Thyroid Hormones And Thyrotropin Research Articles

Approach to the Patient With Raised Thyroid Hormones and Nonsuppressed TSH.

Measurement of free thyroid hormones (THs) and thyrotropin (TSH) using automated immunoassays is central to the diagnosis of thyroid dysfunction. Using illustrative cases, we describe a diagnostic approach to discordant thyroid function tests, focusing on entities causing elevated free thyroxine and/or free triiodothyronine measurements with nonsuppressed TSH levels. Different types of analytical interference (eg, abnormal thyroid hormone binding proteins, antibodies to iodothyronines or TSH, heterophile antibodies, biotin) or disorders (eg, resistance to thyroid hormone β or α, monocarboxylate transporter 8 or selenoprotein deficiency, TSH-secreting pituitary tumor) that can cause this biochemical pattern will be considered. We show that a structured approach, combining clinical assessment with additional laboratory investigations to exclude assay artifact, followed by genetic testing or specialized imaging, can establish a correct diagnosis, potentially preventing unnecessary investigation or inappropriate therapy.

Impaired Sensitivity to Thyroid Hormones Is Associated with Hyperuricemia, Obesity, and Cardiovascular Disease Risk in Subjects with Subclinical Hypothyroidism.

Background: Subclinical hypothyroidism (SCH) is associated with an increased risk of metabolic disorders and cardiovascular events. There is a delicate interplay between thyroid hormones and thyrotropin (TSH) and metabolic homeostasis. However, the association between thyroid hormone sensitivity and metabolic indices has not been elucidated in SCH. Methods: We enrolled 11,109 participants with SCH. All participants had a TSH level >4.2 mIU/L and normal free thyroxine (fT4; 12.0-22.0 pmol/L). Metabolic indices (body mass index [BMI], blood pressure, serum lipid, serum uric acid [sUA], plasma glucose and glycosylated hemoglobin [HbA1C]) were measured. The thyroid hormone sensitivity indices that include thyroid feedback quantile-based index (TFQI), TSH index (TSHI), and thyrotroph thyroxine resistance index (TT4RI) were calculated based on fT4 and TSH. Higher TFQI quartiles indicated lower thyroid hormone sensitivity. The relationship between thyroid hormone sensitivity indices and metabolic indices and cardiovascular disease (CVD) risk were calculated. Results: Participants with decreased central sensitivity to thyroid hormone had lower BMI and higher sUA levels. The odds ratio of the fourth versus the first quartile of TFQI was 0.85 [confidence interval, CI: 0.73-0.96] for obesity, 1.64 [CI: 1.37-1.92] for hyperuricemia (HUA), and 12.22 [CI: 5.32-28.07] for 10-year risk distribution for CVD >20%. Further adjustment for BMI when analyzing HbA1C, HUA, and CVD risk generated similar results. TSHI and TT4RI also yielded similar results. Conclusions: Impaired sensitivity to thyroid hormone in SCH is associated with higher risk of HUA and CVD and lower risk of obesity. These findings are potentially useful for understanding the interaction between thyroid hormone sensitivity and metabolic diseases in SCH.

Assessment of Thyroid Function in COVID-19 Patients

Since the egression of the coronavirus 2019 (COVID-19) disease, more than 200 countries and areas around the world were affected. To the present, it is not clear whether COVID-19 has effects on thyroid function or not. The aim of the current study was to assess thyroid function in COVID-19 patients with history of thyroid disease and those without such a history and to find out the thyroid disturbance in both groups. The present study involved 86 COVID-19 affected patients admitted BioLab and the Balsam Hospital, Erbil/ Iraq between January and April 2021. Confirmation of COVID-19 infection all patients by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) of nasopharyngeal swabs. Thyroid hormones, and thyrotropin (TSH) level was analyzed and assessed. Most of the participants (88.4%) had normal T3 level, and there was no significant difference (p = 0.069) between those with normal T3, TPO and with no history of thyroid disease and those with such a history and/or high TPO. T4 levels of the participants with no history of thyroid disease and normal TPO did not differ significantly (p =0.725) from those with a history of thyroid disease and/or high TPO. Regarding the level of TSH, there was significant difference (p<0.001) between the two fore mentioned groups. There is high prevalence of subclinical hypothyroidism in the COVID-19 patients with family history of thyroid disease and high TPO antibody level.

Insulin-Like Growth Factor Pathway and the Thyroid.

The insulin-like growth factor (IGF) pathway comprises two activating ligands (IGF-I and IGF-II), two cell-surface receptors (IGF-IR and IGF-IIR), six IGF binding proteins (IGFBP) and nine IGFBP related proteins. IGF-I and the IGF-IR share substantial structural and functional similarities to those of insulin and its receptor. IGF-I plays important regulatory roles in the development, growth, and function of many human tissues. Its pathway intersects with those mediating the actions of many cytokines, growth factors and hormones. Among these, IGFs impact the thyroid and the hormones that it generates. Further, thyroid hormones and thyrotropin (TSH) can influence the biological effects of growth hormone and IGF-I on target tissues. The consequences of this two-way interplay can be far-reaching on many metabolic and immunologic processes. Specifically, IGF-I supports normal function, volume and hormone synthesis of the thyroid gland. Some of these effects are mediated through enhancement of sensitivity to the actions of TSH while others may be independent of pituitary function. IGF-I also participates in pathological conditions of the thyroid, including benign enlargement and tumorigenesis, such as those occurring in acromegaly. With regard to Graves’ disease (GD) and the periocular process frequently associated with it, namely thyroid-associated ophthalmopathy (TAO), IGF-IR has been found overexpressed in orbital connective tissues, T and B cells in GD and TAO. Autoantibodies of the IgG class are generated in patients with GD that bind to IGF-IR and initiate the signaling from the TSHR/IGF-IR physical and functional protein complex. Further, inhibition of IGF-IR with monoclonal antibody inhibitors can attenuate signaling from either TSHR or IGF-IR. Based on those findings, the development of teprotumumab, a β-arrestin biased agonist as a therapeutic has resulted in the first medication approved by the US FDA for the treatment of TAO. Teprotumumab is now in wide clinical use in North America.

Distribution of thyroid hormone and thyrotropin receptors in reproductive tissues of adult female rabbits

ABSTRACTPurpose: Thyroid dysfunctions are related to anovulation, miscarriages, and infertility in women and laboratory animals. Mechanisms associated with these effects are unknown, although indirect or direct actions of thyroid hormones and thyrotropin could be assumed. The present study aimed to identify the distribution of thyroid hormones (TRs) and thyrotropin (TSHR) receptors in reproductive organs of female rabbits. Material and Methods: Ovary of virgin and pregnant rabbits, as well as the oviduct, uterus, and vagina of virgin rabbits were excised, histologically processed, and cut. Slices from these organs were used for immunohistochemical studies for TRα1-2, TRß1, and TSHR. Results: The presence of TRs and TSHR was found in the primordial, primary, secondary, tertiary, and Graafian follicles of virgin rabbits, as well as in the corpora lutea, corpora albicans, and wall of hemorrhagic cysts of pregnant rabbits. Oviductal regions (fimbria-infundibulum, ampulla, isthmus, and utero-tubal junction), uterus (endometrium and myometrium), and vagina (abdominal, pelvic, and perineal portions) of virgin rabbits showed anti-TRs and anti-TSHR immunoreactivity. Additionally, the distal urethra, paravaginal ganglia, levator ani and iliococcygeus muscles, dorsal nerve and body of the clitoris, perigenital skin, and prostate had TRs and TSHR. Conclusions: The wide presence of TRs and TSHR in female reproductive organs suggests varied effects of thyroid hormones and thyrotropin in reproduction.

Reference range for thyroid function indices of 8-10 years old school children in certain regions of China

Objective To set up the reference range for thyroid hormones and thyrotropin (TSH) of 8-10 years old school children in certain regions of China to provide reference criteria for diagnosis,treatment,and monitoring of thyroid diseases and related research.Methods A cross-sectional survey was conducted in primary school children aged 8-10 years from six iodine sufficient areas.664 normal school children were selected for establishing reference ranges of thyroid hormones and TSH after crucial screening through questionnaire and laboratory investigation.The serum hormone levels were determined by using chemiluminescent immunoassay (Bayer's reagents),and the reference range of each hormone was displayed as its 95％ central interval.Results The reference ranges of TSH,FT4,FT3,TT4,and TT3 were 1.03-8.42 mIU/L,13.44-20.59 pmol/L,4.75-6.96pmol/L,75.29-152.66 nmol/L,and 1.76-3.35 nmol/L,respectively.There was no significant difference in hormone levels between boys and girls.The eight years old group had slightly higher TT4 level compared with the other age groups.The rural children had higher TSH and TT3 levels and lower FT4 level than the urban children.Conclusion The thyroid hormone and TSH levels are substantially different between school children and adults.Therefore,it is necessary to establish the reference range of thyroid function indices for normal school children in order to diagnose,treat,and monitor thyroid diseases. Key words: School children ; Thyroid hormones ; Thyrotropin ; Reference range

Serum Thyroid Hormone Levels in Preterm Infants Born before 33 Weeks of Gestation and Association of Transient Hypothyroxinemia with Postnatal Characteristics

Fetal thyroid function and the hypothalamopituitary-thyroid axis continue to mature throughout pregnancy. Therefore, thyroid hormone levels of premature infants differ from those of mature ones. Our primary objective was to evaluate the reference values of serum thyroid hormones in preterm infants born before 33 wk gestation. The second objective was to define a cut-off value for transient hypothyroxinemia of prematurity (THOP) according to gestational age and association of THOP with postnatal characteristics in these infants. We recruited a cohort of 200 infants (26-32 wk gestation) admitted to neonatal intensive care units (NICU) between March 2008 and February 2009. We assessed serum levels of thyroid hormones and thyrotropin (TSH), at 1st, 2nd, and 3rd-4th wk of life. Thyroid-binding globulin (TBG), thyroglobulin (Tg), and urinary iodine values were also measured at the 1st wk of life. The infants were divided into two groups according to gestational ages; group 1: 26-29 wk and group 2: 30-32 wk. Association of THOP with postnatal characteristics of these infants were evaluated. TT4 and TT3 values steadily increased from 1st wk to 3rd-4th wk while FT4 value did not significantly changed. FT3 value slightly decreased from 1st wk to 2nd wk and not significantly changed after this period. TSH value steadily decreased from 1st wk to 3rd-4th wk. For all postnatal ages, TT4, TT3, and FT3 values were lower in the lower gestational age group, while there was no significant difference for FT4 and TSH values between two gestational age groups. THOP rate decreased from first wk (24.0%, n=47) to 3rd-4th (14.0%, n=24) in all infants. When adjusted for age, THOP was associated with need for mechanical ventilation (P=0.03, OR:0.65, CI 95% 0.4-0.9) and for having respiratory distress syndrome (RDS) (P=0.02, OR:0.61 CI95%: 0.4-0.9). Longer hospital stay (P=0.006, OR:0.96, CI 95% 0.94-0.99) was also found to be associated with THOP. In preterm infants below 30 wk, thyroid hormones were lower and urinary iodine values were higher compared to infants with older gestational age. THOP at the first wk of life may convey important prognostic information about neonatal morbidity and length of hospitalization stay.

The Thr92Ala Deiodinase Type 2 (DIO2) Variant Is Not Associated with Type 2 Diabetes or Indices of Insulin Resistance in the Old Order of Amish

A common polymorphism of the type 2 deiodinase gene (Thr92Ala DIO2) was found to be associated with insulin resistance in a mixed Caucasian population. The aim of this study was to investigate the association of the Thr92Ala DIO2 variant to indices of insulin resistance in the Old Order Amish. A genotype-phenotype association study was performed at the research clinic in Strasburg, Pennsylvania, and the molecular genetics laboratory at the University of Maryland, Baltimore, Maryland, and the National Institutes of Health, Bethesda, Maryland. A total of 1,268 subjects participated in the Amish Family Diabetes Study. An association among the Thr92Ala DIO2 variant and type 2 diabetes, indices of insulin resistance (HOMA-IR), insulin secretion, free thyroid hormones, and thyrotropin (TSH) was found. No association was found among the Thr92Ala DIO2 variant and type 2 diabetes, impaired glucose tolerance, or body mass index (BMI) in the Amish. In nondiabetics (n = 747), the Ala92 allele tended to be associated with decreased rather then increased insulin secretion. No differences were observed in thyroid hormones or TSH. Contrary to prior findings, the Thr92Ala DIO2 variant tends to be associated with increased rather then decreased insulin sensitivity in the Amish. These findings could be secondary to a different genetic background or to environmental factors specific for this population.

Polychlorinated biphenyls and thyroid status in humans: a review.

Animal studies show that exposure to polychlorinated biphenyls (PCBs) or other persistent organochlorine compounds can disrupt thyroid hormone homeostasis. In some reports dietary exposures to PCBs have also been claimed to affect circulating levels of thyroid hormones and thyrotropin (TSH) in humans. The aim of the present study was to review available epidemiologic studies within this field. A total of 13 studies fulfilled the inclusion criteria for the review. The overall impression is a lack of consistency between studies of reported correlations, neither are there any obvious interstudy dose-response associations. Thus, it cannot presently be concluded that PCB exposure has been convincingly shown to affect thyroid hormone homeostasis in humans. On the other hand, available data do not exclude such associations. It is important to be aware of the intrinsic limitations of the cross-sectional epidemiologic studies used.

The hypothalamic-pituitary-thyroid axis in critical illness.

In severe illness, profound changes occur in the hypothalamic-pituitary-thyroid axis. The observed decrease in serum concentration of both thyroid hormones and thyrotropin (TSH) are not compatible with a negative feedback loop and suggest a major change in setpoint regulation of the hypothalamic-pituitary-thyroid axis. This is supported by post mortem studies showing a decreased expression of thyrotropin-releasing hormone in the hypothalamic paraventricular nucleus of patients with a decreased serum T3 level. In critical illness, serum T3 may even become undetectable without giving rise to an elevated concentration of serum TSH. It is currently not clearly established whether this reflects an adaptation of the organism to illness or instead a potentially harmful condition leading to hypothyroidism at tissue level. There is thus a need for randomized clinical trials in critically ill patients to investigate whether they may benefit from a normalization of thyroid hormone concentration. Recent clinical studies in these patients involving the administration of hypothalamic peptides open up new ways of achieving this.

Mixed anxiety–depressive disorder and major depressive disorder: comparison of the severity of illness and biological variables

Mixed anxiety–depressive disorder (MADD) is a new diagnostic category defining patients who suffer from both anxiety and depressive symptoms of limited and equal intensity accompanied by at least some autonomic features. Patients do not meet the criteria for specific anxiety or depressive disorders. The emergence of the symptoms is independent of stressful life events. There are many issues presently under investigation about the validity of this clinical entity. In this study, a group of 29 patients with MADD was compared with a group of 31 patients with major depressive disorder (MDD) to assess the differences and similarities between these two disease categories in terms of severity measures and biological variables. The dexamethasone suppression test (DST) was employed, and thyroid hormones and thyrotropin (TSH) levels were measured for the evaluation of hypothalamic–pituitary–adrenal (HPA) and hypothalamic–pituitary–thyroid (HPT) axes, respectively. The patients with MADD were found to be less depressive and more anxious compared to those with MDD. DST responses and thyroid functions were found to be similar in the two groups. When severity of depression was controlled, k max and 2300-h cortisol values were found to be significantly higher in the MADD group. Although the patients with MDD and MADD presented with relatively different clinical features, there is not enough biological evidence indicating that MADD represents a discrete diagnostic category. However, there may be relatively higher HPA activity in MADD patients.

Increased plasma levels of endothelin-1 in patients with hyperthyroidism

Plasma concentrations of endothelin-1 (ET-1) were measured in 25 hyperthyroid subjects, 15 hypothyroid subjects, and 21 age-matched normal controls. In hyperthyroid patients, plasma concentrations of ET-1 were significantly higher than in the control group ( P < .0001) and in hypothyroid patients ( P < .0001). In contrast, no differences were found between hypothyroid patients and controls. Plasma levels of ET-1 were similarly elevated as in patients with Graves' disease and those with toxic adenoma. No correlations were found between plasma ET-1 levels, thyroid hormones, and thyrotropin (TSH) in hyperthyroid, hypothyroid, and euthyroid groups. The results of our study clearly indicate that in hyperthyroidism, circulating levels of ET-1 are strongly increased, although the pathogenesis of the increase is unclear.

Alterations in Thyroid Hormones and Thyrotropin (TSH) in Morbidly Obese Patients before and after Vertical Gastroplasty.

BACKGROUND: Published results of studies of thyroid function in obesity and after weight loss have differed. METHODS: The circulating concentrations of thyroid hormones and TSH were studied in 30 consecutive, euthyroid morbidly obese patients before and after weight loss from vertical gastroplasty, with the aim to determine the relation between body weight loss and pituitary-thyroid axis function. Serum TSH, free T3 (FT3) and free T4 (FT4) were measured before operation and repeated 6 and 18 months postoperatively. RESULTS: A significant increase, but within normal levels, in FT3 value at 6 and, mainly, at 18 months after gastroplasty was observed (p = 0.002). The FT4 value was slightly increased, at the same time and serum TSH was found to, be significantly decreased (p = 0.03 and p = 0.01 respectively). The relative increase in FT4 was negatively correlated with excess body weight and Body Mass Index reduction. This correlation was only moderate with values ranging from r = 0.34 to r = 0.47. CONCLUSIONS: Although there were statistically significant differences in thyroid function tests before and after loss of weight, these were not biologically significant. The hypophyseal/thyroid axis remains always active and contributes to body weight homeostasis and its regulation.

Influence of thyroid hormones on morning and evening TSH response to TRH in major depression

The serum levels of thyroid hormones and thyrotropin (TSH) were evaluated before and after 8 PM and 11 PM thyrotropin-releasing hormone (TRH) challenges, on the same day, in 41 drug-free DSM-III-R euthyroid major depressed inpatients and 16 hospitalized controls. Depressed patients exhibited elevated circulating concentrations of thyroid hormones, which were associated with and may have contributed to the blunted TSH response to TRH. This was confirmed by: (a) higher basal levels (albeit not always statistically significant) of free triiodothyronine (FT 3B) and free thyroxine (FT 4B) at 8 AM and 11 PM in the depressed patient population compared with the controls; (b) lower basal levels of TSH in the depressed subjects (even though this was only statistically significant at the 11 PM sampling) compared with the controls; (c) blunted TSH response to TRH (ΔTSH) in the depressed group (although this was only statistically significant at 11 PM) and blunted ΔΔTSH values (differences between 11 PM-ΔTSH and 8 AM-ΔTSH).

Alteration by prolonged oral administration of a thyrotropin-releasing hormone analog, TA-0910, of the pituitary-thyroid axis in subjects with brain stroke.

We evaluated whether prolonged oral administration of a novel analog of thyrotropin-releasing hormone (TRH), TA-0910, may change the pituitary-thyroid axis in human subjects with brain stroke. The subjects were given one oral dose of 2.5-20 mg of TA-0910 daily for 8 weeks, and then blood levels of TA-0910, thyroid hormones and thyrotropin (TSH) were measured. Plasma levels of TA-0910 were elevated with increasing doses. After administration of TA-0910, the basal levels of thyroid hormones and TSH had a tendency to increase and decrease, respectively, but those changes remained in the normal range. The secretion of TSH in response to TRH was not significantly affected by TA-0910 administration. No significant changes in other pituitary hormones were observed after TA-0910 administration. The present data indicate that prolonged oral administration of TA-0910 did not significantly alter the pituitary-thyroid axis in subjects with brain stroke.

Serum levels of thyroid hormones in liver diseases

Concentrations of thyroid hormones and thyrotropin (TSH) were measured in sera of clinically euthyroid patients with various liver diseases and compared with normal controls. The mean serum concentration of 3,3',5'-triiodothyronine (reverse T 3, rT 3) was significantly increased in patients with decompensated liver cirrhosis ( p < 0.01). This increase seemed to be dependent upon the hepatic damage, although it was not significant in patients with acute hepatitis, chronic hepatitis and compensated liver cirrhosis. The mean serum concentration of 3,3',5-triiodothyronine (T 3) was significantly decreased in patients with decompensated liver cirrhosis ( p < 0.05). However, in patients with acute hepatitis, chronic hepatitis and compensated liver cirrhosis, the mean concentration of T 3 was above the normal. The mean value of rT 3/T 3 ratios in patients with acute hepatitis, chronic hepatitis and compensated liver cirrhosis were similar to that of normal controls, but in patients with decompensated liver cirrhosis, the mean value of rT 3/T 3 ratios was markedly higher than that of normal controls. The rT 3/T 3 ratios have little or no correlation with some standard liver function tests. These results suggest that marked alterations of peripheral conversion of thyroxine (T 4) to rT 3 or T 3 may be found only in a state of decompensated liver cirrhosis among the various liver diseases.

Effect of dietary composition on fasting-induced changes in serum thyroid hormones and thyrotropin

To assess the effect of starvation and refeeding on serum thyroid hormones and thyrotropin (TSH) concentrations, 45 obese subjects were studied after 4 days of fasting and after refeeding with diets of varying composition. All subjects showed an increase in both serum total and free thyroxine (T 4), and a decrease in serum total and free triiodothyronine (T 3) following fasting. These changes were more striking in men then in women. The serum T 3 declined during fasting even when the subjects were given oral L-T 4, but not when given oral L-T 3. After fasting, the serum reverse T 3 (rT 3) rose, the serum TSH declined, and the TSH response to thyrotropin-releasing hormone (TRH) was blunted. Refeeding with either a mixed diet ( n = 22) or a carbohydrate diet ( n = 8) caused the fasting-induced changes in serum T 3, T 4, rT 3, and TSH to return to control values. In contrast, refeeding with protein ( n = 6) did not cause an increase in serum T 3 or in serum TSH of fasted subjects, while it did cause a decline in serum rT 3 toward basal value. The present data suggest that: (1) dietary carbohydrate is an important factor in reversing the fall in serum T 3 caused by fasting; (2) production of rT 3 is not as dependent on carbohydrate as that of T 3; (3) men show more significant changes in serum thyroid hormone concentrations during fasting than women do, and (4) absorption of T 3 is not altered during fasting.

Alterations in circulating thyroid hormones and thyrotropin in hepatic cirrhosis: evidence for euthyroidism despite subnormal serum triiodothyronine.

ABSTRACT We studied serum concentrations of thyroid hormones and thyrotropin (TSH) in 23 clinically euthyroid patients with hepatic cirrhosis. The mean serum total thyroxine T4 concentration of 7.5 μg per 100 ml was modestly but significantly lower than the corresponding normal mean value of 8.4 μg per 100 ml. However, since the dialyzable fraction of serum T4 in patients with hepatic cirrhosis was considerably above normal (0.055% vs 0.030%), their mean serum free T4 concentration of 3.9 ng per 100 ml was significantly greater than the mean normal value of 2.8 ng per 100 ml. The mean serum concentration of triiodothyronine (T3) of 33 ng per 100 ml in patients with cirrhosis was markedly lower than the normal mean of 126 ng per 100 ml. The mean serum concentration of free T3, 163 pg per 100 ml, was also significantly lower than the mean of 375 pg per 100 ml in normal subjects; this was the case even though the mean dialyzable fraction of serum T3, 0.52, was significantly higher than that of 0.34 in normal...