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.

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.

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.

¿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)

Association Between Serum Cystatin C and Thyroid Diseases: A Systematic Review and Meta-Analysis.

Background: Cystatin C (CysC) is often used to diagnose and monitor renal diseases. Although some studies have investigated the association between serum CysC levels and thyroid diseases, their reported results were inconsistent. Therefore, the relationship between CysC levels and thyroid diseases remains controversial. Aim: This meta-analysis aimed to statistically evaluate serum CysC levels in patients with thyroid diseases. Methods: A literature search was conducted using the PubMed, Web of Science, Embase, EBSCO, and Wiley Online Library databases. The following search terms were used for the title or abstract: "Cystatin C" or "CysC" in combination with the terms "thyroid disease", "thyroid function", "hypothyroidism", or "hyperthyroidism". The results of the systematic analysis were presented as standardized mean differences (SMDs) with corresponding 95% confidence intervals (CIs). Results: Eleven articles (1,265 cases and 894 controls) were included in the meta-analysis. The results of the meta-analysis showed that the serum CysC levels of patients with hyperthyroidism were significantly higher than those of the controls (SMD: 1.79, 95% CI [1.34, 2.25]), and the serum CysC levels of patients with hypothyroidism were significantly lower than those of the controls (SMD -0.59, 95% CI [-0.82, -0.36]). Moreover, the treatment of thyroid diseases significantly affected serum CysC levels. Conclusions: To the best of our knowledge, this meta-analysis is the first to evaluate serum CysC levels in patients with thyroid diseases. Our findings suggest that thyroid function affects serum CysC levels and that serum CysC may be an effective marker for monitoring thyroid diseases. Systematic Review Registration: PROSPERO [https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=258022], identifier CRD42021258022].

Use of Thyroid Hormones in Hypothyroid and Euthyroid Patients: A 2020 THESIS Questionnaire Survey of Members of the Swedish Endocrine Society.

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

Pregnancy and Neonatal Outcomes With Levothyroxine Treatment in Women With Subclinical Hypothyroidism Based on New Diagnostic Criteria: A Systematic Review and Meta-Analysis.

Background: Subclinical hypothyroidism (SCH) during pregnancy has been associated with multiple adverse maternal and neonatal outcomes. However, the potential benefits of levothyroxine (LT4) supplementation remain controversial. Variations across studies in diagnostic criteria for SCH may, in part, explain the divergent findings on the subject. This study aimed to assess the effect of LT4 treatment on pregnancy and neonatal outcomes among pregnant women who were diagnosed as SCH based on the most recent diagnostic criteria. Methods: We conducted a systematic review and meta-analysis of the literature published from inception to January 2020. The search strategy targeted the studies on pregnancy and neonatal outcomes following LT4 treatment in women with SCH based on 2017 American Thyroid Association diagnostic criteria. Pooled effect sizes were estimated using fixed and random effect models, according to the absence or presence of heterogeneity which was assessed using the I-squared statistic. Sources of heterogeneity and the stability of results were evaluated through sensitivity analysis. Results: Of the 2781 identified references, 306 full-text articles were screened for eligibility. Finally, 6 studies including a total of 7955 participants were retained for analysis. Summary effect estimates indicated that pregnant women with SCH treated with LT4 had a lower risk of pregnancy loss [odds ratio (OR) = 0.55, 95% confidence interval (CI): 0.43-0.71], preterm birth (OR=0.63, 95% CI: 0.41-0.98) and gestational hypertension (OR = 0.78, 95% CI: 0.63-0.97) than those in control group. Conclusion: LT4 treatment in pregnant women with SCH may reduce the risk of pregnancy loss, preterm delivery and gestational hypertension.

Levothyroxine Cessation After Thyroid Lobectomy for Papillary Thyroid Cancer Can Be Achieved at the Same Rate as that for Benign Tumors Regardless of the Duration of Thyroid-stimulating Hormone Suppression.

BACKGROUND/AIM: Thyroid lobectomy may cause post-lobectomy hypothyroidism. We investigated the difference in levothyroxine (LT4) supplementation and cessation between patients with benign disease and those with papillary thyroid carcinoma (PTC) and found that the rate of LT4 cessation could be decreased after thyroid-stimulating hormone (TSH) suppression in PTC. PATIENTS AND METHODS: We retrospectively reviewed 88 patients with benign tumor and 463 patients with PTC and investigated the risk factors for LT4 supplementation after thyroid lobectomy. RESULTS: During the median follow-up of 73.0 months, 207 (37.6%) patients maintained the euthyroid state, while 344 (62.4%) patients continued LT4 supplementation for LT4 replacement or TSH suppression. In patients with benign tumors, only high pre-TSH level (>1.98 mIU/l) was a significant risk factor (odds ratio [OR]=10.09). However, in patients with PTC, pre-TSH level ≥1.98 mIU/l (OR=3.28), pregnancy planning (OR=2.97), and age ≥42.5 years (OR=1.94) were significant risk factors. Moreover, the most potent risk factor was tumor aggressiveness (OR=4.00), which was found to be more significant than high pre-TSH. The overall rate of LT4 cessation in all patients was 37.6%; however, in the 303 patients who underwent the LT4-Off trial, there was no difference in the rate in the benign tumor, low-risk PTC, and intermediate-risk PTC groups (66.2%, 68.8%, and 70.8%, respectively; p=0.886). CONCLUSION: When post-lobectomy TSH levels were adequate and the risk of recurrence was reduced, LT4 cessation in PTC could be achieved at the same rate as that in benign tumors, regardless of the duration of TSH suppression.

Atrioventricular Longitudinal Mechanics Using Novel Speckle-Tracking Improved Risk Stratification Beyond Baseline Thyroid Hormone in Asymptomatic Subclinical Hypothyroidism.

BACKGROUND: Hypothyroidism is reportedly associated with increased cardiovascular risk and heart failure. We aimed to elucidate the mechanistic influence of atrio-ventricular deformations and their prognostic utilizations in asymptomatic subclinical hypothyroidism (SCH). METHODS: We assessed speckle-tracking of deformations among 4173 population-based asymptomatic individuals classified as euthyroid (0.25< thyroid-stimulating hormone [TSH] ≤4.0 µIU/mL, n=3799) or having mild (4< TSH ≤10.0 µIU/mL, n=349) or marked (TSH >10 µIU/mL, n=25) SCH. We further related deformational indices to outcomes of atrial fibrillation and heart failure. RESULTS: Despite borderline differences in indexed left ventricular mass and left atrial volume (P=0.054 and 0.051), those classified as mild and marked SCH presented with modest but significant reductions of global longitudinal strain, and showed elevated E/tissue Doppler imaging (TDI)-e', markedly diminished peak atrial longitudinal strain and higher left atrial stiffness (all P<0.05) when compared with euthyroid subjects. A higher TSH level was independently associated with reduced TDI-s'/TDI-e', worse global atrio-ventricular strains (global longitudinal strain/peak atrial longitudinal strain), elevated E/TDI-e', and worsened left atrial strain rate components (all P<0.05). Over a median 5.6 years (interquartile range, 4.7-6.5 years) follow-up, myocardial deformations yielded independent risk prediction using Cox regression in models adjusted for baseline covariates, N-terminal pro-brain natriuretic peptide, E/e', and treatment effect. Incorporation of global atrio-ventricular strain (global longitudinal strain/peak atrial longitudinal strain) and strain rates further showed improved risk reclassification when added to the baseline TSH strata (classified as euthyroid and mild and marked SCH; all P<0.05). Cox regression models remained significant with improved risk reclassification beyond TSH-based strata by using slightly different deformational cutoffs after excluding marked SCH group. CONCLUSIONS: Hypothyroidism, even when asymptomatic, may widely influence subclinical atrio-ventricular mechanical functions that may lead to higher heart failure and atrial fibrillation risk. We proposed the potential usefulness and prognostic utilization of myocardial strains in such population.

Associations of Hypothyroxinemia With Risk of Preeclampsia-Eclampsia and Gestational Hypertension.

Objective: To investigate the association between hypothyroxinemia and the risk of preeclampsia-eclampsia and gestational hypertension. Design: Historical cohort study. Methods: The study included pregnant individuals who delivered live-born singletons and had at least one thyroid function assessment during pregnancy at a tertiary hospital. Hypothyroxinemia was defined as thyroid-stimulating hormone (TSH) levels within the normal reference range and free thyroxine (FT4) levels lower than the tenth percentile. Risk ratios (RRs) with 95% confidence intervals (95% CIs) for preeclampsia-eclampsia and gestational hypertension between women with and without a diagnosis of hypothyroxinemia during pregnancy were estimated using a generalized estimating equation model. Results: A total of 59,463 women with live-born singletons were included in the analysis. Logistic regression models with restricted cubic spline suggested that there was a U-shaped association between FT4 levels and preeclampsia-eclampsia risk. Compared with euthyroid women, those with hypothyroxinemia had an increased risk of preeclampsia-eclampsia (RR = 1.16, 95% CI: 1.02-1.31), and the risk increased with the increasing severity of hypothyroxinemia (p for trend < 0.001). Moreover, persistent hypothyroxinemia from the first to second trimesters was associated with an increased risk of preeclampsia-eclampsia (RR = 1.37, 95% CI: 1.03-1.83), especially for women with severe hypothyroxinemia (RR = 1.70, 95% CI: 1.12-2.58). In contrast, there was no association between hypothyroxinemia and gestational hypertension. Conclusion: Our study suggested that hypothyroxinemia was only associated with an increased risk of preeclampsia-eclampsia, especially in women with persistent hypothyroxinemia in the first half of pregnancy. Analyses of the associated risk of gestational hypertension with hypothyroxinemia were not significant.

Effects of Chronic Suppression or Oversuppression of Thyroid-Stimulating Hormone on Psychological Symptoms and Sleep Quality in Patients with Differentiated Thyroid Cancer.

In differentiated thyroid cancer (DTC), the standard treatment includes total thyroidectomy and lifetime levothyroxine (LT4) replacement. However, long-term exogenous LT4 has become controversial due to the adverse effects of oversuppression. The study included 191 patients (aged 18-76 years) with a prospective diagnosis of non-metastatic DTC and 79 healthy individuals. The patients with DTC were stratified into three groups according to their TSH levels: suppressed thyrotropin if TSH was below 0.1 µIU/ml, mildly suppressed thyrotropin if TSH was between 0.11 and 0.49 µIU/ml, and low-normal thyrotropin if THS was between 0.5 and 2 µIU/ml. The Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Anxiety Sensitivity Index (ASI), Short Symptom Inventory (SSI), and Pittsburgh Sleep Quality Index (PSQI) were administered to all participants. It was found that the BDI, BAI, SSI and PSQI scores were worse in patients with DTC (p=0.024, p=0.014, p=0.012, and p=0.001, respectively). According to theTSH levels, the mean ASI was found to be higher in the suppressed and mildly suppressed thyrotropin groups (19±14.4 vs. 10.6±11.1; 16.4±14.9 vs. 10.6±11.1, p=0.024, respectively), the mean SSI was found higher in the suppressed group (61.0±55.5 vs. 35.1±37.0, p=0.046), and the mean PSQI was higher in all three groups (7.94±3.97 vs. 5.35±4.13; 7.21±4.59 vs. 5.35±4.13; 7.13±4.62 vs. 5.35±4.13, p=0.006) when compared with the controls. No significant difference was found between the groups. A positive correlation was detected in the duration of LT4 use and BDI and SSI, and a weak, negative correlation was detected between TSH levels and ASI and PSQI. Based on our study, it was found that depression, anxiety disorders, and sleep problems were more prevalent in patients with DTC, being more prominent in the suppressed TSH group. These results were inversely correlated with TSH values and positively correlated with the duration of LT4 use. Unnecessary LT4 oversuppression should be avoided in patients with DTC.

Clinical Characteristics and Follow-Up of 19 Children With Hashimoto's Thyroiditis Aged Below 3 Years: A Single-Center Retrospective Analysis.

Aim: To analyze the clinical characteristics of Hashimoto's thyroiditis (HT) in children below 3 years of age in order to improve the understanding of the disease, avoid misdiagnosis, and achieve early diagnosis and treatment. Methods: The study retrospectively analyzed the clinical data of 19 patients diagnosed with HT in the first three years of life. Results: The patients (12 female, 7 male) had an average age of 26.1 ± 8.2 months (range 10-36 months). At presentation, one patient had euthyroidism, ten had hypothyroidism, seven had subclinical hypothyroidism, and one had hyperthyroidism. The most common reasons for doctor's visits were thyroid enlargement (21.1%), global developmental delay (21.1%), and routine thyroid function tests in patients with type 1 diabetes (26.3%). Sixteen patients provided follow-up data, and the mean follow-up time was 23.31 ± 16.44 months (range 1-48 months). In the hypothyroidism group, one patient stopped levothyroxine (LT4) treatment after 2 months; the remaining patients had been treated with LT4 since their diagnosis. In the subclinical hypothyroidism group, one patient whose thyroid function returned to normal after 1 month of being diagnosed was not treated. The remaining patients received LT4 treatment at their diagnosis or during follow-up. The patient with hyperthyroidism was treated with methimazole after diagnosis, but treatment was discontinued 11 months later and LT4 was initiated 26 months after diagnosis. One in four patients with global developmental delay approached normal mental development after LT4 treatment. Four in six patients with short stature achieved height catch-up. Conclusion: At their initial HT diagnosis, most of the children showed hypothyroidism or subclinical hypothyroidism. Children with global developmental delay require continual screening, even if the thyroid function is normal after birth, to determine whether they have HT-induced hypothyroidism. Thyroxine replacement could partially relieve the clinical manifestations of hypothyroidism and early diagnosis and treatment are essential for improving patient prognosis.

Association of serum proprotein convertase Subtilisin/Kexin Type 9 (PCSK9) level with thyroid function disorders.

OBJECTIVE: We aimed at demonstrating the effect of thyroid function status on proprotein convertase subtilisin kexin type 9 (PCSK9) and determining the effect of thyroid hormones on lipid metabolism by comparing the PCSK9 levels of patients with subclinical hypothyroidism, overt hypothyroidism, and hyperthyroidism. PATIENTS AND METHODS: 124 patients with thyroid disorders, aged between 18 and 65 years, were included in this study. The participants were divided into 3 groups. Group 1 comprised 52 patients with subclinical hypothyroidism, Group 2 comprised 40 patients with overt hypothyroidism, and Group 3 comprised 32 patients with hyperthyroidism. In all of these groups, the thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, total cholesterol, fasting serum glucose, antithyroid peroxidase antibody, antithyroglobulin antibody, and PCSK9 levels were measured. RESULTS: No significant difference was found between the 3 groups in terms of age, gender, and body mass indices. Median PCSK9 measurements were 14.55 ng/mL in Group 1, 14.895 ng/mL in Group 2, and 9.775 ng/mL in Group 3. There was a significant difference in the PCSK9 levels between Group 1-Group 3 and Group 2-Group 3 (p <0.0001 and p <0.0001, respectively). A positive correlation between PCSK9 and the TSH levels (r = 0.211, p= 0.019), and a negative correlation (r = -0,239, p = 0.009 and r = -, 0.218, p = 0.015) between the fT3 and fT4 levels were found. CONCLUSIONS: The serum PCSK9 levels were shown to be associated with thyroid dysfunction. However, no relationship was observed between the serum PCSK9 level and thyroid autoantibody positivity, and obesity in this study.

Association of Thyroid Dysfunction With Cognitive Function: An Individual Participant Data Analysis.

Importance: In clinical guidelines, overt and subclinical thyroid dysfunction are mentioned as causal and treatable factors for cognitive decline. However, the scientific literature on these associations shows inconsistent findings. Objective: To assess cross-sectional and longitudinal associations of baseline thyroid dysfunction with cognitive function and dementia. Design, Setting, and Participants: This multicohort individual participant data analysis assessed 114 267 person-years (median, 1.7-11.3 years) of follow-up for cognitive function and 525 222 person-years (median, 3.8-15.3 years) for dementia between 1989 and 2017. Analyses on cognitive function included 21 cohorts comprising 38 144 participants. Analyses on dementia included eight cohorts with a total of 2033 cases with dementia and 44 573 controls. Data analysis was performed from December 2016 to January 2021. Exposures: Thyroid function was classified as overt hyperthyroidism, subclinical hyperthyroidism, euthyroidism, subclinical hypothyroidism, and overt hypothyroidism based on uniform thyrotropin cutoff values and study-specific free thyroxine values. Main Outcomes and Measures: The primary outcome was global cognitive function, mostly measured using the Mini-Mental State Examination. Executive function, memory, and dementia were secondary outcomes. Analyses were first performed at study level using multivariable linear regression and multivariable Cox regression, respectively. The studies were combined with restricted maximum likelihood meta-analysis. To overcome the use of different scales, results were transformed to standardized mean differences. For incident dementia, hazard ratios were calculated. Results: Among 74 565 total participants, 66 567 (89.3%) participants had normal thyroid function, 577 (0.8%) had overt hyperthyroidism, 2557 (3.4%) had subclinical hyperthyroidism, 4167 (5.6%) had subclinical hypothyroidism, and 697 (0.9%) had overt hypothyroidism. The study-specific median age at baseline varied from 57 to 93 years; 42 847 (57.5%) participants were women. Thyroid dysfunction was not associated with global cognitive function; the largest differences were observed between overt hypothyroidism and euthyroidism-cross-sectionally (-0.06 standardized mean difference in score; 95% CI, -0.20 to 0.08; P = .40) and longitudinally (0.11 standardized mean difference higher decline per year; 95% CI, -0.01 to 0.23; P = .09). No consistent associations were observed between thyroid dysfunction and executive function, memory, or risk of dementia. Conclusions and Relevance: In this individual participant data analysis of more than 74 000 adults, subclinical hypothyroidism and hyperthyroidism were not associated with cognitive function, cognitive decline, or incident dementia. No rigorous conclusions can be drawn regarding the role of overt thyroid dysfunction in risk of dementia. These findings do not support the practice of screening for subclinical thyroid dysfunction in the context of cognitive decline in older adults as recommended in current guidelines.

Association of hypothyroidism with acute COVID-19: a systematic review.

OBJECTIVE: There is an increasing body of literature on the impact of COVID-19 on the pituitary-thyroid axis. Therefore, we conducted a systematic review to assess the prevalence of hypothyroidism in patients with COVID-19. METHODS: A literature review was conducted using LitCOVID for study selection in PubMed and MEDLINE till May 2021. All relevant original articles evaluating thyroid dysfunction were included and information regarding the prevalence of hypothyroid disease in COVID-19 was retrieved from the eligible articles. RESULTS: Out of 32 articles, six articles qualified for the final analysis which included 1160 patients. There was significant heterogeneity among the included articles. Most of the patients had lower mean triiodothyronine (T3) and normal or low thyroid-stimulating hormone (TSH). Increased TSH ranged from 5.1% to 8% while low T3 was present in up to 28% of the patients. In these studies, the prevalence of altered thyroid hormones was significantly more in COVID-19 patients as compared to control groups. A positive correlation between low mean T3 and clinical severity of COVID-19 was reported. CONCLUSION: This systematic review reveals a significant proportion of hypothyroidism associated with COVID-19. Therefore, routine assessment of thyroid function is warranted in hospitalized COVID-19 patients.

Cross-sectional analysis: clinical presentation of children with persistently low ALP levels.

OBJECTIVES: Low activity of serum alkaline phosphatase (ALP) is a hallmark of hypophosphatasia (HPP), but low readings of ALP are not always recognized in clinical routine. Understanding the clinical presentations associated with low ALP may contribute to a timelier diagnosis of HPP. METHODS: Data from paediatric patients with low ALP, excluding patients in intensive care and with oncological/haematological disorders, were analysed. Most recent ALP values, previous diagnoses, medication and relevant symptoms were extracted from patient records at nine specialised centres and analysed descriptively. A relationship between body height and ALP values was scrutinised by linear regression. RESULTS: Of 370 children, 15 (4.1%) had a diagnosis of HPP. In the subgroup without a diagnosis of HPP, 241 (67.9%) out of 355 patients had one or more medical conditions known to be associated with low serum ALP. Of those, hypothyroidism, malnutrition and steroid administration were most frequent. Characteristic symptoms, particularly, short stature, muscle weakness and delay of motor development were more frequent and ALP values were lower in patients with documented HPP diagnosis compared to patients without diagnosis of HPP (Ø z-scores: -2.52) (interquartile range [IQR] = 0.20) vs. -1.96 (IQR = 0.87). A weak positive linear relationship between z-scores of ALP and body height was identified (p<0.001). CONCLUSIONS: This analysis of paediatric patient records elucidates a wide range of disorders associated with low ALP activity. In case of additional specific symptoms, HPP should always be considered as a differential diagnosis.