Higher T4 Concentrations Research Articles

Electrocardiography in euthyroid individuals: a Danish general population study

Thyroid hormones within the euthyroid range have been linked to mortality and differences in heart rate. However, some relations between thyroid hormone concentration and various electrocardiographic measurements remain unassessed. We aimed to investigate the association between thyroid hormone concentrations within the euthyroid range and different electrocardiographic markers in people free of thyroid disease.We obtained electrocardiograms (ECG) and blood samples of free T4, total T3, and thyrotropin (TSH) in 20,852 subjects from the general population (the GESUS study). Relations between concentrations of TSH, free T4, and total T3 and heart rate, QTc, QRS duration, PR interval, P-wave duration and T-wave morphology were assessed in a multivariate adjusted linear model stratified by sex.Roughly half of the 18,046 included participants with thyroid hormone measurements within euthyroid range were men, and the average age was 56 years. Heart rate increased with concentrations of T3 (6.4 bpm/nM, P<0.001 in women and 5.3 bpm/nM, P<0.001 in men) and T4 (3.7 bpm/10pM, P<0.001 in women and 3.1 bpm/10pM, P<0.001 in men). We found no relation between TSH and heart rate. PR interval and QRS duration decreased with higher concentrations of T3 (all P<0.01). QTc increased with higher concentrations of T4 in men (5 ms/10pM), and T waves were flatter, more asymmetric, and more often had notches with higher concentrations of T4 (all P≤0.01).Thyroid hormone concentrations within the euthyroid range in people free of thyroid disease were associated with changes in the electrocardiogram in a general population.

QimmeqHealth\u2014thyroid status of Greenland sled dogs (Canis lupus familiaris borealis)

BackgroundGreenland sled dogs (GSD) are a unique, genetically isolated population of dogs living under exceptional environmental conditions. Metabolism, and thereby thyroid hormones are affected by multiple factors. Among other activity, energy balance and environmental conditions are important. A breed-specific reference interval (RI) can be useful for diagnostics of potential thyroid-related pathologies. The aim of this study was to establish RIs of the thyroid hormones thyroxin (T4), free thyroxin (fT4), and thyroid stimulating hormone (TSH) in GSD. In addition to evaluate the effect of sex, age, season, management, and body condition score (BCS) in GSD. Physical exams and cephalic venous blood sampling were performed in the period of 2018–2019 from 265 GSD managed either privately or by the Danish navy. Serum biochemical analyses, including C-reactive protein, were performed and RIs were determined for TSH, T4 and fT4 in only healthy dogs. The RIs were determined using American Society for Veterinary Clinical Pathology guidelines and the effect of varying factors were evaluated by linear regression and further tested by Mann–Whitney test.Results144 GSD were included in the reference group resulting in RIs: T4: 6.44–48.65 nmol/L; fT4: 3.91–18.51 pmol/L; and TSH: 0.04–0.55 ng/mL. Female GSD had significantly higher concentrations of T4 (P = 0.039) and fT4 (P = 0.015) compared to males; a positive correlation between TSH and aging was found; T4 concentrations were significantly higher (P = 0.003) during summer; and TSH concentrations were lower in GSD managed by the navy (P < 0.0001). BCS was higher (P < 0.0001) in Sirius GSD compared to civilian GSD, and BCS was positively correlated with T4 and negatively correlated with TSH.ConclusionsReference intervals for T4, fT4 and TSH in GSD were established. The RI for T4 and fT4 was lower compared to other breeds. In addition, sex, age, season, management and BCS demonstrated variable effects on thyroid hormones. Our results can be used as a foundation for improving management and further research of GSD.

Electrocardiography in euthyroid individuals: a Danish general population study

Thyroid hormones within the euthyroid range have been linked to mortality and differences in heart rate. However, some relations between thyroid hormone concentration and various electrocardiographic measurements remain unassessed. We aimed to investigate the association between thyroid hormone concentrations within the euthyroid range and different electrocardiographic markers in people free of thyroid disease. We obtained electrocardiograms (ECG) and blood samples of free T4, total T3, and thyrotropin (TSH) in 20,852 subjects from the general population (the GESUS study). Relations between concentrations of TSH, free T4, and total T3 and heart rate, QTc, QRS duration, PR interval, P-wave duration and T-wave morphology were assessed in a multivariate adjusted linear model stratified by sex. Roughly half of the 18,046 included participants with thyroid hormone measurements within euthyroid range were men, and the average age was 56 years. Heart rate increased with concentrations of T3 (6.4 bpm/nM, P<0.001 in women and 5.3 bpm/nM, P<0.001 in men) and T4 (3.7 bpm/10pM, P<0.001 in women and 3.1 bpm/10pM, P<0.001 in men). We found no relation between TSH and heart rate. PR interval and QRS duration decreased with higher concentrations of T3 (all P<0.01). QTc increased with higher concentrations of T4 in men (5 ms/10pM), and T waves were flatter, more asymmetric, and more often had notches with higher concentrations of T4 (all P≤0.01). Thyroid hormone concentrations within the euthyroid range in people free of thyroid disease were associated with changes in the electrocardiogram in a general population.

Is it better to overtreat or undertreat?

Yogi Berra, an exceptionally gifted baseball player, was a font of wisdom. One of his most famous quotes, “When you come to a fork in the road, take it,” applies to the conundrum tackled by Paone et al in this volume of The Journal. Approximately 43% of infants and 10% of older children with congenital hypothyroidism have elevated levels of both thyrotropin (TSH) and thyroxine (T4). When both T4 and triiodothyronine (T3) are elevated, pediatricians are in the untenable position of having to determine if they should overtreat in an attempt to normalize the TSH at the possible expense of increasing the T4 above normal, when studies have demonstrated impaired school performance, lower IQ, and a higher risk of attention deficit in children who had high T4 concentrations in infancy (J Pediatr 2000;136:292-7; Pediatrics 2003;112:923-30). Or, should they attempt to maintain normal T4 values while TSH concentrations remain mildly elevated? Although the evidence that low T4 levels during the time of rapid brain growth affects intellectual functioning, the evidence that elevated TSH values during the first 3 years of life is less robust, though one study reported poorer school performance in children who had TSH elevations in infancy (Acta Paediatr 2001;90:1249-56). Due to the lack of data, we do not know which fork to take in this particular road. The cause of the abnormal lack of suppression of TSH with adequate levothyroxine administration is unknown. Affected infants might have abnormally low thyroid gland secretion of T3, abnormally low conversion of T4 to T3, or abnormal central feedback with lack of normal TSH suppression (ie, central resistance to thyroid hormone). Paone et al hypothesized that the lack of suppression of TSH by appropriate doses of levothyroxine (LT4) could be overcome with the addition of liothyroninie (LT3), as shown in other studies (Horm Res Paediatr 2010;73:108-14; J Pediatr Endocrinol Metab 2011;24:347-50). In order to assess this hypothesis, the authors performed a retrospective analysis of clinical data of 12 patients with CH with both high T4 and TSH values. Six of them had been treated with LT4 alone followed by LT4 + LT3 and 6 only received LT4. The addition of LT3 resulted in the normalization of TSH (mean 4.3 mIU/L, down from 10 mIU/L pre-T3 treatment , vs 8.5 mIU/L in the T4 monotherapy group). The T4 values were likewise normalized, with a mean decrease of 23% ± 9% from pretreatment values. T3 concentrations remained normal for age. Because this was a retrospective study, the groups were neither matched for the age of treatment initiation nor given a neurodevelopmental assessment. However, this is a promising treatment for infants with persistent elevation of TSH and T4 despite appropriate treatment with levothyroxine. Long-term randomized controlled trials are needed to assess the effect of this regimen on thyroid hormone values. But, the real question that must be answered is not whether the laboratory values can be normalized but whether this regimen can improve neurocognitive functioning in these children, including not only intelligence but also school performance. And, hopefully, this study will help us to determine which fork in this particular road we should take. Article page 167▶ Liothyronine Improves Biochemical Control of Congenital Hypothyroidism in Patients with Central Resistance to Thyroid HormoneThe Journal of PediatricsVol. 175PreviewTo assess whether adding liothyronine (LT3) to levothyroxine (LT4) monotherapy normalizes serum thyrotropin (TSH) and thyroxine (T4) concentrations in children with congenital hypothyroidism and central resistance to thyroid hormone. Full-Text PDF

How do overwinter changes in body condition and hormone profiles influenceWeddell seal reproductive success?

SummaryReproductive success can be influenced by maternal physiological condition at the time of embryo implantation and by foraging success during gestation. Polar marine mammals experience drastic fluctuations in body composition (lipid stores) as a result of life‐history events and large‐scale changes in seasonal productivity and environmental conditions. These species provide the opportunity to explore physiological parameters important to reproductive success.There are conflicting physiological demands on Weddell seal (Leptonychotes weddellii) females during the moult period, when animals are at their leanest but still must generate an energetically costly new pelage and begin active gestation.To investigate the impact of post‐moult condition and hormonal mediators on the reproductive success of the southernmost breeding mammal, body composition was determined for post‐moult (fall; 53 non‐reproductive) and pre‐breeding (spring; 31 non‐reproductive, 17 reproductive) adult female Weddell seals. Animals were significantly larger and had greater lipid stores in spring, after the winter foraging period. There were no differences in the proportion of mass or condition gained overwinter between females that gave birth (n = 12) and those that did not (n = 8) the following year.Changes in body condition were correlated with endocrine factors that influence energy allocation, such as cortisol, growth hormone (GH), insulin‐like growth factor (IGF)‐1 and thyroid hormones (T3and T4). Of these,GHand T4were significantly higher during the post‐moult period, likely to promote protein sparing and hair regeneration. In addition, females that had higher T4concentrations in fall were significantly more likely to have a pup the following year, possibly due to the role of thyroid hormones in embryo attachment. This suggests that hormones influencing fuel use during the moult may also impact subsequent reproductive success.Unlike some other large pinnipeds, Weddell seals are not capital breeders. This work indicates that gestating Weddell seals do not gain as much mass or energy overwinter in preparation for lactation the following year as lower‐latitude phocid species, which might explain why female Weddell seals rely on foraging to meet energetic demands during lactation.

Ontogenetic changes of habitat selection and thyroid hormone levels in black rockfish (Sebastes schlegelii) reared in captivity

This study examined the ontogenetic change in vertical distribution associated with algae and the thyroid hormone profiles of black rockfish (Sebastes schlegelii) under rearing conditions. Experimental observations on distribution were carried on black rockfish from the newly born larval stage to juveniles 75 days after birth (DAB). Position was categorized by vertical location [upper layer, mid layer and lower layer (LL)] and by association with artificial algae (floating algae, bottom algae and no association). Position of fish was observed four times a day, at 0400 (dawn), 1200 (noon), 1800 (dusk) and 2400 (midnight) hours. The majority of fish (>80%) reached transforming larval stage [17.8 ± 0.7 mm total length (TL)] at 25 DAB and juvenile stage (24.3 ± 0.6 mm TL) at 35 DAB. Newly born larvae were mainly distributed at surface and middle layers, the shift of vertical distribution to the LL occurred between 10 and 25 DAB, and over 98% of the individuals were distributed near the bottom after 35 DAB. Association behavior with algae was first observed from 20 to 30 DAB depending on the time of day. Percentage of fish associated with bottom algae increased from 25 to 40 DAB and reached 50–70% thereafter. Thyroid hormone (T4) showed two surges at 30 and 50 DAB. The first surge corresponded to the transforming larval stage and the occurrence of association behavior with algae. The results indicate that pelagic larvae settle to the bottom layer before metamorphosis, and association behavior with algae appears at the transforming larval stage. A high T4 concentration at 30 DAB indicates a close relationship with these morphological and behavioral developments.

TSH concentration within the normal range is associated with cognitive function and ADHD symptoms in healthy preschoolers

Thyroid hormone concentrations outside the normal range affect brain development, but their specific influence on behaviour and mental abilities within normal values is unknown. The objective of this study was to investigate whether thyroid hormone concentrations are related to neurodevelopment and ADHD (attention deficit and hyperactivity disorder) symptoms in healthy preschoolers. DESIGN SUBJECTS AND MEASUREMENTS: Children from two general population birth cohorts in Menorca (n = 289) and Ribera d'Ebre (n = 53), Spain, were assessed in a cross-sectional study at the age of 4. Thyroid hormones (free T4 and T3) and TSH concentrations were measured and mental and motor development was assessed using McCarthy's scales for neuropsychological outcomes and ADHD-DSM-IV for attention deficit and hyperactivity/impulsivity symptoms. Children with TSH concentrations in the upper quartile of the normal range performed lower on McCarthy's scales and were at higher risk for attention deficit and hyperactivity/impulsivity symptoms. In the Menorca cohort, a decrease of 5.8 (P < 0.05) and 6.9 (P < 0.01) points was observed in memory and quantitative skills, respectively. In contrast, high T4 concentrations were associated with decreased risk of having 1-5 attention deficit symptoms (odds ratio: 0.25; P < 0.01); these findings were observed in both cohorts despite differences in mean TSH concentrations. No associations were observed with T3. Despite being within the normal range, high TSH concentrations are associated with a lower cognitive function and high TSH and low free T4 with ADHD symptoms in healthy preschoolers. Statistically significant differences were observed in the highest quartiles of TSH, suggesting a need for re-evaluation of the upper limit of the normal TSH range.

Temporal and spatial variation in plasma thyroxine (T4) concentrations in juvenile alligators collected from lake Okeechobee and the northern Everglades, Florida, USA

We examined variation in plasma thyroxine (T4) in juvenile American alligators (Alligator mississippiensis) collected from three sites within the Kissimmee River drainage basin (FL, USA). Based on historical sediment data, Moonshine Bay served as the low contaminant exposure site, Water Conservation Area 3A served as an intermediate contaminant exposure site, and Belle Glade served as the high contaminate exposure site. In May 1999, alligators (n = 22) from Water Conservation Area 3A exhibited higher T4 concentrations than animals from both Belle Glade (n = 22; p = 0.0003) and Moonshine Bay (n = 33; p = 0.001). In May 2000, alligators (n = 29) Water Conservation Area 3A again exhibited higher T4 concentrations than those from Belle Glade (n = 49; p = 0.02) but not those from Moonshine Bay (n = 40). No sexual dimorphism was observed among mean T4 concentrations within any of the sites during either year (p > 0.05). Animals within all sites exhibited higher T4 concentrations in May 2000 when compared to May 1999. When variance was examined, animals from Water Conservation Area 3A exhibited higher variance in plasma T4 concentrations than those from either Moonshine Bay or Belle Glade. We concluded that mean plasma T4 concentrations did not match the sediment contaminant mixture data presently available to us, whereas variance seems to be a more reliable indicator of contaminant exposure.

T4 depresses olfactory responses to L-alanine and plasma T3 and T3 production in smoltifying Atlantic salmon.

During natural or induced smoltification, Atlantic salmon exhibit spring elevations in olfactory activity and plasma L-thyroxine (T4). To determine whether T4 influences olfactory activity, we administered T4 to late parr in early April and measured olfactory bulb electroencephalogram and olfactory epithelium electroolfactorogram responses to L-alanine nasal stimulation, plasma T4 and 3,5,3'-triiodo-L-thyronine (T3) levels, and hepatic and brain monodeiodination. T4 treatment raised plasma T4 to 15 ng/ml, simulating the smolt T4 surge, and depressed plasma T3 and electroencephalogram responses, without modifying electroolfactorogram responses. Decreased plasma T3 may be explained by inhibition of hepatic T4 outer-ring deiodination, generating T3, and stimulation of inner-ring deiodination, degrading T4 and T3. Brain T4 outer-ring deiodination was also strongly inhibited. In conclusion, creation of a high plasma T4 concentration simulating the natural smolt peak depressed olfactory bulb responses to L-alanine due to the high T4 concentration or the depressed T3 availability in brain induced by T4. T4 may terminate the period of heightened olfactory responsiveness during smoltification.

Seasonal changes in systemic hormone profiles and their relationship to patterns of fibre growth and moulting in goats of contrasting genotypes

In a 2 x 2 factorial experiment, seasonal changes in hormone and insulin-like growth factor-1 (IGF-1) profiles were compared in goats of two genotypes (Siberian (S) and Icelandic x Scottish feral (IF); n = 20 per genotype) with differing patterns of secondary fibre growth. Half of the goats of each genotype were fed rations containing either 100 or 180 g crude protein (CP)/kg dry matter. The period of secondary fibre growth was longer and the rate of growth greater in S than IF goats, but there were no effects of dietary protein concentration. Mean plasma concentrations of insulin, cortisol, T3 and T4 were higher in winter and those of prolactin, GH and IGF-1 concentrations were higher in summer. Growth of secondary fibre in S goats between January and March was associated with higher plasma prolactin and lower plasma insulin concentrations at this time than in IF goats in which there was no secondary fibre growth. The observed genotypic differences in times of onset and cessation of fibre growth were not associated with differences in the times of seasonal changes in any of the other hormones measured, and there was no effect of dietary protein level on hormone profiles. The higher mean growth rate and greater diameter of secondary fibre in S goats was associated with higher mean concentrations of T4 than in IF goats, throughout the study. Four S goats which exhibited secondary fibre growth during the summer had higher (P &lt; 0.05) mean plasma insulin concentrations than other animals of that genotype. It is suggested that genotypic differences in prolactin concentrations in late winter/spring may affect the time of onset of secondary fibre growth and that the cessation of growth may be influenced by differences in the timing of the seasonal decline of circulating prolactin concentrations to basal levels. However, the maintenance of relatively high plasma insulin concentrations may prolong growth in some circumstances. The higher concentrations of T4 in S than IF goats may have a role in the enhancement of the rate of fibre growth in these animals. The onset of moult in both genotypes was associated with the spring increase in plasma prolactin concentrations.

Characteristics of infantile hypothyroidism discovered on neonatal screening

Clinical and laboratory data from 146 patients with infantile hypothyroidism diagnosed by neonatal screening over a five-year period are presented. In 95 patients there was adequate thyroid imaging or evidence of dyshormonogenesis; of these, 43% had ectopic thyroid tissue, 22% had goitrous hypothyroidism, and 35% had hypoplastic or aplastic glands. Stanford-Binet IQs of the patients at 3, 4, and 5 years of age were identical with those of control subjects. Patients in whom thyroid tissue was demonstrable on radioactive scanning had higher concentrations of T4 and T3, and lower concentrations of TSH and less retarded bone age, but did not differ in ultimate IQ from patients with no demonstrable thyroid tissue. No significant correlation with ultimate IQ was found for any clinical or laboratory factor except for the adequacy of treatment. Eleven children with inadequate treatment had a mean IQ significantly less than that of other patients, 87 +/- 5 (SEM) vs 105 +/- 2. Inadequate treatment was defined essentially by repeated T4 concentrations less than 8 micrograms/dl during treatment. Thus, T4 values in the lower part of the normal range are probably incompatible with maximal intellectual development, and every effort should be exerted to maintain serum T4 levels in the upper half of the normal range during the first year of life.

Thyroid Activity of Selected, Nonselected, and Dwarf Broiler Lines

Growth rates and serum thyroid hormone concentrations were compared in two trials. In Trial 1 Athens-Canadian (AC) randombred chickens (nonselected) were compared with commercial broiler line chickens (selected). Trial 2 involved the same nonselected and selected lines and a sex-linked dwarf line developed from the same background as the AC population.Selected line birds were heavier than nonselected line birds and nonselected line birds were heavier than dwarf line birds from 1 through 8 weeks of age. Overall, the selected line had lower 3,5,3′-triiodothyronine (T3) concentrations than the nonselected line. No significant differences in thyroxine (T4) concentrations were observed between selected and nonselected lines. The dwarf line had lower T3 and higher T4 concentrations than the other lines. The data suggest a lower rate of T4 deiodination in the dwarf line.

Presence of L-thyroxine and 3,5,3'-triiodo-L-thyronine in tissues from thyroidectomized rats.

Female rats were killed 15 days, 2 months, and 4 months after surgical thyroidectomy that was followed by injection of 100 microCi 131I. The concentrations of T3 and T4 were measured in tissues (liver, kidney, brain, heart, and hindleg muscle) specific RIAs. Results were compared to those found in intact rats. Thyroidectomy resulted in severe hypothyroidism by 2 and 4 months after the operation, as assessed by undetectable levels of T4 and T3 in unextracted plasma, high circulating TSH, hypothermia, stasis of body weight increase, and depletion of pituitary GH content. Concentrations of T4 and T3 in plasma, as determined after extraction and concentration, were very low, being less than 5% of the normal value by the earliest observation period (15 days). In contrast, although tissue concentrations and total organ contents also decreased after thyroidectomy, they were still clearly detectable 4 months after thyroidectomy. The rates of decrease of T4 and T3 concentrations in most tissues were markedly slower than expected from their rapid decrease in plasma. Some tissues still contained 20% of the normal level 2-4 months after ablation of the thyroid. Tissue levels of thyroid hormones were hardly detectable in rats thyroidectomized 6 months before, having decreased in most tissues to less than 5% of the normal value. Several animals from this group had died. It is concluded that tissues from severely hypothyroid thyroidectomized rats may contain higher concentrations of T4 and T3 than previously thought. The idea that thyroid hormone is not essential for life, based on the assumption that thyroidectomized animals survive without thyroid hormones, might have to be reevaluated.

Serum somatomedin stimulation in thyroxine-treated hypophysectomized rats.

Somatomedin activity in rat serum was measured by sulfate incorporation into embryonic chick cartilage. Hypophysectomized male rats were treated daily for 21 days with 20 microgram/kg L-thyroxine (T4) and/or 25 microgram bovine (b) GH. Serum from rats given T4 alone or with bGH had somatomedin potencies of 0.88 and 0.83, respectively, comparable to normal serum (1.00) and significantly greater than serum from bGH-treated hypophysectomized rats (0.62). Hypophysectomized rats had no measurable somatomedin activity. T4 treatment resulted in a return to normal of the basal metabolic rate and serum T4 and T3 concentrations. Addition of T4 or T3 to serum from normal rats to produce concentrations comparable to those found in serum of hypophysectomized rats after T4 and/or bGH treatment did not alter the somatomedin activity. Higher concentrations of T4 (10(-7) M) or T3 (10(-8) or 10(-7) M) did, however, enhance the sulfation potency of normal serum. T4 (10(-9) M to 10(-6) M) or T3 (10(-10) M to 10(-7) M) added to serum-free medium provided minimal sulfation activity that represented only a fraction of the activity of serum. T4 may stimulate production of somatomedin in the absence of adequate bGH or may be metabolized to an active sulfation factor.

OBSERVATIONS CONCERNING THE THYROXINE-BINDING SITE OF PREALBUMIN IN HUMAN SERUM.

It has been suggested by other workers that prealbumin possesses 2 species of binding sites, one of which binds both thyroxine (T4) and tetraiodothyroacetic acid (TA4) and is inhibited by barbital, and the other of which binds only TA4 and is not affected by barbital. To test this hypothesis, 131I-labeled TA4 was synthesized from 131I-labeled T4 by rat kidney cortex incubated with serotonin. Binding of labeled TA4 and T4 in human serum was studied by the technique of filter paper electrophoresis in Tris-maleate buffer, pH 8.6. Relatively low concentrations of TA4 displaced tracer concentrations of T4 from prealbumin completely; in contrast, equimolar concentrations of T4 failed to displace tracer concentrations of TA4. Higher concentrations of T4, however, caused a progressive and ultimately an almost complete displacement of tracer concentrations of TA4 from prealbumin; this displacement conformed to a single linear function of the logarithm of the concentration of T4. In low concentrations, inhibitors of thyroxine-binding, such as barbital and 2,4-dinitrophenol, inhibited binding of T4 to prealbumin completely, but decreased the binding of TA4 only slightly. In higher concentrations, further inhibition of the binding of TA4 occurred, and, in the presence of 2,4-dinitrophenol, the molar concentration of TA4 displaced from prealbumin exceeded the maximum binding capacity for T4. The present data are inconsistent with the existence on prealbumin of 2 species of binding sites of distinctly different properties. They indicate, rather, that prealbumin possesses a single species of binding sites that binds TA4 more avidly than T4. (Endocrinology75: 917, 1964)