Hyperthyroidism due to excess thyrotropin secretion: follow-up studies.

To determine the value of the TRH test, we analyzed the unstimulated serum T(4) and TSH concentrations in 54 children with central hypothyroidism. A TRH test was performed in 30 patients. Midline brain defects (septo-optic dysplasia, 28; holoprosencephaly, 2) and combined pituitary hormone deficiencies were present in 30 and 52 patients, respectively. The mean serum free T(4), total T(4), and basal TSH concentrations were 0.6 ng/dl, 4.0 microg/dl, and 2.8 microU/ml, respectively. Five patients demonstrated elevated basal serum TSH concentrations. A normal TRH test [increase (delta) in TSH, 4.5-17.8], based on data from 30 controls, was documented in 23.3% of patients. Brisk (deltaTSH, >17.8), absent/blunted (deltaTSH, <4.5), and delayed responses were documented in 16.7%, 30%, and 30% of patients, respectively. The mean age at diagnosis was 2.8 yr, with 8 patients evolving into TSH deficiency. It was not possible to differentiate patients as having pituitary or hypothalamic disease based solely on the TRH test results. Patients with septo-optic dysplasia were diagnosed earlier and had elevated basal serum TSH and PRL concentrations, diabetes insipidus, and evolving disease. Although full pituitary function assessment is mandatory to identify combined pituitary hormone deficiencies, a TRH test is not essential, and the diagnosis should be made by serial T(4) measurements.

Hypothalamic-pituitary-thyroidal axis alterations in bulimic patients

Adult rats who had neonatal hyperthyroidism (NH) have reduced BW and serum T4, T3, and TSH concentrations. Pituitary TSH responses to TRH administration under basal, T4-suppressed, and propylthiouracil-stimulated conditions suggest that the thyrotroph of these animals is more sensitive to the feedback effects of thyroid hormones. These studies were undertaken to examine, with the use of various thyroid hormone-responsive variables, thyroid status of adult NH rats. NH was induced by 12 daily sc injections of T4 (0.4 microgram/g BW) to neonatal male Sprague-Dawley rats. Adult NH and control rats were then studied at 120 days of age. Adult NH rats had significantly decreased mean BW (P less than 0.001), and serum T4 (P less than 0.005), T3 (P less than 0.001), and TSH (P less than 0.001) concentrations. The percent decreases were 12% for T4, 20% for T3, and 27% for TSH in adult NH rats. Mean pituitary GH concentration and hepatic alpha-glycerophosphate dehydrogenase and malic enzyme activities were significantly decreased in adult NH rats to 54% (P less than 0.005), 52% (P less than 0.025), and 39% (P less than 0.001), respectively, of control values. Mean pituitary TSH concentrations were similar in adult NH and control rats. Mean hepatic T4 5'-deiodinase activity of adult NH rats [200 +/- (SE) 23 fmol T3/min X mg protein] was significantly decreased to 56% of control levels (355 +/- 31 fmol T3/min . mg protein; P less than 0.005). Mean pituitary T4 5'-deiodinase activity of adult NH rats (32.8 +/- 3.3 fmol T3/min . mg protein) was significantly increased compared with that of control rats (21.2 +/- 1.7 fmol T3/min . mg protein; P less than 0.025). These changes are consistent with a hypothyroid state in adult NH rats. The observation of decreased serum TSH concentration and enhanced thyrotroph sensitivity to thyroid hormones in the face of increased pituitary T4 5'-deiodinase activity suggests that increased thyrotroph monodeiodination of T4 may be the central biochemical aberration responsible for the hypothyroid state in adult NH rats.

Thyroid function was studied in a large number of subjects residing in Varsi, a town in the province of Parma, Italy. In this area, endemic goiter associated with moderate iodine deficiency [59 +/- 3 (+/- SE) microgram iodine/g creatinine], as defined by WHO criteria, affects 65% of the population. Serum T4, T3, thyroglobulin (Tg), and TSH concentrations were measured by RIA in 1218 subjects. The TSH response to TRH was determined in 108 subjects selected randomly from the groups with different grades of goiter. No significant change in serum T4 concentrations was found in subjects with different grades of goiter. Serum T3 concentrations were higher in subjects with the larger goiters. Serum Tg concentration progressively increased, and serum TSH progressively decreased with increasing goiter size. The TSH response to TRH was diminished in subjects with larger goiters. The findings of decreasing serum TSH concentrations and blunted TSH responses to TRH as goiter size increased suggest the possibility of autonomous thyroid function in the larger goiters in subjects residing in this area of moderate iodine deficiency.

Male Sprague-Dawley rats were given graded doses of methylmercaptoimidazole (MMI), propylthiouracil (PTU), KClO4 or KI in drinking water for 4 days, or the lowest effective dose of each drug for various times. The rats were sacrificed at 1--2 p.m. and serum T3, T4 and TSH concentrations were measured by radioimmunoassays. It was found that administration of 5 mg/l of MMI, 10 mg/l of PTU and 100 mg/l of KClO4 for 4--14 days induced a transient rise in serum TSH and a fall in serum T3 or T4 or in both. The effects of KI were not consistent. In another series of experiments, PTU (10 mg/l) was given in drinking water for 4 days, and then graded doses of T3 or T4 were given iv, or 100 ng of TRH was injected into a tail vein, or the animals were exposed to 4 degrees C for 30 min. The initial high TSH levels were further increased by TRH and cold and decreased by T3 and T4. The PTU-treated animals had goitres after 4 days. We infer that low doses, that is to say 10--100 times lower than previously described, of antithyroid drugs induce a hypothyroidism characterized by an increased TSH level and a decreased serum T3 or T4 level or both. A 4 days' treatment with PTU (40 mg/l in tap water) is a suitable tool for studying the effect of various conditions on TSH secretion.

The effects of repeated doses of oral cholecystographic agents on serum thyroxine (T4), 3,3',5-triiodothyronine (T3), 3,3',5'-triiodothyronine (rT3) and thyrotrophin (TSH) concentrations were studied in 37 euthyroid male subjects. Iobenzamic acid, tyropanoic acid, iopanoic acid, and ipodate sodium, in a dosage of 3 g for 3 days, respectively, induced a significant decrease in serum T3 and an increase in rT3 within 24 h after the initial dose, followed by an increase in TSH and a slight increase in T4. The extent of the changes in rT3 varied between the agents, ipodate causing the greatest change, but without any relation to the changes in T3 or T4. Responses of serum T4, T3, rT3 and TSH concentrations to exogenous thyrotrophin-releasing hormone (TRH) and bovine TSH were also studied before and after 3-day doses of iopanoic acid. In 11 subjects given iopanoic acid, the response to TSH to TRH (500 micrograms, iv) was increased but the T3 response was unchanged. A dose of TSH (10 U.S.P. units, im) caused a significant increase in serum T3 and a decrease in TSH concentrations in 5 subjects both before and after cholecystography. It is thus suggested that in euthyroid subjects given multiple doses of oral cholecystographic agents, (1) the primary and consistent events are the reciprocal changes of serum T3 and RT3, although the extent of the changes is not coordinately reciprocal; (2) the responsiveness of the pituitary thyrotrophs and thyroid to TRH is preserved; and (3) the high basal and TRH-induced TSH in the serum may be ascribed to the decrease in the serum T3 concentration.

Ten healthy adult male sheep aged about 1 year old were randomly allocated into two equal groups of control (no treatment group, n = 5) and experiment (n = 5). The two groups were kept under the same conditions of food and environment. Sheep of experimental group received MnSO4, H2O (5 mg/kg/day, SC) from day 0 for 8 weeks. Blood sampling of the two groups were done on days 0, 14, 28, 42, 56, and 70 at 11 a.m. Serum T4, T3, FT3, FT4, TSH, manganese, creatinine, and blood urea nitrogen concentrations were measured. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and serum alkaline phosphatase (ALP) activities were estimated by conventional methods. Serum and urine GGT activities were also measured. Urine samples were tested by urine dipstick analysis. Results indicated that serum manganese concentration was increased significantly on days 14, 28, 42, 56, and 70 of manganese administration (p < 0.05). The changes in serum enzyme activities ALP, GGT, AST, ALT, and urea and creatinine concentrations during these days were not significant. Changes of urine GGT activity were not significant. Serum TSH, FT3, FT4, T3, and T4 concentrations decreased differently on days 14, 28, 42, and 56 (p < 0.05). Urinalysis by urine dipstick analysis was normal.

T4-5'-monodeiodination in pituitary fragments and liver homogenates, serum thyroid hormones, an index of serum thyroid hormone protein binding, and serum TSH were measured in rats aged 2-72 days. Serum T4, T3, and TSH concentrations were lower in the 2-, 4-, and 9-day-old rats than in adult rats. The serum thyroid hormone-binding index was highest in neonatal rats, fell to a nadir at 21 days, and rose thereafter. The intrapituitary T4-5'-monodeiodination rate was 3.5 times the 72-day value in 2- and 4-day-old rats and fell to the 72-day value by 30 days of age. T4-5'-monodeiodination rates in liver homogenates were lower than the adult values in 2-, 4-, and 9-day-old rats, reaching the adult value in 21-day-old rats. When 5 mM dithiothreitol were included in the liver homogenate incubations, the absolute T4-5'-monodeiodination rates were increased, and the differences among 2-, 4-, 9-, 21-, and 72-day-old rats were abolished. Increased rates of intrapituitary T4-5'-monodeiodination may, in part, account for lower serum TSH concentrations in neonatal rats than in adults despite the lower serum T4 concentrations in the former. The differences between changes in pituitary and liver T4-5'-monodeiodination during maturation provide further evidence for local rather than systemic regulation of this reaction.

In order to investigate the role of thyrotropin (TSH) in goiter development and maintenance, the serum TSH concentration, the TSH response to thyrotropin-releasing hormone (TRH), and the increase in serum T3 after TRH were measured in 51 normal subjects and in 65 euthyroid patients with idiopathic nontoxic goiter. Fifteen patients had diffuse goiter, 47 multinodular goiter, and 3 an enlarged gland with a single non-functioning nodule. Serum thyrotropin (TSH) concentrations differed significantly in the two groups, the 95% range of the normal subjects was <0.2–2.0 μU/ml, and of the goitrous patients <0.2–4.5 μU/ml, 17 of whom (26%) had TSH values above the normal range (>2.0 μU/ml). There was no correlation between TSH concentrations and nodularity of goiters. Stimulation with TRH was performed in 52 patients and 39 normal subjects. Patients with basal serum TSH values >0.5 (μU/ml had increases in serum TSH after TRH exceeding those of the controls. However, 1/15 patients with diffuse goiter and 10/37 with nodular goiter had impaired or absent TSH responses to TRH. This finding may be a sign of functional autonomy. The normal subjects and the patients showed the same T3 response to TSH during the TRH test, and the T3 response was significantly correlated with the TSH increase after TRH. This was tentatively interpreted as indicating similar sensitivity to TSH in normal subjects and goitrous patients. However, it is not known whether T3 and growth responsiveness to TSH are associated. It is concluded that goiter development was probably TSH dependent in about one-fourth of the patients. In the majority of cases goiter maintenance and growth seemed not to be TSH dependent at the time of study.

The present study was carried out to evaluate the effectiveness of intramuscular administration of methyl-TRH, a potent analogue of thyrotropin-releasing hormone, for assessing pituitary reserve of TSH and prolactin and for distinguishing euthyroid, hypothyroid and hyperthyroid individuals. Serum samples were taken for 24 hours after intramuscular injection of methyl-TRH, 200 microgram, in 19 euthyroid subjects, 9 hypothyroid men and 9 hyperthyroid men. The mean serum prolactin and TSH concentrations were significantly elevated over baseline levels at 30 min in the euthyroid individuals and remained elevated for 3 to 4 hours. The serum TSH, T3 and T4 responses after intramuscular methyl-TRH in euthyroid subjects were clearly distinguishable from those of hyperthyroid and hypothyroid patients. Significant elevation of the serum T3 and T4 concentrations at 24 hours after intramuscular injection of methyl-TRH shows the sustained effect of this TRH analogue in euthyroid subjects.

A sensitive and specific radioimmunoassay for rat thyrotropin (TSH) has been developed which utilizes 125I-mouse thyrotropic tumor TSH, antibovine TSH serum and USP bovine TSH as a standard. TSH in serum and pituitary homogenates was found in fractions corresponding to those previously shown to contain biological activity after gel filtration on Sephadex G-200. Serum TSH in normal rats after decapitation ranged from 15 to 66 μU/ml. During pentobarbital anesthesia, serum TSH was significantly lower (10–37 /μU/ml). Mean normal rat pituitary TSH content was 44 mU/gland. After 50μg thyroxine (T4) every other day for 14 days, serum TSH became undetectable (<6 μU/ml) in 5 of 7 rats, and pituitary content fell to 25 % of normal. Chronic propylthiouracil (PTU) treatment resulted in a progressive increase in serum TSH over a 12-week period. Pituitary TSH content, however, was below normal after 3 weeks of PTU, but rose progressively thereafter to exceed normal at 12 weeks. Following intravenous administration of t...

Serum T4, T3, rT3, free T4, free T3 and TSH were measured during and after normal pregnancy in 20 women. Special methodological precautions were taken to avoid interference of other hormones and protein alterations in the assays. Serum T4 and T3 were steadily increasing during the last part of the 1st trimester, and remained high and nearly stable during the 2nd and 3rd trimester of the gestation period. The high levels were approximately 1.5 times the values measured 10 weeks post-partum. Serum rT3 was elevated already during the last part of the 1st trimester and remained high throughout pregnancy, compared to the post-partum value. Serum free T4 and free T3 were slightly elevated in early pregnancy. The values decreased gradually during pregnancy and were slightly depressed during the 3rd trimester. A gradual increase in serum TSH was observed during pregnancy and the 2nd and 3rd trimester values were significantly higher than the post-partum value. The mean values for serum TSH, free T4 and free T3 remained always well within the normal range. Thus small variations in serum free iodothyronines and TSH occur during normal pregnancy, the alterations observed in the last trimester of the gestation period resembling those of a slight thyroid insufficiency. These trends in variation of the reference values are worth to remember in the diagnosis of borderline hypo- or hyperthyroidism and in the balanced treatment of pregnant women with thyroid dysfunction.

What is the central question of this study? The relationship between the thyroid system and sleep deprivation has seldom been assessed in the literature, and mounting evidence exists that sleep disturbances influence human lifestyles. The aim of this study was to investigate the hypothalamic-pituitary-thyroid axis and thyroid hormone metabolism in sleep-deprived and sleep-restricted rats. What is the main finding and its importance? Central hypothyroidism and high thyroxine (T4 ) to 3,5,3'-triiodothyronine (T3 ) activation in brown adipose tissue were observed following sleep deprivation. Sleep-restricted rats exhibited normal thyroid-stimulating hormone and T4 concentrations despite increased circulating T3 . Sleep recovery for 24 h did not normalize the high T3 concentrations, suggesting that high T3 is a powerful counterregulatory mechanism activated following sleep deprivation. Modern life has shortened sleep time, and the consequences of sleep deprivation have been examined in both human subjects and animal models. As the relationship between thyroid function and sleep deprivation has not been fully investigated, the aim of this study was to assess the hypothalamic-pituitary-thyroid axis and thyroid hormone metabolism following paradoxical sleep deprivation (PSD) and sleep restriction (SR) in rats. The effects of a 24 h rebound period were also studied. Male Wistar rats (200-250 g, n = 10 per group) were subjected to sleep deprivation via the modified multiple platform method. Rats were assigned to the following seven groups: control, PSD for 24 or 96 h, 24 or 96 h of sleep deprivation with rebound (PSD24R and PSD96R), SR for 21 days (SR21) and SR21 with rebound (SR21R). Blood samples were collected to determine the 3,5,3'-triiodothyronine (T3 ), thyroxine (T4 ) and thyroid-stimulating hormone concentrations. Brown adipose tissue iodothyronine deiodinase type 2 (D2) activity was also evaluated. Body weight gain was dramatically reduced (by ∼50-100%) in all sleep-deprived and sleep-restricted rats; rebound restored this parameter in only the PSD24R group. The serum TSH and T4 concentrations decreased, whereas T3 increased in both the PSD24 and PSD96 groups compared with control animals (P < 0.05). Only PSD24R and PSD96R normalized T4 and thyroid-stimulating hormone concentrations, respectively, independently of the higher circulating T3 concentrations (∼20-30%) noted in all groups compared with control animals (P < 0.05). Brown adipose tissue D2 activity increased in the PSD 24 and 96 h groups (∼10 times), and PSD24R was more effective than PSD96R at restoring basal brown adipose tissue D2 activity. Our data suggest that thyroid hormone metabolism adapts to sleep deprivation-induced hypothalamic-pituitary-thyroid alterations and increases T4 to T3 activation peripherally, thereby increasing circulating T3 in rats.

1. Serum levels of TSH, thyroxine (T4) and triiodothyronine (T3) have been measured during treatment and follow-up of patients with thyroid carcinoma. 2. Serum TSH and thyroid hormone levels were initially normal. Three weeks after total thyroidectomy, TSH was elevated in about 50% of patients and after a subsequent therapy dose of 131I it exceeded 30 mU/l in 90% of patients. Occasionally, TSH did not rise until after the second dose of 131I. Low serum T4 and T3 concentrations were associated with the increase of TSH. 3. Withdrawal of l-thyroxine replacement treatment in athyreotic patients for four weeks before test doses of 131I, led to falls of serum T4 and T3 concentration and a progressive rise of serum TSH after the first weeks but there was considerable variation in the final level reached. In the majority, values greater than 30 mU/l were attained despite some patients having received l-thyroxine for many years. A few patients on prolonged thyroxine maintenance had little or no increase in TSH despite considerable reduction in serum T4 and T3 concentrations. 4. The 131I concentration (muCi/g) developed in tumour tissue was also examined in relation to the serum TSH level. In general a tumour should not be considered as incapable of concentrating 131I adequately until serum TSH levels have exceeded 30 mU/l.

Effects of Phenobarbital on Hypothalamic-Pituitary-Thyroid Axis in the Rat