triiodothyronine--reverse and Thyrotoxicosis

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.

Topics: Adolescent; Adult; Aged; Base Sequence; Diagnosis, Differential; Female; Humans; Hyperthyroxinemia; Male; Middle Aged; Molecular Sequence Data; Mutation; Pedigree; Prealbumin; Thyroid Hormone Resistance Syndrome; Thyrotoxicosis; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse; Valine

This study was designed to assess both central and peripheral aspects of thyroid function in combat-related posttraumatic stress disorder (PTSD), with the particular purpose of finding a mechanistic explanation for an imbalance between serum levels of free thyroxine (T4) and total T4 previously observed in pilot work.. A total of 96 male combat veterans with PTSD diagnosed by DSM-III-R (72 from the West Haven, Conn, Veterans Affairs Medical Center and 24 from the Menlo Park, Calif, Veterans Affairs Medical Center) were compared with 24 male control subjects. One or more serum samples were analyzed by radioimmunoassays for levels of total T4, free T4, total triiodothyronine (T3), free T3, T4-binding globulin, and thyrotropin.. The pilot observation of moderately elevated total T4 levels with no elevation in free T4 levels in patients with PTSD was confirmed, suggesting the hypotheses that (1) there may be an increased peripheral conversion of free T4 by deiodination to T3 or (2) there may be an increased binding of T4 secondary to elevated T4-binding globulin levels. Our findings support both hypotheses. The PTSD groups all showed a marked and sustained elevation in levels of both total T3 and free T3, as well as elevated T3/T4 ratios, supporting the increased T3 conversion hypothesis. The PTSD groups also showed a marked and sustained increase in T4-binding globulin levels, supporting the increased binding hypothesis. Thyrotropin levels did not differ between PTSD and control groups.. These findings demonstrate an unusual pattern of thyroid alterations, featuring substantial elevations in total T3, free T3, and T4-binding globulin levels, in combat-related PTSD that differs from established endocrinopathies, such as classic hyperthyroidism, T3 thyrotoxicosis, or chronic T4-binding globulin elevation.

Topics: Adult; Combat Disorders; Comorbidity; Follow-Up Studies; Humans; Hyperthyroidism; Male; Pilot Projects; Protein Binding; Radioimmunoassay; Thyroid Gland; Thyrotoxicosis; Thyrotropin; Thyroxine; Thyroxine-Binding Proteins; Triiodothyronine; Triiodothyronine, Reverse

Iodine-induced thyrotoxicosis (ITT) has not been reported in Japan. We found that excessive intake of Japanese kombu could elicit ITT. Two Japanese women, 42 and 59 years old, developed thyrotoxicosis one month and one year, respectively, after having eaten foods containing 28-140 mg/day of iodine, calculated from their daily diet. Both patients had high concentrations of serum T3, low ratios of serum T3/T4 or T4/r-T3 compared with untreated Graves' disease, and high concentrations of serum inorganic iodine compared with the mean (M +/- SD: 2.05 +/- 0.99 micrograms/dl) plus 2SD in people eating common foods. Their thyrotoxic signs and symptoms disappeared, and their serum T4, T3, r-T3 and T4/r-T3 normalized one month after the prohibition of kombu intake. To clarify the source of iodine, the iodine content of the kombu and the iodine concentration in water in which the kombu was immersed were measured. Ninety-nine % of the iodine was found in water after 15 min boiling. These findings suggest that a daily intake of more than 28 mg/day of iodine in a diet containing kombu might induce ITT.

Topics: Adult; Female; Foodborne Diseases; Humans; Iodine; Middle Aged; Seaweed; Thyrotoxicosis; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

The effect of subtotal thyroid resection for thyrotoxicosis on concentrations of serum thyroid hormones and thyroglobulin (Tg), was determined in 10 patients during operation and the subsequent 18 days. Mean serum Tg responded drastically, increasing from a pre-operative value of 0.30 nmol/l to a peak value of approximately 26 nmol/l during operation followed by a gradual decline to levels lower than before surgery on day 18. Mean serum total thyroxine was 114 nmol/l pre-operatively and free thyroxine index (FT4I) 105 units. Both fluctuated only slightly during operation. Postsurgically, the mean values decreased to below 50% of the pre-operative level. Mean serum total triiodothyronine (TT3) was 1.46 nmol/l pre-operatively. It decreased during operation, reaching a nadir of 0.55 nmol/l on day 2, whereafter the concentration increased slightly. Mean serum reverse T3 (rT3) was 0.45 nmol/l pre-operatively, increased 62% during surgery, and decreased postsurgically. The mean value of serum thyroid stimulating hormone (TSH) was 0.61 mU/l pre-operatively and remained below 1 mU/l during and after operation, but from day 10 concentration began to rise steadily. It is concluded that the vast release of Tg during thyroid resection did not contribute to the concentration of serum T4 to an extent of clinical relevance.

Topics: Adult; Female; Humans; Male; Middle Aged; Thyroglobulin; Thyroidectomy; Thyrotoxicosis; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Topics: Humans; Reagent Kits, Diagnostic; Thyroid Function Tests; Thyrotoxicosis; Thyrotropin; Thyroxine; Triiodothyronine, Reverse