triiodothyronine--reverse and Body-Weight

An appreciation of the physiology of fasting is essential to the understanding of therapeutic dietary interventions and the effect of food deprivation in various diseases. The practice of prolonged fasting for political or religious purposes is increasing, and a physician is likely to encounter such circumstances. Early in fasting weight loss is rapid, averaging 0.9 kg per day during the first week and slowing to 0.3 kg per day by the third week; early rapid weight loss is primarily due to negative sodium balance. Metabolically, early fasting is characterized by a high rate of gluconeogenesis with amino acids as the primary substrates. As fasting continues, progressive ketosis develops due to the mobilization and oxidation of fatty acids. As ketone levels rise they replace glucose as the primary energy source in the central nervous system, thereby decreasing the need for gluconeogenesis and sparing protein catabolism. Several hormonal changes occur during fasting, including a fall in insulin and T(3) levels and a rise in glucagon and reverse T(3) levels. Most studies of fasting have used obese persons and results may not always apply to lean persons. Medical complications seen in fasting include gout and urate nephrolithiasis, postural hypotension and cardiac arrhythmias.

Topics: Adult; Amino Acids; Arrhythmias, Cardiac; Body Weight; Fasting; Glucagon; Gluconeogenesis; Gout; Humans; Hypotension, Orthostatic; Insulin; Ketosis; Kidney Calculi; Lipid Mobilization; Male; Sodium; Triiodothyronine; Triiodothyronine, Reverse

Thyroid function has been investigated in 24 young military cadets participating in a 5 d ranger training course with heavy physical exercise, calorie deficiency and deprivation of sleep. The cadets were divided into three groups, each differing in the amount of sleep and food consumption. The serum levels of thyroid hormones (T4, FT4, T3, rT3) and TBG showed a biphasic pattern during the course. Initially there was an increased secretion concomitant with an increased deiodination of T4 to T3 and rT3 mainly due to physical exercise. When the activities lasted for several days without sufficient food supply the thyroid secretion decreased simultaneously with an alteration of the peripheral conversion of T4 to rT3 instead of T3. A significant correlation was found between the changes in total and free thyroxine (r = 0.9) and between the increase in rT3 and decrease in T3 (r = 0.6). TSH decreased during the first day of activities and remained low throughout the course. The TSH response to TRH stimulation was greatly reduced during the course due to physical exercise and calorie deficiency. The present investigation demonstrates that the thyroid function is strongly affected by prolonged physical exercise and a negative energy balance, whereas sleep deprivation does not have any significant influence. The results indicate that the alteration observed is not regulated just by the hypothalamo-pituitary-thyroid-axis alone.

Topics: Adult; Body Weight; Energy Intake; Energy Metabolism; Humans; Male; Physical Exertion; Sleep Deprivation; Thyroid Gland; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Thyroxine-Binding Proteins; Triiodothyronine; Triiodothyronine, Reverse

Twenty obese patients were treated as out-patients with a 3.35 MJ (800 Kcal) per day diet, and, by the double-blind method, ten of the patients were prescribed 40 micrograms of triiodothyronine (T3) daily and the other ten placebo. Body weight and serum thyroxine (T4), T3 and reverse T3 (rT3) concentrations were measured before treatment, then monthly over 6 months. No significant difference in mean weight loss was found between the patients receiving T3 and those on placebo. Serum T3 concentration decreased slightly in patients on placebo and increased in those on T3 but these changes were not statistically significant. However, patients on T3 maintained a significantly higher concentration of T3 in serum than those on placebo. Mean serum T4 and rT3 concentrations remained essentially unchanged in the patients on placebo, whereas both decreased significantly in patients receiving T3. We conclude that changes in serum T3 during dietary treatment of obesity are of minor significance in limiting the expected weight loss in the patients.

Topics: Adult; Body Weight; Diet, Reducing; Female; Humans; Male; Middle Aged; Obesity; Thyroid Hormones; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

The effects of thyroid hormone on whole body energy metabolism and compensatory effects on food intake are well established. However, the hypothalamic mechanisms that translate perceived whole body energy demands into subsequent appetitive behavior are incompletely understood. In order to address this question, we tested the effects of T3 on food intake and body weight in rats and measured neuronal Na/K ATPase activity and ATP content in the hypothalamus. Intraperitoneal T3 (100 microg/kg BW) administered for 6 consecutive days increased 24-h rat food intake from control, 26.6+/-1.2, to T3-treated 33.2+/-1.6 g (P<0.01). In T3-treated rats, rubidium-86 (86Rb) uptake (measured as a marker of Na/K ATPase activity) in ex vivo hypothalamic tissue increased (P<0.01) while the content of ATP in the ventral hypothalamus declined following T3 treatment (P<0.01). In another model of energy deficit, which was induced by a very low calorie diet, ATP content was also reduced in the hypothalamus compared to rats fed ad libitum. In summary, increased food intake in response to T3 may be secondary to decreased hypothalamic ATP content, perhaps resulting from both increased Na/K ATPase activity in the hypothalamus and metabolic signaling induced by whole body caloric deficit.

Topics: Adenosine Triphosphate; Animals; Behavior, Animal; Body Weight; Cerebellum; Cerebral Cortex; Diet; Dose-Response Relationship, Drug; Eating; Hypothalamus; In Vitro Techniques; Liver; Male; Rats; Rats, Inbred Strains; Rubidium Radioisotopes; Sodium-Potassium-Exchanging ATPase; Thyroid Hormones; Time Factors; Triiodothyronine, Reverse

The effect of an in ovo infection with a Dutch isolate of avian leukosis virus subgroup J (ALV-J) on the growth of specific pathogen free (SPF) broiler chickens was analysed. During this study, possible immune suppressive effects of ALV-J were assessed by measuring delayed-type hypersensitivity with keyhole limpet haemocyanin (KLH), natural killer (NK) cell activity, the production of radicals of nitric oxide (NO) by macrophages, humoral immune response against Newcastle and infectious bursal disease vaccine viruses, and automated total and differential leukocyte counts. In an attempt to elucidate the underlying causal mechanisms of the induced growth retardation, 3,3',5-triiodothyronine (T3) concentrations in serum were measured. Four experiments were conducted. In experiment 1, ALV-J-injected birds were compared with ALV subgroup A (ALV-A)-injected and negative control chickens. In experiment 2, ALV-J-injected birds were only compared with negative controls. Finally, in experiments 3a and 3b, ALV-J-injected chickens were compared with negative controls and a group of chickens in which only 10% of birds had been injected with ALV-J. Birds were injected in ovo at day 7 of incubation with 10(4) median tissue culture infectious dose (TCID(50)) ALV-J or ALV-A, except in experiment 3a where 10(2) TCID(50) ALV-J was injected. Significant growth suppression was found in all 100% of ALV-J-infected groups. The average growth retardation of ALV-J-infected birds compared with negative controls at 6 weeks of age was approximately 8, 11, 2.5 and 6% for the four successive experiments performed. The delayed-type hypersensitivity test against KLH of ALV-J-infected birds showed a tendency towards lower wattle thickness; however, the difference with controls was not significant (P > 0.05). The same was true for NK cell activity and NO production by macrophages, although the difference was not significant. The total and differential leukocyte counts performed on blood samples from birds at 3, 4 and 6 weeks of age as well as the humoral immune response against Newcastle and infectious bursal disease vaccine viruses did not show significant differences between treatment groups either. Only the number of basophils were significantly higher (P = 0.02) in ALV-J-infected birds at 3 weeks of age. No significant lower T(3) levels were found in ALV-J-infected birds in weeks 2 and 3 (experiment 2) and weeks 3 and 5 (experiment 3b); however, at 4 weeks (experiment 2) and 6 weeks (ex

Topics: Animals; Avian Leukosis; Avian Leukosis Virus; Body Weight; Chickens; Cloaca; Enzyme-Linked Immunosorbent Assay; Hypersensitivity, Delayed; Killer Cells, Natural; Leukocyte Count; Macrophages; Netherlands; Nitric Oxide; Ovum; Poultry Diseases; Specific Pathogen-Free Organisms; Triiodothyronine, Reverse

Effects of starvation on thyroid hormone homeostasis were usually determined after 2 or more days of fasting, however, both in man and in rodents, natural feeding cycles comprise far shorter fasting periods. Therefore serum levels of T4, FT4, T3, FT3 and rT3 were measured in rats refed chow diet for 1, 4, 8 or 24 hours after 14 or 48 hours of starvation. Both short-term (14 h) and long-term fasting (48 h) decreased body weight and serum glucose level. Short-term fast decreased serum FT3 and did not change serum levels of T4, FT4, T3 and rT3. Total T3 and reverse T3 increased after one and 4 hours, free T3 after 4 hours and total T4 after 4 and 8 hours of refeeding. Percent of FT3 did not change after short-term fast, declined after 1 and 4 hours of refeeding, and normalised thereafter. Prolonged starvation (48 h) decreased serum T4, T3, FT3 and % FT3 with no changes in FT4 and rT3. After 24 hours of refeeding only FT3 and % FT3 returned to control levels while total T4 and total T3 were still diminished, and reverse T3 levels did not change. The results suggest that the length of preceding fasting period may strongly influence thyroid hormone homeostasis during fasted-to-fed transition.

Topics: Animals; Blood Glucose; Body Weight; Fasting; Food; Homeostasis; Kinetics; Male; Rats; Rats, Wistar; Thyroid Hormones; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

This study examined the effect of high altitude and cold exposure on thyroid hormone status during a mountaineering expedition. There were 15 males participating in an expedition to climb Mt. McKinley, AK. Resting blood samples were collected and analyzed for thyroid-stimulating hormone (TSH), total (T)-free (f) thyroxine (T4), triiodothyronine (T3), reverse T3 (rT3), and cortisol. Measurements were made on three occasions: baseline in the continental U.S. one week pre-expedition (PRE-I), baseline in Alaska immediately pre-expedition (PRE-II), and immediately upon descent post-expedition (POST). Statistical analysis indicated that no significant trial PRE-I vs. PRE-II (p > 0.05) differences occurred. Significant (p < 0.05) reduction, however, occurred from PRE-II to POST expedition in TSH, TT3, and fT3. Also rT3 and cortisol increased significantly PRE-II to POST while TT4 and fT4 were unchanged. The increase (delta = POST minus PRE-II) in cortisol was negatively correlated with the decrease (delta) in TSH (r = -0.52, p = 0.05) and TT3 (r = -0.49, p < 0.06). Moreover, the reduction in TT3 was inversely correlated with the rT3 increase (delta comparison, r = -0.66, p < 0.01). The findings demonstrate that the resting concentrations of thyroid hormones are disrupted by a mountaineering expedition, specifically an environmental stress-related "low T3 condition" seems to develop. These changes would seem to be related to an impaired peripheral conversion of T4 to T3, possibly brought about by elevations in the circulating cortisol levels.

Topics: Adult; Alaska; Altitude; Blood Pressure; Body Weight; Cold Climate; Heart Rate; Humans; Hydrocortisone; Male; Mountaineering; Rest; Thyroid Hormones; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Undernutrition was induced in rats submitted to food restriction from the fetal stage, and malnutrition was continued after birth until 70 days of life. Body weight was decreased to less than 50%. Plasma T4 and T3 and pituitary TSH content were determined between 8-70 days of life. In control rats, plasma T4 and T3 reached a maximum at 14 and 35 days of life, respectively, and TSH pituitary content at 45 days of life. In undernourished rats, after 8 days of life, plasma T4 and T3 and pituitary TSH content were decreased to about 50% or less, and the pattern of sequential changes observed in control rats was absent or modified. T4 and T3 concentrations were measured in heart, liver, and brain in the fetus (22 days old) and 8, 14, and 23 days after birth, as well as liver and brain 5'-deiodinases (5'D). Hepatic 5'D type I was always decreased in undernourished rats from 8-70 days after birth. Liver and heart T4 and T3 concentrations were decreased in 14-day-old undernourished rats as well as brain T3. Brain 5'D type II was decreased at 8 and 14 days, and total brain 5'D activities at 8 days. These changes occurred during the critical period for brain development (7th to 20th day) during which most processes of myelination take place and T3 brain normal levels are required.

Topics: Aging; Animals; Body Weight; Brain; Embryonic and Fetal Development; Female; Heart; Iodide Peroxidase; Liver; Myocardium; Nutrition Disorders; Organ Size; Organ Specificity; Pituitary Gland; Pregnancy; Propylthiouracil; Rats; Rats, Inbred Strains; Reference Values; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

1. Assay conditions for measuring hepatic 5'-deiodinase (5'D) activity at initial velocity, using reverse T3 as substrate, have been validated for adult chicken liver. 2. The characteristics of hepatic 5'D activity in adult chickens from lines selected for high (HW) and low (LW) juvenile body weight are similar to those in mammals and in the other birds that have been investigated. 3. Chickens from the HW line have significantly higher specific activity of hepatic 5'D, and thus potentially higher T3 production, than those from either the LW line or the F1 cross (HL) between the HW and LW lines.

Topics: Animals; Body Weight; Chickens; Crosses, Genetic; Female; Iodide Peroxidase; Liver; Male; Reproducibility of Results; Triiodothyronine, Reverse

The effect of fasting on circadian and pulsatile TSH secretion was investigated in eight healthy subjects (four men and four women in the follicular phase). Each subject was studied twice, once during 24 h with normal food intake and once during the last 24 h of a 60-h fast. Blood was sampled every 10 min during 24 h for measurement of TSH by a sensitive immunoradiometric assay. Fasting induced a decrease in plasma T3 [1.73 +/- 0.06 vs. 1.36 +/- 0.04 nmol/L; P less than 0.01 (mean +/- SE), control period vs. fasting] and thyroglobulin (52 +/- 8 vs. 35 +/- 7 pmol/L; P less than 0.001) and an increase in plasma rT3 (0.30 +/- 0.06 vs. 0.44 +/- 0.09 nmol/L; P less than 0.02). Plasma T4, thyroid hormone binding index, and free T4 were not statistically different in both periods. The mean plasma 24-h TSH concentration was lower during fasting than in the control period (2.0 +/- 0.3 vs. 1.0 +/- 0.2 mU/L; P less than 0.005). This was associated with a decrease in mean TSH pulse amplitude during fasting (Desade program: 0.6 +/- 0.1 vs. 0.3 +/- 0.1 mU/L; P less than 0.01; Cluster program: 0.5 +/- 0.1 vs. 0.2 +/- 0.1 mU/L; P less than 0.05), whereas TSH pulse frequency during fasting was unchanged (Desade program: 8.4 +/- 0.9 vs. 9.8 +/- 0.8 pulses/24 h; Cluster program: 9.5 +/- 0.5 vs. 7.9 +/- 0.9 pulses/24 h). There was a highly significant correlation between the mean 24-h TSH concentration and the mean TSH pulse amplitude during both the control period and fasting. Although the decrease in TSH concentration during fasting was evident over 24 h, fasting especially decreased the absolute (1.3 +/- 0.3 vs. 0.4 +/- 0.1 mU/L, P less than 0.02) and the relative (101 +/- 18% vs. 40 +/- 14%; P less than 0.02) nocturnal TSH surge (mean TSH 0000-0400 h vs. mean TSH 1500-1900 h). The decreased nocturnal TSH surge during fasting was associated with a significantly decreased TSH pulse amplitude, but with an unaltered number of TSH pulses between 2000-0400 h. In conclusion, fasting decreases 24-h TSH secretion and the nocturnal TSH surge in the absence of a change in plasma T4 concentration. This is associated with a decreased TSH pulse amplitude, whereas TSH pulse frequency remains unchanged.

Topics: Adult; Body Weight; Fasting; Female; Humans; Male; Middle Aged; Periodicity; Thyroglobulin; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

To elucidate the mechanism by which the low T3 and low T4 syndrome occurs in patients with infection, recombinant human interleukin-1 (IL-1) was administered to mice, and their thyroid hormone metabolism was studied. Continuous sc infusion of IL-1 alpha or IL-1 beta at a dose of 0.015-1 microgram/day for 3 days decreased food intake and serum T4, T3, and rT3 concentrations in a dose-dependent manner. In pair-fed control (PFC) mice, serum T4 and T3 also decreased, but rT3 was reciprocally increased. The T3/T4 ratio was greater in IL-1-treated mice than in PFC mice. Although food intake was decreased by 65% in IL-1-treated mice (1 microgram/day) compared with that in fed control mice, type I iodothyronine 5'-deiodinating activity in liver was significantly increased compared with that in fed control mice. Furthermore, the T3 and T4 responses to TSH were greatly diminished in IL-1-treated mice. These findings suggest that IL-1 directly inhibited the effect of TSH on the thyroid gland and decreased the serum concentrations of T4 and T3, and that an increase in type I iodothyronine 5'-deiodinating activity in livers of IL-1-treated mice may account for the greater T3/T4 ratio and lower serum rT3 concentration than those in PFC mice. Since tumor necrosis factor-alpha has a similar effect, we speculate that both cytokines may be synergistically involved in the altered thyroid hormone metabolism in mice (decreased serum T4, T3, and rT3 concentrations) and hypercatabolism in a febrile state.

Topics: Animals; Body Weight; Eating; Interleukin-1; Iodide Peroxidase; Liver; Male; Mice; Mice, Inbred ICR; Recombinant Proteins; Serum Albumin; Thyroid Hormones; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

The hypothalamic-pituitary-thyroidal axis was studied in 17 normal-weight patients with bulimia. Basal levels of serum thyroxine (T4), triiodothyronine (T3), reverse triiodothyronine (rT3), and thyrotropin (TSH) were determined in all patients; responses of TSH and T3 to thyrotropin-releasing hormone (TRH) were investigated in nine patients. Mean basal serum T4, T3, and TSH concentrations were significantly lower in the patients than in the normal control subjects but serum rT3 levels were essentially the same. In nine patients TSH responses to TRH were normal in five, delayed in three, and low in one. The maximum increase in serum TSH and TSH net secretory response were not significantly different from those of control subjects. With respect to the T3 response to TRH, various indices in patients appeared significantly lower than in the control subjects. These results suggest that normal-weight patients with bulimia have abnormalities in the hypothalamic-pituitary-thyroidal axis.

Topics: Adult; Body Weight; Bulimia; Female; Humans; Hypothalamo-Hypophyseal System; Thyroid Gland; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

To elucidate the mechanism by which low T3 and low T4 syndrome occurs in patients with acute or chronic infection or malignancy, recombinant human tumor necrosis factor-alpha (TNF-alpha)/cachectin (TNF) was administered ip to mice and thyroid hormone metabolism was studied. Since administration of TNF caused a decrease in food intake and body weight, all experiments were performed using pair-fed control (PFC) mice. Administration of TNF at a dose of 1-100 micrograms/day for 3 days decreased serum T4, T3, and rT3 concentrations in a dose-dependent manner. In PFC mice, serum T4 and T3 also decreased, but rT3 was significantly increased. T3/T4 ratio was greater in TNF-treated mice than in PFC mice. Type I iodothyronine-5'-deiodinating activity in the liver was significantly decreased in PFC mice but not in TNF-treated mice. The effect of TNF was reversible and could be abolished by boiling the cytokine. Furthermore, T3 and T4 response to TSH was greatly diminished in TNF-treated mice in comparison with PFC mice. These findings suggest that TNF directly inhibited the effect of TSH on the thyroid gland and decreased the serum concentrations of T4 and T3. Although TNF decreased food intake and body weight in TNF-treated mice, it did not decrease type I 5'-deiodinating activity in the liver, resulting in a greater T3/T4 ratio and lower serum rT3 concentration than those in PFC mice. We speculate that TNF is at least partly involved in the altered thyroid hormone metabolism (decreased serum T4, T3, and rT3 concentrations) caused by infections in mice.

Topics: Animals; Body Weight; Dose-Response Relationship, Drug; Feeding Behavior; Humans; Kinetics; Male; Mice; Mice, Inbred ICR; Recombinant Proteins; Reference Values; Serum Albumin; Thyroid Hormones; Thyrotropin; Thyroxine; Triglycerides; Triiodothyronine; Triiodothyronine, Reverse; Tumor Necrosis Factor-alpha

Responses of broiler chickens to a high ambient temperature (35 degrees C) were measured in two experiments. In one experiment temperatures were increased abruptly from 21 degrees C to a daily range of 21-35 degrees C whereas, in the other, temperatures were increased more gradually over 6 days. The high temperatures were maintained for 5 h/day. In both experiments, birds exposed to the high temperatures ate less food and gained less liveweight than birds maintained at 21 degrees C. Efficiency of food conversion to liveweight gain and body composition were not affected by high temperature but there was a tendency for thyroid weight to decrease. Overall, the plasma concentration of triiodothyronine (T3) decreased and the plasma concentration of thyroxine (T4) increased, resulting in a decreased T3/T4 molar ratio, during exposure to high temperature. The concentration of plasma growth hormone, but not plasma reverse T3, was increased by high temperature. The initial responses to increased temperature were variable, with birds exposed more gradually adjusting relatively well until the maximum temperature was increased to 35 degrees C. All heated birds readjusted quickly to the daily reduction in temperature to 21 degrees C.

Topics: Animals; Body Weight; Chickens; Eating; Growth Hormone; Hot Temperature; Male; Organ Size; Thyroid Hormones; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Topics: Body Weight; Humans; Neoplasms; Triiodothyronine; Triiodothyronine, Reverse

The iodine-containing contrast medium iopanoic acid induces alterations of thyroid hormone metabolism comparable to those observed with the iodine-containing antiarrhythmic drug amiodarone. Both compounds inhibit the intracellular conversion of thyroxine (T4) to triiodothyronine (T3). Using iopanoic acid, the question was investigated, in guinea-pigs, whether inhibition of T4----T3 conversion is by itself associated with the same changes in the electrocardiogram, i.e. QT prolongation and bradycardia, as those observed during amiodarone treatment. At a dose of 4 g kg-1, iopanoic acid induced maximal inhibition of the T4----T3 conversion. Although these changes were even more pronounced than those in a control group of animals treated with 2.12 g amiodarone kg-1, neither prolongation of the QT nor a slowing of the heart rate was observed. QT prolongation and bradycardia were induced only by amiodarone treatment but not by iopanoic acid. Iopanoic acid at the high toxic dose of 12 g kg-1 induced the same degree of inhibition of T4----T3 conversion as the 4 g kg-1 dose. QT prolongation and slowing of the heart rate were apparent at this dose in parallel with a loss of weight. It is concluded that even a maximal inhibition of the T4----T3 conversion has no effect on the ECG of guinea-pigs. The inhibition of the T4----T3 conversion alone does not explain the QT prolongation and bradycardia observed with amiodarone treatment. The amiodarone effects on the ECG may represent a combination of interactions with thyroid hormones and antiadrenergic activity.

Topics: Amiodarone; Animals; Benzofurans; Body Weight; Electrocardiography; Guinea Pigs; Heart Rate; Male; Myocardium; Thyroid Hormones; Thyroxine; Time Factors; Triiodothyronine; Triiodothyronine, Reverse

Anorexia nervosa is accompanied by increased serum reverse triiodothyronine levels and decreased serum triiodothyronine levels. We observed 28 women undergoing gastric plication for morbid obesity and found serum reverse triiodothyronine levels to be significantly decreased (p = 0.018) from a preoperative mean (+/- SD) of 0.30 (+/- 0.17) to 0.21 (+/- 0.06) ng/ml after weight loss. As all of our subjects were on semistarvation diets and had a significant weight loss (p less than 0.001), the observed decrease in reverse triiodothyronine rather than increase (as reported in anorexia nervosa) suggests factors other than weight loss or a semistarvation diet are important in the reverse triiodothyronine increase observed in anorexia nervosa.

Topics: Adult; Body Weight; Female; Humans; Obesity; Serum Albumin; Stomach; Thyroxine; Thyroxine-Binding Proteins; Triiodothyronine; Triiodothyronine, Reverse

We have estimated numerous physiological parameters of production, interpool transport, distribution, and metabolism of rT3 in the major rT3 pools of the unanesthetized male Sprague-Dawley rat. These results also have been combined with similar results for T3 and T4, generating a composite model for all three iodothyronines. Three different approaches were used to analyze the rT3 data, determined from five optimally timed blood samples collected in new tracer kinetic studies and processed by Sephadex chromatography and RIA. A model-structure independent approach generated a plasma clearance rate of 2.82 (ml/min)/100 g BW, a plasma turnover rate of 1.05 min-1, a plasma-to-total tissue flux of 0.107 (ng/min)/100 g BW and a plasma appearance rate (PAR) of 0.061 (ng/min)/100 g BW, the latter being the product of the plasma clearance rate and the endogenous rT3 plasma concentration. Multicompartmental analysis resulted in additional parameters of physiological interest, many only as ranges or minimum and maximum possible values, owing to complex factors intrinsic in rT3 kinetics. Whole body rT3 production can be as low as 0.061 (=PAR), and as high as 0.377 (ng/min)/100 g BW, i.e. possibly as much as 5 times greater than the PAR, the conventional estimate of production rate. Plasma contains only 3-12% of total body rT3 (Qtot); slow tissue pools, that exchange rT3 slowly with plasma, possibly muscle, skin, and brain, contain 63-95% of Qtot, and produce more than 42% of total body rT3 from T4 locally; and fast tissues like liver and kidney contain 2-26% of Qtot, and produce more than 12% of total body rT3 from T4 locally. The plasma equivalent distribution volume (VD) of rT3 is 38-146 ml/100 g BW, and its whole body mean residence time is only 14-52 min, both of which are an order of magnitude smaller than corresponding T3 values; but VD for rT3 and T4 are roughly the same. Noncompartmental analysis underestimated VD and mean residence time by somewhere between a factor of 1.2 and 4.6. Overall, these results indicate that tissue pools that exchange rT3 slowly with the plasma pool contain the majority of rT3, T3, and T4 in steady state; and these tissues also are implicated as major sites of T4 monodeiodination, to both rT3 and T3.

Topics: Animals; Body Weight; Kinetics; Male; Models, Biological; Rats; Rats, Inbred Strains; Thyroxine; Tissue Distribution; Triiodothyronine; Triiodothyronine, Reverse

Effects of high fat diet (HFD)-induced obesity and moderate aging on iodothyronine kinetics were studied in young adult (3 month old) chow-fed male rats and two groups of older 9- to 11-month-old) male rats, one on chow and the other on HFD. Labeled T4, T3, and rT3 were each injected via an intraatrial double lumen catheter in unanesthetized rats. Serial blood samples were collected according to optimally designed schedules, and labeled iodothyronines in serum were quantified with three different Sephadex gel chromatographic systems. Comprehensive kinetic analyses indicated the following. Several T4 metabolic indices were markedly different between the two older groups (chow vs. HFD), most notable, increased plasma T4 clearance rate (0.098 vs. 0.15 ml/min), decreased plasma T4 concentration (23 vs. 15 ng/ml), and a plasma T4 fractional turnover rate 2 times greater (0.10 vs. 0.19/min), all in the HFD group. There was also a high negative correlation between T4 concentration and body weight (r = 0.77), but not with age. However, the three groups manifested no significant differences in T4 secretion rates (2.0 vs. 2.2 vs. 2.3 ng/min) or whole body pool sizes (2.1 vs. 2.3 vs. 2.4 micrograms). Accounting for metabolic body size, there still were no differences in T4 secretion rate or pool sizes. For T3, we found an almost 3-fold increase in T3 whole body production rates, and a greater than 2-fold increase (from about 25% to 60%) in the percentage of T4 converted to T3 in both older groups relative to that in the young rats. There were almost no significant differences in T3 kinetics between older HFD and older chow-fed groups, and differences in rT3 kinetics among the three groups revealed no clear pattern. Our results suggest that age-related correlations in T4 concentration are a consequence of body weight differences, not age as such. However, the metabolic fate of T4 changes with age, with more than twice as much converted to T3 in older animals. Constancy of T4 production rate and total pool size in young and older animals, independent of body weight, together with the apparent increase in T4 conversion to T3 suggest that the metabolic needs of the animal are being met by regulation of T3 production from T4 conversion, not by regulation of T4 production as such.

Topics: Aging; Animals; Body Weight; Dietary Fats; Kinetics; Male; Obesity; Rats; Rats, Inbred Strains; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Serum total thyroxine (T4), 3,5,3'-triiodo-L-thyronine (T3), 3,3',5'-triiodo-L-thyronine (reverse T3 or rT3) and free thyroxine (FT4), free 3,5,3'-triiodo-L-thyronine (FT3) concentrations were measured by radioimmunoassay in 52 moderately obese patients and 32 age-matched control subjects with constant body weight and no dietary restriction. The comparisons of iodothyronine concentrations in the obese and control subjects gave the following results: serum T4 and FT4 concentrations were not different in the two samples (mean +/- s.e. T4: 105.8 +/- 3.0 vs 109.4 +/- 4.0 nmol/l, FT4: 10.9 +/- 0.4 vs 10.8 +/- 0.8 pmol/l). A slight but non-significant decrease in serum rT3 concentrations was observed in the obese patients (0.29 +/- 0.02 vs 0.32 +/- 0.02 nmol/l). A slight (10 per cent) but highly significant (P less than 0.01) decrease was observed in the obese patients for serum T3 (2.20 +/- 0.06 vs 2.44 +/- 0.05 nmol/l) and FT3 (6.0 +/- 0.2 vs 6.9 +/- 0.2 pmol/l). Serum FT4 and T4 on the one hand and serum FT3 and T3 on the other were positively correlated both in the obese and control subjects. No correlation was found between serum T3 and weight expressed as body mass index. The results suggest that the most important factor responsible for the decrease in the serum total and free T3 concentrations is the nutrient intake.

Topics: Adolescent; Adult; Body Weight; Female; Humans; Male; Middle Aged; Obesity; Thyroid Hormones; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

In a previous study we have analysed serum free T4 concentrations in a representative population of 70-year-old men. In the present study the effect of previous or present tobacco smoking on free T4, T4, T3, rT3, TSH and thyroid hormone binding proteins was analysed in 181 of the 460 men, excluding those with past or present goitre, those who were obviously ill or had died between 70 and 75 years of age and those who had any disease or medication influencing free T4 concentrations. Smokers had higher T4 and rT3 levels, and lower TSH levels but T3 levels no different from non-smokers. The difference in T4 levels, but not rT3 or TSH levels, between smokers and non-smokers could be attributed to differences in body mass and also to differences in TBG levels. The results indicate that tobacco smoking is associated with long-term alterations in thyroregulatory function.

Topics: Aged; Body Weight; Humans; Male; Smoking; Thyroid Gland; Thyrotropin; Thyroxine; Thyroxine-Binding Proteins; Triiodothyronine; Triiodothyronine, Reverse

In an attempt to evaluate the observed relationship of chronic cigarette smoking and reduced thyroid hormone activity, the major urinary metabolites of nicotine were administered to rats for 78 weeks. The animals were divided equally into one control (n = 33) and three treatment groups. Treatment group 1 received 0.1% (w/v continine, group 2 received 0.02% pure trans-nicotine-N'-oxide, and group 3 received 0.02% of a trans/cis mixture (64/36%) of nicotine-N'-oxide. Plasma and urinary nicotine and cotinine concentrations were determined as well as a variety of thyroid hormone parameters. Pure trans-nicotine-N'-oxide was more extensively metabolized to its cotinine end product, relative to the diasteromeric N'-oxides, mixture. Serum triiodothyronine (T3) was markedly reduced in animals receiving nicotine-N'-oxides, but was not different in the cotinine treatment group when compared to control values. A reduction in serum thyroxine (T4) values was noted only among those rats receiving the pure trans-nicotine-N'-oxide. The T3/T4 ratio, free T3 index, T3 uptake, and rT3 were altered in animals receiving nicotine-N'-oxides. These findings indicate that specific nicotine metabolites alter thyroid hormone concentrations after chronic low-dose administration and possibly do so through back conversion to the parent compound, nicotine.

Topics: Animals; Body Weight; Cotinine; Cyclic N-Oxides; Male; Nicotine; Pyrrolidinones; Rats; Rats, Inbred F344; Thyroid Hormones; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

In 45 type 2 diabetics it was unable to be found a relation between the plasma lipids and the fasting blood glucose (G), HbA1c, reverse T3 (rT3), rT3/T3 ratio, and relative body weight (R.B.W.). The conclusion was reached that the alteration of the lipoprotein metabolism and the thyroid hormones in type 2 diabetics could be primitive and independent from the availability of the insulin.

Topics: Adult; Body Weight; Cholesterol; Diabetes Mellitus; Female; Glycated Hemoglobin; Humans; Insulin; Lipoproteins; Male; Triglycerides; Triiodothyronine; Triiodothyronine, Reverse

Severe calorie restriction for treating the obese reduces serum triiodothyronine (T3) and energy expenditure, and may be counterproductive. In order to avoid severe calorie deficiency, we measured the individual minimum energy requirements (threshold, T) in 17 obese females and fed each on a sub-threshold diet, comprising the maximum number of calories commensurate with weight loss (T-200 cals). Mean T-200 was 1318 +/- 96 cals, but the mean weight loss after 16 weeks on a sub-threshold diet (STD) was identical (17 kg) to that obtained by 22 age-matched female controls on a classical diet of 659 +/- 59 cals, exactly half the intake. Weight loss on the classical diet was initially rapid but decelerated sharply after 8 weeks, while on the sub-threshold diet the rate of loss remained constant throughout. In a second study, thyroid hormone measurements were performed three times weekly in 27 obese females during the 4 week period required to establish T. The mean weight loss was 4.02 +/- 0.3 kg, but T3 levels varied minimally and very transiently. STD produces short-term results similar to those obtained by severe calorie deprivation, but is more acceptable to the patient. It appears not to provoke the fat-saving reflexes provoked by the classical, low-calorie diet.

Topics: Adult; Body Weight; Diet, Reducing; Energy Intake; Energy Metabolism; Female; Humans; Obesity; Thyroid Hormones; Thyrotropin; Thyroxine; Thyroxine-Binding Proteins; Triiodothyronine; Triiodothyronine, Reverse

ātients with end-stage chronic renal failure (CRF) and those receiving dialysis therapy have normal or decreased serum total T4 (TT4), reduced serum total T3 (TT3), and normal total reverse T3 (TrT3) levels. Those with nonrenal nonthyroidal illnesses or malnutrition have low TT4 and TT3 but elevated TrT3 values. To evaluate the mechanism(s) for the normal TrT3 levels in CRF, we performed intravenous bolus kinetic studies of rT3 and T4 in patients with CRF, in those treated with chronic hemodialysis, in patients with nonrenal nonthyroidal illnesses, and in normal subjects. The CRF patients were selected to have good nutritional status as indicated by normal serum transferrin, relative body weight, and body mass index values. The CRF patients had normal TrT3, TT4, and free T4 values, increased free fraction of rT3, free rT3, and thyroxine-binding globulin levels, and decreased TT3 concentrations. Noncompartmental analysis of the rT3 kinetics indicated normal production rate, reduced cellular clearance rate, and increased pool size and residence time values in both the CRF and nonrenal patients. In CRF, the serum clearance rate was normal, but the fractional rate of exit, permeability, extravascular binding, and the apparent volume of distribution were increased. In contrast, the nonrenal patients had reduced serum clearance rate, permeability, and extravascular binding, whereas the fractional rate of exit and apparent volume of distribution were not significantly altered. The T4 kinetics in CRF paralleled those of the nonrenal patients, with a reduced fractional rate of exit and permeability in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Body Weight; Chronic Disease; Female; Humans; Infections; Kidney Failure, Chronic; Kinetics; Liver Diseases; Male; Middle Aged; Nutritional Physiological Phenomena; Renal Dialysis; Respiratory Insufficiency; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse; Uremia

In 21 type 1 diabetics a significative positive correlation was found between plasma triglycerides (TG) and fasting blood glucose (G), HbA1c, reverse T3 (rT3), rT3/T3 ratio and relative body weight (R.B.W.); total cholesterol (C) and HDL-cholesterol (HDL-C) were not correlated. If you consider the R.B.W. during the correlation between TG and the other laboratory tests, the only correlation that remains significant is that between TG and HbA1c. Plasma hyperTG found in type 1 diabetics appears to depend upon poor diabetic control and overweight; HDL-C is within normal limits because the removal of TG was slightly involved.

Topics: Adolescent; Adult; Blood Glucose; Body Weight; Diabetes Mellitus; Female; Glycated Hemoglobin; Humans; Male; Middle Aged; Triglycerides; Triiodothyronine; Triiodothyronine, Reverse

Topics: Animals; Body Weight; Energy Intake; Energy Metabolism; Humans; Obesity; Physical Exertion; Rats; Rest; Sodium-Potassium-Exchanging ATPase; Thyroid Hormones; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Ten patients with primary hypothyroidism (aged 32--66 yr), replaced on constant daily doses of L-T4 (mean +/- SD, 1.90 +/- 0.22 micrograms/kg BW), were used to examine seasonal variations in serum levels of thyroid-related hormones for a period of 14 months. Basal and peak TSH concentrations after TRH (500 micrograms) were higher in winter than in summer. Summer values for basal TSH were all normal (normal range, less than 4.8 microU/ml), while winter values were supranormal in 5 of 10 patients. Summer values for peak TSH were subnormal or normal (normal range, 5.0--40.0 microU/ml), while winter values were supranormal in 3 patients, with the remaining values being normal [log basal TSH, 0.511 +/- 0.438 vs. 0.084 +/- 0.244 (P less than 0.05); log peak TSH, 1.394 +/- 0.410 vs. 1.017 +/- 0.423 (P less than 0.05)]. Serum resin T3 uptake, T4, free T4 index(FT4I), T3, free T3 index, and rT3 levels did not vary seasonally, although T4 and FT4I tended to fall in the winter. The summer and winter QKd interval (the interval from the onset of a QRS complex in the electrocardiogram to the appearance of the Korotkoff sound at diastolic pressure), basal metabolic rate, and serum cholesterol concentrations were all within the normal range. Basal and peak TSH after TRH were inversely correlated with serum T4 and FT4I levels. The basal TSH concentration was further inversely correlated with the seasonally altering ambient temperature. These results indicate that during the treatment of primary hypothyroidism with constant doses of T4, 1) serum TSH and its response to TRH show seasonal variation, 2) the hypersecretion TSH in the winter is related to small changes in serum T4 and FT4I levels, and 3) the seasonal variation in the serum TSH concentration may need to be taken into consideration when evaluating the adequacy of a T4 replacement dose.

Topics: Adult; Aged; Analysis of Variance; Body Weight; Female; Humans; Hypothyroidism; Male; Middle Aged; Seasons; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Topics: Adult; Blood Pressure; Body Weight; Female; Graves Disease; Humans; Ipodate; Kinetics; Male; Middle Aged; Propylthiouracil; Pulse; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Oxygen consumption and plasma thyroid hormone concentrations are modified by both low- and high-calorie diets. It has been suggested that the trigger may be changes in weight ("adipostatic" hypothesis involving the difference between the actual weight and the "set point") or changes in amount of carbohydrate in the diet ("carbohydrate" hypothesis). Two experiments were performed in order to test both hypotheses. Fourteen young healthy volunteers were studied: 1) at their spontaneous stable weight; 2) while losing weight rapidly on a calorically restricted diet; 3) and then at their stable new weight when consuming a refeeding diet. The calorie restricted diet resulted in decrease of VO2, and T3, and an increase of rT3; the refeeding diet resulted in values of VO2, T3, and rT3 intermediate between those of the spontaneous diet and those of the restricted diet. Another group of nine subjects were studied at their spontaneous caloric and proteic levels, comparing a diet containing only protein and carbohydrate with a diet containing only protein and fat. During the low carbohydrate diet rT3 increased and T3 decreased but they remained unchanged during the carbohydrate-rich diet. Thus neither the adipostatic hypothesis nor the carbohydrate hypothesis is sufficient alone to explain the observed changes in serum T3 and rT3.

Topics: Adolescent; Adult; Body Weight; Diet; Dietary Carbohydrates; Dietary Proteins; Energy Intake; Humans; Oxygen Consumption; Thyroid Hormones; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Adjustments to sympathetic nervous system activity may regulate constant body weight despite wide variations in energy intake. To test this six normal weight subjects were studied at three different energy intakes (low, weight maintaining and high). Noradrenaline turnover was measured on the tenth day of each diet. Both noradrenaline appearance rate and noradrenaline clearance increased significantly with increasing energy intake and were a more sensitive indices than the plasma noradrenaline concentrations which rose, but not significantly. Fasting triiodothyronine (T3) rose and reverse T3 fell with increasing energy intake, while thyroxine (T4) concentrations did not change. Systolic blood pressure also rose significantly. Underfeeding resulted in reductions in noradrenaline appearance and clearance rates and in the T3 level. These results demonstrate that sympathetic nervous system activity, as determined by noradrenaline turnover in plasma, varies in response to short-term changes in energy intake in normal weight subjects. These changes may partly explain why some individuals maintain body weight constant despite large differences in food intake. The present findings may also be relevant to the variability in susceptibility to become obese.

Topics: Adolescent; Adult; Blood Pressure; Body Weight; Eating; Epinephrine; Female; Heart Rate; Humans; Kinetics; Male; Norepinephrine; Reference Values; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Serum levels of T4, T3, rT3, RT3U and TSH were estimated in 12 obese women in the course of a 14-day fasting. Seven of these patients were treated with T3 in a daily dose of 60--80 micrograms. Fasting led to a small increase of serum T4, while fasting combined with T3 administration was accompanied by a small decrease of serum T4. Serum T3 decreased in the course of the first 2 days of fasting to 40--50% of initial values and remained at this low level up to the 15th day of fasting. In the T3 treated group a prompt increase of serum T3 was recorded (+80%), followed by a steady decrease, reaching the control values on day 15, in spite of a continuous T3 administration. Serum rT3 in the untreated fasting group steadily increased up to the 12th day (+43%) and then dropped below the control value (-28%). In the treated group after a non-significant increase (+22%), a decrease of serum rT3 was also observed (-42%). Fasting was accompanied by a tendency to increased serum RT3U values, in the T3 treated group no change occurred. TSH in the untreated fasting women remained practically unchanged while T3 administration was accompanied by a tendency to a transient decrease. The heart rate showed a non-significant tendency to increase in the T3 treated group and the last week of fasting was also accompanied in several patients by a larger weight loss. These results suggest that in addition to an enhanced synthesis of rT3 to the detriment of a decreased production of T3 from T4, an increased catabolism of administered T3 and of endogenous rT3 is involved in a strict calorie restriction. An abortive T3-TRH-TSH feed-back may also operate in these conditions.

Topics: Adult; Body Weight; Fasting; Female; Heart Rate; Humans; Obesity; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Previous observations that acute total fasting decreases serum T3 and increase rT3 has prompted the following study. 17 obese women were placed on a 1000 kcal/day weight-reducing diet, and body weight (BW), serum T4, RT3U, T3, rT3, TSH and the Achilles tendon reflex (ATR) were estimated before and after each month for 3 consecutive months of the diet. The results showed a consistent decrease in serum T3, and inconsistent increase in rT3, a consistent prolongation of the ATR and a levelling-off of the BW loss after the second month of the diet. At 3 months there was a negative correlation between the decrease in BW and the increase in ATR, i.e. the more abnormal the ATR became, the less weight the patient lost. It is concluded: 1) Even a moderate hypocaloric diet in ambulatory patients induces a disturbance in the peripheral conversion of T4 to T3 and a secondary state of metabolic insufficiency. 2). This insufficiency is probable related to the observed tendency of the BW loss to level off after two months. 3) A controlled trial of physiologic doses of T3, such as 40 mu g/day, seems indicated, as opposed to pharmacologic dosed of T3 used by previous investigators.

Topics: Achilles Tendon; Adolescent; Adult; Body Weight; Female; Humans; Kinetics; Middle Aged; Obesity; Reflex, Stretch; Triiodothyronine; Triiodothyronine, Reverse

Topics: Adolescent; Age Factors; Body Height; Body Weight; Child; Female; Humans; Male; Sex Factors; Sexual Maturation; Thyroid Function Tests; Thyroid Gland; Thyroid Hormones; Thyrotropin; Thyroxine; Thyroxine-Binding Proteins; Triiodothyronine; Triiodothyronine, Reverse

In ten obese euthyroid subjects the concentration of thyroxine (T4), tri-iodothyronine (T3) and reverse T3 (rT3) were assayed in serum and of T4 and T3 in urine before and after 2 weeks of 2.1 MJ (500 Kcal) per day diet. Mean serum T4 was unchanged, while T3 decreased and rT3 increased. Urinary excretion of both T4 and T3 decreased after diet. In six subjects the concentrations of serum thyroxine binding globulin (TBG), thyroxine binding prealbumin (TBPA) and albumin were measured before and after diet. Free T4 and T3 were calculated using a formula based on measured concentration of hormones and their binding proteins. Calorie restriction resulted in a significant decrease in TBG and a greater decrease in TBPA, while albumin was unchanged. Calculation of free hormones showed a fall in absolute free T3 and rise in percentage free T3, but a rise in both absolute and per cent free T4. Our data indicate a selective effect of calorie restriction on the concentrations of TBPA and to a lesser extent TBG and confirm previous reports of altered peripheral monodeiodination of T4. Decreased urinary excretion of T4, despite a calculated increase of free T4 in serum, suggests intrarenal metabolic adjustment, the mechanism of which awaits elucidation.

Topics: Adolescent; Adult; Body Weight; Diet, Reducing; Female; Humans; Male; Middle Aged; Obesity; Serum Albumin; Thyroxine; Thyroxine-Binding Proteins; Triiodothyronine; Triiodothyronine, Reverse

During starvation the response of TSH to TRH decreases in many subjects. This could be due to an increased sensitivity to TSH secretion to circulating thyroid hormones. To study this hypothesis, 13 subjects were starved twice for 2-day periods. After both starvation periods, a standard TRH test (200 micrograms TRH, iv) was performed; during 1 starvation period 15 micrograms T3 were injected iv 24 h before the TRH test. The TRH tests were also performed while on normal nourishment, once without pretreatment and once 24 h after the iv injection of 15 micrograms T3. The spontaneous decrease of the TSH response to TRH was seen in 10 of 13 subjects. In these 10 subjects it decreased from 18.0 +/- 1.9 to 9.7 +/- 1.2 microU/ml (mean +/- SEM; P < 0.001). The additional inhibition of the TRH test with T3 was small compared with the one observed under normal conditions. In starvation, T3 decreased the maximal TSH response from 9.7 +/- 1.2 to 8.4 +/- 1 microU/ml (P = NS), while during the control period the maximal TSH response fell from 18.0 +/- 1.9 to 11.4 +/- 1.3 microU/ml (P < 0.001). These data indicate a diminished effectiveness of T3 in inhibiting TSH secretion and are consistent with the hypothesis of a more generalized resistance of target organs to T3 during starvation in man.

Topics: Adult; Blood Glucose; Body Weight; Female; Humans; Hydroxybutyrates; Kinetics; Male; Prolactin; Starvation; Thyrotropin; Thyrotropin-Releasing Hormone; Triiodothyronine; Triiodothyronine, Reverse

The enzymatic deiodination of thyroxine (T(4)) is thiol dependent. Fasting (72 h) depresses hepatic T(4) deiodination and lowers the hepatic content of nonprotein sulfhydryls (NP-SH) and reduced glutathione (GSH). It has been proposed that the fasting effect may be mediated through these alterations in hepatic sulfhydryls. To test the importance of tissue (hepatic) thiol content in the modification of T(4) deiodination consequent to dietary manipulation, we examined the sequential deiodination of T(4) to 3,5,3'-triiodothyronine (T(3)) (5'-deiodination) and 3,3',5-triiodothyronine (reverse T(3), rT(3)) (5-deiodination) in liver homogenates without added thiol from groups of rats fed Purina lab chow (P) (a protein-rich diet), glucose alone (G), or glucose plus cysteine (G(c)) for 72 h or fasted (F) for the same period. The initial rate of each reaction was compared to the tissue concentrations of NP-SH and GSH. Dietary manipulation induced significant changes in hepatic deiodination of T(4) to T(3) and rT(3) and sulfhydryl content. There was a marked dissociation between the rate of each reaction and hepatic NP-SH and GSH levels. T(4) deiodination by the alternative pathways was significantly higher (P < 0.01) in G > P > F. In contrast both hepatic NP-SH and GSH concentrations were greater (P < 0.05) in P > F > G. The lack of a relationship between these parameters was further emphasized on analysis of tissue from rats fed G(c). Despite the clearcut (P < 0.01) increase in hepatic NP-SH and GSH consequent to G(c) feeding, there was no alteration in iodothyronine deiodination compared to the group fed glucose alone. These data indicate that the effects of diet on T(4) monodeiodination in liver are not mediated by changes in the tissue level of sulfhydryl compounds but rather involve alterations in the concentrations of the deiodinases.

Topics: Animals; Biotransformation; Blood Glucose; Body Weight; Diet; Fasting; Glutathione; Liver; Male; Rats; Sulfhydryl Compounds; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Caloric deprivation (feeding 50 and 25% of the original maintenance requirement for 126 days), followed by overnutrition (feeding 133 and 200% of the original maintenance requirement) for 37 days, were induced in 7 adult sheep. Before and after the periods of undernutrition and after overnutrition the animals were fasted (total energy withdrawal) for 5 days. Energy- and nitrogen-balances were determined and related to concentrations of thyroxine (total: T4; free: FT4), 3,5,3'-triiodothyronine (total: T3; free FT3) and 3,3',5'-triiodothyronine (reverse T3,rT3). caloric deprivation led to decreased T3 and FT3 levels, overnutrition to increased T3 and FT3 concentration. T3 was significantly correlated with energy- and nitrogen-balances (r = 0.73 and 0.71, respectively; P less than 0.001). T4 and FT4 behave similar to T3, but correlations between T4 levels and energy- and nitrogen-balances were low. In contrast to T3, rT3 levels increased during energy withdrawal and decreased during overnutrition. After an overnutrition for months, an additional fasting for 5 days did not increase rT3 levels, however, rT3 was significantly correlated with energy- and nitrogen-balances (r = -0.50 and -.50, respectively; P less than 0.01).

Topics: Animal Nutritional Physiological Phenomena; Animals; Body Weight; Energy Intake; Energy Metabolism; Male; Nitrogen; Sheep; Starvation; Thyroid Hormones; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Propranolol alone was given to sixteen hyperthyroid, and concomitantly with thyroxine therapy to ten hypothyroid patients. Following treatment of the hyperthyroid group for 1-2 weeks there was a significant decrease in serum triiodothyronine (T3) which correlated with the plasma propranolol steady state concentration. The serum reverse T3 (rT3) rose significantly. Weight loss ceased in this group while weight gain occurred in patients who had a marked fall in serum T3. One patient with T3 toxicosis went into remission. The reduction in serum T3 was maintained in six patients receiving propranolol for more than 1 month. In the hypothyroid group the mean serum T3 level achieved with 0.15 mg thyroxine per day was significantly lower than in a control group who did not receive propranolol. In five patients following propranolol withdrawal there was a significant rise in T3, a fall in rT3 and TSH, and weight loss. Propranol may therefore have a clinically significant and direct action on the peripheral conversion of thyroxine to T3 and rT3.

Topics: Adolescent; Adult; Aged; Body Weight; Humans; Hyperthyroidism; Hypothyroidism; Middle Aged; Propranolol; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Diet-induced alterations in thyroid hormone concentrations have been found in studies of long-term (7 mo) overfeeding in man (the Vermont Study). In these studies of weight gain in normal weight volunteers, increased calories were required to maintain weight after gain over and above that predicted from their increased size. This was associated with increased concentrations of triiodothyronine (T3). No change in the caloric requirement to maintain weight or concentrations of T3 was found after long-term (3 mo) fat overfeeding. In studies of short-term overfeeding (3 wk) the serum concentrations of T3 and its metabolic clearance were increased, resulting in a marked increase in the production rate of T3 irrespective of the composition of the diet overfed (carbohydrate 29.6 +/- 2.1 to 54.0 +/- 3.3, fat 28.2 +/- 3.7 to 49.1 +/- 3.4, and protein 31.2 +/- 2.1 to 53.2 +/- 3.7 microgram/d per 70 kg). Thyroxine production was unaltered by overfeeding (93.7 +/- 6.5 vs. 89.2 +/- 4.9 microgram/d per 70 kg). It is still speculative whether these dietary-induced alterations in thyroid hormone metabolism are responsible for the simultaneously increased expenditure of energy in these subjects and therefore might represent an important physiological adaptation in times of caloric affluence. During the weight-maintenance phases of the long-term overfeeding studies, concentrations of T3 were increased when carbohydrate was isocalorically substituted for fat in the diet. In short-term studies the peripheral concentrations of T3 and reverse T3 found during fasting were mimicked in direction, if not in degree, with equal or hypocaloric diets restricted in carbohydrate were fed. It is apparent from these studies that the caloric content as well as the composition of the diet, specifically, the carbohydrate content, can be important factors in regulating the peripheral metabolism of thyroid hormones.

Topics: Adult; Body Weight; Diet; Dietary Carbohydrates; Dietary Fats; Dietary Proteins; Energy Intake; Humans; Kinetics; Metabolic Clearance Rate; Thyroxine; Time Factors; Triiodothyronine; Triiodothyronine, Reverse

This report describes the effect of administration of repeated doses of ipodate (Oragrafin; 3 g orally every third day for five doses) in six hyperthyroid patients. Baseline serum concentrations of immunoassayable T3, rT3, and T4, were 926 +/- 206 ng/100 ml, 165 +/- 31 ng/100 ml and 21 +/- 2.7 micrograms/100 ml (mean +/- SEM), respectively. Within 24 h after the first dose of ipodate, serum T3 fell by 54% and it remained between 66-77% below baseline until the third day after the fifth dose; subsequently, there was a gradual recovery from the effect of ipodate. Serum T4 also decreased after ipodate administration; it was 23-31% lower than baseline from the second day after the third dose to the sixth day after the fifth dose. Serum rT3 increased after each dose of ipodate; peak values of 97%-203% above baseline value were observed at 24-48 h after each dose. There was a subjective improvement in clinical symptoms of hyperthyroidism in all cases. Resting pulse rate and pulse pressure dropped significantly (P less than 0.02) by the ninth day of study and remained so thereafter. Body weight increased significantly by the ninth day of the study. The various data suggest that ipodate may serve as a useful adjunct in the early treatment of hyperthyroidism.

Topics: Adolescent; Adult; Body Weight; Drug Evaluation; Female; Graves Disease; Humans; Ipodate; Male; Middle Aged; Pulse; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

The functional state of the hypothalamo-pituitary-thyroid axis was assessed in 14 women and girls with anorexia nervosa when at low body weight and again in 12 cases after they had gained weight. Mean serum thyroxine concentrations were low before and after weight gain. Mean serum triiodothyronine (T3) concentrations were substantially reduced at low weight and doubled after weight gain, the absolute values being linearly correlated with body weight expressed as a percentage of the ideal. Concentrations of reverse T3 were greatly increased in some patients initially and fell with weight gain. Basal concentrations of thyroid-stimulating hormone (TSH) were unchanged after weight gain but the TSH response to thyrotrophin-releasing hormone was significantly augmented; delayed patterns of response were found in seven out of 12 patients tested before and three out of 12 patients tested after weight gain. Changes in the hypothalamo-pituitary-thyroid axis are common in anorexia nervosa and probably represent both peripheral and central adaptations to the altered nutritional state.

Topics: Adolescent; Adult; Anorexia Nervosa; Body Weight; Female; Humans; Hypothalamo-Hypophyseal System; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse