Biochemical Markers Reflecting Thyroid Function in Athyreotic Patients on Levothyroxine Monotherapy

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.

Babies born to mothers with thyroid disease

Measurement of serum concentrations of free triiodothyronine (FT3) is considered to be an accurate index of thyroid function in the patient. In this study, we measured serum concentrations of FT3, free thyroxine (FT4) and reverse triiodothyronine (rT3) by radioimmunoassay in blood samples taken from the navel cord of 20 newborns as well as 20 nonpregnant women, 20 pregnant women, 10 patients with liver diseases, 25 patients with diabetes mellitus, 65 patients with hyperthyroidism, 30 patients with primary hypothyroidism and 29 normal subjects. In pregnant women, serum FT3 and FT4 levels gradually decreased as the pregnancy progressed. In cord blood, FT3 levels were less than a quarter of the values found during the first trimester of pregnancy or that of non-pregnant women, whereas serum rT3 levels were drastically increased. In chronic hepatitis, liver cirrhosis and diabetes mellitus, serum FT3 and FT4 levels were significantly lower than that in the controls. In thyroid diseases, serum FT3 levels varied parallel to other thyroid hormone levels. In primary hypothyroidism, however, serum FT3 levels were still lower than these in the controls after treatment with 1-thyroxine, whereas other thyroid hormone levels and TSH levels returned to control levels.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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&lt;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%).

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

Background: Hypothyroidism is a common hormonal disorder affecting various organs including lungs and pulmonary dysfunction in hypothyroid patients has been noted.&#x0D; Objective: To observe maximum voluntary ventilation (MVV) in hypothyroid female patients.&#x0D; Materials and method: This cross-sectional study was carried out in the Department of Physiology, BSMMU, Dhaka, Bangladesh, from 1st July 2008 to 30th June 2009 on 60 hypothyroid female patients of 30-50 years old. Based on treatment, hypothyroid patients were divided into B1 (untreated patients on their 1st day of diagnosis) and B2 (patients treated for at least 12-18 months). For comparison, 30 age and BMI matched apparently healthy subjects (Group A) were also studied. The study group was selected from the Out Patient Department of Endocrinology, BSMMU, Dhaka, Bangladesh, and the control group was selected by personal contact. Serum TSH and serum FT4 levels were measured by Microparticle Enzyme Immunoassay (MEIA) principle in AxSYM system. Maximum voluntary ventilation (MVV), which is a lung function parameter, was measured by a digital MicroDL spirometer. Data were analyzed by one way ANOVA test, independent sample t-test and Pearson’s correlation coefficient test.&#x0D; Results: The mean percentage of predicted values of lung function parameter of MVV in control subjects and treated hypothyroids were within normal ranges. However, this value was significantly lower in untreated hypothyroid subjects in comparison to those of control and treated hypothyroid subjects. In addition, MVV showed negative correlation with serum TSH level and positive correlation with serum FT4 level and these relationships were statistically significant in control group and treated hypothyroid subjects.&#x0D; Conclusion: This study reveals that MVV may be lower in untreated hypothyroid female patients compared to control and treated hypothyroids and the deterioration may be positively correlated with serum FT4 level and negatively correlated with serum TSH level. Treatment of hypothyroids may reverse these changes.&#x0D; Delta Med Col J. Jul 2020;8(2): 55-60

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.

A strong evidence has been demonstrated for an increased risk of stroke in patients with autoimmune thyroiditis. Monocyte chemoattractant protein-1 (MCP-1) plays an active role in vascular disease leading to stroke in consequence of acute thrombosis. The relationship between free thyroxine (FT4) and MCP-1 serum levels was investigated in 72 postmenopausal, 37 obese and 16 healthy, control women without manifest thyroid disease. Serum levels of MCP- 1 were measured with enzyme-linked and FT4 with chemiluminescence immunoassays. The results were evaluated according to age, body mass (BMI) index and thyroid gland volume (TGV) of patients. An inverse correlation between FT4 and MCP-1 serum levels was found in the whole group (P<0.018, r=-0.4648), and a positive correlation between FT4 and age (P<0.003, r=0.5177). In detail, MCP-1 levels inversely correlated with FT4 levels in postmenopausal (P<0.01, r=0.5586), and positively with BMI index (P<0.04, r=0.5788) in obese women. In controls, FT4 serum levels showed a strong association with TGV (P<0.02, r=0.7918). MCP-1 serum levels increased in postmenopausal and obese women compared with those in controls (17.46±2.96 and 19.55±3.03 ng/ml vs. 15.93±0.56 ng/ml, P<0.043 and P<0.0001, respectively). Surprisingly, FT4 levels were significantly decreased (13.9±2.58 vs. 15.61±2.81 pmol/l, P<0.003) and MCP-1 levels increased (P<0.01) in obese women compared with those in postmenopausal women. In summary, elevated MCP- 1 serum levels are present in postmenopausal and obese women without manifest thyroid disease. MCP-1 levels were inversely associated with FT4 in postmenopausal and positively with BMI index in obese women. In postmenopausal and obese women without manifest thyroid disease, the reduced FT4 serum levels can be regarded as a marker of risk for atherosclerosis via elevated MCP-1 levels.

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

To determine the average cutoff values of serum-free and total testosterone (FT, TT) and dehydroepiandrosterone sulfate (DHEAS) among healthy premenopausal women. Participants were women aged 18-55 years without signs and symptoms of hyperandrogenism (n = 489). Participants if Ferriman-Gallwey (FG) scores between 6 and 8 were considered a group located in the upper spectrum related to the normal hirsutism score (n = 30). DHEAS, TT, and FT levels were compared between different populations. Upper limits of 97.5 and 95 and lower limits of 5 and 2.5 percentiles were calculated to provide the reference intervals for DHEA, TT, and FT in the total sample and in the population with FG 6-8. In the total population, the mean ± standard deviation (SD) serum FT, TT, and DHEAS levels were 1.40 ± 0.63 pg/mL, 0.42 ± 0.17 ng/mL, and 1.5 ± 0.97 µg/ml, respectively. The cutoff values of FT at 1.35 and TT at 0.49 were obtained for differentiating the patients with FG 6-8 scores from the normal population, with the corresponding specificity of 0.60, the sensitivity of 0.67, and area under the ROC curve (AUC) (confidence interval 95%) of 0.63 (0.52-0.73), P = 0.01 and 0.68 (0.58-0.78) P = 0.001, respectively. In our study, the mean ± SD serum FT level was 1.40 ± 0.63 pg/mL, the TT level was 0.42 ± 0.17 ng/mL, and the DHEAS level was 1.5 ± 0.97 µg/ml, in premenopausal women between 18 and 49 years of age. Furthermore, in a population with FG 6-8 score, a cutoff value of FT at 1.35 and TT at 0.49 was obtained. Although the irregular menstrual cycle did not change the reference range when compared with the normal group.

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.

It is well known that TSH plays a major role in the secretion of thyroid hormones, maintenance of thyroid specific gene expression, and gland growth. In this study, we aimed to evaluate association between tests of thyroid functions (fT3, fT4, TSH) and differentiated thyroid carcinoma. 441 patients operated for nodular goiter between 2005 and 2008 were analyzed. Thyroid functions were studied in the period of 1-30 days prior to surgery. In postoperative histopathological examination, differentiated thyroid carcinoma and benign thyroid disease were detected in 166 (37.6%) and 275 (62.4%) patients, respectively. Patients with thyroid malignancy had significantly lower serum fT3 (P = 0.001), lower fT4 (P = 0.022), and higher TSH levels (P < 0.001) compared to patients with benign disease, although all analytes were within the normal range. We subdivided by quartile serum fT3, fT4, and TSH in normal limits into three groups. The odds ratio (ORs) for the risk of thyroid cancer with a serum TSH between 0.63 and 1.67 μIU/ml and 1.68-4.00 μIU/ml, compared with a serum TSH between 0.40 and 0.62 μIU/ml were calculated as 2.60 (95% CIs 1.49-4.54) and 6.50 (95% CIs 3.51-12.03), respectively. There was also a greater risk of thyroid cancer in patients with fT3 levels of 1.57-3.00 pg/ml, compared with patients with fT3 levels of 3.89-4.71 pg/ml (OR 2.95, 95% CIs 1.68-5.20). For fT4, OR for the risk of thyroid cancer between 0.85 and 1.17 ng/dl compared with 1.48-1.78 ng/dl was 2.14 (95% CIs 1.22-3.74). In conclusion, lower fT3, fT4, and higher TSH concentrations within normal limits were related with increased thyroid cancer independent from sex and nodule type. Particularly, the association between lower fT3, fT4 levels and a diagnosis of thyroid cancer is a novel finding.

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.

Serum levels of T3, T4, FT4 and TSH were determined in 9 euthyroid patients during 6 h after intake of morning thyroxine replacement medication. Four hypothyroid patients were studied in the same way after the intake of 50 micrograms thyroxine. In the euthyroid patients the FT4 level increased by 31%, while the increase of T4 was 16% and the increase of T3 11%. In the hypothyroid patients levels of T3, T4 and FT4 did not change after ingestion of 50 micrograms thyroxine, while the TSH level was decreased by 30%. It is concluded that during thyroxine replacement therapy hormone analysis must be interpreted in relation to the time of thyroxine administration.