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Biomedical subjects

R D Utiger

Publications and source records attributed to R D Utiger.

At least 37 records · Page 2Linked to original sources
PubMed1992

The ophthalmopathy of Graves' disease.

Ophthalmopathy is an integral component of Graves' disease. It usually appears at the same time as hyperthyroidism, and is characterized by proptosis (exophthalmos), periorbital and conjunctival edema, eye muscle dysfunction, and on occasion corneal ulceration or optic neuropathy. Graves' ophthalmopathy, like Graves' hyperthyroidism, is an autoimmune disease, but the mechanisms that initiate and maintain it are not known. Most patients can be treated conservatively, but a few require anti-inflammatory or surgical therapy to relieve symptoms and preserve vision.

Autoantibodies↗
PubMed1991

Age, sex, and serum thyrotropin concentrations in primary hypothyroidism.

We studied the relationship between age, sex, serum thyroxine concentrations, and serum thyrotropin concentrations in 202 patients with primary hypothyroidism whose ages ranged from 10 to 89 years. The results from two groups of patients were analysed, both combined and separately, by multiple linear regression analysis of the factors age, sex, group, and serum free T4 index or serum T4 concentration, to predict serum TSH. The serum free T4 index or T4 values and age were negatively correlated with the serum TSH concentrations (p less than 0.001) for all comparisons. In contrast, there was no significant relationship between sex and serum TSH concentrations in these hypothyroid patients. The age-related decline in serum TSH concentrations in hypothyroidism was apparent during adolescence and early adult life (ages 10 to 39 years) and in elderly subjects (ages 61 to 89 years). We conclude that age is a determinant of TSH secretion independent of the level of thyroid secretion.

Adolescent↗
PubMed1988

Thyroid hormone analog inhibition of hepatic 5'-iodothyronine deiodinase activity.

Studies using thyroid hormone analogs have provided insight into the structural requirements for thyromimetic activity and for thyroid hormone binding to thyroxine-binding globulin, thyroxine-binding prealbumin, and nuclear T3 receptors. To determine the structural specifications for iodothyronine interaction with 5'-iodothyronine deiodinase (5'-ITD), we examined the ability of 35 thyroid hormone analogs to inhibit hepatic T4 5'-deiodination in vitro. The compounds were incubated in concentrations of 0.1-500 microM with rat liver homogenates, and concentrations producing 50% inhibition of T3 production were calculated. Those iodothyronine analogs which likely serve as substrate for 5'-ITD, e.g.rT3 and 3',5'-T2, and those which have one tyrosyl iodide were the most potent inhibitors of 5'-ITD activity. The presence of tyrosyl iodides enhanced inhibition by compounds with alkyl and halogen substitutions. Inhibition was likely due to direct interaction with the enzyme, since it was readily reversed by DTT. The terminal amino and phenolic hydroxyl groups, as well as the ether linkage, do not appear to be essential components of enzyme interaction.

Animals↗
PubMed1988

Effects of low dose oral iodide supplementation on thyroid function in normal men.

Previous studies have demonstrated that short-term oral iodide administration, in doses ranging from 1500 micrograms to 250 mg/day, has an inhibitory effect on thyroid hormone secretion in normal men. As iodide intake in the USA may be as high as 800 micrograms/d, we investigated the effects of very low dose iodide supplementation on thyroid function. Thirty normal men aged 22-40 years were randomly assigned to receive 500, 1500, and 4500 micrograms iodide/day for 2 weeks. Blood was obtained on days 1 and 15 for measurement of serum T4, T3, T3-charcoal uptake, TSH, protein-bound iodide (PBI) and total iodide, and 24 h urine samples were collected on these days for measurement of urinary iodide excretion. TRH tests were performed before and at the end of the period of iodide administration. Serum inorganic iodide was calculated by subtracting the PBI from the serum total iodide. We found significant dose-related increases in serum total and inorganic iodide concentrations, as well as urinary iodide excretion. The mean serum T4 concentration and free T4 index values decreased significantly at the 1500 micrograms/day and 4500 micrograms/day doses. No changes in T3-charcoal uptake or serum T3 concentration occurred at any dose. Administration of 500 micrograms iodide/day resulted in a significant increase (P less than 0.005) in the serum TSH response to TRH, and the two larger iodide doses resulted in increases in both basal and TRH-stimulated serum TSH concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Effects of oral erythrosine (2',4',5',7'-tetraiodofluorescein) on thyroid function in normal men.

Erythrosine (Er), a tetraiodinated derivative of fluorescein, is a coloring agent widely used in foods, cosmetics, and pharmaceutical products. Because of its high iodine content and previous reports demonstrating an inhibitory effect of erythrosine on hepatic 5'-monodeiodination, we studied the effects of this compound on thyroid function and serum and urinary iodide concentrations in normal subjects. Thirty normal men, equally divided into three treatment groups, each received a 14-day course of oral Er in doses of 20, 60, or 200 mg/day. Serum thyroxine (T4), triiodothyronine (T3), reverse T3 (rT3), thyroid stimulating hormone (TSH), protein-bound iodide (PBI), and total iodide concentrations, serum T3-charcoal uptake, and 24-hour urinary iodide excretion were measured on Days 1, 8, and 15. Thyrotropin-releasing hormone (TRH) tests were performed on Days 1 and 15. There were no significant changes in serum T4, T3, rT3, and T3-charcoal uptake values at any dose. In men receiving 200 mg Er/day, the mean basal serum TSH concentration increased significantly from 1.7 +/- 0.1 (SE) on Day 1 to 2.2 +/- 0.1 microU/ml on Day 15 (p less than 0.05), and the mean peak TSH increment after TRH increased from 6.3 +/- 0.5 to 10.5 +/- 1.0 microU/ml (p less than 0.05). There were no significant changes in basal or peak TSH responses in the men receiving 20 or 60 mg Er/day. Significant dose-related increases in serum total iodide and PBI concentrations occurred during all three doses, and significant dose-related increases in urinary iodide excretion occurred during the 60 and 200 mg/day Er doses. These data suggest that the increase in TSH secretion induced by Er was related to the antithyroid effect of increased serum iodide concentrations, rather than a direct effect of Er on thyroid hormone secretion or peripheral metabolism.

Adult↗
PubMed1987

Thyrotropin-releasing hormone and thyrotropin secretion.

Thyrotropin (TSH) secretion is regulated primarily by thyroid hormones and thyrotropin-releasing hormone (TRH). Normally, TSH secretion is exquisitely sensitive to small increases and decreases in serum thyroid hormone concentrations when they occur as a result of alterations in thyroid secretion. Serum TSH responses to TRH are altered by even smaller decreases and increases in serum thyroid hormone concentrations. This sensitivity explains the value of measurements of basal serum TSH concentrations and serum TSH responses to TRH in the diagnosis of hypothyroidism and hyperthyroidism, respectively. How TRH secretion is regulated is unknown, but the direct inhibitory effect of thyroid hormones on the thyrotrophs minimizes the stimulatory effect of any chronic changes in TRH secretion that may occur. In patients with nonthyroid illness, however, the normal relationships between serum thyroxine and triiodothyronine concentrations and TSH secretion are altered. Slightly or moderately ill patients have decreases in extrathyroidal triiodothyronine production that are not followed by an increase in TSH secretion, although the sensitivity of the thyrotrophs to further reduction or to an increase in triiodothyronine concentration is maintained. More severe illness may result in impaired TSH secretion and thus in decreased thyroidal as well as decreased extrathyroidal thyroid hormone production. These alterations in thyrotroph sensitivity and secretion, so that TSH secretion is not increased when extrathyroidal triiodothyronine production is decreased and thyroid secretion is decreased in more severe illness, suggest that decreased thyroid hormone production is a beneficial adaptation to nonthyroid illness.

Animals↗
PubMed1986

Characteristics of thyroxine 5'-deiodinase activity in human liver.

The conversion of thyroxine (T4) to triiodothyronine (T3) was studied in homogenates and subcellular fractions of 10 human liver specimens obtained postmortem. Preliminary studies indicated that T4 5'-deiodinase activity did not decline in rat liver kept at 5 degrees C for 6 and 24 hr after death. All human liver homogenates but one catalyzed T3 production, although the quantity of T3 produced varied greatly, from 8-fold in the absence of dithiothreitol (DTT) to 100-fold in its presence. The wide variation in activity found may reflect either postmortem loss or premortem decline in enzyme activity due to unrecognized nonthyroidal illness. The amount of T3 produced was dependent on substrate availability, protein concentration, time, pH and temperature, and enzyme activity was greatest in the microsomal fraction. T3 production was stimulated by DTT and inhibited by propylthiouracil (PTU). Thus, human liver T4 5'-deiodinase has properties very similar to the same enzyme in rat liver. These data suggest that results of studies of the effects of nonthyroidal illnesses and drugs on T4 5'-deiodinase activity in rat liver may be extrapolated to humans.

Adolescent↗
PubMed1986

Diminished hepatic triiodothyronine production in Gunn rats.

The liver is a major site of conversion of thyroxine (T4) to the more active thyroid hormone 3,5,3'-triiodothyronine (T3). Hepatic T4 to T3 conversion is altered by a variety of pathological processes and pharmacological agents. We studied T4 to T3 conversion in glucuronyl transferase deficient homozygous Gunn rats because they have a hepatic enzyme abnormality which leads to hyperbilirubinaemia, and also because they have been reported to have alterations in thyroid hormone metabolism. An in vitro incubation system employing the 10,000 X g supernatant of liver homogenate was used, and T3 production was measured by radioimmunoassay. Experiments were done using substrate concentrations ranging from 0.56 to 20 microM, tissue protein in concentrations ranging from 0.625 to 20 mg and incubation times of 15 to 60 min. T3 production by liver homogenates from homozygous Gunn rats in these studies ranged from 29 to 70% of that produced by liver homogenates from phenotypically normal heterozygous Gunn rats. The deficit in hepatic T3 production by homozygous rats could not be overcome by increasing cofactor concentrations. After ultracentrifugation at 100,000 X g, T4-5'-deiodinase activity was found primarily in the 100,000 X g sediment fraction. Homozygous rat liver 100,000 X g sediment T3 production was 55% of that of the heterozygous rat liver 100,000 X g sediment. Liver cytosol from both homozygous and heterozygous rats inhibited microsomal T4-5'-deiodinase activity similarly. Addition of unconjugated bilirubin to liver homogenates resulted in reduction of T3 production in livers from both homozygous and heterozygous rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Caloric restriction does not alter thyrotropin secretion in hypothyroidism.

The effect of caloric restriction, as a model of nonthyroid illness, on serum thyroid hormone and TSH concentrations in hypothyroid patients was studied to determine if pituitary-thyroid function is altered in such patients, as it is in euthyroid subjects. Serum T4, T3, and TSH concentrations and serum TSH responses to TRH were measured in 5 untreated hypothyroid patients and 10 hypothyroid patients receiving T4 replacement therapy before and after restriction of caloric intake to 500 cal daily for 7 days. In 5 untreated hypothyroid patients, the mean serum T3 concentration declined 17%, from 75 +/- 14 (+/- SE) to 62 +/- 11 ng/dl. The mean basal serum TSH concentrations were 154 +/- 67 (+/- SE) microU/ml before and 161 +/- 75 microU/ml at the end of the period of caloric restriction, and the serum TSH responses to TRH were similar on both occasions. In 10 T4-treated hypothyroid patients, the mean serum T3 concentration declined 35%, from 110 +/- 8 to 71 +/- 8 ng/dl. In this group, mean basal serum TSH concentrations were 17 +/- 5.1 microU/ml before and 18.2 +/- 7.0 microU/ml at the end of the period of caloric restriction, and as in the untreated hypothyroid patients, the serum TSH responses to TRH were similar on both occasions. Mean serum T4 concentrations and serum free T4 index values did not change in either group. These results indicate that caloric restriction in both untreated and T4-treated hypothyroid patients is accompanied by 1) reduced serum T3 concentrations, as it is euthyroid subjects, and 2) no alterations in basal or TRH-stimulated TSH secretion.

Adult↗
PubMed1984

Myxedema coma during long-term amiodarone therapy.

Amiodarone is a potent new antiarrhythmic drug that has multiple effects on thyroid function, including inhibition of extrathyroidal triiodothyronine production and rarely, iodine-induced hypothyroidism. This report describes a man with recurrent ventricular tachycardia in whom hypothyroidism developed during amiodarone therapy and who died of probable myxedema coma. Parenteral and oral thyroxine therapy promptly reduced serum thyroid-stimulating hormone concentrations without increasing the patient's very low serum triiodothyronine concentration. This response to thyroxine suggests that thyroxine itself may have biologic activity and participate directly in regulation of thyrotropin secretion. Because amiodarone-induced hypothyroidism may be life-threatening, thyroid function should be monitored before and during amiodarone therapy, and the drug discontinued or appropriate therapy instituted if hypothyroidism develops.

Aged↗
PubMed1984

Triiodothyronine production by isolated rat hepatocytes: characterization and lack of glucoregulatory hormone effects.

Triiodothyronine (T3) production from thyroxine (T4) was studied in isolated rat hepatocytes. With an initial T4 concentration of 0.56 microM, hepatocyte T3 production was 0.029 +/- 0.003 (SEM) pmoles/min/mg protein. T3 production was greater in hepatocytes than in homogenates from the same liver prepared either before or after liver perfusion with collagenase. Most T3 produced remained within the cells under the conditions employed. Hepatocyte T3 production was dependent on cell number, medium bovine serum albumin concentration and temperature. It was stimulated by dithiothreitol, and inhibited by propylthiouracil, 3,3',5'-triiodothyronine and dinitrophenol; glutathione and ouabain had no effect. Alterations in medium glucose concentration and exposure to insulin or glucagon at several glucose concentrations in vitro did not alter T3 production. These results indicate that in hepatic tissue T3 production is enhanced when intact cellular organization is present and that insulin and glucagon do not acutely influence cell production of T3 in vitro.

2,4-Dinitrophenol↗