Plasma Thyrotropin Research Articles

Replacement therapy for hypothyroidism with thyroxine alone does not ensure euthyroidism in all tissues, as studied in thyroidectomized rats.

We have studied whether, or not, tissue-specific regulatory mechanisms provide normal 3,5,3'-triiodothyronine (T3) concentrations simultaneously in all tissues of a hypothyroid animal receiving thyroxine (T4), an assumption implicit in the replacement therapy of hypothyroid patients with T4 alone. Thyroidectomized rats were infused with placebo or 1 of 10 T4 doses (0.2-8.0 micrograms per 100 grams of body weight per day). Placebo-infused intact rats served as controls. Plasma and 10 tissues were obtained after 12-13 d of infusion. Plasma thyrotropin and plasma and tissue T4 and T3 were determined by RIA. Iodothyronine-deiodinase activities were assayed using cerebral cortex, liver, and lung. No single dose of T4 was able to restore normal plasma thyrotropin, T4 and T3, as well as T4 and T3 in all tissues, or at least to restore T3 simultaneously in plasma and all tissues. Moreover, in most tissues, the dose of T4 needed to ensure normal T3 levels resulted in supraphysiological T4 concentrations. Notable exceptions were the cortex, brown adipose tissue, and cerebellum, which maintained T3 homeostasis over a wide range of plasma T4 and T3 levels. Deiodinase activities explained some, but not all, of the tissue-specific and dose related changes in tissue T3 concentrations. In conclusion, euthyroidism is not restored in plasma and all tissues of thyroidectomized rats on T4 alone. These results may well be pertinent to patients on T4 replacement therapy.

Temporal link between plasma thyrotropin levels and electroencephalographic activity in man

Plasma thyrotropin (TSH) levels have been previously shown to be associated with the internal sleep structure determined by conventional scoring of sleep stages. This temporal relationship was re-evaluated using spectral analysis of the sleep electroencephalogram (EEG). Eight healthy male subjects underwent two randomized night studies after having received either placebo or 5 mg ritanserin, a selective 5-HT 2 receptor antagonist known to increase slow-wave sleep. Delta relative power and TSH levels, determined at 10 min intervals, were found to be inversely related with an average cross-correlation coefficient highly significant ( P < 0.0001) in both experimental conditions. Alpha slow-wave index, an estimator of awakenings, and TSH pulses exhibited a significant temporal association in both conditions. These results demonstrate that TSH fluctuations are linked to the sleep EEG activity in man.

Effects of antidepressants on thyroid stimulating hormone release in rats under ether stress.

We found inhibitory effects of antidepressants (clomipramine, maprotyline, mianserin and zimelidine) and 5-hydroxytryptophan (5-HTP) on thyroid stimulating hormone (TSH) release induced by ether stress in freely moving rats. We confirmed that ether stress suppressed the plasma TSH levels after 30 min. We then injected intravenously 250 ng thyrotropin releasing hormone (TRH), 0.1 mg/kg clomipramine, 2.5 mg/kg maprotyline, 2.5 mg/kg mianserin, 0.5 mg/kg zimelidine and 25 mg/kg 5-HTP simultaneously. These materials blocked the influences on plasma TSH levels by the ether stress. Serotonergic antidepressants (clomipramine, zimelidine) and 5-HTP (precursor of serotonin) had a higher potency against the ether stress. These results suggest that antagonizing effects against the ether stress may involve the serotonergic system in the pituitary gland.

Body temperature and thyroid hormone metabolism of copper-deficient rats

The hypothesis that the effects of copper deficiency on body temperature are mediated via the thyroid hormone system was examined in 24 male Sprague-Dawley rats, weighing 240 to 250 g, matched by weight and fed ad libitum diets containing adequate (78.7 μmol/kg), marginal (31.5 μmol/kg), or deficient (<7.9 μmol/kg) amounts of copper for 35 days. Anemia was not found in the copper-restricted groups. Plasma cholesterol concentrations increased (P < 0.05) and plasma copper, ceruloplasmin, and liver copper concentrations decreased (P < 0.05) in the rats fed the copper-restricted diet as compared with the copper-adequate diet. Cytochrome c oxidase and glutathione peroxidase activities in liver and brown adipose tissue were decreased (P < 0.05) in the copper-deprived rats. Body temperatures at 24 °C were less (P < 0.05) in the severely copperdeficient as compared with the moderately copper-deficient and copper-adequate animals. Plasma thyroxine concentrations were decreased (P < 0.05) in severely copper-deficient as compared with moderately copperdeficient and copper-adequate rats. Plasma tri-iodothyronine concentrations were reduced (P < 0.05) and plasma thyroid-stimulating hormone concentrations were elevated (P < 0.05) in both groups of copper-restricted rats relative to the copper-adequate rats. Thyroxine 5′-monodeiodinase activities in liver and brown adipose tissue were decreased (P < 0.05) in the copper-restricted animals. Hepatic triiodothyronine receptors were increased (P < 0.05) by dietary copper restriction. Body fatness was greater (P < 0.05) in copper-restricted as compared with copper-adequate rats. These findings indicate that copper deficiency without anemia decreases tissue copper and selenium status and is associated with impaired thyroid hormone metabolism and mild hypothermia in rats at maintained at 24 °C. (J. Nutr. Biochem. 6:445-451, 1995.)

The Yin-Yang Model of TSH Regulation: Disappearance of Triiodothyronine Inhibition on the Response of Plasma Thyrotropin to Thyrotropin-Releasing Hormone in Aged Male Rats

The inhibitory effects of thyroid hormones on the release of thyrotropin (TSH) in response to thyrotropin-releasing hormone (TRH) in old and young male rats were examined. Old (21 months) and young (3 months) male rats were challenged with TRH (10 μg/kg) and/or triiodothyronine (0-1 μg/kg) via right jugular vein catheters. Blood was collected at 0, 10, 40 and 60 min following intravenous injection of TRH. One day after in vivo study, all rats were decapitated. The anterior pituitary glands (APs) were excised, bisected and incubated with TRH (10 nM) and T3(10^(-8)-10^(-5)M) at 30 min intervals. Finally, all APs were incubated with 60mM KC1 for checking the viability. At the end of incubation, the medium samples were collected and the tissues were weighed. The concentration of TSH in plasma and medium samples was measured by radioimmunoassay, The spontaneous and TRH-stimulated levels of TSH both in vivo and in vitro were not altered by aging. The inhibitory effect of T3 on the plasma TSH levels in response to TRH was dose-dependent in young, but was not significant in old rats. The in vitro release of TSH in response to TRH was dose-dependently inhibited by the administration of T3 in both old and young male rats. These results suggest that the disappearance of T3 inhibition on the response of plasma TSH to TRFI in old male rats is independent of T3 action on the anterior pituitary gland.

Interleukin-1 receptor blockade does not affect endotoxin-induced changes in plasma thyroid hormone and thyrotropin concentrations in man.

Interleukin-1 (IL-1) has been implicated as a mediator of the euthyroid sick syndrome. The effects of IL-1 can be blocked by the naturally occurring IL-1 receptor antagonist (IL-1ra). In the present study, iv administration of endotoxin was used as a human model of the euthyroid sick syndrome. To assess the role of endogenous IL-1 in endotoxin-induced changes in plasma thyroid hormone and TSH concentrations, 18 healthy postabsorptive humans were studied on a control study day, followed 3 days later by a study day on which they were randomly assigned to one of three treatments: a 6-h infusion of recombinant human IL-1ra alone (133 mg/h), endotoxin alone (lot EC-5; 20 U/kg), or both endotoxin and IL-1ra. Administration of IL-1ra alone did not affect the plasma concentrations of thyroid hormones or TSH compared with those on the control day. Endotoxin injection was associated with decreases in T4 (P = 0.06 vs. the control day), free T4 (P = 0.02), T3 (P < 0.001), and TSH (P < 0.0001) and a rise in rT3 (P < 0.001), reproducing the major features of the euthyroid sick syndrome. Coinfusion of IL-1ra did not influence these endotoxin-induced changes. Our results suggest that endogenous IL-1 does not play an important role in the alterations in plasma thyroid hormone and TSH concentrations induced by mild endotoxemia in healthy humans.

Stress-induced inhibition of the hypothalamic-pituitary-thyroid axis is attenuated in the aged Fischer 344/N male rat.

Aging is associated with a progressive decrement in the basal activity of the hypothalamic-pituitary-thyroid axis in male Fischer 344/N rats. The aim of this study was to determine whether stress influences the activity of this axis in young and old rats. As prolactin and growth hormone share some regulatory mechanisms with thyrotropin-releasing and thyroid-stimulating hormones, which are influenced by stress, the plasma levels of these two hormones were also determined during immobilization (Immo). To accomplish this, young (3-month-old) and old (23-month-old) male 344/N Fischer rats were immobilized for 2 h; blood was collected by cannulation from the tail artery at different intervals during Immo (0, 5, 30, 60, and 120 min), and brains were removed at the end of Immo. The basal plasma levels of thyroid-stimulating hormone were similar in both groups, but were significantly and progressively inhibited by Immo in young, but not in old rats. The baseline plasma levels of total triiodothyronine were slightly lower in old than in young rats; Immo caused a significant decrease of total triiodothyronine levels only in the young animals. The baseline plasma levels of free triiodothyronine were similar and were not altered by Immo in either age group. The paraventricular nucleus thyrotropin-releasing hormone mRNA levels were lower in old than in young rats under basal conditions; under stress they were significantly inhibited in young, but remained unchanged in old rats. The basal thyroid-stimulating hormone beta mRNA levels in the anterior pituitary were significantly lower in old than in young rats, but were not affected by Immo in either age group. The plasma prolactin levels were similar at baseline and were significantly increased by Immo in both age groups, but significantly more in old than in young rats. The plasma growth hormone levels were also similar at baseline; they were significantly decreased by Immo to a similar extent in both age groups. In summary, these data indicate that the stress-induced decrease in plasma thyroid-stimulating hormone is in part mediated at the level of the hypothalamic thyrotrophin-releasing hormone neuron and that this phenomenon is attenuated in the aged rat.

Role of progesterone in regulating the effect of estradiol on the secretion of thyrotropin-releasing hormone and dopamine into hypophysial portal blood in ovariectomized rats.

In this study, an investigation was undertaken regarding the effects of estradiol and progesterone on the secretion of thyrotropin-releasing hormone (TRH) and dopamine into hypophysial portal blood and on the concentrations of arterial plasma thyroid-stimulating hormone (TSH) and prolactin (PRL) in ovariectomized (Ovx) rats. Ovx rats were injected subcutaneously with either estradiol benzoate (25 micrograms/kg BW/day) or progesterone (10 or 50 mg/kg BW/day), or both estradiol benzoate and progesterone daily for 3 days. The control group was injected with sesame oil. The hypophysial portal blood was collected and mixed either with or without 2,3-dimercaptopropanol before extraction by methanol for measuring TRH or by perchloric acid for measuring dopamine. The femoral arterial blood was also collected. The concentrations of TRH in hypophysial portal plasma and that of PRL and TSH in femoral arterial plasma were measured by radioimmunoassay. The concentrations of catecholamine in portal plasma were measured by radioenzymatic assay. Concomitant estradiol benzoate and progesterone caused a dose-dependent increase in TRH concentration in portal plasma and that of PRL in arterial plasma in Ovx rats. Progesterone alone did not alter the concentration of portal plasma TRH and the concentration of arterial plasma PRL, but rather increased the concentrations of dopamine in the hypophysial portal plasma. These above results indicated that the increase in plasma PRL and TSH levels is associated with a rise in hypophysial portal plasma dopamine and TRH following injection of both progesterone and estradiol benzoate. We can conclude that stimulation of progesterone on the secretion of hypothalamic TRH is involved in the increase in plasma PRL following concomitant treatment of estradiol.

Effects of thyroid hormone deiodination on regulation of thyroid axis in undernourished rats

The possible influence of hypothalamic and pituitary 5'-deiodinase II (5'-D-II) activity and 3,5,3'-triiodothyronine (T3) content on the modulation of thyroid-stimulating hormone (TSH) synthesis was studied. 1) Alterations in 5'-D-II activity and hypothalamic and pituitary T3 content produced by undernutrition were observed in fetal (21 days) and neonatal rats vs. controls. 2) After thyroidectomy, plasma TSH increased in both populations, undernourished and control, but pituitary TSH increased only in the former and not in the latter. The results obtained by giving small doses of thyroxine (T4; 0.5 micrograms/100 g body wt) to intact and thyroidectomized rats suggest a lower inhibitory effect by T4 on the pituitary in undernourished than in control rats. Although hypothalamic and pituitary 5'-D-II activity increased in both groups after thyroidectomy, the percentage increase was lower in undernourished vs. control rats, resulting in lower overall T3 content in tissues from undernourished animals. These studies on thyroid axis regulation show the in vivo regulation of TSH synthesis by hypothalamic and pituitary 5'-D-II activity and T3 content.

Relationship of endocrinopathy to iron chelation status in young patients with thalassaemia major.

Disturbances of growth and development in patients with thalassaemia receiving hypertransfusion programmes are well recognised and are most likely to be due to iron overload. The extent of endocrine dysfunction was investigated in a group of 18 patients thought to have been treated by acceptable modern standards, 11 of whom could be considered as well chelated. Assessment of growth and puberty showed a wide variation in height SD scores with five patients having significantly short stature. Most patients are progressing through puberty normally with the exception of two boys with marked pubertal delay. The most prominent finding was that growth hormone responses to glucagon stimulation were significantly impaired in all of the patients with iron overload. Basal endocrine assessment showed primary hypothyroidism in two patients aged 16.8 and 12.9 years with plasma thyroxine-concentrations of 86 and 59 nmol/l (normal range 65-165 nmol/l) and plasma thyroid stimulating hormone 10.2 and 30.3 mU/l (normal range 0.5-5 mU/l). One patient had diabetes mellitus. These results show that even when ideal management is sought a significant amount of endocrine damage occurs; surveillance of these patients is thus essential.

Demonstration of rapid light-induced advances and delays of the human circadian clock using hormonal phase markers.

To determine the magnitude and direction of phase shifts of human circadian rhythms occurring within 1 day after a single exposure to bright light, plasma thyrotropin, melatonin, and cortisol levels and body temperature were monitored for 38 h in 17 men who were each studied two times, once during continuous dim light conditions and once with light exposure. After a period of entrainment to a fixed sleep-wake cycle, a 3-h light pulse (5,000 lux) was presented under constant routine conditions, and the resultant phase shifts were measured, also under constant routine conditions, on the 1st day after pulse presentation. The phase shifts in response to light occurred within 24 h and were in the delaying direction for most of the nocturnal period, with the crossover to phase advances occurring approximately 1 h after the temperature minimum. Phase shifts averaged 1 h, with delays being larger than advances, and were achieved without significant changes in rhythm amplitude. The immediate response of the human circadian clock to a single 3-h light pulse is thus characteristic of "type 1" resetting.

Rapid Changes in Somatostatin and TRH mRNA in Whole Rat Hypothalamus in Response to Acute Cold Exposure

Acute cold stimulus induces activation of the thyreotropic axis characterized by a rapid increase in plasma thyrotropin (TSH). Since pituitary TSH release is mainly regulated by two hypothalamic hormones: thyrotropin-releasing hormone (TRH) and somatostatin, the aim of this study was to analyse whether changes in the steady state mRNA levels and peptide content of these neurohormones occur under acute cold stimulation in rats. Northern blot analysis of hypothalamic somatostatin mRNA levels after 15, 30, 60 or 180 min of cold exposure revealed a 2.0-fold increase after 15 min at 4 degrees C. This augmentation was followed by a return to control values at 30 min. However, the hypothalamic content of somatostatin was not significantly modified at any cold exposure time. TRH mRNA showed a similar pattern to somatostatin, with a 2.5-fold increase after 15 min at 4 degrees C. In contrast, hypothalamic TRH content was significantly decreased after 15 min cold exposure, returning to control values at 30 min. The increase in mRNA levels was specific for the two hypothalamic hormones, since there was no concomitant variation in GAPDH mRNA used as negative control. These results suggest that the organism is quickly aroused by cold stimulus, triggering rapid activation in transcription of the two neurohormones involved in the regulation of the thyreotrope axis. Since the peptide contents did not show the same pattern, a quantitative change in transcription or in mRNA stability does not appear to be a prerequisite for increased peptide expression, suggesting that somatostatin and TRH gene expressions could be regulated at translational or post-translational steps.

Interrelationship between thyroxine and estradiol on the secretion of thyrotropin-releasing hormone and dopamine into hypophysial portal blood in ovariectomized-thyroidectomized rats.

Effects of thyroxine (T4) on the secretion of thyrotropin-releasing hormone (TRH) and catecholamines into hypophysial portal blood and on the concentrations of arterial plasma thyroid-stimulating hormone (TSH) and prolactin (PRL) in ovariectomized and thyroidectomized (Ovx-Tx) rats were studied. Immediately after ovariectomy, rats were Tx or sham Tx. The Ovx-Tx rats were injected subcutaneously with estradiol benzoate (EB, 0.5 microgram/kg b.w.) or sesame oil, and T4 (20 micrograms/kg b.w.) or saline once daily for 2 weeks. The Ovx rats with intact thyroid gland were injected with saline and oil only. The hypophysial portal blood samples were collected and mixed with or without 2,3-dimercaptopropanol before extraction by methanol or perchloric acid, respectively. The femoral arterial blood was also collected. The concentrations of TRH in methanol-extracted portal plasma and that of TSH and PRL in arterial plasma were measured by radioimmunoassay. The concentrations of catecholamines in perchloric acid-extracted portal plasma samples were measured by radioenzymatic assay. Thyroidectomy in Ovx rats resulted in an increase in portal plasma TRH and arterial plasma TSH. Despite the presence or absence of estradiol, T4 replacement in Ovx-Tx rats decreased portal plasma TRH and arterial plasma TSH to euthyroid levels. Combination of the injection of T4 and EB in vivo caused significantly decreased levels of portal plasma dopamine and increased arterial plasma PRL compared with those in vehicle-injected Ovx-Tx animals. Concentrations of neither norepinephrine nor epinephrine in hypophysial portal plasma paralleled the altered concentrations of PRL or TSH in arterial plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenohypophyseal Vasoactive Intestinal Peptide and Neuropeptide Y Responses to Hypothyroidism Are Abolished after Anterolateral Deafferentation of the Hypothalamus

We examined whether hypothyroidism-induced increases in the anterior pituitary content of vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY) are mediated by the hypothalamus. Male Sprague-Dawley rats were anesthetized and one of the following surgeries was performed: (1) sham thyroidectomy, (2) thyroidectomy, (3) thyroidectomy plus surgical anterolateral deafferentation of the medial basal hypothalamus, or (4) thyroidectomy and sham deafferentation of the hypothalamus (knife was inserted but not rotated). Two weeks after surgery, animals were killed and tissue samples collected for measurement of the anterior pituitary VIP and NPY and plasma thyroid-stimulating hormone (TSH), thyroxine, and prolactin concentrations (by RIA). Reverse-phase HPLC showed that VIP and NPY immunoreactivities in the anterior pituitary extracts are eluted in the positions identical to synthetic VIP and NPY, respectively. Only data from those animals with complete symmetric cuts located at the posterior border of the optic chiasm were included for analysis. In the thyroidectomized rats the anterior pituitary contents of VIP and NPY were significantly increased. These responses were almost completely prevented by the anterolateral deafferentation of the hypothalamus. Sham hypothalamic deafferentation had no effect on the pituitary neuropeptide responses to hypothyroidism. Anterolateral deafferentation of the hypothalamus also significantly blunted plasma TSH responses to hypothyroidism. These data suggest that some hypothalamic factor is involved in the mediation of the effect of hypothyroidism on the pituitary content of VIP and NPY.

Plasma TSH, T3, T4 and cortisol responses to swimming at varying water temperatures.

The acute effect of 30-min swimming at a moderate speed, at three water temperatures (20, 26 and 32 degrees C) on plasma thyroid stimulating hormone (TSH), free thyroxine (F.T4), triiodothyronine (T3) and cortisol concentrations was studied in 15 élite male swimmers. Blood was sampled before and immediately after the events. The heart rate, which was continuously monitored during exercise, had the highest response at 32 degrees C and the lowest at 20 degrees C. Blood lactate concentrations were found to be similar after the three tests. Plasma TSH and F.T4 were found to be significantly increased (by 90.4% and 45.7% respectively) after swimming at 20 degrees C, decreased at 32 degrees C (by 22.3% and 10.1% respectively) and unchanged at 26 degrees C. Exercise at these three water temperatures did not significantly affect T3. Finally, plasma cortisol was found to be increased after swimming at 32 degrees C (by 82.8%) and 26 degrees C (by 46.9%), but decreased at 20 degrees C (by 6.1%).

Increased plasma thyroid stimulating hormone in treated congenital hypothyroidism: relation to severity of hypothyroidism, plasma thyroid hormone status, and daily dose of thyroxine.

Plasma thyroid stimulating hormone (TSH) concentrations obtained during the first four years of treatment in 418 children with congenital hypothyroidism, identified by neonatal screening, were examined in relation to paired measurements of plasma thyroxine (n = 1945), free thyroxine (n = 836), triiodothyronine (n = 480), and free triiodothyronine (n = 231), and estimated daily dose of thyroxine at the time of blood sampling. Overall, plasma TSH was above 7 mU/l in 1280 out of 2960 samples (43%); the percentage was not related to severity of hypothyroidism at diagnosis. Mean values for thyroxine and free thyroxine, and to a lesser extent free triiodothyronine, were consistently lower in samples with TSH concentrations over 7 mU/l and this was the case in patients with either severe or less severe hypothyroidism. Raised TSH concentrations were also associated with lower mean doses of thyroxine (micrograms/kg/day) but here the mean doses of thyroxine in children with severe hypothyroidism were higher than in the children with less severe hypothyroidism. The mean dose of thyroxine associated with low/normal TSH values was highest in the first 6 months and fell progressively. Thyroxine dose was significantly related to thyroxine and free thyroxine concentrations but not to triiodothyronine and free triiodothyronine and the latter appeared to be of limited value as measures of plasma thyroid hormone status during treatment.

Endocrine profile of catch-up growth in the cynomolgus monkey.

We studied catch-up growth following withdrawal of glucocorticoid administration in seven intact prepubertal cynomolgus monkeys. To reduce stress during blood sampling, a vascular access port was implanted subcutaneously in each animal for the duration of the study. After a baseline observation period of 50 weeks, the monkeys received injections of dexamethasone at a dose of 100 micrograms.kg-1.day-1 for 15 weeks. Growth velocity was monitored every 3 weeks by measuring lower leg length and body weight. Spontaneous serum growth hormone (GH) concentrations and GH levels after insulin and L-dopa stimulation, as well as serum insulin-like growth factor I (IGF-I) and plasma thyrotropin, triiodothyronine and thyroxine, were measured during the study. Differences between animals were analyzed by repeated measures analysis of variance and Student's paired t-test. Mean +/- SEM growth velocity (mm/3 weeks) decreased from 0.90 +/- 0.08 during the baseline period to 0.29 +/- 0.07 (p < 0.001) during the period of growth retardation, and increased to 1.23 +/- 0.2 (p < 0.001) during the period of catch-up growth. Spontaneous GH and peak GH levels following insulin did not show any significant variation during the study. Peak GH during the L-dopa test decreased from 15.4 +/- 3.2 micrograms/l during the baseline period to 6.2 +/- 2.4 micrograms/l during the period of growth retardation (p < 0.05), and increased to 23.0 +/- 5.9 micrograms/l during the period of catch-up growth (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Endogenous neuropeptide Y regulates thyroid blood flow.

Neuropeptide Y (NPY) is present in thyroid sympathetic nerve fibers. To assess the involvement of endogenous NPY in the regulation of thyroid function, a NPY antiserum was produced in a rabbit, characterized, and used for immunization of normal and hyperthyroid rats. Plasma thyroxine, thyroid-stimulating hormone (TSH), thyroidal, and other organ blood flows (BF) were measured in anesthetized (ketamine and pentobarbital sodium) male Sprague-Dawley rats at 1 h after intravenous administration of 1 ml of the antiserum, normal rabbit serum, or saline. Immunization against NPY had no effect on the plasma levels of thyroxine, TSH, or arterial blood pressure, but it significantly increased thyroidal BF in normal rats. In the hyperthyroid rats (treated with 5 micrograms.100 g body wt-.day-1 thyroxine for 6 days), the NPY antiserum reversed the hyperthyroidism-induced decrease in thyroid BF and significantly increased duodenal and testicular BF values, but it did not alter BF values in four other organs. These results indicate that endogenous NPY regulates thyroid BF in normal rats. They also provide an example of NPY involvement in the pathophysiological adjustment of some organs to hyperthyroidism.

Bromine and thyroid hormone activity.

To examine the possible consequences of high plasma concentrations of bromine on thyroid hormone. Bromine was measured by inductively coupled plasma mass spectrometry in the plasma of 799 patients consulting for thyroid disorders. Because the mean (SD) bromine concentration in the plasma of healthy subjects is 4 (1) mg/l, concentrations above 6 mg/l were regarded as outside the normal range. Bromine, free thyroxine (FT4), and thyroid stimulating hormone (TSH) values were compared. The percentage of patients with normal, low, and high FT4 and TSH plasma activities, measured separately, did not differ between patients with low and high bromine concentrations. The percentage of patients with high TSH but normal FT4 values was significantly higher in the group with bromine values of more than 6 mg/l than in the group with bromine concentrations below this (p < 0.02). An increase in plasma bromine could potentiate an increase in plasma TSH concentration, probably as a consequence of a minor inhibitory effect on thyroid activity.

Relationships between the thyroid and somatotropic axes in steers II: Effects of thyroid status on plasma concentrations of insulin-like growth factor I (IGF-I) and the IGF-I response to growth hormone

Three studies assessed the effect of thyroid status on regulation of plasma IGF-I in cattle. First, four Angus-Hereford steers (av wt 345 kg) were fed 4 mg/d propylthiouracil daily for 35 d. With continued feeding of PTU steers were sequentially injected with thyroxine (T 4, 5 mg/d, IM for 5 d) followed by triiodothyronine (T 3, 2 mg/d, IM for 5 d). An injection of bovine pituitary growth hormone (GH, 0.1 mg/kg, IM) was given to each steer on day 35 of PTU, day 5 of T 4 and again on day 5 of T 3. PTU alone increased plasma thyroid stimulating hormone (TSH), decreased plasma T 4 and T 3 but had no influence on IGF-I. T 3, but not T 4, lowered plasma TSH, IGF-I and IGF-I response to GH (P<.05). Next, twelve bull calves (av wht 167 kg) were divided equally into two groups. A control group was injected daily for five d with buffered saline; the experimental group was concurrently treated with T 3 (5 mg/d, sc) for five d. Beginning the sixth day, all calves were injected with GH (0.1 mg/kg, IM daily) for three d with the respective buffer or T 3 treatments continuing. Plasma IGF-I was depressed 29% by T 3. The incremental area under the three-d response curve was less (P<.03) in T 3 cattle. A growth trial was conducted in which twenty-four Angus × Hereford steers were injected daily with T 3 (2 mg/kg, bi-daily × 56 d) or implanted with Synovex-S (S) in a 2 × 2 factorial arrangement. Synovex increased empty body protein gain (EBPG) and plasma IGF-I 15.5 and 27.9% (P<.01), respectively; T 3 decreased EBPG and plasma IGF-I 13.9 and 15.1% (P<.07), respectively, in steers which maintained suppression in plasma TSH. The data support the conclusion that elevated T 3 decreases plasma IGF-I, in part, through a diminished GH-responsiveness and anabolic treatments such as S can reverse the effects of excess T 3.