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PURPOSE: The potential benefits of treating subclinical hypothyroidism (SCH) are unclear and still controversial. Thus, we surgically induced SCH in rats and evaluated the effects of thyroxine (T4) replacement on the gene expression levels of deiodinases and thyroid hormone (TH) transporters in different tissues. METHODS: SCH was induced by hemithyroid electrocauterization. The control animals underwent the same surgical procedure but were not subjected to electrocauterization (sham). After 14 days, half of the SCH animals were treated with T4 (SCH + T4). At the end of the experimental protocol, all of the rats were euthanized, serum hormone concentrations were measured, and RNA analyses were performed on different tissues and organs. RESULTS: Consistent with previous studies, we observed increased TSH levels, normal TH levels, and reduced hypothalamic TRH expression in the SCH group. Additionally, Dio2 mRNA expression was downregulated in the hippocampus and pituitary, and Dio1 was upregulated in the kidney and pituitary of the SCH animals. The changes in Dio3 expression were tissue-specific. Concerning TH transporters, Mct10 expression was upregulated in the pituitary, kidney, hypothalamus, and hippocampus, and Mct8 expression was downregulated in the kidney of the SCH group. Crym expression was upregulated in the kidney and pituitary. Notably, T4 replacement significantly attenuated serum TSH levels and reverted Dio1, Dio2, Mct10, and Crym expression in the pituitary, hippocampus, and kidney to levels that were similar to the sham group. Tissue-specific responses were also observed in the liver and hypothalamus. CONCLUSION: Our results indicate that treatment of SCH should be considered before the appearance of clinical symptoms of hypothyroidism.

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There are few data available about changes in thyroid hormone profiles after hormone replacement therapy (HRT). We analyzed the effect of two different oral estrogens/progestins (E/P) associations on thyroid hormones and thyroxine-binding globulin (TBG) levels in 14 postmenopausal normal women distributed at random into two groups. Both groups received daily for a year 2 mg of estradiol valeriante per os. In Group A (n = 7), estrogen was associated with norethisterone acetate. In Group B, estrogen was associated with promegestone in a similar schedule to Group A. Blood samples were withdrawn to measure estradiol (E2), thyroxine (T4), triiodothyronine (T3), free T4 (fT4), thyroid-stimulating hormone (TSH) and TBG before and after 3, 6 and 12 months of treatment. Estradiol level increased significantly in both groups, being higher in Group A than in B. Under therapy, T4 and TBG levels were increased in both groups, but within the normal range. T4 mean level increased by 34% in Group A and 20% in Group B. TBG increment was slightly significant for Group A (p < 0.02); with only a trend in Group B (p = 0.08). T3, fT4 and TSH levels did not change significantly and remained within the normal range. Oral therapy with associated E/P produces moderate increases in T4 and TBG levels. Our results suggest that in postmenopausal women on oral HRT, fT4 and TSH levels are the most useful tools to evaluate the thyroid axis status.

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OBJECTIVE: The abnormalities reported in some thyroid function tests in children with renal disease could be adaptive phenomena, shared by a variety of other nonthyroidal illnesses, or could reflect hypothyroidism. STUDY DESIGN: To answer this question, we studied thyroid function and serum thyroid binding proteins in 36 prepubertal and 23 pubertal patients with renal disease receiving three different therapies: conservative treatment, hemodialysis, and care after renal transplantation. RESULTS: During prepuberty, the serum concentration thyroxine binding globulin (mean +/- SE) in the three groups of patients (294 +/- 18, 303 +/- 18, and 323 +/- 16 nmol/L, respectively) was significantly lower than in prepubertal control subjects (451 +/- 71 nmol/L). Only in prepubertal patients after renal transplantation (3583 +/- 573 nmol/L) were serum thyroxine binding prealbumin values lower than in respective control subjects (5999 +/- 908 nmol/L). The serum total thyroxine concentration in the three groups of patients (108 +/- 41.9, 121 +/- 5.7, and 123 +/- 5.5 nmol/L, respectively) was significantly lower than in prepubertal control subjects (149 +/- 10 nmol/L), whereas serum free thyroxine and serum albumin-bound thyroxine concentrations were similar to those in control subjects. The serum total triiodothyronine level in the three groups of patients (2.29 +/- 0.82, 2.13 +/- 0.13, and 2.01 +/- 0.20 nmol/L respectively) was significantly lower than in prepubertal control subjects (3.04 +/- 0.24 nmol/L), whereas serum levels of free triiodothyronine and serum albumin-bound triiodothyronine were similar to those in prepubertal control subjects. During puberty, serum thyroxine binding globulin and serum thyroxine binding prealbumin levels in the three groups of patients were not statistically different from those in pubertal control subjects (309 +/- 47 and 4950 +/- 1230 nmol/L, respectively). Serum levels of total thyroxine, free thyroxine, albumin-bound thyroxine, total triiodothyronine, free triiodothyronine, and albumin-bound triiodothyronine were similar to those in pubertal control subjects except for pubertal patients undergoing hemodialysis. In all clinical groups the basal serum thyrotropin concentration was similar to those in respective control subjects. The frequency of goiter was increased in patients undergoing hemodialysis, probably as a result of iodide washout with dialysis. CONCLUSION: Children and adolescents with chronic renal insufficiency or endstage renal disease or after renal transplantation do not have a primary abnormality of thyroid function and therefore are not candidates for thyroid hormone treatment.

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Recent advances in molecular biology and the use of modern techniques made possible the identification and cloning of DNA portions of the human genome encoding proteins that are important for the synthesis, storage, transport and action of thyroid hormones. These achievements have led to the diagnosis of the basic defects at the DNA level and the understanding of the biochemical disturbance in the genetic disorders of thyroid metabolism. In patients with defective expression of thyroid peroxidase (TPO) the presence of polymorphism (RFLP) associated with Bgl-I segregates with the affected individual with goiter, hypothyroidism and positive perchlorate discharge test. Defects in the thyroglobulin are either quantitative (no Tg is synthetized) or qualitative (an abnormal Tg is expressed). Low messenger RNA codifying for Tg was present in one of the families with virtual absence of Tg in serum and thyroid tissue. In another family absence of sialic acid incorporation into the Tg molecule produced a Tg with structural defect, incapable of T3 and T4 generation. A point mutation in the nucleotide 281 of exon 5 has been claimed as the mutation producing a defective TBG. Finally, the resistance to thyroid hormone action is linked to a mutation in the c-erb-A beta, detected by the presence of a polymorphism EcoRV, that will encode a defective protein or will produce a protein that might block the T3 binding to the receptor.

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Abnormal binding of thyroxin (T4) to serum albumin of subjects with familial dysalbuminemic hyperthyroxinemia (FDH) is generally demonstrated by the T4-loaded charcoal uptake test, with T4 added in excess (0.1 mmol/L) to accentuate T4 binding to albumin in FDH. I describe a binding study involving T4 tracer in which thyroxin-binding globulin is denatured in samples by treatment with mild acid at pH less than 3.0. The tracer is bound to the serum albumin and, to a greater extent, to the FDH albumin, because the binding by thyroxin-binding prealbumin is blocked by barbital buffer. The result of the [125I]T4 binding to the albumin is expressed as a T4 binding index, based on results for pooled sera from patients with normal thyroid function as a reference. The mean index in FDH was 4.08 (SD 0.92, n = 5); in hypoalbuminemia, 0.66 (SD 0.18, n = 8); in normal subjects, 1.00 (SD 0.11, n = 20). This albumin-binding index enables the rapid and unequivocal diagnosis of subjects with FDH, without the addition of unlabeled T4.

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In the cord blood of seven infants with congenital hypothyroidism detected in our newborn screening programs, thyroxine values ranged from 2.5 to 6.7 mug/dl and thyrotropin, from 105 to 975 muU/ml; triiodothyronine values were normal. On follow-up, T3 levels increased to normal in five infants, there was a significant negative correlation between the T3 value and the severity of thyroprevia as reflected in the TSH levels and the number of clinical features present. This increase in T3 may explain in part why the diagnosis of this disease is difficult during the first few months of life and why early treatment is effective. This observation provides further rationale for the widespread institution of newborn screening programs for congenital hypothyroidism.

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The binding characteristics of Thyroxine Binding Globulin(TBG) Pre-albumin (TBPA) and Transcortin in Jamaicans were found to be similar to those described elsewhere. The previously reported diminution in adrenocortical and thyroidal function associated with normal plasma cortisol and thyroxine levels cannot therefore be ascribed to an increase in the plasma protein binding of these hormones (AU)

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