Plasma Thyrotropin Research Articles

Assessment of Thyroid Function in Dogs with Low Plasma Thyroxine Concentration

Differentiation between hypothyroidism and nonthyroidal illness in dogs poses specific problems, because plasma total thyroxine (TT4) concentrations are often low in nonthyroidal illness, and plasma thyroid stimulating hormone (TSH) concentrations are frequently not high in primary hypothyroidism. The serum concentrations of the common basal biochemical variables (TT4, freeT4 [fT4], and TSH) overlap between dogs with hypothyroidism and dogs with nonthyroidal illness, but, with stimulation tests and quantitative measurement of thyroidal 99mTcO4(-) uptake, differentiation will be possible. In 30 dogs with low plasma TT4 concentration, the final diagnosis was based upon histopathologic examination of thyroid tissue obtained by biopsy. Fourteen dogs had primary hypothyroidism, and 13 dogs had nonthyroidal illness. Two dogs had secondary hypothyroidism, and 1 dog had metastatic thyroid cancer. The diagnostic value was assessed for (1) plasma concentrations of TT4, fT4, and TSH; (2) TSH-stimulation test; (3) plasma TSH concentration after stimulation with TSH-releasing hormone (TRH); (4) occurrence of thyroglobulin antibodies (TgAbs); and (5) thyroidal 99mTcO4(-) uptake. Plasma concentrations of TT4, fT4, TSH, and the hormone pairs TT4/TSH and fT4/TSH overlapped in the 2 groups, whereas, with TgAbs, there was 1 false-negative result. Results of the TSH- and TRH-stimulation tests did not meet earlier established diagnostic criteria, overlapped, or both. With a quantitative measurement of thyroidal 99mTcO4(-) uptake, there was no overlap between dogs with primary hypothyroidism and dogs with nonthyroidal illness. The results of this study confirm earlier observations that, in dogs, accurate biochemical diagnosis of primary hypothyroidism poses specific problems. Previous studies, in which the TSH-stimulation test was used as the "gold standard" for the diagnosis of hypothyroidism may have suffered from misclassification. Quantitative measurement of thyroidal 99mTcO- uptake has the highest discriminatory power with regard to the differentiation between primary hypothyroidism and nonthyroidal illness.

Assessment of Thyroid Function in Dogs with Low Plasma Thyroxine Concentration

Background: Differentiation between hypothyroidism and nonthyroidal illness in dogs poses specific problems, because plasma total thyroxine (TT4) concentrations are often low in nonthyroidal illness, and plasma thyroid stimulating hormone (TSH) concentrations are frequently not high in primary hypothyroidism.Hypothesis: The serum concentrations of the common basal biochemical variables (TT4, freeT4[fT4], and TSH) overlap between dogs with hypothyroidism and dogs with nonthyroidal illness, but, with stimulation tests and quantitative measurement of thyroidal99mTcO4‐uptake, differentiation will be possible.Animals: In 30 dogs with low plasma TT4concentration, the final diagnosis was based upon histopathologic examination of thyroid tissue obtained by biopsy. Fourteen dogs had primary hypothyroidism, and 13 dogs had nonthyroidal illness. Two dogs had secondary hypothyroidism, and 1 dog had metastatic thyroid cancer.Methods: The diagnostic value was assessed for (1) plasma concentrations of TT4, fT4, and TSH; (2) TSH‐stimulation test; (3) plasma TSH concentration after stimulation with TSH‐releasing hormone (TRH); (4) occurrence of thyroglobulin antibodies (TgAbs); and (5) thyroidal99mTcO4‐uptake.Results: Plasma concentrations of TT4, fT4, TSH, and the hormone pairs TT4/TSH and fT4/TSH overlapped in the 2 groups, whereas, with TgAbs, there was 1 false‐negative result. Results of the TSH‐ and TRH‐stimulation tests did not meet earlier established diagnostic criteria, overlapped, or both. With a quantitative measurement of thyroidal99mTcO4‐uptake, there was no overlap between dogs with primary hypothyroidism and dogs with nonthyroidal illness.Conclusions and Clinical Importance: The results of this study confirm earlier observations that, in dogs, accurate biochemical diagnosis of primary hypothyroidism poses specific problems. Previous studies, in which the TSH‐stimulation test was used as the “gold standard” for the diagnosis of hypothyroidism may have suffered from misclassification. Quantitative measurement of thyroidal99mTcO‐uptake has the highest discriminatory power with regard to the differentiation between primary hypothyroidism and nonthyroidal illness.

Effect of Hypothyroidism on the NO/cGMP Pathway of Corpus Cavernosum in Rabbits

The incidence of hormonal dysfunction as a cause of impotence remains controversial. However, several recent studies have reported evidence of hormonal abnormalities in 25-35% of impotent men. Hypothyroidism has been reported to occur in 6% of impotent men. There is some evidence suggesting that hypothyroidism may be a cause of impotence. We aimed to investigate the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway in hypothyroidism in an experimental rabbit model and compared hypothyroid rabbits with controls to evaluate the possible involvement of the NO/cGMP pathway. The study comprised 20 male New Zealand white rabbits. The rabbits were divided into two equal groups. The first group had hypothyroidism induced surgically by thyroidectomy for 6 weeks. The second group underwent a sham operation. There was no significant change in the mean body weight of hypothyroid rabbits and controls. Triiodothyronine and thyroxine levels were significantly lower in hypothyroid rabbits. Plasma thyroid-stimulating hormone and prolactin levels were significantly higher in hypothyroid rabbits. Plasma total calcium and parathormone levels remained in the normal range in both groups. Papaverine-induced concentration-dependent relaxations were similar in both groups. Carbachol-induced relaxation responses decreased in hypothyroid rabbits. There were significant differences between control and hypothyroid rabbits in frequency-dependent relaxations induced by electrical-field stimulation (EFS). YC-1-induced relaxation responses did not change significantly in hypothyroid rabbits. Concentration-dependent relaxations induced by diethylamine (DEA)/NO were similar in both groups. Amrinone-induced relaxation responses did not change significantly in hypothyroid rabbits. Reductions of relaxant responses to EFS and carbachol in hypothyroid rabbits can depend on the decrease of released or synthesized NO from nitrergic nerves and endothelium.

Relation of Plasma Thyroid-Stimulating Hormone Levels to Vascular Lesions and Atrophy of the Brain in the Elderly

Context: Recent studies suggest that thyroid disease is associated with cardiovascular and peripheral vascular disease. However, little is known about the underlying pathophysiology and the relation with cerebrovascular disease or brain atrophy in the elderly. Objective: To determine if plasma thyroid-stimulating hormone (TSH) levels are associated with vascular brain changes and cortical atrophy in the elderly. Design: Community based, cross-sectional study. Participants and Setting: 268 participants of the Memory and Morbidity in Augsburg Elderly Study, 65–83 years of age and without contraindications for magnetic resonance imaging (MRI) of the brain. Main Outcome Measures: The presence of brain lesions and atrophy was determined using a standardized MRI protocol, an established rating scale and a single rater. Plasma TSH levels were assessed using standard laboratory methods. The association between plasma TSH levels and MRI findings was analyzed using logistic and linear regression models. Results: Higher TSH levels within the normal clinical range were significantly associated with severer cortical atrophy (p = 0.04) and a higher proportion of infarct-like vascular lesions (p = 0.005) in men. These associations were independent of potential confounders, including thyroid hormone therapy, in multivariable regression analysis. No association between plasma TSH levels and both MRI outcomes were observed in women. In addition, neither in men nor in women was an association between TSH levels and white-matter lesions found. Conclusions: Increasing TSH levels even within the normal clinical range are associated with severer brain atrophy and infarct-like vascular lesions in elderly men.

Median Nerve Conduction Velocity and Central Conduction Time Measured With Somatosensory Evoked Potentials in Thyroxine-Treated Infants With Down Syndrome

The aim of this study was to determine whether thyroxine treatment would improve nerve conduction in infants with Down syndrome. A single-center, nationwide, randomized, double-blind, clinical trial was performed. Neonates with Down syndrome were assigned randomly to thyroxine (N = 99) or placebo (N = 97) treatment for 2 years. Daily thyroxine doses were adjusted regularly to maintain plasma thyrotropin levels in the normal range and free thyroxine concentrations in the high-normal range. The outcome measures were nerve conduction velocity and central conduction time, determined through median nerve somatosensory evoked potential recording, at the age of 24 months. At the age of 24 months, somatosensory evoked potential recordings for 81 thyroxine-treated and 84 placebo-treated infants were available for analysis. Nerve conduction velocity and central conduction time did not differ significantly between the 2 treatment groups (nerve conduction velocity: thyroxine: 51.0 m/second; placebo: 50.1 m/second; difference: 0.9 m/second; central conduction time: thyroxine: 8.83 milliseconds; placebo: 8.73 milliseconds; difference: 0.1 milliseconds). Postnatal thyroxine treatment of infants with Down syndrome did not alter somatosensory evoked potential-measured peripheral or central nerve conduction significantly. The absence of favorable effects suggests that pathologic mechanisms other than mild postnatal hypothyroidism underlie the impaired nerve conduction. The absence of adverse effects suggests that longstanding plasma free thyroxine concentrations in the high-normal range are not harmful to nerve maturation.

Induction of a Hypothyroid State During Juvenile Development Delays Pubertal Reactivation of the Neuroendocrine System Governing Luteinising Hormone Secretion in the Male Rhesus Monkey (Macaca mulatta)

The present study aimed to determine the influence of thyroid status on the timing of the pubertal resurgence in gonadotrophin-releasing hormone pulse generator activity [tracked by circulating luteinising hormone (LH) levels] in male rhesus monkeys. Six juvenile monkeys were orchidectomised and then treated with the antithyroid drug, methimazole, from 15-19 months until 36 months of age, at which time thyroxine (T(4)) replacement was initiated. Four additional agonadal monkeys served as controls. Blood samples were drawn weekly for hormonal assessments. Body weight, crown-rump length and bone age were monitored at regular intervals. By 8 weeks of methimazole treatment, plasma T(4) had fallen sharply, and the decline was associated with a plasma thyroid-stimulating hormone increase. In controls, plasma LH levels remained undetectable until the pubertal rise occurred at 29.3 +/- 0.2 months of age. This developmental event occurred in only half of the methimazole-treated animals before 36 months of age when T(4) replacement was initiated. The hypothyroid state was associated with a profound arrest of growth and bone maturation, but increased body mass indices and plasma leptin levels. T(4) replacement in methimazole-treated monkeys was associated with the pubertal rise in LH in the remaining three animals and accelerated somatic development in all six animals. Although pubertal resurgence in LH secretion occurred at a later chronological age in methimazole-treated animals compared to controls, bone age, crown-rump length and body weight at that time did not differ between groups. There were no long-term differences in plasma prolactin between groups. We conclude that juvenile hypothyroidism in male primates causes a marked delay in the pubertal resurgence of LH secretion, probably occasioned at the hypothalamic level. Whether this effect is meditated by an action of thyroid hormone directly on the hypothalamus or indirectly as a result of the concomitant deficit in somatic development remains to be determined.

In vivo protective effect of melatonin on cadmium‐induced changes in redox balance and gene expression in rat hypothalamus and anterior pituitary

Cadmium (Cd) is widely used in industrial applications and is an important side contaminant of agricultural products. As an endocrine disruptor, Cd modifies pituitary hormone release. It has been shown that this metal causes oxidative stress in primary cultures of anterior pituitary cells. To examine whether Cd induces redox damage in the hypothalamic-pituitary axis in vivo and to evaluate the efficacy of the antioxidant molecule melatonin to prevent Cd activity, rats were exposed to Cd (5 p.p.m. in drinking water) with or without melatonin (3 microg/mL drinking water) for 1 month. In the anterior pituitary, Cd increased lipid peroxidation and mRNA levels for heme oxygenase-1 (HO-1) at both time intervals tested (09:00 and 01:00 hr, beginning of rest span and middle of activity span, respectively). Melatonin administration prevented the Cd-induced increase in both parameters. In the hypothalamus, Cd affected the levels of mRNA for HO-1 by decreasing it in the evening. Melatonin reduced hypothalamic HO-1 gene expression. Cd treatment augmented gene expression of nitric oxide synthase (NOS)1 and NOS2 in the pituitary whereas melatonin decreased it, impairing the activity of Cd. Exposure to Cd increased the levels of hypothalamic NOS1 mRNA at 09:00 hr and decreased the levels of NOS2 mRNA at 01:00 hr, with melatonin treatment preventing Cd effects. Cd treatment decreased plasma thyroid-stimulating hormone levels at both examined times, while melatonin reversed the effect of Cd at 09:00 hr and partially counteracted the effect at 01:00 hr. There were important variations between day and night in the expression of all the genes tested in both tissues. Melatonin treatment was effective reducing all examined effects of Cd, documenting its effectiveness to protect the rat hypothalamic-pituitary axis from the toxic metal effects.

Trisomy 21 Causes Persistent Congenital Hypothyroidism Presumably of Thyroidal Origin

Lowered neonatal plasma thyroxine (T(4)) and mildly elevated thyrotropin concentrations together with developmental benefits from neonatally started T(4) treatment in a randomized clinical trial demonstrated Down syndrome (DS) neonates to be mildly hypothyroid, at least during their first weeks of life. To prove that this hypothyroid state persists beyond this period in all, and to elucidate its etiology, we evaluated the course of the thyroid function determinants in all DS infants participating in this 24-month trial. Mean plasma thyrotropin concentrations and thyrotropin frequency distributions of 97 placebo-treated infants were persistently shifted to substantially higher concentrations, while free T(4) frequency distributions were in the lower two thirds of the reference interval. Mean thyroglobulin concentrations were normal. To normalize plasma thyrotropin, T(4)-treated DS infants (N = 99) needed rather high free T(4) concentrations, like T(4)- treated non-DS children with thyroidal congenital hypothyroidism. At ages 12 and 24 months, thyroid peroxidase antibodies were detected in 1.1% and 5.4% of all DS infants. These findings suggest that as a group DS infants have a novel type of persistent mild congenital hypothyroidism, presumably of thyroidal origin. The group character suggests a direct relation with the trisomic state of chromosome 21, hypothetically through genomic dosage imbalance of dosage-sensitive genes interfering with thyroid hormone production.

Effects of acute and chronic relaxin-3 on food intake and energy expenditure in rats

The effects of acute and repeated intraparaventricular (iPVN) administration of human relaxin-3 (H3) were examined on food intake, energy expenditure, and the hypothalamo–pituitary thyroid axis in male Wistar rats. An acute high dose iPVN injection of H3 significantly increased food intake 1 h post-administration [0.4 ± 0.1 g (vehicle) vs 1.6 ± 0.5 g (180 pmol H3), 2.4 ± 0.5 g (540 pmol H3) and 2.2 ± 0.5 g (1620 pmol H3), p < 0.05 for all doses vs vehicle]. Repeated iPVN H3 injection (180 pmol/twice a day for 7 days) significantly increased cumulative food intake in ad libitum fed animals compared with vehicle [211.8 ± 7.1 g (vehicle) vs 261.6 ± 6.7 g ( ad libitum fed H3), p < 0.05]. Plasma leptin was increased in the H3 ad libitum fed group. Plasma thyroid stimulating hormone was significantly decreased after acute and repeated administration of H3. These data suggest H3 may play a role in long-term control of food intake.

Dopamine Infusion and Anterior Pituitary Gland Function in Very Low Birth Weight Infants

Background: Previous studies demonstrated that dopamine infusion reduces plasma concentration of thyroxine (T4), thyroid stimulating hormone (TSH), prolactin (PRL), and growth hormone (GH) in adults, children, and infants. Objectives: The purpose of this prospective observational study was to evaluate the relationship between dopamine infusion and the dynamics of T4, TSH, PRL, and GH in preterm newborns weighing less than 1,500 g (very low birth weight infants, VLBW) admitted in a neonatal intensive care unit of a university hospital over a one year period. Methods: A total of 97 preterm newborns were enrolled and divided into two groups: group B included hypotensive infants treated with plasma expanders and dopamine infusion; group A was the control group including newborns who were never treated with dopamine. The newborns were studied dynamically through blood samples taken every day till 10 days. Newborns of group B were studied during dopamine infusion and after its withdrawal. Results: Among the VLBW newborns who were given dopamine, the four pituitary hormones had different dynamics: a reduction of T4, TSH, and PRL levels was noticed since the first day of treatment, and a rebound of their levels was evident since the first day after its interruption. On the contrary, the postprandial GH levels were roughly constant: GH plasma concentrations were in fact a little lower in newborns treated with dopamine, and a slight increase was observed after its withdrawal. However, observed differences were not statistically significant. Conclusions: The results suggest that dopamine infusion reduces T4, TSH, and PRL plasma levels in preterm VLBW infants and have no effect on postprandial GH rate. This hormonal suppression reverses rapidly after dopamine withdrawal. This observation suggests that the iatrogenic pituitary suppression probably cannot produce long-term injuries.

Endocrine Intervention During Irradiation Does Not Prevent Damage To the Thyroid Gland

Radiation to the head-neck region may damage the thyroid gland, leading to hypothyroidism or thyroid carcinoma. Outcomes of radiation protection by lowering plasma thyroid-stimulating hormone (TSH) have thus far been ambiguous. Our aim was to evaluate the radioprotective effect of inhibiting the thyroid gland's activity during x-radiation. For this purpose, of 80 5-week old Wistar rats, 64 received cervical irradiation with 15 Gy (single dose). During irradiation, endocrine intervention was done, using thyroxine (T(4)), T(4) plus iodine, or iodine alone compared to placebo. During the endocrine interventions and follow-up, TSH and T(4) concentrations were measured periodically. Histologic examination of thyroid, pituitary gland, or the hypothalamus and any suspect lymph nodes, lungs, and liver was performed after 6 and 54 weeks. It was found that during the endocrine intervention, plasma levels of TSH were lower in rats given T(4) and higher in rats given iodine. After 6 and 54 weeks, no significant reduction in hypothyroidism or thyroid carcinoma was found between the different groups of rats given any endocrine intervention or no intervention. In conclusion, the administration of T(4), iodine or the combination during x-irradiation does not protect against radiation-induced thyroid damage.

Polybrominated diphenyl ether (PBDE)-induced alterations in vitamin A and thyroid hormone concentrations in the rat during lactation and early postnatal development

In experimental animals fed standard laboratory diets, penta-BDE mixtures can decrease circulating thyroid hormone and liver vitamin A concentrations. A substantial number of pregnant women and their children have marginal vitamin A status, potentially increasing their risk of adverse effects to penta-BDE exposure. The current study investigated the effects of maternal gestational and lactational penta-BDE exposure on thyroid hormone and vitamin A homeostasis in rats of sufficient vitamin A (VAS) or marginal vitamin A (VAM) status and their offspring. Dams were administered daily oral doses of 18 mg/kg DE-71 (a penta-BDE mixture) or a corn oil vehicle from gestation day 6 through lactation day (LD) 18. Thyroid hormone and vitamin A homeostasis were assessed in plasma and tissues of LD 19 dams and postnatal day (PND) 12, 18, and 31 pups. DE-71 exposure induced hepatomegaly in VAS and VAM pups at all timepoints and increased testes weights at PND 31. While liver vitamin A concentrations were low in DE-71 treated dams and pups, plasma retinol concentrations and plasma retinol binding protein levels were only low in VAM animals exposed to DE-71. DE-71 exposure lowered plasma thyroxine concentrations in VAS and VAM dams and pups. Plasma thyroid stimulating hormone concentrations were high in VAM dams exposed to DE-71, suggesting that marginal vitamin A status enhances the susceptibility to thyroid hormone axis disruption by DE-71. These results support the concept that marginal vitamin A status in pregnant women may increase the risk for PBDE-induced disruptions in vitamin A and thyroid hormone homeostasis.

Effects of Long-Term Treatment with Resveratrol and Subcutaneous and Oral Estradiol Administration on the Pituitary-Thyroid-Axis

The lack of estrogen during menopause is associated with various symptoms including osteoporosis, cardiovascular diseases, and menopausal symptoms. For many years, conventional hormone replacement therapy has been successfully used to treat these conditions. However, in light of recent studies that draw attention to potential hazards of conventional HRT, various attempts were undertaken to search for alternatives of classical HRT. Phytoestrogens are supposed to ameliorate various discomforts associated with menopause. Resveratrol (RES) is present in red wine, grapes and peanuts and has been implicated in cardioprotection and prevention of adverse side effects observed after regular HRT. As the pituitary-thyroid axis is a target of estrogen action, we first assessed the effects of E2 administration on thyroid hormone stimulating hormone releasing hormone (TRH)-induced thyroid stimulating hormone (TSH) secretion from pituitary cell cultures in vitro. Our data reveal that E2 treatment augments the TRH-induced TSH secretion. We furthermore designed a long-term study of three months to assess the effects of subcutaneous and oral administration of 17beta-estradiol (E2), as well as the actions of RES on the pituitary-thyroid axis in ovariectomized (OVX) female rats. Our results demonstrate that serum levels of 1.0 and 8.1 microM RES lead to a significant increase in total serum triiodthyronine (T3) levels. OVX induces TSHbeta mRNA in the adenohypohysis and E2 treatment attenuates this effect. Treatment of rats with subcutaneous implants of E2 does not affect the pituitary-thyroid axis, whereas orally applied E2 benzoate (E2B) increases plasma TSH and total thyroxine (T4) in OVX rats. In all animals, we could not detect changes in thyroid morphology as assessed by hematoxylin-eosin (HE) and Perjod-Acid Schiff's (PAS) staining.

Thyroid and hypoxic stress in the newtTriturus carnifex

When specimens of the newt Triturus carnifex, under anaesthesia by submersion in a 0.2% chlorbutol solution for 25 min, are isolated in a respiratory chamber at 18 degrees C containing water with only 1.3 ppm of oxygen, they consume the oxygen completely in about 3 hr, but they can stay alive for many more hours and wake up with no apparent exterior consequences. Hypoxia induces rapid onset of hepatic steatosis and melanosis, as well as a controlled haemolytic process involving a pool of red blood cells of the same order of size as that held as a reserve in the spleen by animals in an aerial habitat. At the origin of the phenomena is an intense response by the hypophysis, histologically detectable 1 hr from the onset of treatment and confirmed 2 hr later by a highly significant increase in the plasma thyroidstimulating hormone (TSH) concentration compared with the controls (41.5 +/- 13.7 microU/L vs. 15.5 +/- 6.2; P < 0.005). The thyroid follicles react by reabsorbing their colloid, but instead of an increase in the plasma free T3 and T4 concentrations, fT3 falls significantly (1.5 +/- 0.3 pg/mL vs., the 2.4 +/- 0.7; P < 0.05), whereas fT4 remains stationary (4.0 +/- 0.5 pg/mL vs. 4.6 +/- 0.8; N.S.). After 6 hr, the plasmatic TSH concentration is still higher than in the controls (27.0 +/- 3.0 microU/L vs. 15.5 +/- 6.2; P < 0.05), whereas fT3 and fT4 remain stable (1.5 +/- 0.3 and 4.4 +/- 0.5 pg/mL, respectively). If T3 or T4 labelled with 125I is administered prior to hypoxia, after 6 hr of treatment the radioactivity is found to be limited exclusively to the liver and kidney; the thyroid, gall bladder and gut result negative, and this does not agree with hypotheses of hormone inactivation by deiodination, sulphation or glucuronidation. This apparently peculiar endocrine path has not been observed in previous studies on hypoxia in vertebrates, because the experiments were always designed to analyse plasma hormone levels after at least 24 hr of hypoxia or during chronic treatments, losing the most interesting phases of the endocrine response. The possibility that the hypoxic newt possesses alternative or complementary metabolic pathways to anaerobic glycolysis to sustain steatogenesis and melanogenesis and maintain the same cardiac activity as the controls is briefly discussed.

High- or low-salt diet from weaning to adulthood: Effect on body weight, food intake and energy balance in rats

Objective To get some additional insight on the mechanisms of the effect of salt intake on body weight. Design and methods Rats were fed a low (LSD), normal (NSD), or high (HSD) salt diet. In a first set, body weight, tail-cuff blood pressure, fasting plasma thyroid-stimulating hormone, triiodothyronine, l-thyroxine, glucose, insulin, and angiotensin II were measured. Angiotensin II content was determined in white and brown adipose tissues. Uncoupling protein 1 expression was measured in brown adipose tissue. In a second set, body weight, food intake, energy balance, and plasma leptin were determined. In a third set of rats, motor activity and body weight were evaluated. Results Blood pressure increased on HSD. Body weight was similar among groups at weaning, but during adulthood it was lower on HSD and higher on LSD. Food intake, l-thyroxine concentration, uncoupling protein 1 expression and energy expenditure were higher in HSD rats, while non-fasting leptin concentration was lower in these groups compared to NSD and LSD animals. Plasma thyroid-stimulating hormone decreased on both HSD and LSD while plasma glucose and insulin were elevated only on LSD. A decrease in plasma angiotensin II was observed in HSD rats. On LSD, an increase in brown adipose tissue angiotensin II content was associated to decreased uncoupling protein 1 expression and energy expenditure. In this group, a low angiotensin II content in white adipose tissue was also found. Motor activity was not influenced by the dietary salt content. Conclusions Chronic alteration in salt intake is associated with changes in body weight, food intake, hormonal profile, and energy expenditure and tissue angiotensin II content.

Colchicine treatment differently affects releasable thyrotropin-releasing hormone (TRH) pools in the hypothalamic paraventricular nucleus (PVN) and the median eminence (ME).

1. Hypophysiotropic thyrotropin-releasing hormone (TRH) is synthesized in the hypothalamic paraventricular nucleus (PVN) and transported to the median eminence (ME) where it enters the hypophyseal portal blood. TRH in the ME is situated exclusively in nerve terminals, whereas TRH in the PVN and septum is of extrinsic (nerve terminals) as well as intrinsic (perikarya) origin. 2. To determine the source and possible differential regulation of TRH release from these structures, we blocked TRH axonal delivery by i.c.v. administration of colchicine into the lateral cerebral ventricle of euthyroid or hypothyroid rats in doses of 7.5 mug or 7.5, 75 and 100 microg, respectively, two days prior to the evaluation of the TRH secretion from the PVN, ME and the septum in vitro. 3. In euthyroid rats a low dose of colchicine did not significantly affect plasma TSH. The secretory response to both ethanol in an isosmolar medium and a high K+ in the ME as well as the PVN explants was well preserved. However, colchicine treatment resulted in the significant increase of basal secretion of TRH from the PVN. 4. Hypothyroidism induced by 200 mg/l methimazole in drinking water for two weeks resulted in growth arrest, elevated plasma thyrotropin and decreased TRH content in the PVN and the ME. Colchicine partially decreased elevated plasma thyrotropin and increased the TRH content in the PVN and its basal release in vitro which was independent of extracellular Ca2+. Interestingly, a TRH release from the PVN could not be further stimulated either by K+ membrane depolarization or by ethanol. TRH responsiveness to the stimulation remained unaffected in the ME. The effect of colchicine on the septal TRH secretion was intermediate between the effect observed in the PVN and the ME. 5. In conclusion, the absence of a TRH secretory response to stimuli in the PVN after colchicine disruption of the microtubules and Golgi system suggests that stimulated TRH release observed from the PVN explants in vitro occurs from nerve terminals projecting to the PVN from other brain regions. The independence from extracellular calcium implies that TRH released under the non-stimulating conditions occurs most likely via the constitutive secretory pathway from dendrites and/or perikarya. Regulation of septal TRH is markedly different from the hypophysiotropic one.

The effect of cervical X-irradiation on activity index of thyrocytes and plasma TSH: A pre-clinical model for radiation-induced thyroid damage

Because radiotherapy in the head and neck region is necessary in the treatment of childhood cancer, possibilities to prevent damage to the thyroid gland must be explored. We developed a model in which radiation-induced effects can be investigated in a way that these effects can be quantified, using thyroid dysmorphology and plasma TSH. Thirty-five Wistar rats, 5 weeks old, were X-irradiated on the cervical region, with a single dose varying from 0 to 20 Gy. After 6 weeks, TSH, T4 and T3 were determined, and thyroid glands were processed for histological examination by two independent pathologists. A histological classification scale was developed, using follicular size, colloid density and cell height of thyrocytes to measure hyperplasia and hypertrophy. By the sum of these scores, a cell-activity index was calculated, which was related to plasma TSH concentration. Numbers of PAS-positive droplets and epithelial desquamation were also counted. Inter-observer reliability was assessed. Good to very good reliability was found for scores of follicular size, colloid density and cell height. Significant increase of cell-activity index was found after 10, 15 and 20 Gy. The plasma TSH concentration was positively correlated to the cell-activity index, increasing with radiation-doses up to 15 Gy. The number of desquamated cells was significantly increased after radiation doses >10 Gy, with moderate reliability. In conclusion, this model using cell-activity index of thyrocytes together with plasma thyrotropin concentrations and desquamation of cells can be used for interpretation and future (pre-clinical) studies of prevention of radiation-induced thyroid damage.

Dimethoate effects on thyroid function in suckling rats

The aim of our work is to study dimethoate effects on thyroid function given in drinking water (40 mg/kg body weight, equivalent to 0.2 g/L) to mothers from day zero until the 10th day after delivery. Pups and their mothers were sacrificed on day ten after parturition. Compared to a control group, dimethoate-treated pups showed a 48% decrease in body weight which could be attributed to a defect in thyroid hormones. Indeed, after treatment by dimethoate, plasma rates of free T4 and T3 decreased by 56% and 40% in the young and by 27% and 15% in dams respectively. We can attribute the reduction in plasma thyroxine and triiodothyronine rates to a decrease in thyroid iodine levels (-75%) in the young and (-24%) in their mothers. The decrease in production of thyroid hormones after dimethoate treatment affect thyroid stimulating hormone (TSH) levels. In fact, plasma TSH levels were multiplied in dimethoate-treated group by factors of 2.31 in dams and 1.96 in their offspring. These biochemical modifications confirmed the histological thyroid aspects of pups and dams. In fact, in dimethoate-treated rats, some thyroid follicles of pups presented vesicular cavities without colloid; others contained colloid. However in dams, thyroid follicles presented cubical epithelial cells which surrounded empty vesicular cavities.

Multivariate Analysis on Factors Affecting Suppression of Thyroid-Stimulating Hormone in Treated Congenital Hypothyroidism

Aims: To determine the factors which influence the suppression of thyroid-stimulating hormone (TSH) in infants with congenital hypothyroidism (CH) following treatment. Methods: We examined retrospectively the patterns of thyroid function tests from diagnosis to 3 years of age in 140 infants diagnosed with CH from screening. Patients were classified into 3 groups: athyreosis, ectopia and presumed dyshormonogenesis on the basis of thyroid scans. Adequate TSH suppression was defined as plasma TSH concentration <6 mU/l. The factors affecting the suppression of TSH at 6 months and 1 year of age which were evaluated were: initial confirmatory plasma TSH, initial plasma thyroxine (T4), mean age of starting treatment with L-T4, dose of L-T4 at diagnosis, 6 weeks, 3 months and 6 months, and aetiology of the congenital hypothyroidism. Variables were then entered in a stepwise logistic regression model for TSH suppression at 6 months and 1 year of age. Results: All infants had radionuclide scans prior to treatment: athyreosis (n = 39), ectopia (n = 78) and dyshormonogenesis (n = 23). 58% of patients had persistently raised TSH at 6 months of age while 31% of patients had a persistently raised TSH at 1 year of age. There was a significant delay in the normalisation of plasma TSH in athyreosis and ectopia groups compared with dyshormonogenesis. Multiple regression analysis for TSH suppression at 6 months of age found plasma T4 levels and aetiology of CH as independent factors affecting the timing of TSH suppression. Aetiology of CH was the only independent factor affecting TSH suppression at 1 year of age. Conclusion: At 6 months of age, plasma T4 levels at 6 weeks and 3 months, and aetiology of CH were independent factors affecting timing of TSH suppression. However, by 1 year of age, the aetiology of CH was the only independent factor affecting suppression of TSH.

Effect of ethanol on 24-hour hormonal changes in peripubertal male rats

We analyzed the effect of chronic (4 weeks) ethanol feeding on 24-h variation of pituitary–testicular function in peripubertal male Wistar rats by measuring circulating concentrations of prolactin, follicle-stimulating hormone, luteinizing hormone, testosterone, and thyrotropin. Animals were maintained under a 12-h light:12-h dark photoperiod and received a liquid diet for 4 weeks, starting on day 35 of life. The ethanol-fed group received a diet similar to that provided to control animals, except that maltose was replaced isocalorically with ethanol. Ethanol replacement provided 36% of the total caloric content of the diet. Rats were killed at one of six times around the clock, beginning at zeitgeber time (ZT) 1 (ZT 0 = lights on). In ethanol-fed rats globally, secretion of prolactin was augmented, whereas secretion of follicle-stimulating hormone, luteinizing hormone, testosterone, and thyrotropin was decreased. Significant changes in the 24-h secretory pattern of circulating hormones occurred in rats receiving ethanol, including the appearance of two peaks (at ZT 1 and ZT 9), rather than one peak, of follicle-stimulating hormone during the inactive phase of the daily cycle, suppression of the maximum plasma luteinizing hormone concentration during the first part of the inactive phase, and appearance of a second peak of testosterone and prolactin during the second part of the inactive phase (at ZT 5 and ZT 9, respectively) and of a second peak of plasma thyrotropin during the first part of the active phase (at ZT 13). The significant positive correlation between testosterone and individual luteinizing hormone and prolactin concentrations in control animals was no longer observed after ethanol administration. Chronic ethanol administration presumably affects the endogenous clock that modulates the circadian variation of the pituitary–gonadal axis and thyrotropin release in growing male rats.