MATURATION OF THYROID FUNCTION IN NORMAL HUMAN FOETUSES

Babies born to mothers with thyroid disease

Background: Some bacteria and viruses cause thyroid gland inflammation. Periodontal diseases lead to the production of numerous bacteria in the mouth that spread to other tissues and organs, causing infection in those sites. This investigation’s goal was to the correlation between thyroid abnormalities with periodontal disorders. Methods: The research study was carried out on 96 patients who provided blood samples from the total of 1012 applicants who enrolled to the periodontology clinic. The patients were categorized into 4 categories based on their age: (i) ages ranging 0-20, (ii) ages ranging 21-40, (iii) ages ranging 41–60, and (iv) ages over 61. In addition, they were additionally divided into three groups according to both TSH and FT4 levels: The TSHa and FT4a group included patients with below-normal values, the TSHb and FT4b group included patients with normal TSH and FT4 values, and the TSHc and FT4c group included patients with above-normal TSH and FT4 values. The statistical analysis was performed using SPSS 21. Frequency analysis and the Mann-Whitney U Analyses were utilized for statistical analysis., and the level of significance was set at P<0.05. Results: The median TSH and FT4 levels of the patients were 1.98±1.28 mIU/L and 1.19±0.32 mIU/L, in that order there were no significant statistical differences seen in TSH and FT4 levels between genders or age groups. According to their FT4 and TSH levels, 7.3% of the patients had subclinical hypothyroidism and 4.2% had subclinical hyperthyroidism. In total, 11.5% of the patients had thyroid dysfunction. Conclusion: The results indicated that thyroid dysfunction was present in a remarkably high proportion of patients (11.5%).

PurposeA multifold association relates the hypothalamo-pituitary-thyroid axis to body weight. The potential underlying mechanisms are incompletely understood. Further, the mild severity of obesity and the small proportion of individuals with obesity in so far published cohort studies provide little insights on metabolic correlates of thyroid function in obesity.MethodsWe retrospectively enrolled 5009 adults with obesity (F/M, 3448/1561; age range, 18-87 years; BMI range, 30.0-82.7 kg/m2), without known thyroid disease in a study on TSH and fT4 levels, lipid profile, glucose homeostasis and insulin resistance, anthropometric parameters including BIA-derived fat mass (%FM) and fat-free mass (FFM).ResultsThe overall reference interval for TSH in our obese cohort was 0.58-5.07 mIU/L. As subgroups, females and non-smokers showed higher TSH levels as compared to their counterparts (p<0.0001 for both), while fT4 values were comparable between groups. There was a significant upward trend for TSH levels across incremental BMI classes in females, while the opposite trend was seen for fT4 levels in males (p<0.0001 for both). Expectedly, TSH was associated with %FM and FFM (p<0,0001 for both). TSH and fT4 showed correlations with several metabolic variables, and both declined with aging (TSH, p<0.0001; fT4, p<0.01). In a subgroup undergoing leptin measurement, leptin levels were positively associated with TSH levels (p<0.01). At the multivariable regression analysis, in the group as a whole, smoking habit emerged as the main independent predictor of TSH (β=-0.24, p<0.0001) and fT4 (β=-0.25, p<0.0001) levels. In non-smokers, %FM (β=0.08, p<0.0001) and age (β=-0.05, p<0.001) were the main significant predictors of TSH levels. In the subset of nonsmokers having leptin measured, leptin emerged as the strongest predictor of TSH levels (β=0.17, p<0.01).ConclusionsOur study provides evidence of a gender- and smoking-dependent regulation of TSH levels in obesity.

Thyroid axis abnormalities are common in obese patients. Their contribution in the development of metabolic obesity complications remains unclear. To assess the influence of thyroid axis dysfunction on the occurrence of metabolic obesity complications. A cross-sectional review of the thyroid function in 100 obese patients (59 girls and 41 boys, mean age 13.5 years) with alimentary obe-sity (mean standardised body mass index [BMI SDS] in boys 4.175 and girls 4.723) complicated by metabolic syndrome (MS) diag-nosed on the basis of the IDF 2006 criteria (MS, 25 patients) and uncomplicated (75 patients). TSH, fT4, fT3 thyroid peroxidase anti-bodies (TPOAb), and thyroglobulin antibodies (TGAb) were assessed in a single fasting blood sample. There was no case of overt thyroid disease within the whole analysed group. There were no significant differences in mean TSH, fT4, and fT3 levels in patients with and without MS (2.7 µIU/ml vs. 3.0 µIU/ml, 14.5 vs. 14.0 pmol/l, and 5.6 vs. 6.2, respectively; p > 0.05). In the MS group only two patients (8%) presented with a TSH level above the upper limit of the normal range; in the group without MS elevated TSH was noticed in 18 (24%) patients. The maximal value of TSH (10.44 µIU/ml) was noticed in one boy without MS. Positive TPOAb and/or TGAb were present in 11% of all patients: two patients (8%) with MS and nine (12%) without MS. Isolated increased TSH level is common in obese adolescents, although there is no correlation between TSH, fT3, and fT4 levels and BMI SDS value. Isolated increased TSH level is not associated with the occurrence of MS in obese adolescents. The occurrence of asymptomatic autoimmune thyroiditis (AITD) in obese adolescents is more common than in the general population.

Background Thyroid hormones are associated with arrhythmic risk, but their relationship to ASCVD is unclear. The Rotterdam Study* reported associations of higher fT4 and lower thyroid stimulating hormone (TSH) levels with ASCVD, including within the euthyroid range. Free T3 (fT3) was not assessed. Methods We tested whether fT4, fT3, and TSH levels were associated with ASCVD in Intermountain Healthcare. All patients &gt;18 y old with an fT4 level in the electronic medical record database were included. The hormone reference ranges were divided into quartiles (Q), and associations with prevalent and incident ASCVD were assessed by multivariable regression and trend tests. Results A total of 212,202 patients (age = 64.4±11.2 y; 66.6% women) were included and followed for 6.1±4.4 y. Of these, 8.3%, 86.6%, and 5.1% had fT4 levels below, within, and above the reference range. CAD was prevalent in 18.9% of fT4 Q1 patients. The adjusted odds ratio (OR) for coronary artery disease (CAD) increased through (Q4/Q1 OR=1.36) and beyond (High/Q1 OR=1.71) the normal range, p-trend&lt;0.001 (Table). Smaller incremental risks were noted for fT3 (Q4/Q1 OR=1.13; High/Q1 OR=1.25). The frequencies of incident MI (Q1=2.5%) and stroke (Q1=5.4%) were low and did not show a concentration-related risk gradient. Incident all-cause death (Q1=24.3%) increased slightly for Q4 and high fT4 (OR=1.05, 1.06) but not fT3; death also increased with low fT4 (OR=1.28). TSH showed no consistent gradient within the normal range for prevalent or incident events; however, mortality increased with both high and low TSH. Thyroid Hormone Levels and Prevalent CAD Prevalent CAD (adjusted OR) Low Normal Q1 Normal Q2 Normal Q3 Normal Q4 High fT4 (n=212,202) OR=1.08, p=0.02 OR=1.00 referent OR=1.11, p&lt;0.001 OR=1.21, p&lt;0.001 OR=1.36, p&lt;0.001 OR=1.71, p&lt;0.001 fT3 (n=30,200) OR=1.12, p&lt;0.001 OR=1.00 referent OR=0.98, p=0.61 OR=1.02, p=0.53 OR=1.13, p&lt;0.001 OR=1.25, p&lt;0.001 TSH (n=183,227) OR=1.39, p&lt;0.001 OR=1.00 referent OR=0.93, p=0.42 OR=0.88, p=0.15 OR=0.92, p=0.35 OR=1.73, p&lt;0.001 Reference Q 1–4 are: fT4: 0.75–0.90; 0.91–1.01; 2.02–1.14; 1.15–1.50 ng/dL; TSH: 0.54–1.30; 1.31–2.04; 2.05–3.68; 3.69–6.80 uIU/mL; fT3: 2.40–2.60; 2.70–2.80; 2.90–3.10; 3.20–4.20 pg/dL. Conclusions Consistent with the Rotterdam Study, we found an increase in prevalent CAD with increasing fT4 levels within and beyond the normal range and, uniquely, a more modest relationship with fT3. We could not confirm a normal-range relationship between hormone levels and incident events or between TSH and prevalent disease. The relationship of fT4 levels to ASCVD is intriguing, is deserving of further study, and may have important implications for ASCVD prevention. *A Bano, et-al. Circ Res 2017; 121:1397–1400

背景与目的电视辅助胸腔镜手术（video-assisted thoracoscopic surgery, VATS）是胸部微创手术的代表，相对于传统开胸手术（traditional open surgery, TOS），VATS具有创伤小、疼痛轻、恢复快等优势。本研究旨在比较VATS与传统开胸肺叶切除治疗非小细胞肺癌（non-small cell lung cancer, NSCLC）围手术期甲状腺激素水平的变化。方法选取卫生部北京医院胸外科2010年10月-2012年8月收治的NSCLC患者44例，根据手术方式的不同分为：胸腔镜组（VATS组，25例）及传统开胸组（TOS组，19例）。两组于手术前1天、术后第1天、2天、3天、7天分别测定游离T3（free T3, FT3）、游离T4（free T4, FT4）、反T3（reverse T3, rT3）、促甲状腺激素（thyroid stimulating hormone, TSH）的水平，观察两组术后各指标的变化规律，比较两组间变化的差异。结果术前患者甲状腺激素水平均在正常值范围内，两组比较无统计学差异（P>0.05）。FT3及TSH术后均表现为先降低后升高，分别于术后第3天、术后第1天达到最低水平，术后第7天时VATS组已恢复至术前水平，但TOS组FT3仍明显低于术前（P=0.032）；FT4及rT3术后均表现为先升高后降低，均于术后第2天达到峰值，TOS组术后第1天、2天、3天rT3水平均明显高于VATS组（P < 0.05）。术后FT3降低及rT3升高均超出正常值范围，而FT4及TSH变化均在正常值范围内。两组间各指标变化趋势比较，rT3变化有统计学差异（F=7.557, P=0.009）。结论NSCLC患者行肺叶切除术后均出现正常甲状腺功能病态综合征，相对于传统开胸手术，胸腔镜手术对机体甲状腺激素水平影响小，机体应激反应小，利于肺癌患者术后恢复。

Thyroid function is strongly associated with obesity. The aim of this study is to investigate whether serum free thyroxine (FT4) and/or thyrotropin (TSH) levels are associated with the efficacy of weight reduction therapy in obese patients. We enrolled a total of 283 obese patients and cross-sectionally investigated the association of serum FT4 and/or TSH levels with metabolic features. Furthermore, in 97 obese patients who received 6-month weight reduction therapy, we assessed the relationship of serum FT4 and/or TSH levels to the efficacy of weight reduction therapy. Neither baseline serum FT4 nor TSH levels showed any correlations with body weight (BW) and body mass index (BMI) in these obese patients. However, in 57 obese female patients who underwent weight reduction therapy for six months, serum FT4 levels prior to the therapy was negatively correlated with the degrees of reduction of BW (r = -0.354, p = 0.007) and BMI (r = -0.373, p = 0.004). The correlation between baseline serum FT4 levels with the efficacy of weight reduction therapy was not observed in obese male or postmenopausal female patients. This study demonstrates that baseline serum FT4 levels are associated with weight reduction in obese female premenopausal patients. Therefore, baseline FT4 levels can be used as a clinical, noninvasive, hormonal predictor of weight reduction efficacy in obese patients.

Transient elevation of serum free T4 (gestational transient hyperthyroxinaemia; GTH) occurs occasionally during normal pregnancy, especially in early gestation. However, the frequency of GTH and its clinical features remain unclear to date. The aim of this study was to determine the occurrence rate of GTH and the relation between serum levels of hCG, free T4 (fT4), and TSH in a large number of pregnant women. The four criteria of GTH were as follows: (1) no past history of thyroid disease, (2) negative tests for MCHA and TGHA, (3) no multiple pregnancies or trophoblastic disease and (4) transient hyperthyroxinaemia at less than 16 weeks of gestation. Thyroid function and hCG levels in 23,163 pregnant women were evaluated by mass sreening. If individual fT4 levels were more than the upper limit, blood re-sampling and the clinical and laboratory analysis of thyroid function were performed to exclude women with thyroid disease. The concentrations of hCG, fT4, and TSH in women with GTH and normal pregnant controls (n = 218) were compared. Regression analysis was performed for the comparison between hCG, fT4, and TSH levels in women with GTH. Blood samples were obtained using dried blood spots. Blood levels of fT4 was measured by radioimmunoassay, TSH and hCG were measured by fluoroimmunoassay. Anti-microsome antibody (MCHA) and anti-thyroglobulin antibody (TGHA) were measured by indirect agglutination reaction. GTH was observed in 66 of 23,163 women. The overall occurrence rate of GTH was 0.285%. In 22 of the 66 GTH women, serum TSH was undetectable. Using regression analyses, the concentration of fT4 was correlated with hCG levels in women with GTH (P < 0.05, r = 0.269), whereas the concentration of TSH was not correlated with hCG or fT4 level. The concentrations (M +/- SD) of fT4, TSH, and hCG in women with GTH were 42.5 +/- 12.3 pmol/l, 0.20 +/- 0.31 mU/l and 190.2 +/- 98.8 x 10(3) IU/l, whereas those of controls were 14.6 +/- 3.8 pmol/l, 1.43 +/- 1.25 mU/l and 60.1 +/- 45.1 x 10(3) IU/l. The concentrations of fT4 and hCG were significantly (P < 0.0001) higher than those of normal controls, and TSH was significantly (P < 0.0001) lower than those of normal controls. The occurrence rate of gestational transient hyperthyroxinaemia was 0.285%, and could possibly be attributed to increased levels of circulating hCG. Based on the data obtained from a large number of pregnant women, we propose gestational transient hyperthyroxinaemia as a definite clinical entity.

Thyroid under siege: Unravelling the toxic impact of real-life metal mixture exposures in Wistar rats

PurposeA potential involvement of thyrotropic axis in influencing the state of consciousness could be hypothesized. We aimed at investigating thyroid function tests as predictors of disorders of consciousness (DoC) and relating recovery in a large cohort of patients with DoC secondary to acquired brain injury (ABI).MethodsThis retrospective, multicenter, cohort study included 151 patients with DoC following ABI, consecutively admitted for a 6-month neurorehabilitation program. Data on etiology of brain injury, evolution of DoC, disability and rehabilitation assessments, and death during rehabilitation were collected at baseline and on discharge. Thyroid function tests (serum TSH, fT4 and fT3 levels) were assessed on admission in all patients and at final discharge in 50 patients.ResultsLower baseline TSH levels and greater TSH increments (ΔTSH) after neurorehabilitation predicted a favorable change in DoC independent of age, sex, BMI, etiology of brain injury and initial DoC subtype (TSH: OR=0.712, CI 95% 0.533-0.951, p=0.01; ΔTSH: OR=2.878, CI 95% 1.147-7.223, p=0.02). On the other hand, neither fT4 nor fT3 or their variations appeared to play any role on DoC changes after 6-months inpatient neurorehabilitation. A lower magnitude of ΔfT4 acted as a strong predictor of improved functional disability level (β=0.655, p=0.002) and cognitive functions (β=-0.671, p=0.003), implying that smaller changes in fT4 were associated with higher outcomes.ConclusionsSerum TSH levels assessed in the subacute post-ABI phase and its variation during neurorehabilitation could represent a potential biomarker of DoC evolution, while variations in fT4 levels seem to be associated with rehabilitation and cognitive functions. Further studies are needed to investigate the mechanisms underlying these associations.

Insulin resistance and pancreatic β cell dysfunction are associated with thyroid hormone functions: A cross-sectional hospital-based study in Turkey

Low levels of arsenic exposure during pregnancy and maternal and neonatal thyroid hormone parameters: The determinants for these associations

Background: Although the relationship between subclinical hypothyroidism and major depressive disorder (MDD) has been studied in adults in cross-sectional and prospective population-based studies, this has not yet been done in adolescents. However, since thyroid function and MDD risk are subjected to maturational processes and ramifications of illness duration over the life span, these findings may not readily transfer to adolescents. Methods: The relationship between subclinical hypothyroidism and MDD was studied in a representative subsample of the nationwide KIGGS ("The German Health Interview and Examination Survey for Children and Adolescents") survey. A total of 4118 adolescents were examined over a median period of 6 years, and data were analyzed by a logistic regression approach accounting for important covariates related to thyroid function and/or MDD risk. The same approach was chosen to investigate the relationship between quartiles of thyrotropin (TSH) and free thyroxine (fT4) levels and incident MDD in euthyroid participants to broaden the focus on the relationship between thyroid hormone levels and MDD in a dose-response manner. Results: During the observation period, 121 cases of MDD were reported. There was no association between subclinical hypothyroidism and MDD when comparing 111 adolescents with subclinical hypothyroidism with 4007 euthyroid adolescents, representative of ∼106,000 and 3,610,000 adolescents from the general pediatric population, respectively. This also applied when studying the relationship between quartiles of TSH and fT4 levels and MDD in euthyroid participants. All results were confirmed by sensitivity analyses accounting for thyroid autoimmunity. Conclusions: Consistent with findings in adults, there is no association between subclinical hypothyroidism or quartiles of TSH and fT4 levels in the normal range and MDD in adolescents, despite potential age-related differences regarding thyroid function and MDD risk.

Background Coronovirus disease 2019 (COVID-19) infection from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus was officially declared a pandemic by the World Health Organization in March 2020. According to a search of PubMed for the term COVID-19 on May 5, 2021, thus far, there have been more than 130,000 papers on COVID-19 published in the medical literature. Since the previous comments on thyroid function in COVID-19 in Clinical Thyroidology (1,2) the number of papers on this topic has increased from a handful to 120 (PubMed search for the term COVID-19, thyroid disease on May 5, 2021), including a systematic review (3). One of these articles, the article by Campi et al. reviewed here (4), is a prospective study of thyroid function in patients hospitalized with COVID-19 infection at a single center in Milan, Italy. Methods The study included 144 consecutive patients with COVID-19 infection and associated pneumonia (97 men and 47 women; mean [±SD] age, 68.1±14.67 years [range, 26–96]) admitted to a single center in intensive or subintensive care units between March and May 2020 because of respiratory insufficiency of variable severity. SARS-Cov-2 infection was confirmed in all patients by RT-PCR testing on a nasopharyngeal swab. Those with previous thyroid dysfunction or who were taking interfering drugs were excluded. There was no control group. Different from previous reports, serum concentrations of thyrotropin (TSH), free triiodothyronine (FT3), free thyroxine (FT4), thyroglobulin (Tg), and anti-Tg autoantibodies (TgAbs) were measured at baseline and every 3 to 7 days thereafter. Serum C-reactive protein (CRP), cortisol, and interleukin-6 (IL-6) were also assayed. The overall mortality rate was 25% (36 of 144). The mean length of hospital stay was 21 days (range, 2–108). Serum Tg and TgAb concentrations were retrospectively measured in the subset of serum with reduced/suppressed TSH levels in order to diagnose or exclude destructive thyroiditis. Results Most patients had a normal TSH concentration at admission; most of these patients also had normal FT4 and FT3 levels. Low TSH concentrations were found either at admission or during hospitalization in 39% of patients, which was associated with low FT3 levels in half of these cases. Serum FT4 and Tg levels were normal, and TgAb was negative. Serum TSH and FT3 levels were invariably restored to normal at the time of discharge in survivors, whereas they were permanently low in most deceased cases. Only serum FT3 concentrations predicted mortality. Serum cortisol, CRP, and IL-6 concentrations were higher in patients with low TSH and FT3 concentrations. Almost half of the COVID-19 patients who were not taking interfering drugs had normal thyroid function tests both at admission and during follow-up. In this series, the transient finding of low TSH with normal FT4 and low FT3 levels inversely correlated with CRP, cortisol, and IL-6 levels and were associated with normal Tg concentrations and without clinical signs of a destructive thyroiditis. Longitudinal evaluations during the hospital stay showed that TSH suppression was transient in all the survivors, with 5 days (range, 2–9) as the median time to normalization. Serum Tg concentrations were invariably normal in the absence of TgAb interference in all 39 patients with low TSH, either at admission or during follow-up (median Tg, 7.6 µg/L, range: 3–70.3 µg/L). Conclusions The study suggests that cytokine release associated with COVID-19 infection causes slight transient central and peripheral thyroid function alterations, as characterized by reduced TSH with normal FT4 and low-normal FT3 levels. Serum thyroid function assessment during acute COVID-19 infection is not recommended. Clinical and biochemical monitoring after discharge/improvement are appropriate, as subacute thyroiditis may complicate the recovery.

Background: Some investigators reported that among athyreotic patients on levothyroxine (LT4) monotherapy following total thyroidectomy, the patients with normal serum thyrotropin (TSH) levels had mildly low serum free triiodothyronine (fT3) levels, whereas the patients with mildly suppressed serum TSH levels had normal serum fT3 levels, and the patients with strongly suppressed serum TSH had elevated serum fT3 levels. The objective of the present study was to clarify which of these three patient groups is closer to their preoperative euthyroid condition.Methods: A total of 133 consecutive euthyroid patients with papillary thyroid carcinoma who underwent a total thyroidectomy were prospectively studied. The patients' serum levels of lipoproteins, sex hormone-binding globulin, and bone metabolic markers measured preoperatively were compared with the levels measured at postoperative LT4 therapy 12 months after the thyroidectomy.Results: The postoperative serum sex hormone-binding globulin (p < 0.001) and bone alkaline phosphatase (p < 0.01) levels were significantly increased in the patients with strongly suppressed TSH levels (≤0.03 μIU/mL). The postoperative serum low-density lipoprotein cholesterol levels were significantly increased (p < 0.05), and the serum tartrate-resistant acid phosphatase-5b levels were significantly decreased (p < 0.05) in the patients with normal TSH (0.3 < TSH ≤5 μIU/mL). In the patients with mildly suppressed TSH (0.03 < TSH ≤0.3 μIU/mL) and fT3 levels equivalent to their preoperative levels, all metabolic markers remained equivalent to their preoperative levels.Conclusions: The serum biochemical markers of thyroid function in patients on LT4 following total thyroidectomy suggest that the patients with mildly suppressed TSH levels were closest to euthyroid, whereas those with normal TSH levels were mildly hypothyroid and those with strongly suppressed TSH levels were mildly hyperthyroid. These data may provide novel information on the management of patients following total thyroidectomy for thyroid cancer or benign thyroid disease.