Plasma Thyrotropin Research Articles

Melanin-concentrating hormone (MCH) suppresses thyroid stimulating hormone (TSH) release, in vivo and in vitro, via the hypothalamus and the pituitary.

Melanin-concentrating hormone (MCH) is an orexigenic peptide encoded in the pre-pro MCH gene. Targeted deletion of MCH causes a phenotype of hypophagia and leanness with an inappropriately high metabolic rate, suggesting a role for MCH in the control of energy balance. In order to further elucidate the mechanism by which MCH controls, energy expenditure, we have investigated the effects of MCH on the hypothalamic pituitary thyroid (HPT) axis. The thyroid axis is important in energy homeostasis and starvation leads to profound suppression of the HPT axis. MCH significantly reduces plasma TSH in vivo at 10 min (0.5 +/- 0.07 ng/ml, p < 0.05, n = 8) and 60 min (0.33 +/- 0.04 ng/ml, p < 0.01, n = 10) compared to saline (0.7 +/- 0.07 ng/ml and 0.69 +/- 0.07 ng/ml respectively) when administered intracerebroventricularly. Release of TRH form hypothalamic explants was significantly reduced in the presence of MCH production (7.1 +/- 0.99 fmol/explant to 2.3 +/- 0.4 fmol/explant p < 0.01, n = 18) and Neuropeptide EI (NEI) (8.47 +/- 1.28 fmol/explant to 4.6 +/- 1.13 p < 0.05, n = 16), a peptide, also encoded in the pre-pro-MCH gene. MCH was also shown to significantly reduce TRH stimulated TSH release from dispersed pituitary cell cultures (basal = 0.5 +/- 0.06 ng/ml, 100 nM TRH = 0.9 +/- 0.2 ng/ml, p < 0.05 0.1 nM MCH = 0.5 +/- 0.1 ng/ml, p < 0.05, 1 nM MCH = 0.3 +/- 0.03 ng/ml, p < 0.01, 10 nM MCH = 0.4 +/- 0.02 ng/ml, p < 0.01, 1000 nM MCH = 0.4 +/- 0.05 ng/ml, P < 0.01, n = 4), although basal release of TSH from these cultures was unaffected. These data suggest a possible role for MCH in the control of energy homeostasis via inhibition of the thyroid axis.

Suprathreshold repetitive transcranial magnetic stimulation elevates thyroid-stimulating hormone in healthy male subjects.

Repetitive transcranial magnetic stimulation (rTMS) has been introduced as a new antidepressive treatment strategy. The mode of action by which the antidepressive effect is brought about is not yet clear. Other antidepressive treatment strategies such as sleep deprivation are associated with an increase of plasma thyroid-stimulating hormone (TSH) levels that correlate with clinical improvement. In the present study, the effect of left prefrontal suprathreshold (120% of motor threshold) rTMS on TSH plasma levels of 19 healthy male subjects was investigated in comparison with subthreshold (80% of motor threshold) and sham stimulation. Suprathreshold rTMS was followed by a significant relative increase of TSH levels 10 and 60 minutes after stimulation in comparison with subthreshold and sham stimulation. The more pronounced effect of suprathreshold rTMS on TSH plasma levels might be important for the determination of optimal stimulation parameters in the treatment of depressed patients.

Plasma levels of persistent organohalogens and hormone levels in adult male humans.

In this study the authors assessed the possible relationship between high dietary exposure to persistent organohalogens (OHS) through fatty fish from the Baltic Sea and hormone levels in adult men. Blood samples were drawn from 110 men who consumed varying amounts of fish (i.e., 0-32 meals per month) for analysis of plasma levels of 18 polychlorinated biphenyl (PCB) congeners, 5 hydroxy-PCBs, 1,1,1-trichloro-2,2-bis(4-chlorophenyl)-ethane (p,p'-DDT), 1,1-dichloro-2,2-bis(4-chlorophenyl)-ethene (p,p'-DDE), hexachlorobenzene, and 2,2',4,4'-tetrabromodiphenyl ether. In addition, plasma levels of follicle-stimulating hormone, luteinizing hormone, prolactin, plasma thyrotropin, free and total T3, free and total T4, and free testosterone were analyzed. The authors adjusted for age, and the only significant associations that remained were negative correlations between 2,2',4,4'-tetrabromodiphenyl ether and plasma thyrotropin (p < .001), and between pentachlorophenol and follicle-stimulating hormone (p = .04). The authors expected that there would be some significant correlations that resulted from pure chance. High consumption of organohalogen-polluted fish did not appear to affect plasma concentrations of pituitary, thyroid, or testosterone hormone levels in male adults.

Selective modulation of thyroid hormone receptor action

Thyroid hormones have some actions that might be useful therapeutically, but others that are deleterious. Potential therapeutically useful actions include those to induce weight loss and lower plasma cholesterol levels. Potential deleterious actions are those on the heart to induce tachycardia and arrhythmia, on bone to decrease mineral density, and on muscle to induce wasting. There have been successes in selectively modulating the actions of other classes of hormones through various means, including the use of pharmaceuticals that have enhanced affinities for certain receptor isoforms. Thus, there is reason to pursue selective modulation of thyroid hormone receptor (TR) function, and several agents have been shown to have some β-selective, hepatic selective and/or cardiac sparring activities, although development of these was largely not based on detailed understanding of mechanisms for the specificity. The possibility of selectively targeting the TRβ was suggested by the findings that there are α- and β-TR forms and that the TRα-forms may preferentially regulate the heart rate, whereas many other actions of these hormones are mediated by the TRβ. We determined X-ray crystal structures of the TRα and TRβ ligand-binding domains (LBDs) complexed with the thyroid hormone analog 3,5,3′-triiodithyroacetic acid (Triac). The data suggested that a single amino acid difference in the ligand-binding cavities of the two receptors could affect hydrogen bonding in the receptor region, where the ligand's 1-position substituent fits and might be exploited to generate β-selective ligands. The compound GC-1, with oxoacetate in the 1-position instead of acetate as in Triac, exhibited TRβ-selective binding and actions in cultured cells. An X-ray crystal structure of the GC-1-TRβ LBD complex suggests that the oxoacetate does participate in a network of hydrogen bonding in the TR LBD polar pocket. GC-1 displayed actions in tadpoles that were TRβ-selective. When administered to mice, GC-1 was as effective in lowering plasma cholesterol levels as T 3, and was more effective than T 3 in lowering plasma triglyceride levels. At these doses, GC-1 did not increase the heart rate. GC-1 was also less active than T 3 in modulating activities of several other cardiac parameters, and especially a cardiac pacemaker channel such as HCN-2, which may participate in regulation of the heart rate. GC-1 showed intermediate activity in suppressing plasma thyroid stimulating hormone (TSH) levels. The tissue/plasma ratio for GC-1 in heart was also less than for the liver. These data suggest that compounds can be generated that are TR-selective and that compounds with this property and/or that exhibit selective uptake, might have clinical utility as selective TR modulators.

Effects of chronic central nervous system administration of agouti-related protein in pair-fed animals.

The melanocortin receptor (MC3-R and MC4-R) antagonist, agouti-related protein (AGRP), is a potent stimulant of food intake. We examined the effect of chronic intracerebroventricular (ICV) AGRP treatment on energy metabolism and pituitary function in ad libitum fed rats and rats administered AGRP and then pair-fed to a saline control group. Chronic ICV AGRP (83-132) administration (1 nmol/day for 7 days) significantly increased food intake and body weight in ad libitum fed animals compared with saline-treated controls (body weight on day 7: 272 +/- 6 [saline] vs. 319 +/- 8 g [AGRP ad libitum fed]; P < 0.001). A significant increase in the epididymal fat pad weight, interscapular brown adipose tissue (BAT) weight, and plasma leptin was also observed in the ad libitum fed group. In the AGRP pair-fed group, a significant increase in the epididymal fat pad weight, BAT weight, and plasma leptin was again observed, suggesting that AGRP caused metabolic changes independent of increased food intake. BAT uncoupling protein 1 (UCP-1) content was significantly decreased compared with saline controls in both the AGRP ad libitum fed (21 +/- 8% of saline control; P < 0.01) and AGRP pair-fed groups (24 +/- 7% of saline control; P < 0.01). Plasma thyroid-stimulating hormone (TSH) was significantly suppressed compared with saline controls in both the AGRP ad libitum fed and AGRP pair-fed groups (3.5 +/- 0.3 [saline] vs. 2.7 +/- 0.4 [AGRP ad libitum fed] vs. 2.1 +/- 0.2 ng/ml [AGRP pair-fed]; P < 0.01). This study demonstrates that independent of its orexigenic effects, chronic AGRP treatment decreased BAT UCP-1, suppressed plasma TSH, and increased fat mass and plasma leptin, suggesting that it may play a role in energy expenditure.

Plasma thyrotropin bioactivity in Down's syndrome children with subclinical hypothyroidism.

Subclinical hypothyroidism occurs in a number of children with Down's syndrome (DS). The reason for the mildly elevated plasma thyrotropin (TSH) concentrations is not known. The present study investigated whether decreased TSH bioactivity plays a role in this phenomenon. A retrospective study of plasma specimens from DS children with mildly elevated plasma TSH concentrations and thyroid hormone levels within the reference range, using a TSH receptor-adenylate cyclase mediated bioassay. Strain JP26 Chinese hamster ovary (CHO) cells, stable transfected with the human TSH receptor, were incubated with unfractionated plasma (1/10 diluted in hypotonic incubation medium) of 10 DS children with subclinical hypothyroidism and nine euthyroid children with insulin-dependent diabetes mellitus as controls. cAMP released in the incubation medium was measured by RIA. Mock-transfected CHO cells were used to correct for non-specific CHO response. WHO Second International Reference Preparation of human TSH was dissolved and diluted in pooled normal human plasma and simultaneously bioassayed to match patient and control results. Plasma TSH levels were slightly increased in DS (mean +/- S.D., 6.5+/-1.3 mU/l, reference range 0.4-4.0 mU/l). Plasma TSH levels for controls (1.3+/-0.4 mU/l) were within the reference range. Plasma thyroid hormone levels in patients and controls were normal, plasma TSH binding inhibitory immunoglobulin and thyroid peroxidase antibodies were negative. cAMP levels (corrected for non-specific CHO response) in DS patients (18.4+/-3.9 pmol/well) and in controls (14.3+/-1.3 pmol/well) did not significantly differ from cAMP levels generated by patient-TSH equivalent TSH standards (16.3+/-0.9 pmol/well). The present results demonstrate normal TSH bioactivity in plasma of DS children, indicating that subclinical hypothyroidism in these patients is of primary (thyroidal) origin.

Effects of cyproheptadine clorhydrate ,a serotonin receptor antagonist ,on endocrine parameters in weight-loss related amenorrhea

The aim of the study was to evaluate the possible interactions and/or modulations of the serotoninergic system on hormonal parameters and the reproductive axis in amenorrheic subjects. Hypogonadotropic,underweight ,amenorrheic patients (n = 8) were studied before and during cyproheptadine clorhydrate administration (4 mg/day for 3 months). A pulsatility study (4 hours ,sampling every 10 minutes) and analoxone test were performed before and after 4 and 12 weeks of treatment. Plasma luteinizing hormone (LH) ,follicle-stimulating hormone (FSH) ,growth hormone (GH) ,estradiol ,thyroid-stimulating hormone(TSH) ,free tri-iodothyronine (fT3) ,free thyroxine (fT4) and total triiodothyonine (total T3) ,insulin-like growth factor-I (IGF-I) concentrations were determined. Pulsedetection analysis was performed using the DETECT program.Serotoninergic receptor blockade affected neither the naloxone-inducted LH response nor the gonadotropin pulsatile parameters. Body mass index(BMI) did not vary; conversely ,integrated mean gonadotropins ,GH and fT3 concentrations increased during the treatment. In conclusion ,cyproheptadine administration affects some of the abnormalendocrine parameters of underweight amenorrheic subjects with no modulation of the opioidergic system. It is likely that the gonadotropin and the fT3 increases take place owing to a change inthe metabolic signals modulating hypothalamic function and/or an increased energy availability. Our study suggests a specific central effect of cyproheptadine on the serotonergic pathway controlling foodintake at the hypothalamic level.

Morphological and biochemical changes in the thyroid gland of the lizard Podarcis sicula (Reptilia, Squamata) induced by VIP treatment

The effects of exogenous vasoactive intestinal polypeptide (VIP) involvement in the regulation of thyroid function were detected in the lizard Podarcis sicula. Variations in thyroid gland morphology, thyroid‐stimulating hormone (TSH), 3,5,3'‐triiodo‐L‐thyronine (T3) and L‐thyroxine (T4) plasma levels, were studied in this species after treatment with VIP, during winter and summer. The polypeptide had a stimulatory effect on thyroid hormone secretion throughout the year. Plasma T4 and T3 levels significantly increased; maximal values were reached in specimens exposed longer to treatment. No difference in plasma TSH levels was observed between control and treated specimens, indicating that, in P. sicula, the site of VIP action might be better identified at thyroidal rather than hypophyseal level. Consistently with these results, the morphology of the thyroid gland also appeared stimulated after treatment with VIP, showing an increase in thyroid‐cell height, numerous intracellular colloid droplets PAS‐positive, and enlarged blood vessels around the follicles.

Regulation of Hepatocyte Thyroxine 5′-Deiodinase by T3 and Nuclear Receptor Coactivators as a Model of the Sick Euthyroid Syndrome

The syndrome of nonthyroidal illness, also known as the sick euthyroid syndrome, is characterized by a low plasma T3 and an "inappropriately normal" plasma thyrotropin in the absence of intrinsic disease of the hypothalamic-pituitary-thyroid axis. The syndrome is due in part to decreased activity of type I iodothyronine 5'-deiodinase (5' D-I), the hepatic enzyme that converts thyroxine to T3 and that is induced at the transcriptional level by T3. The hypothesis tested is that cytokines decrease T3 induction of 5' D-I, resulting in decreased T3 production and hence a further decrease in 5' D-I. The proposed mechanism is competition for limiting amounts of nuclear receptor coactivators between the 5' D-I promoter and the promoters of cytokine-induced genes. Using primary cultures of rat hepatocytes, we demonstrate that interleukins 1 and 6 inhibit the T3 induction of 5' D-I RNA and enzyme activity. This effect is at the level of transcription and can be partially overcome by exogenous steroid receptor coactivator-1 (SRC-1). The physical mass of endogenous SRC-1 is not affected by cytokine exposure, and exogenous SRC-1 does not affect 5' D-I in the absence of cytokines. The data support the hypothesis that cytokine-induced competition for limiting amounts of coactivators decreases hepatic 5' D-I expression, contributing to the etiology of the sick euthyroid syndrome.

Involvement of thyroid hormones in the effect of intracerebroventricular leptin infusion on uncoupling protein-3 expression in rat muscle.

We have shown previously that continuous (6 days) intracerebroventricular (ICV) leptin infusion in normal rats resulted in decreases in food intake and body weight. A reduction of food intake imposed on control rats (pair-feeding), aimed at mimicking leptin-induced hyperphagia, produced a marked decrease in the expression of muscle uncoupling protein-3 (UCP-3), whereas ICV infusion of leptin prevented such a decrease in UCP-3. To investigate an involvement of thyroid hormones in this effect of leptin, plasma levels of these hormones were determined in ICV leptin-infused, ICV vehicle-infused ad libitum fed or pair-fed controls. ICV leptin infusion and pair-feeding resulted in decreased plasma thyroid-stimulating hormone (TSH) and T4 levels relative to ad libitum fed controls. ICV leptin infusion maintained plasma levels of T3, but the levels were decreased by pair-feeding. The activity of the enzyme (hepatic 5'-monodeiodinase) responsible for T4/T3 conversion was measured. In the leptin-infused group, the activity of 5'-monodeiodinase was maintained at the values measured in ad libitum fed rats; in pair-fed rats, activity was reduced. Thus, conversion of T4 to T3 is decreased by pair-feeding, whereas such is not the case during leptin infusion. To further substantiate an involvement of thyroid hormones in the effect of leptin on muscle UCP-3 expression, hypothyroid rats were ICV infused with leptin or vehicle. It was observed that in hypothyroid rats, ICV leptin was unable to maintain muscle UCP-3 expression at values measured in ad libitum fed controls. These results suggest that central leptin stimulates T3 production via an activation of T4 to T3 conversion, and that this stimulation could be responsible for the effect of leptin on muscle UCP-3 expression. Thyroid hormones could thus be important mediators of the effect of leptin on energy expenditure.

The central melanocortin system affects the hypothalamo-pituitary thyroid axis and may mediate the effect of leptin.

Prolonged fasting is associated with a downregulation of the hypothalamo-pituitary thyroid (H-P-T) axis, which is reversed by administration of leptin. The hypothalamic melanocortin system regulates energy balance and mediates a number of central effects of leptin. In this study, we show that hypothalamic melanocortins can stimulate the thyroid axis and that their antagonist, agouti-related peptide (Agrp), can inhibit it. Intracerebroventricular (ICV) administration of Agrp (83-132) decreased plasma thyroid stimulating hormone (TSH) in fed male rats. Intraparaventricular nuclear administration of Agrp (83-132) produced a long-lasting suppression of plasma TSH, and plasma T4. ICV administration of a stable alpha-MSH analogue increased plasma TSH in 24-hour-fasted rats. In vitro, alpha-MSH increased thyrotropin releasing hormone (TRH) release from hypothalamic explants. Agrp (83-132) alone caused no change in TRH release but antagonized the effect of alpha-MSH on TRH release. Leptin increased TRH release from hypothalami harvested from 48-hour-fasted rats. Agrp (83-132) blocked this effect. These data suggest a role for the hypothalamic melanocortin system in the fasting-induced suppression of the H-P-T axis.

Severe hypothyroidism in patients dependent on prolonged thyroxine infusion through a jejunostomy

Background and aims: Enteral absorption of thyroxine (T4) is variable; the duodenum and jejunum appear to be the most important sites of absorption. Our objective is to demonstrate that T4 infused via a standard jejunostomy may occasionally be poorly absorbed.Methods: Two patients underwent esophagolaryngeal resection for carcinoma of the cervical esophagus. The procedure was accompanied by complete removal of the thyroid and parathyroid glands. A neck fistula at the gastropharyngeal anastomosis led to a restriction of oral intake; daily requirements of T4 and nutrients were given via the jejunostomy. T4 plasma levels deteriorated and thyroid-stimulating hormone (TSH) levels increased and in the third postoperative week, T4 (300 μg) was administered via a nasogastric tube.Results: Although given a high dose (300 μg) of T4, both patients developed severe hypothyroidism. Infusion of T4 through the nasogastric tube precipitated the normalization of T4 and TSH plasma levels. Both patients (cases 1 and 2) resumed oral intake during the fifth and sixth postoperative weeks respectively.Conclusion: T4 malabsorption may occur in patients dependent on prolonged T4 infusion via a standard jejunostomy.

The Role of Selenium in Iodine Metabolism in Children with Goiter

Possible interactions between selenium and iodine metabolism were investigated in 7- to 16-year-old children with goiter (n = 136) living in southeastern Poland in iodine-deficient areas influenced by a sulfur industry. The Se-iodine interactions in these children were compared to the interactions in children from outside of that region (n = 38). Blood selenium (BSe) concentration and plasma glutathione peroxidase activity were much lower in the study group (64.1 +/- 15.7 microg/L; 111.0 +/- 27.6 U/L) than in the control group (85.3 +/- 19.6 microg/L; 182.4 +/- 35.6 U/L). Almost all of the data [plasma thyroid-stimulating hormone (TSH) concentration, plasma free thyroxine (fT(4)) concentration] fell within the reference limits. There was no statistically significant difference between the control and the study groups with respect to fT(4) and TSH. However, statistically significant differences of fT(4) and TSH in the study group were revealed between females belonging to the lower (n = 21; fT(4), 16.1 +/- 3.3 pmol/L; TSH, 1.83 +/- 1.05 mU/L) and upper Se quartiles (n = 24; fT(4), 14.5 +/- 2.2 pmol/L; TSH, 1. 26 +/- 0.90 mU/L), p &lt; 0.05. Neither group differed in iodine in urine concentration, age, and body mass index. The difference in fT(4) concentrations can be attributed to an Se deficiency. The relationship exists only for females, which suggests a sex-linked hormonal response to concomitant Se and iodine deficiencies.

Effects of a Single Venous Dose of Zinc on Thyroid Status in Healthy Individuals and Patients With Graves′ Disease

Zinc metabolism may regulate thyroid function acting at TRH (thyrotropin-releasing hormone) synthesis, peripheral deiodination of T4 (tetraiodothyronine), and binding of thyroid hormones to nuclear receptors. The aim of this study was to investigate the effect of acute zinc administration on TSH (thyroid-stimulating hormone), FT3 (free triiodothyronine), and FT4 (free tetraiodothyronine) in 10 healthy individuals and 12 hyperthyroid patients with Graves' disease. All these individuals were studied following 25 mg Zn++ administered intravenously, at 7:00 a.m. after 12 h fast. Blood samples collected at 0, 3, 30, 60, 90, and 120 min after zinc administration showed no significant alteration in the plasma levels of TSH, FT3, and FT4 in hyperthyroid patients. There were no changes in the plasma levels of FT3 and FT4 in the control subjects, but TSH levels were acutely depressed by zinc administration. This study suggests that zinc given acutely and in pharmacological doses does not affect thyroid function in hyperthyroid subjects, but affect plasma TSH levels in healthy individuals.

Secretion pattern of thyroid-stimulating hormone in dogs during euthyroidism and hypothyroidism

In as many as one third of dogs with primary hypothyroidism a plasma thyrotropin (TSH) concentration within the reference range for euthyroid dogs is found. To determine whether this is due to fluctuations in the release of TSH, the plasma profiles of TSH were analyzed in 7 beagle bitches by collecting blood samples every 10 min for 6 hr, both before and after induction of primary hypothyroidism. After induction of primary hypothyroidism, a 37-fold increase in mean basal plasma TSH concentration and a 34-fold increase in mean area under the curve for TSH were found. Analysis by the Pulsar program demonstrated pulsatile secretion of TSH in the hypothyroid state, characterized by relatively low amplitude pulses (mean [±SEM]) amplitude 41 ± 3% of basal plasma TSH level) and a mean pulse frequency of 2.0 ± 0.5 pulses/6 hr. In the euthyroid state, significant TSH pulses were identified in only 2 dogs. The mean basal plasma TSH level correlated positively (r = 0.84) with the mean amplitude of the TSH pulses, and correlated negatively (r = −0.88) with the TSH pulse frequency. The results of this study demonstrate pulsatile secretion of TSH in dogs during hypothyroidism and only small fluctuations in plasma TSH concentrations during euthyroidism. The findings also suggest that the low TSH values occasionally found in dogs with spontaneous primary hypothyroidism may in some cases in part be the result of ultradian fluctuations.

The role of selenium in iodine metabolism in children with goiter.

Possible interactions between selenium and iodine metabolism were investigated in 7- to 16-year-old children with goiter (n = 136) living in southeastern Poland in iodine-deficient areas influenced by a sulfur industry. The Se-iodine interactions in these children were compared to the interactions in children from outside of that region (n = 38). Blood selenium (BSe) concentration and plasma glutathione peroxidase activity were much lower in the study group (64.1 +/- 15.7 microg/L; 111.0 +/- 27.6 U/L) than in the control group (85.3 +/- 19.6 microg/L; 182.4 +/- 35.6 U/L). Almost all of the data [plasma thyroid-stimulating hormone (TSH) concentration, plasma free thyroxine (fT(4)) concentration] fell within the reference limits. There was no statistically significant difference between the control and the study groups with respect to fT(4) and TSH. However, statistically significant differences of fT(4) and TSH in the study group were revealed between females belonging to the lower (n = 21; fT(4), 16.1 +/- 3.3 pmol/L; TSH, 1.83 +/- 1.05 mU/L) and upper Se quartiles (n = 24; fT(4), 14.5 +/- 2.2 pmol/L; TSH, 1. 26 +/- 0.90 mU/L), p < 0.05. Neither group differed in iodine in urine concentration, age, and body mass index. The difference in fT(4) concentrations can be attributed to an Se deficiency. The relationship exists only for females, which suggests a sex-linked hormonal response to concomitant Se and iodine deficiencies.

The Effect of Particle Size of Whole-Grain Flour on Plasma Glucose, Insulin, Glucagon and Thyroid-Stimulating Hormone in Humans

Objective: Although it is well known that consumption of whole-grain foods with higher fiber content results in beneficial health effects, most Americans usually prefer bread made with white flour. Changes in bread texture and undesirable intestinal responses have been reported as reasons for avoiding consumption of whole-grain foods or high-fiber menus. The purpose of this study was to determine whether consumption of bread made with ultra-fine-ground whole-grain wheat flour retained beneficial effects while reducing undesirable effects.Methods: Twenty-six men and women, 31 to 55 years of age, consumed glucose solutions or bread made with traditional white, conventional whole-grain wheat (WWF), or ultra-fine whole-grain wheat (UFWF) flour (1 g carbohydrate/kg body weight) in a Latin square design after two days of controlled diet. The effect on glycemic response was determined by comparing blood variables, after a tolerance test with white bread, WWF bread, and UFWF bread, with those after a glucose tolerance test.Results: Men and women had similar responses to all tolerances except postprandial TSH. Glucose and insulin levels one half hour after the glucose load were significantly higher than after any of the bread tolerances. Glucose, but not insulin, areas under the curve were significantly higher after the glucose load than areas after the three breads. Consumption of UFWF resulted in glucose and insulin responses, as well as areas under the curve, similar to those after consumption of conventional whole-wheat bread.Conclusion: The particle size of whole grain wheat flour did not substantially affect glycemic responses.

In Vitro and in Vivo Study of the Antithyroid Side Effects of Trimeprazine

Trimeprazine (TMP), a phenothiazine used as antipsychotic drug, was previously shown to induce a decrease in thyroid hormone serum levels in rats. Different mechanisms might be involved, mainly (i) a central mechanism, involving a reduction of thyroid-stimulating hormone (TSH) secretion; (ii) a peripheral mechanism, acting upon the synthesis of thyroid hormones, by inhibition of thyroperoxidase (TPO) or trapping of molecular iodine present in the thyroid gland. These different hypotheses were investigated in the present study, using in vitro and in vivo experiments.In vitro studies concerned TMP and its three main metabolites: trimeprazine sulphoxide (TSO), N-desmethyl trimeprazine (NDT), and 3-hydroxy-trimeprazine (3-OHT). TMP and TSO expressed a high affinity for iodine in vitro, contrary to NDT, which did not complex iodine. Only 3-OHT inhibited TPO in vitro. Administration of 5 mg/kg TMP ip twice daily for 11 days to Wistar rats induced a decrease of free triiodothyronine and free thyroxine (fT3 and fT4) and a trend toward an increase of TSH serum levels. Thyroid concentrations of TMP, NDT, and TSO were significantly higher than serum levels, while 3-OHT was never detected. An iodine-supplemented diet administered to a group of rats treated with TMP significantly increased the thyroid concentration of TMP and TSO, but not that of NDT, while it did not affect the concentrations observed in serum and other organs.The increase in plasma TSH is not consistent with the central mechanism hypothesis, and the absence of TPO inhibition by TMP, TSO, and NDT contradicts the TPO inhibition hypothesis. On the contrary, three findings support the hypothesis of iodine trapping through formation of a complex with TMP and TSO: these molecules complex iodine in vitro, they accumulate in the thyroid, and their thyroid concentration is increased when the rats are fed an iodine-supplemented diet.

The drop in plasma thyrotropin concentrations in fasted chickens is caused by an action at the level of the hypothalamus: role of corticosterone

Fasting has severe effects on thyroid metabolism in the chicken: plasma thyroxine (T 4) concentrations increase, whereas 3′,5,3-triiodothyronine (T 3) concentrations decrease. In the present report we studied the effect of fasting at the level of: 1) the pituitary (plasma thyrotropin (TSH) concentrations; the sensitivity of thyrotrophs to corticotropin-releasing hormone (CRH) and TSH-releasing hormone (TRH)); and 2) the hypothalamus (TRH content). A regulatory role of corticosterone is discussed. One day of fasting resulted in a drop in plasma TSH concentrations. Fed and nonfed animals were treated with ovine CRH (oCRH) or TRH. The sensitivity of thyrotrophs to the respective hypothalamic hormones was increased when animals were subjected to a 1-d period of fasting. A 75% (TRH) and 50% (oCRH) increase in plasma TSH was recorded in fasted animals, whereas both secretagogues did not evoke any response in their fed counterparts. The drop in plasma TSH cannot, therefore, be attributed to a loss in sensitivity of thyrotrophs to hypothalamic stimulatory control. In an identical experiment, plasma TSH concentrations decreased, whereas hypothalamic TRH content was higher in fasted animals, suggesting a decreased hypothalamic TRH release toward the pituitary. In both fasting experiments, plasma corticosterone concentrations were increased after 1 d of fasting. Because an iv injection of corticosterone-elevated hypothalamic TRH contents and decreased plasma TSH concentrations, a corticosterone-induced TSH decrease during fasting is suggested through an action at the level of the hypothalamus.

Characteristics of recovery from the euthyroid sick syndrome induced by tumor necrosis factor alpha in cancer patients

Cytokines have been implicated in the pathogenesis of the euthyroid sick syndrome. Isolated limb perfusion (ILP) with recombinant human tumor necrosis factor alpha (rTNF) and melphalan in patients with melanoma or sarcoma is accompanied by high systemic TNF levels. We examined the prolonged effects (7 days) of ILP on thyroid hormone metabolism with respect to induction and recovery of the euthyroid sick syndrome in six cancer patients. After ILP, when the limb is reconnected to the systemic circulation, leakage of residual rTNF resulted in systemic peak levels at 10 minutes postperfusion followed by a parallel increase in plasma interleukin-6 (IL-6) and cortisol, with maximum levels at 4 hours ( P < .05). A rapid decrease was observed at 5 minutes for plasma triidothyronine (T3), reverse T3 (rT3), thyroxine (T4), and thyroxine-binding globulin (TBG) ( P < .05), whereas free T4 (FT4) and T3-uptake showed a sharp increase, with peak levels at 5 minutes ( P < .05). T3, T4, and TBG levels remained low until 24 hours after ILP. In contrast, rT3 increased above pretreatment values to maximum levels at 24 hours ( P < .05). Plasma thyrotropin (TSH) showed an initial decrease at 4 hours postperfusion ( P < .05) but exceeded pretreatment values from day 1 to day 7 (by +94% ± 43% to + 155% ± 66%, P < .05), preceding the recovery of T4 and T3 levels. T3 and rT3 returned to initial values at day 4. T4 and TBG levels recovered at day 2. T4 exceeded basal values at days 5 to 7 ( P < .05). It is concluded that ILP with rTNF induces a euthyroid sick syndrome either directly or indirectly through other mediators such as IL-6 or cortisol. The recovery from this euthyroid sick syndrome is, at least in part, TSH-dependent, since the prolonged elevation of TSH values preceded and persisted during the normalization of T3 and the elevation of T4 levels. This biphasic pattern of induction of and recovery from the euthyroid sick syndrome may be a general feature of nonthyroidal disease. The euthyroid sick syndrome should be interpreted not only in relation to the presence of nonthyroidal diseases but also in relation to the recovery from these diseases.