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Biomedical subjects

R D Utiger

Publications and source records attributed to R D Utiger.

At least 19 recordsLinked to original sources

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

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

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

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

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