Serum Reverse T3 Concentrations Research Articles

A new family with hyperthyroxinemia caused by transthyretin Val109 misdiagnosed as thyrotoxicosis and resistance to thyroid hormone--a clinical research center study.

Serum transthyretin (TTR) is a protein of liver origin that under normal conditions transports approximately 20% T4. Missense mutations of the TTR gene produce familial amyloidotic polyneuropathy and rarely, euthyroid hyperthyroxinemia (EHT). Of the 3 TTR variants so far identified with increased affinity for T4, Ser6, Thr109, and Met119, only TTR-Thr109 has high enough affinity for T4 to produce consistent hyperthyroxinemia in the heterozygous individuals. Because the mutation GCC-->ACC in codon 109 results in the loss of one Bso FI site in exon 4 of the TTR gene, the use of this enzyme was suggested to screen for TR-Thr109 in subjects with EHT. We investigated a family with dominantly inherited EHT, in which two of eight affected members received ablative thyroid treatment for presumed thyrotoxicosis, and one was misdiagnosed as having resistance to thyroid hormone. All affected individuals had serum reverse T3 concentrations above normal and average T4 50% above the mean of unaffected relatives. Total T3 and TSH levels were within the normal range. Although loss of the Bso FI site in one allele of the two TTR suggested the presence of Thr109, gene sequencing revealed a different mutation in the same codon (GCC-->GTC) producing TTR-Val109. T4-binding to TTR-Val109 was compared to that of the normal TTR-Ala109 and the formerly identified variant TTR-Thr109. Association constants were 1.3, 9.5, and 13.6 X 10(7) M-1 for TTR-Ala109, Val109, and Thr109, respectively. Thus, for equally expressed mutant and normal allele and 20% of serum T4 bound to TTR, the calculated mean serum T4 concentration of heterozygotes for TTR-Val109 should be 50% above the normal mean; the observed value being 55%. These results are in agreement with the observations based on the crystallographic structure of TTR-Thr109 indicating that the extra atoms in Val as in Thr, which are absent in the Ala of the wild type TTR, widen the ligand binding site.

Calorie restriction and iopanoic acid effects on thyroid hormone metabolism

We measured the effects of iopanoic acid on thyroid hormone metabolism in obese men during severe calorie restriction to study the nutrition regulation of thyroid hormone metabolism. Eight morbidly obese men received a weight-maintenance diet followed by 6 wk of 600 kcal/d. During underfeeding, patients received iopanoic acid or placebo for 2-wk periods in a double-blind crossover fashion. Underfeeding alone (UF) produced a 28.3% decline in the serum triiodothyronine (T3) concentration, and iopanoic acid plus underfeeding (IOP) produced a 49.5% decline in T3 concentration from baseline. Serum reverse T3 concentrations increased 289% during IOP compared with UF alone (p less than 0.001). Serum TSH concentration was unchanged by underfeeding but increased twofold during IOP treatment. Thyroid hormone kinetics demonstrated a decrease in T3 production during IOP compared with UF. These findings suggest that calorie restriction regulates T3 production by modulating only type I 5'-deiodinase activity.

Endocrinology and metabolism: an annotated bibliography of recent literature. References to journal articles and other papers.

Endocrinology and metabolism: an annotated bibliography of recent literature. References to journal articles and other papers.

Comparison of propranolol and metoprolol in the management of hyperthyroidism.

1 Propranolol and metoprolol were both effective in controlling the symptoms and signs of hyperthyroidism. 2 Propranolol caused a highly significant increase in serum reverse T3 concentrations with lesser changes in other serum thyroid hormone levels, whereas metoprolol did not have this effect. 3 Steady-state plasma propranolol and metoprolol levels showed marked inter-individual variation. Metoprolol concentrations showed relatively little intra-individual variability, and could be related to the clinical efficacy of the drug, whereas no such relationship was demonstrated for propranolol.

A Radioimmunoassay for 3,3′,5′-L-Triiodothyronine (Reverse T3): Assessment of Thyroid Gland Content and Serum Measurements in Conditions of Normal and Altered Thyroidal Economy and Following Administration of Thyrotropin Releasing Hormone (TRH) and Thyrotropin (TSH)

The present report describes the development of a radioimmunoassay for 3,3',5'-L-triiodothyronine (reverse T3) which is performed on unextracted serum. Utilizing this radioimmunoassay, 21 normal subjects had a mean (+/-SD) serum reverse T3 level of 60 +/- 12 ng/100 ml, 17 of 19 hyperthyroid patients had elevated serum reverse T3 levels, and 10 of 11 hypothyroid subjects had decreased serum reverse T3 concentrations. Thyroidal secretion of reverse T3 was assessed by measurements in samples obtained from the internal carotid artery and jugular vein of sheep following the administration of thyrotropin releasing hormone (TRH) or bovine thyrotropin (TSH). Reverse T3 levels were increased 45-60 min after TRH administration, but TSH administration produced inconsistent alterations in reverse T3, although 18 of 27 samples obtained after TSH injection were higher than their average respective baseline concentration and the mean peak reverse T3 level was 14% higher than baseline. Following TRH administration to 10 normal human subjects, mean serum reverse T3 levels significantly increased from 53.6 ng/100 ml to 56.3ng/100 ml (P less than .05). The thyroid gland content of reverse T3 in human autopsy material was 6.5 +/- 1.5 microng/g tissue. Both pregnancy and estrogen administration were associated with increases in serum reverse T3 concentrations presumably because of their ability to augment thyroxine binding globulin synthesis.