: The indirect determination of laboratory-specific reference intervals using patients' laboratory data is a relatively easy and inexpensive method. Also, indirect reference limits will be more precise and true if skewness and kurtosis of the distribution are not too large.

Indirect estimation of age-related reference limits of thyroid parameters: a cross-sectional study of outpatients' results.

OBJECTIVES: Defining adequate reference limits (RLs) for thyroid hormones is an important task for support monitoring and the treatment of subclinical thyroid disease. We determined whether there are age-related RLs for thyroid parameters in male and female outpatients free of overt thyroid disease. DESIGN: We analyzed 22,860 results (11,440 male and 11,420 female outpatients above the age of 18) for thyrotropin (TSH), free thyroxine (fT4) and total triiodothyronine (T3) that were stored in our laboratory information system between 2008 and 2011. We calculated the 2.5th and 97.5th centiles for the analyzed thyroid parameters. RESULTS: Our results indicate higher TSH levels with ageing, with a significant difference (p < 0.05) between the 97.5th centiles for males and females older than 70 (5.07 mIU/L and 4.10 mIU/L), but also a significant difference between male and female fT4 from 31 to 40 and from 41 to 50 years old (18.4 vs 14.9 pmol/L and 19.0 vs 15.9 pmol/L, p < 0.05), respectively. Overall indirect estimates of the 97.5th centiles for TSH for males and females were not significantly different and were below the generally recommended upper limit (4.01 mIU/L and 4.20 mIU/L, respectively). In addition, we found no statistically significant change in mean T3 values in the analyzed population. CONCLUSIONS: This cross-sectional study indicates change in TSH and fT4 levels with ageing and gender-related upper limits. This suggests that by using indirect estimation a laboratory could provide clinicians with more accurate gender- and age-specific RLs for thyroid parameters.

Associations of GSTM1*0 and GSTA1*A genotypes with the risk of cardiovascular death among hemodialyses patients.

BACKGROUND: The presence of glutathione transferase (GST) M1 null genotype (GSTM1-null) in end-stage renal disease (ESRD) patients is associated with lower overall survival rate in comparison to those with GSTM1-active variants. We examined association between GSTM1 and GSTT1 deletion polymorphisms as well as SNPs in GSTA1/rs3957357 and GSTP1/rs1695 genes with overall and cause-specific cardiovascular mortality in ESRD patients. METHODS: Total of 199 patients undergoing hemodialysis were included in the study. Median value of time elapsed from dialysis initiation until the death, or the end of follow-up was 8 ± 5 years. The effect of GSTM1, GSTT1, GSTP1 and GSTA1 gene polymorphisms on predicting overall and specific cardiovascular outcomes (myocardial infarction, MI or stroke) was analyzed using Cox regression model, and differences in survival were determined by Kaplan-Meier. RESULTS: GSTM1-null genotype in ESRD patients was found to be independent predictor of overall and cardiovascular mortality. However, after false discovery rate and Bonferroni corrections this effect was lost. The borderline effect modification by wild-type GSTA1*A/*A genotype on associations between GSTM1-null and analyzed outcomes was found only for death from stroke. Homozygous carriers of combined GSTM1*0/GSTA1*A genotype exhibited significantly shorter time to death of stroke or MI in comparison with carriers of either GSTM1-active or at least one GSTA1*B gene variant. The best survival rate regarding cardiovascular outcome was found for ESRD patients with combined GSTM1-active and mutant GSTA1*B/*B genotype. CONCLUSIONS: Combined GSTM1*0/GSTA1*A genotypes might be considered as genetic markers for cardiovascular death risk in ESRD patients, which may permit targeting of preventive and early intervention.

A small opening in the storm clouds: overview of the registry-based study on the management of thyroid storm.

Due to the high mortality rate of TS, effective guidance for its diagnosis and treatment is essential. The diagnostic criteria introduced by the JTA in 2012, along with the Burch-Wartofsky Point Scale, constitute valuable tools for the diagnosis of TS. In 2016, Guidelines on the management of TS were produced by the JTA and the JES. Recently, a prospective multicenter register-based study compared the prognosis and outcome of 110 new-onset TS patients with the results of previous comparable studies and evaluated the efficacy of the Guidelines. The study revealed higher APACHE II scores and significant correlations between lower BMI, post-resuscitation shock, and fever with outcomes and, overall, improved TS prognosis. Most patients in the study received methimazole and potassium iodide, the timely administration of which was linked to lower fatality rates. Adherence to treatment guidelines correlates with lower mortality rates, emphasizing the importance of experienced multidisciplinary teams in ICU settings and the necessity for periodic review of the guidelines to enhance therapeutic approaches and reduce mortality.

Adrenal hypoplasia congenita and hypogonadotropic hypogonadism due to a novel NR0B1 (DAX1) gene mutation associated with common variable immunodeficiency and Hashimoto's thyroiditis.

Not required for Clinical Vignette.

Glucose and Lipid Metabolism Disorders in Adults with Spinal Muscular Atrophy Type 3.

BACKGROUND: Spinal muscular atrophy type 3 (juvenile SMA, Kugelberg-Welander disease) is a genetic disease caused by changes in the survival motor neuron 1 (SMN) gene. However, there is increasing evidence of metabolic abnormalities in SMA patients, such as altered fatty acid metabolism, impaired glucose tolerance, and defects in the functioning of muscle mitochondria. Given that data in the literature are scarce regarding this subject, the purpose of this study was to estimate the prevalence of glucose and lipid metabolism disorders in adult patients with SMA type 3. METHODS: We conducted a cross-sectional study of 23 adult patients with SMA type 3 who underwent a comprehensive evaluation, including a physical examination, biochemical analysis, and an oral glucose tolerance test during 2020-2023. RESULTS: At least one lipid abnormality was observed in 60.8% of patients. All four lipid parameters were atypical in 4.3% of patients, three lipid parameters were abnormal in 21.7% of patients, and two lipid parameters were altered in 8.7% patients. A total of 91.3% of SMA3 patients met the HOMA-IR criteria for insulin resistance, with 30.43% having impaired glucose tolerance. None of the patients met the criteria for a diagnosis of overt DM2. CONCLUSIONS: The prevalence of dyslipidemia and altered glucose metabolism in our study sets apart the adult population with SMA3 from the general population, confirming a significant interplay between muscle, liver, and adipose tissue. Ensuring metabolic care for aging patients with SMA 3 is crucial, as they are vulnerable to metabolic derangements and cardiovascular risks.

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.

Thyroid hormones for euthyroid patients with simple goiter growing over time: a survey of European thyroid specialists.

BACKGROUND: Treatment of simple goiter (SG) growing over time with thyroid hormone (TH) therapy is discouraged by international guidelines. PURPOSE: To ascertain views of European thyroid specialists about TH treatment for euthyroid patients with growing SG and explore associations with management choice. METHODS: Online survey on the use of TH for growing SG among thyroid experts from 28 European countries. RESULTS: The response rate was 31.5% (5430/17,247). Most respondents were endocrinologists. Twenty-eight percent asserted that TH therapy may be indicated in euthyroid patients with a growing SG. National and regional differences were noted, from 7% of positive responses in The Netherlands to 78% in Czech Republic (p < 0.0001). TH was more frequently prescribed by respondents over 40 years old (OR 1.77, 2.13, 2.41 if 41-50, 51-60, >60, respectively), and working in areas of former iodine insufficiency (OR 1.24, 95% CI 1.03-1.50). TH was less frequently prescribed by endocrinologists (OR 0.77, 95% CI 0.62-0.94) and respondents working in Southern Europe (OR 0.40, 95% CI 0.33-0.48), Northern Europe (OR 0.28, 95% CI 0.22-0.36) and Western Asia (OR 0.16, 95% CI 0.11-0.24) compared to Western Europe. Associations with respondents' sex, country, availability of national thyroid guidelines, and gross national income per capita were absent or weak. CONCLUSIONS: Almost a third of European thyroid specialists support treating SG with TH, contrary to current guidelines and recommendations. This calls for urgent attention.

Inter-observer Variability of Clinical Activity Score: Assessments in Patients With Thyroid Eye Disease.

PURPOSE: Thyroid eye disease (TED) can be difficult to manage. The range of available treatments is expanding rapidly; however, cost is a concern and some patients do not respond. The Clinical Activity Score (CAS) was devised as a measure of disease activity and a potential predictor of response to anti-inflammatory treatment. Despite the widespread use of the CAS, inter-observer variability has not been investigated. The aim of the study was to determine the inter-observer variability of the CAS in patients with TED. DESIGN: Prospective reliability analysis. METHODS: Nine patients with a spectrum of clinical features of TED were assessed by 6 experienced observers on the same day. Agreement among the observers was analyzed using the Krippendorff alpha. RESULTS: The Krippendorff alpha for the total CAS was 0.532 (95% CI = 0.199-0.665), whereas alpha values for the individual components of the CAS varied between 0.171 (CI = 0.000-0.334) for lid redness and 0.671 (CI = 0.294-1.000) for spontaneous pain. Assuming that a CAS value ≥3 implies suitability of the patient for anti-inflammatory treatment, the calculated Krippendorff alpha for agreement among assessors on whether treatment should be given or not given was 0.332 (95% CI = 0.0011-0.5862). CONCLUSIONS: This study has shown unreliable inter-observer variability in total CAS and most individual CAS components, thus highlighting the need for improving the performance of the CAS or seeking other methods to assess activity.

Pregnancy outcomes and newborn characteristics in women with follicular fluid thyroid autoantibodies undergoing assisted reproduction.

Background: Higher levels of thyroid autoantibodies in follicular fluid (FF) of thyroid autoimmunity (TAI) positive women are strongly correlated with serum levels and may have effect on the post-implantation embryo development. Literature highlights that levothyroxine (LT4) treatment may attenuate the risk of adverse pregnancy outcomes. The aim of the study was to estimate the pregnancy and newborn outcomes in women with FF thyroid autoantibodies undergoing assisted reproductive technology (ART). Methods: The study population included 24 women with confirmed clinical pregnancy, 8 TAI positive and 16 TAI negative women. LT4 supplementation was applied in 20.8% patients, TAI positive. Results: Pregnancy outcomes were: twin pregnancy rate 41.7%, early miscarriage rate 8.3%, late miscarriage rate 4.2%, preterm birth rate 16.7%, term birth rate 70.8%, live birth rate 96.0%. There was significant difference in serum and in FF TgAbs (p< 0.001)between the groups according to TAI, while serum fT3 was lower in the group with TAI (p = 0.047). Serum P4 was higher in LT4 treated group (p = 0.005), with TAI, and newborns in this group had higher birth weight (p = 0.001) and height (p = 0.008). Maternal complications occurred in 23.8% of patients. No congenital malformations in newborns were noted. Conclusions: Thyroid autoantibodies present in FF may have an effect on the post-implantation embryo development, but have no effect on further course of pregnancy. The special benefit of LT4 treatment for successful ART outcome was demonstrated for newborn anthropometric parameters.

Nickel as a potential disruptor of thyroid function: benchmark modelling of human data.

Introduction: Nickel (Ni) is one of the well-known toxic metals found in the environment. However, its influence on thyroid function is not explored enough. Hence, the aim of this study was to analyse the potential of Ni to disrupt thyroid function by exploring the relationship between blood Ni concentration and serum hormone levels (TSH, T4, T3, fT4 and fT3), as well as the parameters of thyroid homeostasis (SPINA-GT and SPINA-GD) by using correlation analysis and Benchmark (BMD) concept. Methods: Ni concentration was measured by ICP-MS method, while CLIA was used for serum hormone determination. SPINA Thyr software was used to calculate SPINA-GT and SPINA-GD parameters. BMD analysis was performed by PROAST software (70.1). The limitations of this study are the small sample size and the uneven distribution of healthy and unhealthy subjects, limited confounding factors, as well as the age of the subjects that could have influenced the obtained results. Results and discussion: The highest median value for blood Ni concentration was observed for the male population and amounted 8,278 µg/L. Accordingly, the statistically significant correlation was observed only in the male population, for Ni-fT4 and Ni-SPINA-GT pairs. The existence of a dose-response relationship was established between Ni and all the measured parameters of thyroid functions in entire population and in both sexes. However, the narrowest BMD intervals were obtained only in men, for Ni - SPINA-GT pair (1.36-60.9 µg/L) and Ni - fT3 pair (0.397-66.8 µg/L), indicating that even 78.68 and 83.25% of men in our study might be in 10% higher risk of Ni-induced SPINA-GT and fT3 alterations, respectively. Due to the relationship established between Ni and the SPINA-GT parameter, it can be concluded that Ni has an influence on the secretory function of the thyroid gland in men. Although the further research is required, these findings suggest possible role of Ni in thyroid function disturbances.