Association between serum Klotho levels and hypothyroidism in older adults: NHANES 2007-2012.

Whether Klotho plays any role in hypothyroidism is unknown. This study aimed to determine the relationship between serum Klotho levels and hypothyroidism in older adults. From the 2007 to 2012 National Health and Nutrition Examination Survey (NHANES), 1444 older adults aged 65-79 were included in this cross-sectional study. Hypothyroidism was diagnosed using participants' reports of current medications and TSH tests. Klotho was measured using an enzyme-linked immunosorbent assay. The relationship between serum Klotho levels and hypothyroidism in older people was analyzed by one-way analysis of variance, multiple linear regression models, subgroup analyses, interaction tests, smoothed curve fitting, and threshold effects. A total of 209 (14.47%) participants were identified as having hypothyroidism. Serum Klotho (ln transformation) is independently and significantly negatively associated with the risk of hypothyroidism after complete adjustment for confounders (OR = 0.49, 95% CI 0.31-0.80; P = 0.0039). The results remained stable based on subgroup analyses and interaction tests. However, we observed an inverted U-shaped curve between the two using a smoothed curve fitting in the subgroups of 70 < age ≤ 75 years and females, with inflection points of 6.26 and 6.17, respectively. The results of our study indicate that serum Klotho levels negatively correlate with hypothyroidism among older adults.

Are resting metabolic rate and clinical symptoms affected by variation of serum thyroid stimulating hormone levels within the normal range in healthy and women with hypothyroidism? A case-control study.

BACKGROUND: It is unclear whether variation in thyroid stimulating hormone (TSH) levels within the reference range affect energy expenditure and clinical symptoms and even within the normal range of TSH levels, resting energy expenditure may alter. The aim of the present study was to determine whether treated hypothyroid subjects and healthy subjects with a low-normal TSH range (0.3-2.3 mIU/L) have better clinical outcomes and increased energy expenditure than those with a high-normal TSH range (2.3-4.3 mIU/L). METHODS: This was a case-control study of 160 overweight/obese women with TSH levels across the reference range of 0.3-4.3 mU/l. Subjects were paired in four groups: healthy subjects with low-normal target TSH (n = 40), healthy subjects with high-normal target TSH (n = 40), subjects with treated hypothyroidism with low-normal target TSH (n = 40), and subjects with treated hypothyroidism with high-normal target TSH (n = 40). Resting energy expenditure (RMR), dietary intake, body composition, physical activity, and biochemical markers were assessed. RESULTS: Subjects with low-normal (≤2.3 mU/L) and high-normal (>2.3 mU/L) TSH levels did not differ in terms of RMR, serum T3 levels, and clinical symptoms except fatigue (P = 0.013). However, serum fT4 levels were found to be significantly different between the study groups (P = 0.002). Serum fT4 concentration was the highest in subjects with treated hypothyroidism with low-normal target TSH. CONCLUSION: Variation in serum TSH levels within the reference range did not significantly affect REE and clinical symptoms except fatigue in healthy and women with hypothyroidism.

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.

Changes in thyroid hormone concentrations over time in dogs with autoimmune thyroiditis.

OBJECTIVE: The objective of this study was to follow long-term changes in the concentration of thyroid hormones in dogs with subclinical thyroiditis. SAMPLES: Samples were obtained from 125 dogs with subclinical thyroiditis. The study population included 70 female and 55 male dogs. The mean testing interval was 3.9 years from initial testing (SD, 2.3 years; range, 1 to 9 years). METHODS: Dogs with subclinical thyroiditis were identified retrospectively using results from the Orthopedic Foundation for Animals Canine Thyroid Profile performed by the Endocrinology Section of the Michigan State University Veterinary Diagnostic Lab. Owners were invited to submit follow-up serum samples with their veterinarian along with a medical history form, including subsequent treatments. RESULTS: At the time of retesting, 30% of the dogs had progressed to hypothyroidism and/or were treated with thyroxine. Fifty percent maintained positive or equivocal thyroglobulin autoantibody (TgAA) results while remaining euthyroid. Fourteen percent of the dogs became TgAA negative and remained euthyroid. In 6% of the cases tested, proper medical histories were not available, and a final classification could not be determined. CLINICAL RELEVANCE: These results indicate that most dogs with elevated thyroglobulin autoantibodies either exhibit persistent autoimmune thyroiditis with continued risk of hypothyroidism or progress to hypothyroidism when monitored for more than 1 year. Thyroid function in dogs with subclinical thyroiditis should be monitored every 12 months or if there is change in the clinical presentation.

Protective effect of higher free thyroxine levels within the reference range on biliary tract cancer risk: a multivariable mendelian randomization and mediation analysis.

Background: Hepatobiliary cancer (HBC), including hepatocellular carcinoma (HCC) and biliary tract cancer (BTC), is currently one of the malignant tumors that mainly cause human death. Many HBCs are diagnosed in the late stage, which increases the disease burden, indicating that effective prevention strategies and identification of risk factors are urgent. Many studies have reported the role of thyroid hormones on HBC. Our research aims to assess the causal effects and investigate the mediation effects between thyroid function and HBC. Methods: Utilizing the Mendelian randomization (MR) approach, the study employs single nucleotide polymorphisms (SNPs) as instrumental variables (IVs) to explore causal links between thyroid function [free thyroxine (FT4), thyroid stimulating hormone (TSH), hyperthyroidism and hypothyroidism] and HBC. Data were sourced from the ThyroidOmic consortium and FinnGen consortium. The analysis included univariable and multivariable MR analysis, followed by mediation analysis. Results: The study found a significant causal association between high FT4 levels and the reduced risk of BTC, but not HCC. However, TSH, hyperthyroidism and hypothyroidism had no causal associations with the risk of HBC. Notably, we also demonstrated that only higher FT4 levels with the reference range (FT4-RR) could reduce the risk of BTC because this protective effect no longer existed under the conditions of hyperthyroidism or hypothyroidism. Finally, we found that the protective effect of FT4-RR on BTC was mediated partially by decreasing the risk of metabolic syndrome (MetS) and reducing the waist circumference (WC). Conclusion: The findings suggest that higher FT4-RR may have a protective effect against BTC, which is partially mediated by decreased risk of MetS and a reduction in WC. This study highlights the potential role of FT4 in the pathogenesis of BTC and underscores that MetS and WC may play mediation effects as two mediators in this process.

Levothyroxine for subclinical hypothyroidism during pregnancy: an updated systematic review and meta-analysis of randomized controlled trials.

PURPOSE: We aimed to perform a systematic review and meta-analysis addressing the efficacy of levothyroxine therapy in pregnant women with subclinical hypothyroidism considering most recent evidence and subgroups of interest for clinical practice. METHODS: PubMed, Embase, and Cochrane Central were searched from inception for randomized controlled trials (RCTs) comparing levothyroxine with placebo or no intervention in pregnant women with subclinical hypothyroidism. We used a random-effects model and conducted subgroup analyses based on thyroid peroxidase antibody status, thyroid stimulating hormone levels, fertility treatment, and recurrent miscarriage. RESULTS: We included 11 RCTs comprising 2,749 pregnant women with subclinical hypothyroidism. Patients treated with levothyroxine (1,439; 52.3%) had significantly lower risk of pregnancy loss (risk ratio 0.69; 95% confidence interval 0.52-0.91; p < 0.01; 6 studies). However, there was no significant association between levothyroxine and live birth (risk ratio 1.01; 95% confidence interval 0.99-1.03; p = 0.29; 8 studies). No statistically significant interaction was observed across subgroups (p > 0.05). CONCLUSION: Levothyroxine replacement therapy for subclinical hypothyroidism during pregnancy may decrease pregnancy loss when early prescribed. Nevertheless, further investigation is needed in patients with thyroid stimulating hormone above four milliunits per liter, especially when associated with recurrent miscarriage or infertility.

Changes in TgAb and TPOAb titers are greater in thyrotoxicosis than isolated hypothyroidism induced by PD-1 blockade.

Anti-thyroglobulin antibodies (TgAb) and/or anti-thyroid peroxidase antibodies (TPOAb) positivity at baseline is a risk marker for thyroid immune-related adverse events (thyroid-irAEs) in anti-programmed cell death-1 antibody (PD-1-Ab) treatment; however, it is unknown if TgAb and TPOAb titers are associated with clinical characteristics of thyroid-irAEs. Among 586 patients treated with PD-1-Ab at Nagoya University Hospital between 2 November 2015 and 30 September 2021, 57 patients developed thyroid-irAEs (thyrotoxicosis [n = 38]; hypothyroidism without prior thyrotoxicosis {isolated hypothyroidism} [n = 19]) in whom thyroid function, and TgAb and TPOAb titers were determined at baseline and at the onset. The changes in TgAb (median, 54.8 vs. 0.2 IU/mL; p = 0.002) and TPOAb titers (31.6 vs. 0 IU/mL; p = 0.032) from baseline to onset of developing thyroid-irAEs were greater in patients with thyrotoxicosis than patients with isolated hypothyroidism. Higher TgAb and TPOAb titers, and the TgAb titer at baseline were associated with an earlier onset of thyrotoxicosis and higher peak free thyroxine levels, respectively. Twenty-eight patients who developed hypothyroidism after thyrotoxicosis had higher TgAb (54.5 vs. 10.7 IU/mL; p = 0.011) and TPOAb titers at baseline (46.1 vs. 9.0 IU/mL; p < 0.001) and greater changes in TgAb (61.7 vs. 7.8 IU/mL; p = 0.025) and TPOAb titers (52.8 vs. -0.8 IU/mL; p < 0.001) than patients who did not develop hypothyroidism. The TgAb titer at baseline and changes in the TgAb and TPOAb titers were greater in patients with thyrotoxicosis than patients with isolated hypothyroidism, suggesting that the magnitude of the thyroid autoimmune response reflects the clinical types of thyroid-irAEs.

Relationship Between Urinary Iodine Concentration and the Prevalence of Thyroid Nodules and Subclinical Hypothyroidism.

The aim of the study was to investigate the iodine intake in the resident population in Xi'an and analyze the relationship between iodine nutritional status and the prevalence of subclinical hypothyroidism and thyroid nodules (TNs). A total of 2507 people were enrolled in Xi'an. Venous serum thyroid stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb), urinary iodine concentration (UIC), and thyroid ultrasonography were collected. Patients with abnormal TSH were checked for free thyroxine (FT4) and triiodothyronine (FT3). Adults in Xi'an had median UICs of 220.80 µg/L and 178.56 µg/l, respectively. A sum of 16.78% of people had subclinical hypothyroidism. Both iodine excess and iodine deficit increased the frequency of subclinical hypothyroidism. The lowest was around 15.09% in females with urine iodine levels between 200 and 299 µg/l. With a rate of 10.69%, the lowest prevalence range for males was 100-199 µg/l. In Xi'an, 11.37% of people have TNs. In comparison to other UIC categories, TN occurrences were higher in females (18.5%) and males (12%) when UIC were below 100 µg/l. In conclusion, iodine intake was sufficient in the Xi'an area, while the adults' UIC remains slightly higher than the criteria. Iodine excess or deficiency can lead to an increase in the prevalence of subclinical hypothyroidism. Patients with iodine deficiency are more likely to develop TNs.

Impact of subclinical hypothyroidism on outcomes after coronary artery bypass grafting: a systematic review and meta-analysis.

INTRODUCTION: Coronary artery bypass grafting (CABG) is a surgical procedure that restores blood flow to heart muscle by bypassing the blocked or narrowed coronary arteries. On the other hand, subclinical hypothyroidism (SCH) is characterized by an elevated serum concentration of thyroid stimulating hormone with normal levels of serum free thyroxine. With limited research into the impact of SCH on postoperative CABG outcomes, this systematic review and meta-analysis was performed. EVIDENCE ACQUISITION: An electronic search of PubMed, Cochrane Library, and Scopus was performed from inception to April 2023. After the inclusion of five studies, a total of 2,786 patients were pooled in this quantitative synthesis. EVIDENCE SYNTHESIS: It was observed that SCH significantly increased cardiovascular mortality (OR: 2.80; 95% CI: 1.37, 5.72; P=0.005), and all-cause mortality (OR: 2.62; 95% CI: 1.80, 3.80; P<0.00001). However, no significant differences were observed for secondary outcomes, including major adverse cardiac events, incidence of postoperative stroke, and incidence of postoperative myocardial infarction. CONCLUSIONS: To the best of our knowledge, this is the first meta-analysis conducted that evaluates the impact of SCH on outcomes after CABG. The preoperative assessment of thyroid function may be considered prior to cardiovascular procedures, particularly within CABG. However, future comprehensive studies, with individual participant-level data, are necessary in order to arrive at a valid conclusion and recommendation.

Evaluation of a novel, sensitive thyroid-stimulating hormone assay as a diagnostic test for thyroid disease in cats.

OBJECTIVE: Clinicians commonly use thyroid-stimulating hormone (TSH) concentrations to diagnose thyroid disorders in humans and dogs. In cats, canine TSH chemiluminescent immunoassays (CLIA) assays are commonly used to measure TSH, but these TSH-CLIAs cannot measure low TSH concentrations (< 0.03 ng/mL) and therefore cannot distinguish between low-normal concentrations and truly low TSH concentrations (characteristic of hyperthyroidism). Our aim was to evaluate a novel TSH assay based on bulk acoustic wave (BAW) technology that has lower functional sensitivity (0.008 ng/mL) than TSH-CLIAs. ANIMALS: 169 untreated hyperthyroid cats, 53 cats treated with radioiodine (131I), 12 cats with chronic kidney disease (CKD), and 78 clinically healthy cats. METHODS: Serum concentrations of T4, TSH-CLIA, and TSH-BAW were measured in all cats. Untreated hyperthyroid cats were divided into 4 severity groups (subclinical, mild, moderate, and severe), whereas 131I-treated cats were divided into euthyroid and hypothyroid groups. RESULTS: Test sensitivity, specificity, and positive predictive value for identifying hyperthyroidism were higher for TSH-BAW (90.5%, 98.9%, and 86.9%) than TSH-CLIA (79.9%, 76.7%, and 21.7%; P < .001). Test sensitivity for identifying 131I-induced hypothyroidism was only 45.5% for T4 versus 100.0% for both TSH-CLIA and TSH-BAW (P = .03), whereas TSH-BAW had a higher positive predictive value (100%) than did either TSH-CLIA (81.2%) or T4 (71.9%). CLINICAL RELEVANCE: Serum TSH-BAW alone or together with T4 is a highly sensitive and specific diagnostic test for evaluating feline hyperthyroidism and iatrogenic hypothyroidism. Finding low serum TSH-BAW concentrations is most useful for diagnosing subclinical and mild hyperthyroidism, in which serum T4 remains within or only slightly above the reference interval.

Hypothyroidism and autoimmune thyroid disorders in rheumatoid arthritis: relationship with disease activity.

Background and aims: Thyroid function abnormalities and thyroid autoantibodies have previously been described in rheumatoid arthirits (RA) with limited data. In some studies, a relationship was found between thyroid autoantibodies and RA disease activity. However, there are not strong studies in the literature indicating the relationship between thyroid diseases and RA. The aim of this study was to determine the frequency of hypothyroidism and to investigate the relationship between thyroid hormone levels, autoantibodies and disease activity in patients with rheumatoid arthritis (RA). Methods : 1017 patients with the diagnosis of RA were recruited. This observational study was conducted between January 2014 and July 2015. Demographic variables were recorded. Anti-nuclear antibodies (ANA), anti-cyclic citrulli-nated peptide antibody (anti-CCP), Rheumatoid Factor (RF), C reactive protein (CRP), Erythrocyte Sedimentation Rate (ESR), thyroid stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), anti-microsomal antibody (anti-TPO )and anti-thyroglobulin antibody (anti-TG) were determined. Visual analog score and Disease Activiy Score 28 (DAS-28) ESR and DAS-28 CRP were recorded. The relationship between thyroid hormone levels and thyroid antibodies and disease activity parameters were determined. Results: 98 (%9,7) patients had hypothyroidism and 61 (%6) patients had hyperthyroidism. 210 (20,7%) patients with RA was positive for TPOAb and 165(16,3%) for anti-TG. Positive correlation was detected between anti-TPO positivity and anti-CCP levels (p:0.005, r:0,274). In anti-TG antibody positive patients, there was a significant positive correlation of thyroid hormone levels with CRP and DAS 28-CRP (p:0.01, r:0,120; p:0.01, r:0,169). Conclusion: Thyroid autoantibodies were found to be positive in 16-21% of patients with RA. Though hypothyroidism is not very frequent in RA patients, autoimmune thyroid disease is quite common, which may be related to disease activity.

Are We Missing Hypothyroidism among Children with Sickle Cell Anaemia?

Background: Children with sickle cell anaemia have been reported to have potential risk of hypothyroidism from chronic blood transfusions and probable thyroid tissue ischaemia. However, few studies on hypothyroidism status of children with sickle cell anaemia in Nigeria are available. The objective of this study was to determine the prevalence of hypothyroidism among children with sickle cell anaemia. Methods: A cross sectional study that assayed the thyroid hormones and thyroid stimulating hormone (TSH) of 71 children with sickle cell anaemia was conducted at Olabisi Onabanjo University Teaching Hospital Sagamu. Using age appropriate hormonal reference values, the subjects were classified into subclinical, primary and secondary hypothyroidism. Results: The mean serum TSH, Free T3, and Free T4 were comparable irrespective of age category (p > 0.05). No subject was identified to have low TSH value while 7.0% had high TSH value. Low free T3 was identified in 1.4% and 8.5% had high free T3 values. Low free T3 and free T4 were seen in 11.3% each of the subjects. The overall prevalence of primary, secondary and subclinical hypothyroidism was 0%, 0% and 4.2%, respectively. Conclusion: Sub-clinical hypothyroidism does occur in Nigerian children with sickle cell anaemia. Routine screening for hypothyroidism is advocated in all children with sickle cell anaemia.

Prevalencia de hipotiroidismo subclínico y biomarcadores de riesgo cardiovascular en pacientes del Hospital General de Riobamba / Prevalence of subclinical hypothyroidism and biomarkers of cardiovascular risk in patients of the General Hospital of Riobamba

El Hipotiroidismo subclínico (HSC) es definido bioquímicamente por una elevación en la concentración sérica de la hormona TSH con niveles normales de T4 libre. El objetivo de este estudio fue determinar la prevalencia de HSC en los pacientes que asistieron a la consulta de medicina interna del Hospital General IESS de Riobamba. Así como, analizar la correlación entre los parámetros hormonales y ciertos marcadores bioquímicos asociados con el incremento de riesgo cardiovascular. Se realizó una investigación de tipo descriptiva, observacional, con un diseño no experimental de corte transversal, que abarcó el periodo comprendido desde enero de 2019 hasta septiembre de 2021. 245 pacientes fueron diagnosticados con HSC, lo cual representó el 10.58 % del universo poblacional estudiado, 61.2% eran del sexo femenino, mientras que el 38.8% del sexo masculino. El mayor número de casos (59.61 %) se observó en el grupo etario mayor de 65 años, distribuidos de la siguiente manera: (22.86% hombres y 36.75% mujeres), también se encontró que el HSC está asociado con un perfil lipídico aterogénico, caracterizado por un incremento en la concentración de colesterol total y LDL los cuales se correlacionaron positivamente con las concentraciones de TSH.

Subclinical hypothyroidism (SH) is biochemically defined by an elevation in the serum concentration of TSH hormone with normal levels of free T4. The aim of this study was to determine the prevalence of SH in patients attending the internal medicine clinic of the General Hospital IESS of Riobamba. Also, to analyze the correlation between hormonal parameters and certain biochemical markers associated with increased cardiovascular risk. A descriptive, observational, non-experimental cross-sectional design was performed, covering the period from January 2019 to September 2021. 245 patients were diagnosed with SH, which represented 10.58 % of the population universe studied, 61.2% were female, while 38.8% were male. The highest number of cases (59.61 %) was observed in the age group over 65 years, distributed as follows: (22.86% men and 36.75% women), it was also found that SH is associated with an atherogenic lipid profile, characterized by an increase in the concentration of total cholesterol and LDL which correlated positively with TSH concentrations.

Optimized Replacement T4 and T4+T3 Dosing in Male and Female Hypothyroid Patients With Different BMIs Using a Personalized Mechanistic Model of Thyroid Hormone Regulation Dynamics.

Objective: A personalized simulation tool, p-THYROSIM, was developed (1) to better optimize replacement LT4 and LT4+LT3 dosing for hypothyroid patients, based on individual hormone levels, BMIs, and gender; and (2) to better understand how gender and BMI impact thyroid dynamical regulation over time in these patients. Methods: p-THYROSIM was developed by (1) modifying and refining THYROSIM, an established physiologically based mechanistic model of the system regulating serum T3, T4, and TSH level dynamics; (2) incorporating sex and BMI of individual patients into the model; and (3) quantifying it with 3 experimental datasets and validating it with a fourth containing data from distinct male and female patients across a wide range of BMIs. For validation, we compared our optimized predictions with previously published results on optimized LT4 monotherapies. We also optimized combination T3+T4 dosing and computed unmeasured residual thyroid function (RTF) across a wide range of BMIs from male and female patient data. Results: Compared with 3 other dosing methods, the accuracy of p-THYROSIM optimized dosages for LT4 monotherapy was better overall (53% vs. 44%, 43%, and 38%) and for extreme BMI patients (63% vs. ~51% low BMI, 48% vs. ~36% and 22% for high BMI). Optimal dosing for combination LT4+LT3 therapy and unmeasured RTFs was predictively computed with p-THYROSIM for male and female patients in low, normal, and high BMI ranges, yielding daily T3 doses of 5 to 7.5 µg of LT3 combined with 62.5-100 µg of LT4 for women or 75-125 µg of LT4 for men. Also, graphs of steady-state serum T3, T4, and TSH concentrations vs. RTF (range 0%-50%) for untreated patients showed that neither BMI nor gender had any effect on RTF predictions for our patient cohort data. Notably, the graphs provide a means for estimating unmeasurable RTFs for individual patients from their hormone measurements before treatment. Conclusions: p-THYROSIM can provide accurate monotherapies for male and female hypothyroid patients, personalized with their BMIs. Where combination therapy is warranted, our results predict that not much LT3 is needed in addition to LT4 to restore euthyroid levels, suggesting opportunities for further research exploring combination therapy with lower T3 doses and slow-releasing T3 formulations.

Management of Hypothyroidism and Hypothyroxinemia During Pregnancy.

OBJECTIVE: To review the diagnosis and management of hypothyroidism during pregnancy, in the preconception period, and in the postpartum period. METHODS: A literature review of English-language papers published between 1982 and 2022, focusing on the most recent literature. RESULTS: During pregnancy, thyroid function laboratory tests need to be interpreted with regard to gestational age. Overt hypothyroidism, regardless of the thyroid-stimulating hormone (TSH) level, should always be promptly treated when it is diagnosed before conception or during pregnancy or lactation. Most women with pre-existing treated hypothyroidism require an increase in levothyroxine (LT4) dosing to maintain euthyroidism during gestation. LT4-treated pregnant patients need close monitoring of their serum TSH levels to avoid overtreatment or undertreatment. There is no consensus about whether to initiate LT4 in women with mild forms of gestational thyroid hypofunction. However, in light of current evidence, it is reasonable to treat women with subclinical hypothyroidism with LT4, particularly if the TSH level is >10 mIU/L or thyroperoxidase antibodies are present. Women who are not treated need to be followed up to ensure that treatment is initiated promptly if thyroid failure progresses. Additional studies are needed to better understand the effects of the initiation of LT4 in early gestation in women with subclinical hypothyroidism and hypothyroxinemia and determine optimal strategies for thyroid function screening in the preconception period and during pregnancy. CONCLUSION: The diagnosis and management of hypothyroidism in the peripregnancy period present specific challenges. While making management decisions, it is essential to weigh the risks and benefits of treatments for not just the mother but also the fetus.

Aging-related Characteristics of Subclinical Hypothyroidism Detected in General Practice.

Subclinical hypothyroidism (SCH) is diagnosed when serum thyrotropin (TSH) is elevated despite a normal thyroxine level and is known to increase the risk of metabolic disorders. This study was conducted to identify potential laboratory markers suspicious for latent SCH. We retrospectively reviewed 958 outpatients in whom thyroid functions had been examined. Eighty-five (9.1%) of the 939 analyzed subjects had SCH (73% females). In the SCH group, median serum TSH and FT4 levels were 5.04 µU/ml and 1.19 ng/dl, respectively, and auto-thyroid antibodies were detected in 53.8% of patients. SCH group patients were significantly older than patients in the euthyroid group, while there was no intergroup difference in BMI. However, 56.5% of the SCH patients were asymptomatic. In the SCH group, serum aspartate aminotransferase and low-density lipoprotein cholesterol (LDL-C) levels were significantly higher, and the estimated glomerular filtration rate (eGFR) was significantly lower than in the euthyroid group. Among patients less than 65 years of age, SCH patients tended to have lower eGFR and higher LDL-C than euthyroid patients. Age-dependent reductions of red blood cells and serum albumin were more prominent in the SCH than the euthyroid group. Biochemical changes with aging are useful as potential clues for suspecting latent SCH.

Transient vs Permanent Congenital Hypothyroidism in Ontario, Canada: Predictive Factors and Scoring System.

CONTEXT: The apparent increased incidence of congenital hypothyroidism (CH) is partly due to increased detection of transient disease. OBJECTIVE: This work aims to identify predictors of transient CH (T-CH) and establish a predictive tool for its earlier differentiation from permanent CH (P-CH). METHODS: A retrospective cohort study was conducted of patients diagnosed with CH from 2006 to 2015 through Newborn Screening Ontario (NSO). RESULTS: Of 469 cases, 360 (76.8%) were diagnosed with P-CH vs 109 (23.2%) with T-CH. Doses of levothyroxine predicting T-CH were less than 3.9 µg/kg at age 6 months, less than 3.0 µg/kg at ages 1 and 2 years, and less than 2.5 µg/kg at age 3 years. Descriptive statistics and multivariable logistic modeling demonstrated several diverging key measures between patients with T-CH vs P-CH, with optimal stratification at age 1 year. Thyroid imaging was the strongest predictor (P < .001). Excluding imaging, significant predictors in the first year of life included thyroxine dose/kg (P < .001-.002), increase in thyrotropin (TSH) above the reference interval during treatment (P = .002), screening TSH (P = .03), and a history of maternal thyroid disease (P = .02). Based on the 1-year model without imaging, a risk score was developed to identify children with T-CH who may benefit from an earlier trial off therapy, to reduce excess medicalization and health care costs. CONCLUSION: A levothyroxine dose of less than 3 µg/kg at ages 1 and 2 years and less than 2.5 µg/kg at age 3 years can be predictive of T-CH. A novel risk score was developed that can be clinically applied to predict the likelihood of a successful trial off therapy for a given patient at age 1 year.

Association of Maternal Thyroid Function with Gestational Hypercholanemia.

Background: High bile acid concentration is associated with adverse perinatal outcomes (i.e., stillbirth and preterm birth) and experimental studies indicate that thyroid hormone regulates bile acid metabolism, but this has not yet been translated to clinical data in pregnant women. We aim to explore the association of thyroid function with bile acid concentrations and the risk of gestational hypercholanemia. Methods: This study comprised 68,016 singleton pregnancies without known thyroid or hepatobiliary diseases before pregnancy and thyroid medication based on a prospective cohort. Thyroid function and serum total bile acid (TBA) were routinely screened in both early (9-13 weeks) and late pregnancy (32-36 weeks). Hypercholanemia was defined as serum TBA concentration ≥10 µmol/L. Multiple linear regression models and multiple logistic regression models were performed. Results: A higher free thyroxine (fT4) during both early or late pregnancy was associated with a higher TBA concentration and a higher risk of hypercholanemia (all p < 0.01). A higher thyrotropin (TSH) in early pregnancy was associated with a higher TBA concentration in early pregnancy (p = 0.0155), but with a lower TBA concentration during later pregnancy (p < 0.0001), and there was no association of TSH with hypercholanemia. Overt hyperthyroidism in late pregnancy was associated with a 2.12-fold higher risk of hypercholanemia ([confidence interval; CI 1.12-4.03], p = 0.021) and subclinical hyperthyroidism during later pregnancy was associated with a 1.5-fold higher risk of hypercholanemia ([CI 1.14-1.97], p = 0.0034). Sensitivity analyses indicated that a high fT4 throughout pregnancy was associated with a higher risk of hypercholanemia rather than only in early or late pregnancy. Conclusions: A higher fT4 concentration during either early or late pregnancy, but not the TSH concentration, is associated with higher TBA and a higher risk of gestational hypercholanemia. Furthermore, hyperthyroidism during pregnancy could be a novel risk factor for hypercholanemia.

¿El tratamiento del hipotiroidismo subclínico tiene efecto sobre la morbimortalidad cardiovascular? / Does treatment of subclinical hypothyroidism have an effect on cardiovascular morbidity and mortality?

Un estudio mostró que el aumento de valores de la hormona estimulante de la tiroides se asoció a un aumento de mortalidad por todas las causas, estimando que las enfermedades cardiovasculares mediaban dicha asociación en aproximada-mente el 14 % de los casos. Asimismo se observó que el reemplazo con levotiroxina disminuiría los niveles de colesterol, lo cual podría tener un efecto en la reducción de enfermedades cardiovasculares. Partiendo de una viñeta clínica la autora intenta, a través de una búsqueda bibliográfica y análisis de la evidencia, determinar si el tratamiento del hipotiroidismo subclínico en adultos mayores reduciría la morbimortalidad por eventos cardiovasculares. (AU)

A study showed that increased thyroid-stimulating hormone levels were associated with increased all-cause mortality, with cardiovascular disease estimated to mediate this association in approximately 14 % of cases. Additionally, levothyroxine replacement was found to lower cholesterol levels, which could have an effect in reducing cardiovascular diseases. Basedon a clinical vignette, the author attempts, through a literature search and an analysis of the evidence, to determine whether treatment of subclinical hypothyroidism in older adults would reduce morbidity and mortality from cardiovascular events. (AU)