triiodothyronine--reverse and Disease

In systemic nonthyroidal illness (NTI), peripheral production of T3 from T4 is decreased, resulting in a decreased serum T3 concentration. We investigated whether factors in serum of NTI patients may play a role in this energy-saving adaptation mechanism. Metabolism of T4 and T3 by rat hepatocytes in primary culture was measured in the presence of 10% serum of normal subjects or of patients with NTI and related to the severity of disease. Patients with NTI were grouped according to serum thyroid hormone abnormalities: group I, serum rT3, T3, and T4 normal; group III, rT3 elevated, T3 decreased, T4 normal; group IV, rT3 elevated, T3 and T4 decreased. Compared with metabolism in the presence of normal serum, metabolism of T4 and to a lesser extent of T3 was progressively decreased in the presence of serum of patients of groups I-IV. A decreased net deiodination of T4 and T3 (corrected for differences in free hormone concentration) without an increase in conjugated T4 and T3 (corrected for differences in free hormone concentration) was observed, similar to results in experiments with compounds inhibiting transport into the cells and not the metabolic processes (5' deiodination) per se. Deiodination of T4 in vitro was correlated with serum T3 concentration of the patient (r = 0.69). Serum of patients with NTI influences thyroid hormone handling by hepatocytes comparable to the effect of transport inhibitors and not to that of the 5'-deiodinase inhibitor propylthiouracil, suggesting that decreased thyroid hormone transport over the cell membrane may play a role in lowered T3 production in NTI.

Topics: Animals; Cells, Cultured; Culture Media; Disease; Humans; Hyperthyroidism; Hypothyroidism; Liver; Male; Monensin; Ouabain; Propylthiouracil; Rats; Rats, Wistar; Reference Values; Regression Analysis; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

The "euthyroid sick syndrome", representing the changes of thyroid hormone metabolism in disease, embraces the following hormonal changes: 1) A decrease in serum T3 levels which is often accompanied by an increase in rT3 levels. Serum T4 levels remain normal. These changes are extremely frequent in many varied diseases. 2) In very severe disease, serum T4 levels may also decrease. The free T4 index is often decreased and the free T4 may either be normal or decreased. These changes reflect alterations of thyroid hormone metabolism and can be distinguished from primary hypothyroidism by a normal serum TSH level. 3) Occasionally there are transient increases of total and free T4. This disturbance of serum thyroid hormone levels is mostly due to drug interference with thyroid hormone metabolism (amiodarone etc.). Differentiation from hyperthyroidism is difficult. It is important to diagnose the "euthyroid sick syndrome" since this will avoid erroneous diagnosis and treatment or hypo- and hyperthyroidism.

Topics: Diagnosis, Differential; Disease; Humans; Hyperthyroidism; Hypothyroidism; Thyroid Hormones; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Thyroxine-Binding Proteins; Triiodothyronine; Triiodothyronine, Reverse

Topics: Acclimatization; Disease; Fasting; Female; Fetus; Humans; Infant, Newborn; Kinetics; Obesity; Pregnancy; Receptors, Cell Surface; Receptors, Thyroid Hormone; Starvation; Temperature; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Thyroxine, the major secretory product of the thyroid gland, is metabolized in the peripheral tissues by phenolic conjugation, deamination, decarboxylation, and a cascade of monodeiodinations. This brief review focuses on the deiodination reactions, which currently are under intensive investigation. One product, 3,5,3'-triiodothyronine (T3), is the major active form of the thyroid hormone, and about 80% of the T3 produced in the body is derived extrathyroidally. Furthermore, a greater fraction of the T3 found on nuclear receptors in pituitary and brain cells is derived intracellularly, as compared to liver and kidney cells. The latter tissues, on the other hand, appear to be the source of most of the circulating T3. Another deiodinase, acting on the nonphenolic ring of T4, gives rise to the hormonally inactive 3,3',5'-triiodothyronine ("reverse" T3 or rT3). A number of physiological and pathological events perturb the deiodination pathway, leading to a decrease in T3 neogenesis and reciprocal changes in the circulating level of T3 (which decreases) and rT3 (which increases). This so-called "low T3 syndrome" is also produced by a number of pharmacological agents. The biological effects resulting from these changes are incompletely understood, but they are potentially important in the body's adjustment to stress and as a site of action of toxic agents. In addition, they are of obvious importance clinically because of their influence on serum T3 and TSH levels, which are commonly used tests of thyroid function.

Topics: Age Factors; Aged; Animals; Disease; Female; Fetus; Humans; Pharmacology; Pregnancy; Thyroid Gland; Thyroxine; Tissue Distribution; Triiodothyronine; Triiodothyronine, Reverse

Topics: Adult; Diiodothyronines; Disease; Female; Humans; Hypothyroidism; Kinetics; Male; Middle Aged; Reference Values; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Serum concentrations of T4, T3, T3, free T4, free T3, and TSH were determined in four groups of adult subjects: group A, 27 healthy young volunteers (aged 18-29 yr); group B, 24 carefully selected healthy elderly subjects (aged 70-90 yr); group C, 41 subjects living at a municipal nursing home for the elderly (aged 70-90 yr); and group D, 35 hospitalized patients (aged 70-90 yr). Identical levels of iodothyronines in serum were found in the young and in the elderly healthy subjects. Moderate and severe disease induced alterations in iodothyronine concentrations in serum comparable to those reported earlier. Serum T3 and free T3 levels were low and serum rT3 levels were high in groups C and D subjects; serum free T4 was elevated in group D, while serum T4 was low. Serum TSH was lower in the healthy elderly subjects than in the young subjects. Serum TSH was higher in the elderly sick subjects (groups C and D) than in the healthy subjects (group B). We conclude that advanced age per se is not accompanied by alterations in free or total serum iodothyronine levels.

Topics: Adolescent; Adult; Aged; Aging; Disease; Female; Humans; Male; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse