Biomedical subjects

B N Premachandra

Publications and source records attributed to B N Premachandra.

At least 37 records · Page 2Linked to original sources

PubMed1985

Glucagon administration induces lowering of serum T3 and rise in reverse T3 in euthyroid healthy subjects.

Euthyroid sick syndrome is characterized by low serum T3 and raised reverse T3 (rT3). Most of the states with this syndrome are also documented to manifest hyperglucagonemia. Furthermore, several recent studies have suggested that glucagon may play a role in T4 monodeiodination in some of these states such as starvation and uncontrolled diabetes mellitus. Therefore, hyperglucagonemia was induced by intravenous glucagon administration in euthyroid healthy volunteers and thyroid hormone levels were determined at frequent intervals up to six hours. Plasma glucose and insulin rose promptly on glucagon administration, thus establishing the physiologic effect of glucagon. Serum T4, free T4, T3 resin uptake, and TSH concentrations remained unaltered throughout the study period. Serum T3 declined to a significantly low level (P less than 0.05) between 60-90 minutes. Serum rT3 rose significantly (P less than 0.05) by four hours and the rise was progressive till the end of the study period. Therefore, these results suggest that hyperglucagonemia may be one of the factors responsible for lowering of T3 and a rise in rT3 in euthyroid sick syndrome.

Female↗

PubMed1985

Transport of thyroxine bound to human prealbumin into rat liver.

The transport into rat liver of thyroxine (T4) bound to human prealbumin was studied with the use of sera obtained from patients with thyroid hormone-binding globulin (TBG) deficiency and with purified human prealbumin. The unidirectional extraction of 125I-T4 by liver was measured after rapid injection of isotope mixed in human serum into the portal vein of ketamine-anesthetized rats. The percentage of total serum T4 transported into liver was 47.6 +/- 5.2% in subjects with TBG deficiency, and this represented a 50% increase in hepatic T4 transport relative to control human serum. Since T4 is bound to albumin and to prealbumin in complete TBG deficiency, these results suggested that T4 bound to human prealbumin was transported into rat liver. This was confirmed using portal vein injections of human prealbumin at physiological concentrations (0.1-0.3 mg/ml). At these concentrations, T4 bound to human prealbumin was readily transported into liver. These studies suggest factors present in the liver microcirculation inhibit the binding of T4 to human prealbumin such that T4 bound to human prealbumin is highly transportable in liver; conversely, T4 bound to rat prealbumin is not transportable in rat liver. The inability of human prealbumin to sequester T4 in plasma may provide the basis for the selective advantage in humans of TBG, which does sequester T4 in plasma.

Adult↗

PubMed1985

Hepatic bioavailability of thyroxine and testosterone in familial dysalbuminemic hyperthyroxinemia.

The bioavailability of [125I]T4 or [3H]testosterone in serum obtained from normal subjects and from subjects with familial dysalbuminemic hyperthyroxinemia (FDH) was studied with a portal vein injection technique in ketamine-anesthetized rats. In the present studies this technique was modified by performing uptake measurements in the presence of serum loaded with either 25 microM T4 or 1 microM testosterone. Loading of serum with these high concentrations displaced the labeled hormone from the lower capacity globulin or prealbumin-binding sites to the high capacity albumin or dysalbumin-binding sites, and allowed for the analysis of hormone availability in liver when the labeled hormone was delivered to the tissue bound either to albumin or to dysalbumin binding sites. In the presence of normal serum, 33 +/- 3% (SE) of T4 was available to rat liver, as opposed to 20 +/- 2% for FDH serum. When normal serum was loaded with 25 microM T4, the bioavailable T4 increased to 97 +/- 2%, consistent with the availability of T4 bound to albumin. However, the hepatic bioavailability of T4 in the presence of 25 microM T4 in FDH serum was only 33 +/- 4%. Testosterone bioavailability was similar in normal and in FDH sera, and was 49 +/- 7% in the absence and 99 +/- 4% in the presence of 1 microM testosterone. These studies suggest that T4 bound to the FDH albumin binding site is not readily available for entry into liver, whereas T4 bound to the normal albumin binding site is freely available for uptake in vivo. The differential bioavailability of T4 is compatible with the model that the normal and FDH binding sites are situated on different parts of the albumin molecule, and that only T4 bound to the normal binding site is freely available for delivery to the liver.

Animals↗

PubMed1984

Ethanol feeding and thyroid hormone monodeiodination.

Adult male rats were placed on a 3 week regimen of ethanol (as 20% of total calories) in a nutritionally adequate diet, and controls were matched equicalorically without ethanol. Serum measurements of T4, T3, FT4, rT3, and TSH were performed in both the fed and the fasted state (18 hours). In the fed state, serum hormone measurements did not differ between control and ethanol-treated rats. Overnight fasting had a significant effect in decreasing serum T3 level in both experimental and control rats and in decreasing serum T4 level in ethanol-treated animals; FT4 and rT3 levels were not affected. Fasting also decreased in vitro hepatic T4 to T3 production to an equivalent degree in control and ethanol-treated rats, but did not alter hepatic T4 to rT3 production rates in control animals. In the fed state, hepatic rT3 neogenesis in animals given ethanol declined relative to the levels observed in control fed rats; fasting restored the depressed rT3 neogenesis to the levels noted in the fed state. Because decreased rT3 production in ethanol-treated rats in the fed state could not be explained on the basis of a change in 5'-deiodinase activity, it is suggested that ethanol administered with a nutritionally adequate diet may inhibit hepatic rT3 generation by inhibiting T4(5)-deiodinase.

Analysis of Variance↗

PubMed1984

Low triiodothyronine and raised reverse triiodothyronine levels in patients over fifty years of age who have type II diabetes mellitus: influence of metabolic control, not age.

Several studies have demonstrated that the uncontrolled diabetic state in both type I as well as type II diabetes mellitus is characterized by altered thyroid hormone metabolism, which results in the lowering of serum triiodothyronine (T3) levels and a reciprocal elevation of T3 (rT3) levels. Because the majority of type II diabetics are over 50 years of age and because numerous previous reports have implicated aging as a cause of low T3 and high rT3 levels, we studied 220 type II diabetics from 40-85 years of age to assess the influence of aging and metabolic control on thyroid hormone levels. Serum thyroxine (T4) free T4, T3 resin uptake, and thyroid-stimulating hormone (TSH) measurements in diabetic patients were not significantly altered compared with 37 young normal control subjects, irrespective of age or the grade of metabolic control. Serum T3 levels declined and rT3 levels rose in the diabetic patients with worsening of the metabolic control. However, with comparable metabolic control, the levels were not significantly different from the younger patients. Therefore, low T3 and high rT3 levels observed in patients of any age who have type II diabetes mellitus may be exclusively caused by deranged metabolic control of their disease.

Adult↗

PubMed1984

Ethanol inhibition of pituitary-thyroid axis: an effect secondary to nutritional deficiency.

Ethanol as either 20% or 36% of total calories in a Lieber diet was administered to male rats. At these concentrations, ethanol consumption relative to body weight did not differ. Pair-fed controls were restricted to the amount of calories consumed by rats given ethanol. Under these conditions, a direct effect of ethanol on the hypothalamic-hypophyseal-thyroid axis could not be demonstrated. There were no differences between pair-fed control and ethanol treated rats in serum or pituitary TSH, TSH response to TRH, or T4 and T3 levels. On the other hand, in rats given ethanol as 36% of total calories ("36%" ethanol-treated), and in their pair-fed controls, a marked decrease in serum T4 levels occurred (25% and 30%), relative to the corresponding "20%" groups. The decreased T4 in the "36%" groups was associated with a pronounced fall in caloric intake, decreased serum TSH, and declines in adenohypophyseal and body weights -- all of which were of similar magnitude in experimental and control rats. Thus, inanition was probably the primary cause of reduced thyroid function in the "36%" groups. An interesting aspect of this change was the finding of no difference in serum T3 levels between pair-fed control and ethanol treated rats in the 36% and 20% groups despite the reduced T4 and caloric intake in 36% animals; the lack of decrease in T3 concentration in 36% animals may reflect augmented peripheral conversion of T4 to T3 or reduced T3 clearance.

Animals↗

PubMed1983

Familial resistance to thyroid hormone associated with decreased transport across the plasma membrane.

Resistance to thyroid hormone associated with a defect in hormone transport across the plasma membrane occurred in a 74-year-old eumetabolic woman. She had marked elevations in the serum levels of total thyroxine (T4), free T4, and reverse triiodothyronine (rT3). Levels of T3 were only minimally increased. The hyperthyroxinemia was thyrotrophin (TSH) dependent, but was not due to an alteration in the binding of T4 to serum proteins. Refractoriness to thyroxine was only partial, as indicated by the increase in the basal metabolic rate and suppression of the response of TSH to thyrotrophin-releasing hormone (TRH) after the administration of L-thyroxine, 600 micrograms daily, for 3 weeks. The basic abnormality involved a selective decrease of T4 plasma membrane transport shown by in-vitro studies of erythrocytes. Screening of family members showed similar biochemical abnormalities in two other relatives. In this familial syndrome characterized by eumetabolic hyperthyroxinemia, the alteration of thyroid hormone metabolism seems to involve primarily the partition of T4 between the intra- and extracellular spaces.

Adult↗

PubMed1983

Serum T3 and reverse T3 levels in hepatic cirrhosis: relation to hepatocellular damage and normalization on improvement in liver dysfunction.

Liver is one of the major sites of T4 metabolism. Several studies have reported low serum T3 concentrations and elevated reverse T3 (rT3) levels in hepatic cirrhosis. This study examined the influence of degree of the hepatocellular damage and the effect of improvement in clinical state on thyroid hormone concentrations in 44 cirrhotic patients. Low serum T4 and T3 as well as raised rT3 were observed in cirrhotic patients with advanced liver dysfunction alone. T3 resin uptake was increased in some of these patients suggesting decrease in serum thyroid-binding globulin concentration. In patients with histological changes but with normal liver function tests, serum T4, T3, and rT3 were not altered. Serum T3 and rT3 correlated significantly with liver function tests. T4, T3, and rT3 normalized on improvement in clinical status and liver function tests. Lowest levels of T4 and T3 with extremely high rT3 were seen in patients with extremely advanced liver dysfunction. In these patients, the mortality was high. Therefore, in hepatic cirrhosis, 1) T4 metabolism is altered with lowering of T4 and T3 and a rise in rT3. 2) These changes may be dependent on the degree of hepatocellular damage and reverse on improvement in liver function. 3) T4, T3, and rT3 levels are useful prognostic indices.

Adult↗

PubMed1982

Euthyroid familial hyperthyroxinemia due to abnormal thyroid hormone-binding protein.

A family is described in which three members had an elevated total serum thyroxine level and free thyroxine index. Each affected subject was clinically euthyroid and had a normal pulse wave arrival time (QKd), serum triiodothyronine and free thyroxine levels, and a normal serum thyroxine-binding globulin (TBG) concentration. Electrophoresis of their serum with 125I-labeled thyroxine revealed increased thyroxine binding in the albumin region. In addition, this abnormal protein, like thyroxine-binding globulin, bound 125I-labeled triiodothyronine and 125I-labeled reverse triiodothyronine. However, electrophoresis of serum treated by sialidase (neuraminidase) digestion suggested that this abnormal protein is not an anomalous form of thyroxine-binding globulin "buried" in the albumin area. These cases of euthyroid familial hyperthyroxinemia due to an abnormal thyroid hormone-binding protein show that an elevated serum thyroxine level or free thyroxine index is not always sufficient to confirm the presence of thyrotoxicosis.

Child↗

PubMed1982

Effects and clinical significance of exogenous thyroxine therapy in patients with circulating thyroid hormone autoantibodies.

The effects of exogenous L-thyroxine therapy (0.2-0.3 mg/day) on spontaneously occurring thyroid hormone autoantibodies (THAA) and on serum levels of thyroxine (T4), triiodothyronine (T3) and reverse triiodothyronine (rT3) are described in a boy with lymphocytic thyroiditis. Prior to T4 medication, THAA bound virtually all thyroid hormones as noted by serum gamma globulin binding of tracer hormones. During T4 therapy, however, gamma globulin binding of tracer thyroid hormones decreased markedly. T4 and T3 levels as determined by radioimmunoassay (RIA) were grossly distorted prior to thyroxine therapy and bore no relation to clinical status, the single antibody technics yielding falsely low values whereas the double antibody procedures spuriously exaggerating serum hormone concentration. That spontaneously occurring THAA interfered in RIA hormone measurements was clearly shown by the lack of inconsistencies in laboratory and clinical evaluation when hormone determinations were performed in protein free serum extracts (to remove circulating THAA), or when RIAs were carried out in sera during thyroxine therapy when THAA were saturated by exogenous hormones. The thyroid stimulating hormone (TSH) level prior to therapy was 300 microunits/ml which decreases to less than 3 microunits/ml during T4 medication (0.3 mg/day). There was a gross inverse correlation between TSH secretion and T4 antibody saturation. The marked inhibition of antibody binding of tracer thyroid hormones observed during therapy suggested possible masking of thyroid hormone antibody activity during T4 treatment; experiments involving addition of tracer thyroid hormones to hormone stripped serums from thyroxine treated patients confirmed the hypothesis in two cases of hypothyroidism--one of which was diagnosed in the boy with chronic thyroiditis and the other a woman with postradioactive iodine-induced hypothyroidism. The pathophysiologic significance of thyroid hormone autoantibodies in the transport of thyroid hormones is briefly discussed.

Autoantibodies↗

PubMed1982

Familial elevations of total and free thyroxine in healthy, euthyroid subjects without detectable binding protein abnormalities.

Elevations of serum thyroxine without thyrotoxicosis or binding protein abnormalities have been documented in 8 of 13 family members, representing 4 generations. This syndrome appears to represent an elevated threshold for the amount of free thyroxine substrate required to maintain adequate T3 production form the peripheral monodeiodination of T4. It reiterates the need for a prudent re-evaluation of all clinically euthyroid patients with elevated serum thyroxine concentrations before concluding that they are indeed thyrotoxic.

Adult↗

PubMed1982

Familial hyperthyroxinemia due to abnormal thyroid hormone binding.

A patient had an elevated serum total thyroxine (T4) free thyroxine (free T4), free T4 index, and T4/thyroxine-binding globulin ratio. The serum triiodothyronine (T3), as well as the thyrotrophin response to thyrotrophin-releasing hormone was normal and consistent with the clinical euthyroid status. The basis for the elevated serum total T4, free T4 index, and T4/thyroxine binding globulin is the abnormally enhanced binding of thyroid hormone by albumin, or by an anomalous protein migrating with a mobility similar to albumin as determined in paper electrophoretic systems. The abnormal T4 protein binding was also seen in several members of the patient's family indicating that the condition was familial. A new type of serum T4 protein binding abnormality that results in hyperthyroxinemia may falsely indicate thyrotoxicosis in clinically euthyroid subjects.

Adult↗

PubMed1981

Circulating reverse triiodothyronine in humans during exercise.

Circulating thyroxine (T4), triiodothyronine (T3) and reverse triiodothyronine (rT3) as well as blood lactate and glucose concentrations were measured in a group of 12 trained volunteer subjects prior to and after swimming 0.18 or 0.9 km, to determine if increase in metabolic activity was accompanied by diversion of T4 monodeiodination from the active (T4 to T3) to the inactive (T4 to rT3) pathway. The resting T4, T3, and rT3 levels were 8.5 micrograms . 100 ml-1, 108 ng . 100 ml-1, and 57 ng . 100 ml-1, respectively, whereas after 0.18 km of swimming the corresponding levels were 9.5 micrograms . 100 ml-1, 135 ng. 100 ml-1 and 70 ng . 100 ml-1. After 0.9 km of swimming, T4, T3, and rT3 levels were 9.0 micrograms . 100 ml-1, 126 ng . 100 ml-1, and 66 ng . 100 ml-1, respectively. The swimming was accompanied by hemoconcentration and increase in blood lactate but not in glucose concentrations. In two other investigations thyroid hormones were measured prior to and after 60 or 90 min of moderate exercise on a bicycle ergometer. This exercise had no effect on circulating thyroid hormone levels. Free thyroxine (FT4) concentration and thyroxine binding globulin (TBG) capacity were unaltered after exercise. In conclusion, brief strenuous swimming or moderate bicycle exercise had minor or no effect on thyroid hormone concentrations when consideration was given to the attendant hemoconcentration. Even when exercise induced small T3 and rT3 changes were noted, they were in the same direction (increase) thus demonstrating a lack of diversion of peripheral T4 monodeiodination.

Adolescent↗

PubMed1981

Peripheral markers of thyroid status unaffected by endurance training in rats.

In order to more clearly define the relationship between endurance exercise training and thyroid activity we have measured T4 turnover in exercise-trained and sedentary rats under conditions of controlled food intake and body weight. Rats were run on rodent treadmills at gradually increasing speeds and durations until at the end of 12 weeks they were running 2 h per day at 31 m/min. Sedentary rats were either allowed to eat ad libitum or were food restricted so that they gained weight at the same rate as controls. Relative heart weight and plantaris citrate synthase activity were both significantly increased in trained animals compared to controls. The thyroxine secretion and degradation rates were not affected by the training. In addition, liver mitochondrial alpha-glycerophosphate dehydrogenase and citrate synthase were measured as indicators of the thyroid state at the tissue level. Neither of these enzymes were increased in the trained rats. We conclude that increased thyroid activity is not essential for inducing and maintaining the adaptations in muscle mitochondrial enzymes which occur in response to prolonged endurance exercise training.

Animals↗

PubMed1981