<h4>Aims</h4>Understanding the exact relationship between serum thyrotropin/thyroid stimulating hormone (TSH) and free thyroxine (FT(4)) is a prerequisite for improving diagnostic reliability and clinical decision making.<h4>Methods</h4>We (1) retrospectively studied the relationship between TSH and FT(4) in a large unselected clinical sample (n=6641) of primary hypothyroid, euthyroid and hyperthyroid subjects, and (2) applied a mathematical model of thyroid hormone feedback control to assess the relation between structural parameters and TSH levels in the different functional states.<h4>Results</h4>When separately analysing total sample and untreated subjects, the correlation slope for logTSH versus FT(4) for hypothyroid subjects was significantly different from that of the euthyroid panel and hyperthyroid subjects (the latter being compromised by reaching the TSH assay's lower detection limit). As trends between functional states changed, each functional segment appeared to become differently regulated. Theoretical modelling and sensitivity analysis revealed that the influence of various structural parameters on TSH levels also depends on the overall function of the feedback loop.<h4>Conclusions</h4>Our data suggest that the states of hypothyroidism, euthyroidism and hyperthyroidism can be regarded as differently regulated entities. The apparent complexity could be replicated by mathematical modelling suggesting a hierarchical type of feedback regulation involving patterns of operative mechanisms unique to each condition. For clinical purposes and assay evaluation, neither the standard model relating logTSH with FT(4), nor an alternative model based on non-competitive inhibition can be reliably represented by a single correlation comparing all samples for both hormones in one all-inclusive group.

Abstract Background The inverse log-linear relationship between Thyroid-stimulating hormone (TSH) and free thyroxine (FT4) is well established and reliably used for evaluation of hypothalamus-pituitary-thyroid (HPT) axis function. However, there are limited data regarding oncologic states in the TSH-FT4 relationship. The purpose of this study was to evaluate thyroid pituitary hypothalamic feedback regulation by the inverse log TSH and FT4 relationship in the cancer patient population at the Ohio State University Comprehensive Cancer Center (OSUCCC-James). Methods This retrospective study analyzed the correlation between TSH and FT4 results from 18846 outpatient subjects collected in August 2019-November 2021 at the Department of Family Medicine (OSU Wexner Medical Center), Department of Oncology (OSUCCC-James). Patients with diagnoses related to cancers were included in the oncology group. Patients with diagnoses not related to cancers were included in the non-oncology group. Patients of the Department of Endocrinology, Department of Cardiology, Department of Obstetrics &amp; Gynecology and Department of Hematology were excluded from this study. Time of collection for TSH and FT4 was from 7am to 7pm. Data were analyzed by morning (7am-12pm) and afternoon (12pm-7pm). Spearman correlation and non-linear fit were used for data analysis. Sex differences were analyzed as well in each group. Results Overall, an inverse correlation was observed between TSH and FT4 in both groups (non-oncology and oncology) regardless of sample collection time and sex differences. Further analysis by linear model in log TSH and FT4 showed a significant inverse fit in males compared with females in the oncology group of oncology, both in the afternoon (p &lt; 0.05). Data were further analyzed by ranges of FT4, as lower or higher (pathophysiology) or within (physiology) the reference interval of FT4. There was no statistical significance between the non-oncology and oncology groups, but better correlation in non-oncology in either physiological or pathophysiological FT4 levels and sample collection time. Interestingly, the best correlation between TSH and FT4 was found in the non-oncology group at pathophysiological FT4 concentrations (abnormally high). In addition, at pathophysiological FT4 concentrations (abnormally low), the oncology group demonstrated a significant TSH response in the morning than in the afternoon (p &lt; 0.05). Conclusions Though overall the TSH-FT4 curves showed an inverse relationship, there are variations of TSH-FT4 relationship for collection times when considering FT4 in physiological or pathophysiological states. The results advance understanding of TSH response, which is beneficial for the interpretation of thyroid disease. It is not recommended to evaluate thyroid pituitary hypothalamic axis by TSH results when FT4 is abnormally high in oncology patients or low in non-oncology patients, due to poor predictability and the potential for misdiagnosis. A better understanding of the complex nature of the TSH-FT4 relationship may need further study with better defining subclinical states of cancer patients.

Abstract Objectives Previous studies have shown that there may be a positive correlation between serum uric acid levels and hyperthyroidism. However, the relationship between thyroid function and serum uric acid in healthy people is unclear. This study analyzed the relationship between impaired thyroid hormone sensitivity and serum uric acid levels, and presented them in quantitative form. Research design and methods This is a cross-sectional study of 4460 adults (male: 2300; female: 2160) who participated in the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2010. Parameters representing central sensitivity to thyroid hormones were calculated as: thyroid feedback quantile-based index (TFQIFT4), thyroid stimulating hormone index (TSHI), and total thyroxine (T4) resistance index (TT4RI); Peripheral sensitivity to thyroid hormone was evaluated by FT3/FT4 ratio. In addition, we have innovated total triiodothyronine (T3) resistance index (TT3RI) and TFQIFT3 indexes based on FT3 and TSH. Multiple linear regression models were used to evaluate the correlation between thyroid resistance index and serum uric acid, and the results were presented graphically as smooth curve fittings. Results Higher levels of serum uric acid were associated with decreased sensitivity to thyroid hormones in euthyroid individuals. In conjunction with an increase in the thyroid hormone sensitivity index value, uric acid levels gradually increased as well. Furthermore, we found a seg

Abstract OBJECTIVE Previous studies have shown that there may be a positive correlation between serum uric acid level and hyperthyroidism. However, the relationship between thyroid function and serum uric acid in healthy people is not clear. The purpose of this study was to analyze the relationship between sensitivity to thyroid hormones and serum uric acid levels, and to present them in quantitative form. RESEARCH DESIGN AND METHODS This study is a cross-sectional study of 4,600 adults (male: 2,366; female: 2,234) who participated in the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2010. Parameters representing central sensitivity to thyroid hormones were calculated as: Thyroid Feedback Quantile-based Index (TFQIFT4), TSH index (TSHI), and thyrotropin T4 resistance index (TT4RI); Peripheral sensitivity to thyroid hormone was evaluated by FT3/FT4 ratio. In addition, we have innovated TT3RI and TFQIFT3 indices based on FT3 and TSH. The relationship between thyroid hormone sensitivity and serum uric acid concentration was analyzed by multiple linear regression. RESULTS Higher levels of serum uric acid were associated with decreased sensitivity to thyroid hormones in euthyroid individuals. Further analysis revealed that TFQIFT4, TFQIFT3, TT4RI, TT3RI, TSHI had a significant correlation with serum uric acid levels in women and obese people; in people aged 20-39, except for TFQIFT4, other thyroid sensitivity indexes were positively correlated with serum u

reason for the observation that the relation between free T4 concentration and TSH levels deviates from a pure loglinear relation that has previously been The hypothalamic–pituitary–thyroid axis (HPT axis for short, a.k.a. thyroid homeostasis or thyrotropic feedback control) is part of the neuroendocrine system responsible for the regulation of metabolism and also responds to stress. As its name suggests, it depends upon the hypothalamus, the pituitary gland, and the thyroid gland. The hypothalamus senses low circulating levels of thyroid hormone (T The… Thyroid homeostasis results from a multi-loop feedback system that is found in virtually all higher vertebrates. Proper function of thyrotropic feedback control is indispensable for growth, differentiation, reproduction and intelligence. Very few animals (e.g. axolotls and sloths) have impaired thyroid homeostasis that exhibits a very low set-point that is assumed to underlie the metabolic and ontogenetic anomalies of these animals. The pituitary gland secretes thyrotropin (TSH; Thyroid Stimulating Hormone) that stimulates the thyroid to secrete thyroxine (T4) and, to a lesser degree, triiodothyronine (T3). The major portion of T3, however, is produced in peripheral organs, e.g. liver, adipose tissue, glia and skeletal muscle by deiodination from circulating T4. Deiodination is controlled by numerous hormones and nerval signals including TSH, vasopressin and catecholamines. Both peripheral thyroid hormones (iodothyronines) inhibit thyrotropin secretion from the pituitary (negative feedback). Consequently, equilibrium concentrations for all hormones are attained. TSH secretion is also controlled by thyrotropin releasing hormone (thyroliberin, TRH), whose secretion itself is again suppressed by plasma T4 and T3 in CSF (long feedback, Fekete–Lechan loop). Additional feedback loops are ultrashort feedback control of TSH secretion (Brokken-Wiersinga-Prummel loop) and linear feedback loops controlling plasma protein binding. Recent research suggested the existence of an additional feedforward motif linking TSH release to deiodinase activity in humans. The existence of this TSH-T3 shunt could explain why deiodinase activity is higher in hypothyroid patients and why a minor fraction of affected individuals may benefit from substitution therapy with T3. Convergence of multiple afferent signals in the control of TSH release including but not limited to T3, cytokines and TSH receptor antibodies may be the reason for the observation that the relation between free T4 concentration and TSH levels deviates from a pure loglinear relation that has previously been proposed. Recent research suggests that ghrelin also plays a role in the stimulation of T4 production and the… TSH…

La elevada frecuencia de disfunción tiroidea en gestación hace necesario disponer de valores de referencia propios de TSH en primer trimestre. Existe controversia sobre los métodos de detección y diagnóstico de la disfunción tiroidea durante el embarazo y también sobre su posible a asociación a peores resultados obstétricos o neonatales. El objetivo consiste en comparar gestantes que presentan TSH > 4,5 mU/L con aquellas que presentan una función tiroidea normal en el primer trimestre de gestación en cuanto a resultados gestacionales y neonatales. Conocer la prevalencia real de disfunción tiro

thyroxine and TSH in an euthyroid patient........ 271 G. Wolf, A. Passath, W. Langsteger TSH-levels after … regulatory loop is a classic example of negative-feedback control of endocrine function [1]. TSH is a complex … [9] our investigations showed that TSH levels in serum and TSH contence in the pituitary glands of rats