Associations of TSH, free T3, free T4, and conversion ratio with incident hypertension: results from the prospective Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

Objective: To evaluate the association of TSH, free T3 (FT3), free T4 (FT4), and conversion (FT3:FT4) ratio values with incident hypertension. Materials and methods: The study included data from participants of the ELSA-Brasil study without baseline hypertension. Serum TSH, FT4 and FT3 levels, and FT3:FT4 ratio values were assessed at baseline, and incident hypertension (defined by blood pressure levels ≥ 140/90 mmHg) was estimated over a median of 8.2 years of follow-up. The risk of incident hypertension was evaluated considering a 1-unit increase in TSH, FT4, FT3, and conversion ratio values and after dividing these variables into quintiles for further analysis using Poisson regression with robust variance. The results are presented as relative risks (RR) and 95% confidence intervals (CIs) before and after adjustment for multiple variables. Results: The primary analysis incorporated data from 5,915 euthyroid individuals, and the secondary analysis combined data from all euthyroid individuals, 587 individuals with subclinical hypothyroidism, and 31 individuals with subclinical hyperthyroidism. The rate of incident hypertension was 28% (95% CI: 27%-29.3%). The FT4 levels in the first quintile (0.18-1.06 ng/dL) were significantly associated with incident hypertension (RR: 1.03, 95% CI: 1.01-1.06) at follow-up. The association between FT4 levels in the first quintile and incident hypertension was also observed in the analysis of combined data from euthyroid individuals and participants with subclinical thyroid dysfunction (RR: 1.04, 95% CI: 1.01-1.07). The associations were predominantly observed with systolic blood pressure levels in euthyroid individuals. However, in the combined analysis incorporating euthyroid participants and individuals with subclinical thyroid dysfunction, the associations were more pronounced with diastolic blood pressure levels. Conclusion: Low FT4 levels may be a mild risk factor for incident hypertension in euthyroid individuals and persons with subclinical thyroid dysfunction.

Potential Determinants of Thyroid Peroxidase Antibodies and Mortality Risk: Results From the ELSA-Brasil Study.

CONTEXT: The presence of thyroid peroxidase antibodies (TPOAbs) may be considered as an indicator of adverse health outcomes. OBJECTIVE: We aimed to investigate the potential determinants of TPOAb levels and to analyze the association between TPOAb titers and the risk of all- and specific-cause mortality. METHODS: Baseline and longitudinal data of 13 187 participants from the ELSA-Brasil Study were analyzed. We investigated the association of TPOAb, detectability, positivity, and persistent positivity with sociodemographic and lifestyle factors using logistic regressions. Cox proportional hazards and Fine-Gray subdistribution hazard regression analyses were used to verify the association of TPOAbs with mortality. RESULTS: The determinants of TPOAb detectability and positivity were younger age, higher body mass index, female sex, and former and current smoking status. Black, mixed, and other self-reported races, intermediate and higher education, and heavy drinking were determinants of detectable and positive TPOAb levels. Female sex, White race, and former smoking were determinants of persistent TPOAb positivity at 2 visits, although only the female sex maintained its association at 3 visits. Moreover, after multivariate adjustment, there were associations between higher levels of TPOAbs and higher risk of cancer-related mortality among men, and TPOAb detectability and mortality by other causes among women. CONCLUSION: Sociodemographic and lifestyle-related factors were determinants of multiple TPOAb categories. TPOAb levels were associated with mortality risk; however, the low mortality rate in this sample might have compromised this finding. We suggest further studies to explore the clinical importance of detectable TPOAb levels, not only its positivity, as a potential marker of inflammation.

Impact of Bariatric Surgery on Thyroid Morphology and Thyroid Function.

INTRODUCTION: Few studies have evaluated the impact of bariatric surgery (BS) on thyroid function and morphology, and how it correlates to inflammatory and metabolic markers. We aimed to evaluate all those parameters together. METHODS: A longitudinal study included 70 patients with severe obesity. The bariatric group (BG) enrolled 40 patients who underwent BS, and the control group (CG) enrolled 30 patients who did not undergo BS. Both were submitted (pre- and 2nd-year) to thyroid ultrasound and laboratory analyses to determine the levels of thyroid hormones, inflammatory, and metabolic markers. RESULTS: Thyroid volume (TV) decreased after BS (-1.5 cm3), differing significantly from the CG (+0.6 cm3; p = 0.003). ΔTV was independently and positively correlated with ΔHOMA-IR (0.41 (0.11/7.16) p = 0.007) and ΔIL6 (0.02 (0.01/0.3) p = 0.016). A nonsignificant correlation between ΔTV and ΔBMI was detected (0.38 (-0.01/0.09) p = 0.152). We also observed a negative correlation between ΔTV and ΔTSH (-2.03 (-2.87/-1.19) p = 0.000) and ΔT3/T4 ratio (-0.06 (-0.09/-0.02) p = 0.001). TSH had a nonsignificant reduction with BS (-0.3872 vs. -0.2483 p = 0.128). The conversion of T4 to T3 had a significant increase after BS, as demonstrated by the T3/T4 ratio (+5.16 p = 0.01). Despite an increase in the prevalence of thyroid nodules in the BG, it was not statistically significant (p = 0.340). CONCLUSION: BS was associated with a reduction in TV and a nonstatistically significant reduction in TSH. The variations in TV were related to the metabolic markers and inflammatory changes. An increase in the conversion of T4 to T3 with BS was detected, possibly related to inflammatory improvement.

GlycA as a Novel Biomarker of Systemic Inflammation in Hypothyroidism.

Background: GlycA is a novel glycoprotein biomarker of systemic inflammation and cardiovascular risk. Our objective was to assess the levels of GlycA in individuals with hypothyroidism. We also explored whether levothyroxine (LT4)-treated patients had different levels of GlycA, with attention to thyrotropin (TSH) levels. Methods: We performed a cross-sectional analysis, using baseline data from the ELSA-Brasil cohort study. We included only participants with serum TSH and GlycA levels measurements, using magnetic resonance spectroscopy (n = 4745). We excluded individuals with endogenous hyperthyroidism and those using drugs impacting thyroid function. Participants not taking LT4 and whose serum TSH was 0.4-4.0 mIU/L were classified as euthyroid (EU) and those with elevated TSH as undiagnosed hypothyroidism (UH). For those on LT4 (n = 345), adequacy of treatment was defined as TSH within the reference range. Those with TSH <0.4 mIU/L were considered over-treated (OT), and those >4.0 mIU/L, under-treated (UT). Both (UT+OT) were considered inadequately treated (IT). Group comparisons were performed by Kruskal-Wallis, adjusted Chi-square, and the post hoc Dunn test. Additional subgroup analysis were performed in patients with circulating thyroperoxidase antibodies (TPO-Ab+). Respective multivariable analyses were performed to evaluate the relationship between thyroid-related variables and GlycA levels (Generalized Linear Model), as well as an abnormal GlycA (>400 µmol/L; Logistic Binary Regression). Results: The prevalence rate of UH was 9.8% (467/4745) and, among those on LT4, only 61.7% (213/345) were adequately treated (AT). GlycA levels were higher in IT in comparison to EU (429 vs. 410 µmol/L, p < 0.01) but did not differ between UH (413 µmol/L) and euthyroidism. However, the subgroup analysis of those TPO-Ab+ showed that not only those with IT, but also those with UH, had higher levels of GlycA in comparison to euthyroidism (423 and 424 vs. 402 µmol/L, p = 0.04). This association between higher levels of GlycA and IT was maintained even in multivariable analysis (odds ratio 1.53, confidence interval 1.03 to 2.31) Lower levels of GlycA were detected in AT (405 µmol/L,) compared with OT (432 µmol/L, 0.04) and UT (423 µmol/L, p = 0.02). Conclusions: Patients with IT, both OT and UT, had higher GlycA levels, which may be associated with low-grade systemic inflammation and, possibly, increased cardiovascular risk.

Does a three-degree hypoechogenicity grading improve ultrasound thyroid nodule risk stratification and affect the TI-RADS 4 category? A retrospective observational study

ABSTRACT Objective: The aim of this study was to determine whether classifying hypoechogenicity in three degrees (mild, moderate, and marked) could improve the distinction between benign and malignant nodules and whether such an approach could influence Category 4 of the Thyroid Imaging Reporting and Data System (TI-RADS). Materials and methods: In total, 2,574 nodules submitted to fine needle aspiration, classified by the Bethesda System, were retrospectively assessed. Further, a subanalysis considering solid nodules without any additional suspicious findings (n = 565) was performed with the purpose of evaluating mainly TI-RADS 4 nodules. Results: Mild hypoechogenicity was significantly less related to malignancy (odds ratio [OR]: 1.409; CI: 1.086-1.829; p = 0.01), compared to moderate (OR: 4.775; CI: 3.700-6.163; p < 0.001) and marked hypoechogenicity (OR: 8.540; CI: 6.355-11.445; p < 0.001). In addition, mild hypoechogenicity (20.7%) and iso-hyperechogenicity (20.5%) presented a similar rate in the malignant sample. Regarding the subanalysis, no significant association was found between mildly hypoechoic solid nodules and cancer. Conclusion: Stratifying hypoechogenicity into three degrees influences the confidence in the assessment of the rate of malignancy, indicating that mild hypoechogenicity has a unique low-risk biological behavior that resembles iso-hyperechogenicity, but with minor malignant potential when compared to moderate and marked hypoechogenicity, with special influence on the TI-RADS 4 category.

Screening, diagnosis and management of hypothyroidism in pregnancy: Number 10 - October 2022

Key points Pregnancy places a metabolic overload on the maternal thyroid, especially in the first trimester, mainly because of the demand imposed by the conceptus. The fetal thyroid becomes functionally mature only around pregnancy week 20. Until then, the fetus depends on the transfer of maternal thyroid hormones (THs). Thyroid hormones are essential for the adequate fetal neurofunctional and cognitive development. Hypothyroidism brings higher risks of obstetric and fetal complications, namely, first-trimester miscarriage, preeclampsia and gestational hypertension, placental abruption, prematurity, low birth weight, and higher perinatal morbidity and mortality. Primary hypothyroidism (involvement of the gland with difficulty in producing and/or releasing TH) is the most common form of disease presentation, with the main etiology of Hashimoto's thyroiditis of autoimmune origin. In about 85%-90% of cases of Hashimoto's thyroiditis, antithyroid antibodies are present; the antithyroperoxidase (ATPO) is the most frequent. Positivity for ATPO is determined when circulating values exceed the upper limit of the laboratory reference. It implies greater risks of adverse maternal-fetal outcomes. Such a correlation occurs even in ranges of maternal euthyroidism. The critical point for the diagnosis of hypothyroidism during pregnancy is an elevation of thyroid-stimulating hormone (TSH). The measurement of free thyroxine (FT4) differentiates between subclinical and overt hypothyroidism. In subclinical hypothyroidism, FT4 is within the normal range, whereas in overt hypothyroidism, FT4 values are below the lower limit of the laboratory reference. Treatment of hypothyroidism is performed with levothyroxine (LT4) replacement with the aim of achieving adequate TSH levels for pregnancy. Some women have a previous diagnosis of hypothyroidism, and may or may not be compensated at the beginning of pregnancy. Even in compensated cases, the increase in LT4 dose is necessary as soon as possible. In the postpartum period, adjustment of the LT4 dose depends on the condition of previous disease, on the positivity for ATPO, and also on the value of LT4 in use at the end of pregnancy. Recommendations In places with full technical and financial conditions, TSH testing should be performed for all pregnant women (universal screening) as early as possible, ideally at the beginning of the first trimester or even in preconception planning. In places with less access to laboratory tests, screening is reserved for cases with greater risk factors for decompensation, namely: previous thyroidectomy or radioiodine therapy, type 1 diabetes mellitus or other autoimmune diseases, presence of goiter, previous history of hypo or hyperthyroidism or previous ATPO positivity. The TSH dosage should be repeated throughout pregnancy only in these cases. The diagnosis of hypothyroidism is made from the TSH value > 4.0 mIU/L. Pregnant women with previous hypothyroidism, overt hypothyroidism diagnosed during pregnancy or those with the above-mentioned higher risk factors for decompensation should be referred for risk antenatal care, preferably in conjunction with the endocrinologist. Overt hypothyroidism in pregnancy is identified when TSH > 10 mIU/L, and treatment with LT4 is readily recommended at an initial dose of 2 mcg/kg/day. TSH values > 4.0 mUI/L and ≤ 10.0 mUI/L require FT4 measurement with two diagnostic possibilities: overt hypothyroidism when FT4 levels are below the lower limit of the laboratory reference, or subclinical hypothyroidism when FT4 levels are normal. The treatment for subclinical hypothyroidism is LT4 at an initial dose of 1 mcg/kg/day, and the dose should be doubled upon diagnosis of overt hypothyroidism. In cases of TSH > 2.5 and ≤ 4.0 mIU/L, if there are complete conditions, ATPO should be measured. If positive (above the upper limit of normal), treatment with LT4 at a dose of 50 mcg/day is indicated. If conditions are not complete, the repetition of the TSH dosage should be done only for cases at higher risk. In these cases, treatment with LT4 will be established when TSH > 4.0 mIU/L at a dose of 1 mcg/kg/day; if needed, the dose can be adjusted after FT4 evaluation. Women with previous hypothyroidism should have their LT4 dose adjusted to achieve TSH < 2.5 mIU/L at preconception. As soon as they become pregnant, they need a 30% increase in LT4 as early as possible. In practice, they should double the usual dose on two days a week. Levothyroxine should be given 30-60 minutes before breakfast or three hours or more after the last meal. Concomitant intake with ferrous sulfate, calcium carbonate, aluminum hydroxide and sucralfate should be avoided. The target of LT4 therapy during pregnancy is to achieve a TSH value < 2.5 mIU/L. Once the therapy is started, monthly control must be performed until the mentioned goal is reached. In the postpartum period, women with previous disease should resume the preconception dose. Cases diagnosed during pregnancy in use of LT4 ≤ 50 mcg/day may have the medication suspended. The others should reduce the current dose by 25% to 50% and repeat the TSH measurement in six weeks. Cases of ATPO positivity are at higher risk of developing postpartum thyroiditis and de-escalation of LT4 should be performed as explained.

Thyroid-Stimulating Hormone and Thyroid Hormones and Incidence of Diabetes: Prospective Results of the Brazilian Longitudinal Study of Adult Health (ELSA-BRASIL).

Background: There are conflicting data regarding the association of thyroid function with incident diabetes. We prospectively investigated thyrotropin (TSH), free thyroxine (fT4), free triiodothyronine (fT3), and its conversion ratio (fT3:fT4) with the risk of developing diabetes in euthyroid subjects and those with subclinical thyroid dysfunction. Our hypothesis is that this relationship is a U-shaped curve since both subclinical thyroid diseases may be associated with diabetes. Methods: ELSA-Brasil is a highly admixed cohort study of 35-74 years old at baseline (2008-2010). Levels of TSH, fT4, fT3, and fT3:fT4 ratio were evaluated at baseline and incident diabetes was estimated over an 8.2-year follow-up (2017-2019). Diabetes was identified based on medical diagnosis, prescriptions, and laboratory tests. The risk of diabetes was evaluated according to quintiles of TSH, fT4, fT3, and fT3:fT4 ratio using Poisson regression with robust variance presented as relative risk (RR) with confidence interval [CI] of 95% after multivariable adjustment for sociodemographic and cardiovascular risk factors (reference third quintile), and as continuous variables. Results: We included 7948 participants (mean age, 50.2 [standard deviation 8.6] years; 54.4% female): 7177 euthyroid, 726 with subclinical hypothyroidism, and 45 with subclinical hyperthyroidism. Incidence of diabetes was 14.8%. No association was found for TSH, fT4, fT3, and fT3:fT4 ratio quintiles with incident diabetes. Using continuous variables, the increase of 1-unit (1-U) of fT4 decreased the risk of diabetes (RR 0.94 [CI 0.91-0.99]), while the increase of 1-U of the fT3:fT4 ratio increased the diabetes risk (RR 1.37 [CI 1.15-1.63]). The increase of 1-U of fT3 was associated with an increased risk of diabetes, but without significance after multivariable adjustment. In body mass index-stratified analysis, people with overweight or obesity presented a modest significantly higher risk of diabetes in the lowest quintile of fT4 (RR 1.04 [CI 1.01-1.07]) and an inverse association with incident diabetes in the first quintile of fT3:fT4 ratio (RR, 0.95 [CI 0.93-0.98]). The analyses using continuous variables presented similar findings. Conclusion: These findings suggest that fT4 and fT3 levels and the conversion rate might be additional risk factors associated with incident diabetes, especially in the presence of overweight or obesity. However, they need to be confirmed in future studies. (ClinicalTrials.gov Identifier: NCT02320461).

Performance of Thyroid-Stimulating Immunoglobulin Bioassay and Thyrotropin-Binding Inhibitory Immunoglobulin Assay for the Diagnosis of Graves' Disease in Patients With Active Thyrotoxicosis.

OBJECTIVE: Graves' disease (GD) is caused by the stimulation of thyrotropin receptors by autoantibodies. We compared the diagnostic accuracy of the thyroid-stimulating immunoglobulin (TSI) bioassay and thyrotropin-binding inhibitory immunoglobulin (TBII) assay in differentiating GD from other causes of thyrotoxicosis. METHODS: We retrospectively evaluated 493 patients with thyrotoxicosis who were tested with the third-generation TSI and TBII assays simultaneously. Patients were classified according to the clinical, histopathologic, and imaging criteria into the following groups: positive reference group (PRG) (patients with GD), negative reference group (NRG) (patients without GD), and inconclusive group (patients without a definitive diagnosis). RESULTS: TSI and TBII assays were concordant in 88% of the cases and showed a strong positive correlation (rs = 0.844, P < .01). When analyzed collectively, TSI and TBII assays confirmed the diagnosis of GD in 79% of the PRG cases and excluded GD in 92.5% of patients in NRG. Combined TSI and TBII assays or TBII assay alone showed similar accuracy to the diagnosis of GD (81.4% and 77.5%, respectively). Tests in 40 of 191 patients in PRG were negative for both TSI and TBII assays, whereas 3 of 40 cases in NRG had at least 1 positive thyrotropin receptor antibody test. False-negative cases were associated with subclinical hyperthyroidism, normal radionuclide uptake, longer duration of thyrotoxicosis, and absence of goiter or Graves' ophthalmopathy. CONCLUSION: TSI and TBII assays showed similar performance in differentiating GD from other causes of thyrotoxicosis in a real-world sample of patients with active thyrotoxicosis. In combination, both tests showed little benefit compared with the TBII assay alone. Thyrotropin receptor antibody assay results should be carefully interpreted in patients with mild GD or longstanding disease.

Choosing Wisely for Thyroid Conditions: Recommendations of the Thyroid Department of the Brazilian Society of Endocrinology and Metabolism

ABSTRACT Objective: Choosing Wisely (CW) is an initiative that aims to advance the dialogue between physicians and patients about low-value health interventions. Given that thyroid conditions are frequent in clinical practice, we aimed to develop an evidence-based list of thyroid CW recommendations. Materials and methods: The Thyroid Department of the Brazilian Society of Endocrinology and Metabolism (SBEM) named a Task Force to conduct the initiative. The Task Force work was based on an electronic Delphi approach. The 10 recommendations that received the highest scores by the Task Force were submitted for voting by all SBEM associates. The 5 recommendations that received the highest scores by SBEM associates are presented herein. Results: The Task Force was composed of 14 thyroidologists from 10 tertiary-care, teaching-based Brazilian institutions. The brainstorming/ideation phase resulted in 69 recommendations. After the removal of duplicates and recommendations that did not adhere to the initiative's scope, 35 remained. Then the Task Force voted to attribute a grade (0 [lowest agreement] to 10 [highest agreement]) for each recommendation. The 10 recommendations that received the highest scores by the Task Force were submitted to all SBEM associates. A total of 683 associates voted electronically, attributing a grade (0 to 10) for each recommendation. The 5 recommendations that received the highest scores by the SBEM associates compose our final list. Conclusion: A set of recommendations to avoid unnecessary medical tests, treatments, or procedures for thyroid conditions are offered with a transparent methodology. This initiative aims to foster productive interactions between physicians and patients, stimulating shared decision-making.

Combining the American Thyroid Association's Ultrasound Classification with Cytological Subcategorization Improves the Assessment of Malignancy Risk in Indeterminate Thyroid Nodules.

Background: The risk of malignancy (RoM) of indeterminate thyroid nodules (ITNs) shows a high variability in interinstitutional cohorts. The RoM is partially associated with the cytological degree of atypia and the ultrasound (US) pattern. This study evaluated the cancer risk of ITNs by jointly considering the cytological subcategory and the American Thyroid Association (ATA)-based US risk classification. Methods: This study features a retrospective cohort from two Brazilian centers comprising 238 ITNs with confirmed outcomes. US classification, according to ATA-based guidelines, and cytological subcategorization were determined. The cytological subgroups were as follows: (1) nuclear atypia (NA) related to papillary thyroid carcinoma (PTC) but insufficient to categorize the cytology as suspicious for malignancy; (2) architectural atypia without NA (AA); (3) both architectural and nuclear atypia (ANA); (4) oncocytic pattern (OP) without NA; and (5) NA not related to PTC (NANP). NA was divided into three subgroups: nuclear size and shape, nuclear membrane appearance, and/or chromatin aspects. Results: The overall frequency of malignancy was 39.5%. Among the cytological subcategories, the highest RoM was related to the NA (43.9%) and to the ANA (43.5%), followed by AA (29.4%), and OP (9.4%). NA was positively and independently associated with cancer (odds ratio [OR]: 4.5; confidence interval [CI: 1.2-16.6]) as was the occurrence of ANA (OR 6.6 [CI 1.5-29.5]). AA and OP were not independently associated with cancer. Both ATA-based high- and intermediate-risk categories showed an independent association with cancer (OR 6.8 [CI 2.9-15.5] and OR: 2.6 [CI 1.1-5.8], respectively). ITNs with cytological findings of NA or ANA when combined with intermediate US patterns had RoM values of 47.5% and 56.7%, respectively. Both cytological subcategories, when combined with the ATA high-suspicion class reached an RoM >70%. The type of NA with the highest odds for cancer was related to the nuclear membrane (OR 11.5). Conclusions: The RoM of ITNs can reach almost 80% when both NA and ATA-based high-risk US features are present. The presence of such cytological features also increased the RoM in the ATA-based intermediate-risk US category. In addition, AA and OP were not independently related to higher cancer risk. These results strengthen the recommendations for combing cytological subcategorization and US risk classification in the workup for ITNs before the decision of a molecular testing, clinical observation, or diagnostic surgery.

The role of thyroid hormone in metabolism and metabolic syndrome.

Metabolic syndrome (MetS) and thyroid dysfunction are common in clinical practice. The objectives of this review are to discuss some proposed mechanisms by which thyroid dysfunctions may lead to MetS, to describe the bidirectional relationship between thyroid hormones (THs) and adiposity and finally, to resume a list of recent studies in humans that evaluated possible associations between thyroid hormone status and MetS or its clinical components. Not solely THs, but also its metabolites regulate metabolic rate, influencing adiposity. The mechanisms enrolled are related to its direct effect on adenosine triphosphate (ATP) utilization, uncoupling synthesis of ATP, mitochondrial biogenesis, and its inotropic and chronotropic effects. THs also act controlling core body temperature, appetite, and sympathetic activity. In a bidirectional way, thyroid function is affected by adiposity. Leptin is one of the hallmarks, but the pro-inflammatory cytokines and also insulin resistance impact thyroid function and perhaps its structure. MetS development and weight gain have been positively associated with thyroid-stimulating hormone (TSH) in several studies. Adverse glucose metabolism may be related to hyperthyroidism, but also to reduction of thyroid function or higher serum TSH, as do abnormal serum triglyceride levels. Hypo- and hyperthyroidism have been related to higher blood pressure (BP), that may be consequence of genomic or nongenomic action of THs on the vasculature and in the heart. In summary, the interaction between THs and components of MetS is complex and not fully understood. More longitudinal studies controlling each of all confounding variables that interact with endpoints or exposure factors are still necessary.

Selective case finding versus universal screening for detecting hypothyroidism in the first trimester of pregnancy: a comparative evaluation of a group of pregnant women from Rio de Janeiro.

Objective Maternal hypothyroidism during pregnancy may lead to adverse outcomes. Recently published guidelines by the American Thyroid Association (ATA) do not advocate for universal screening but recommend a case-finding approach in high-risk pregnant women. The present study aims to evaluate the accuracy of this approach in identifying women with thyroid dysfunction during early pregnancy. Subjects and methods This is a multiple-center, cross-sectional study. Three hundred and one pregnant women were enrolled. Anamnesis and a physical examination were performed to detect which women fulfilled the criteria to undergo laboratory screening of thyroid dysfunction, according to the ATA's 2017 guidelines. The Zulewski's validated clinical score was applied to assess signs and symptoms of hypothyroidism. Serum levels of thyrotropin (TSH), free thyroxine (FT4), anti-thyroperoxidase (TPO-Ab), and anti-thyroglobulin (Tg-Ab) antibodies were determined. Results Two hundred and thirty one women (78%) were classified as high risk, and 65 (22%) were classified as low risk for thyroid dysfunction. Regarding the clinical score, 75 patients (31.2%) presented mild symptoms that were compatible with SCH, of which 22 (7.4%) had symptoms as the only risk factor for thyroid disease. 17 patients (5.7%) had SCH, of which 10 (58.8%) belonged to the high-risk group, and 7 (41.2%) belonged to the low-risk group. OH was found in 4 patients (1.4%): 3 (75%) in the high-risk group and 1 (25%) in the low-risk group. Conclusions The ATA's proposed screening criteria were not accurate in the diagnosis of thyroid dysfunction in pregnancy. Testing only the high-risk pregnant women would miss approximately 40% of all hypothyroid patients.

Adrenal Venous Sampling in Primary Aldosteronism: The Usefulness of Contralateral Suppression Index.

Adrenal venous sampling (AVS) is the gold standard test to differentiate the unilateral from the bilateral form in patients with primary aldosteronism (PA) although it may be a difficult procedure, especially the successful cannulation of the right adrenal vein. In this report, we describe a 49-year-old female patient diagnosed with PA, after investigating resistant hypertension and refractory hypokalemia. Abdominal computed tomography scan revealed a 2.5 cm adenoma on the right adrenal vein. AVS was performed under cosyntropin infusion. Aldosterone and cortisol concentrations were obtained from the right and left adrenal veins and inferior vena cava (IVC). Cortisol on each adrenal vein divided by cortisol on IVC confirmed successful cannulation of the left side only, which makes it impossible to calculate the lateralization index (LI). From the data on the left adrenal vein and IVC, the aldosterone-to-cortisol ratio divided by the IVC aldosterone-to-cortisol ratio was less than 1.0, suggesting that the left adrenal vein was suppressed with the excess aldosterone originating from the contralateral side (contralateral suppression index (CSI)). Right adrenalectomy was performed; postoperative hypoaldosteronism was confirmed. This report highlights the importance of CSI obtained in AVS when technical difficulties occur making it impossible to obtain LI, which is most commonly used to decide between surgical and clinical management of PA.

Effects of Metformin on TSH Levels and Benign Nodular Goiter Volume in Patients Without Insulin Resistance or Iodine Insufficiency.

Objectives: To evaluate the impact of metformin (MTF) use on TSH levels, thyroid volume and volume of benign thyroid nodules (TNs). Additionally, to study if iodine status influences the outcomes. Methods: A total of 23 euthyroid patients (42 TNs) with benign thyroid nodules, diagnosed by fine needle aspiration biopsy, were randomly assigned to MTF or placebo (P) use for 6 months. Serum TSH, homeostatic model assessment for insulin resistance (HOMA-IR), and urinary iodine concentrations (UIC) were assessed. Ultrasound was used to evaluate TNs and thyroid volumes (TV) and their variations throughout the study. Diabetic patients, those undergoing levothyroxine replacement, and/or using thyroid- or insulin level-influencing drugs were excluded. Results: The sample consisted predominantly of patients without IR. Both intervention groups were similar regarding several confounding variables and showed a comparable median UIC. Serum TSH decreased significantly after MTF (-0.21 vs. 0.09 mUI/L in the P group; p = 0.015). At 6 months, no significant variations were found between groups with respect to TN volumes, TV, HOMA-IR, or body mass index (BMI). However, a tendency toward enlargement of TV with placebo (16.0%; p = 0.09) and a protective effect of MTF on growing TN (OR: 0.25; CI 0.05-1.20) was detected after excluding patients with IR (a lower UIC subgroup). The reduction on TSH levels with MTF maintained in the population without iodine insufficiency (-0.24 vs. +0.07 in the P group; p = 0.046) and was accentuated in those with excessive or more than adequate UIC (-0.69; p = 0.043). A protective effect of MTF on growing TN was suggested (OR: 0.11; IC: 0.02-0.84) in those with higher UIC. Conclusions: This study demonstrated that MTF caused a reduction in TSH levels in benign nodular goiter. This effect was more accentuated in patients with higher levels of UIC and was accompanied by a suggested protective effect on TN enlargement.

Variation of iodine status during pregnancy and its associations with thyroid function in women from Rio de Janeiro, Brazil.

OBJECTIVE: To assess iodine status and its effects on maternal thyroid function throughout pregnancy. DESIGN: In the present prospective cohort study, three urinary samples were requested for urinary iodine concentration (UIC) determinations in both the first and third gestational trimesters. Serum thyrotropin (TSH) and free thyroxine (FT4) were analysed in both trimesters and thyroid antibodies were assessed once. SETTING: Rio de Janeiro, Brazil.ParticipantsFirst-trimester pregnant women (n 243), of whom 100 were re-evaluated during the third trimester. RESULTS: Iodine sufficiency was found in the studied population (median UIC=216·7 µg/l). The first- and third-trimester median UIC was 221·0 and 208·0 µg/l, respectively. TSH levels (mean (sd)) were higher in the third trimester (1·08 (0·67) v. 1·67 (0·86) mIU/l; P<0·001), while FT4 levels decreased significantly (1·18 (0·16) v. 0·88 (0·12) ng/dl; P<0·001), regardless the presence of iodine deficiency (UIC<150 µg/l) or circulating thyroid antibodies. UIC correlated (ß; 95% CI) independently and negatively with age (-0·43; -0·71, -0·17) and positively with multiparity (0·15; 0·02, 0·28) and BMI (0·25; 0·00, 0·50). Furthermore, median UIC per pregnant woman tended to correlate positively with TSH (0·07; -0·01, 0·14). Women with median UIC≥250 µg/l and at least one sample ≥500 µg/l throughout pregnancy had a higher risk of subclinical hypothyroidism (OR=6·6; 95% CI 1·2, 37·4). CONCLUSIONS: In this cohort with adequate iodine status during pregnancy, excessive UIC was associated with an increased risk of subclinical hypothyroidism.

Technetium-99m-anti-tumour necrosis factor alpha scintigraphy as promising predictor of response to corticotherapy in chronic active Graves' ophthalmopathy.

It has been suggested that technetium-99m (99mTc)-anti-tumour necrosis factor alpha (TNF-α) scintigraphy (SCI) may be a useful diagnostic tool in Graves' ophthalmopathy (GO). This study evaluated whether orbit total radioactivity uptake on SCI could be used to predict corticosteroid therapy (CorT) responses in active-GO patients. A longitudinal study of patients with active GO defined by Clinical Active Score (CAS) >3/7 was done. Clinical, laboratory and SCI evaluations were performed at baseline and 3 months after concluding intravenous CorT. SCI (planar and tomographic) was assessed after intravenous injection of 10 mCi of 99mTc-anti-TNF-α. Orbits and cerebral hemispheres were defined as regions of interest (ROIs) to enable orbit/hemisphere ROI-ratios of total radioactive uptake. ROI-ratios were considered positive at >2·5. Average total radiation uptake (TRU) was also determined for each orbit (AVGROI ). Clinical, laboratory and SCI data were compared between responders (CAS became inactive) and non-responders to CorT (18 patients). At baseline, AVGROI were higher in active OG orbits (67·3 cps) than in inactive ones (33·6 cps; P<0·05). AVGROI (absolute values) reduced (-29·9 cps) in CorT responders and tended (P = 0·067) to differ from variations occurred in non-responders (+6·9 cps in patients with maintained CAS positivity post-treatment). Higher baseline ROI-ratios (4·9 versus 3·3; P = 0·056) and its pronounced reductions following CorT (-37% versus +56% in non-responders; P = 0·036) tended to be associated with good CorT responses in the subgroup of GO history ≥1 year. SCI showed a good association with active eye disease and may be an additional tool to identify CorT responders.