triiodothyronine--reverse and Syndrome

The increased serum reverse T3 and decreased T3 during caloric deprivation and non-thyroidal illness is caused by decreased T3 production (with intact degradation) and reversed T3 degradation (with intact production) respectively. These changes can ensue from two mechanisms i.e. decreased 5'D of T4 and of reverse T3 (possibly caused by a decrease in naturally occurring reducing agents) or by decreased transport of T4 and reverse T3 into the liver (possibly caused by decreased ATP concentrations in the liver). The effects of the low T3 syndrome at the tissue level are in many instances comparable to those seen in hypothyroidism. The effects lead to conservation of energy and decrease of protein breakdown. These effects are considered to constitute a beneficial adaptative mechanism in situations in which the organism is endangered. There is no evidence that treatment of patients with the low T3 syndrome with thyroid hormones is of any benefit. Knowledge at the present moment suggests that administration of thyroid hormones during caloric deprivation or non-thyroidal illness should be avoided.

Topics: Food Deprivation; Humans; Syndrome; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Topics: Aged; Humans; Hypothyroidism; Syndrome; Thyroid Gland; Thyroid Hormones; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Thyroxine-Binding Proteins; Triiodothyronine; Triiodothyronine, Reverse

"Syndromes related to defective iodothyronine metabolism" have been frequently observed in clinical practice. As for methodological and pathophysiological reasons T4, T3, rT3 and TSH estimations are of limited value in these situations, thus, the interpretation of the laboratory findings becomes frequently difficult. Furthermore determining the individual "whole body"- or "organ-thyroid state" requires more than measuring the serum concentrations of thyroid hormones. Iodothyronine metabolism is strongly organ specific, therefore, alterations in plasma thyroid hormone concentrations cannot reflect the specific cellular and subcellular thyroid hormone concentrations of individual organs. However, there is some experimental evidence, that disease-induced alterations in plasma thyroid hormone levels are a simple reflection of the catabolic state of the organisms. At present the biological implication of altered thyroid hormone economy in non-thyroidal illness should not be considered as an energy sparing, i.e. protein sparing effect, anymore: Thyroid hormones in their physiological concentrations act as anabolic hormones. There is no general indication for substituting diminished T3. Up to now, preliminary data suggest the benefit of T3-substitution in septic shock or in "respiratory distress syndrome". However, the possible benefit of improved cardiovascular of respiratory function should be compared carefully to the harm of the therapy, i.e. T3-induced increase in protein catabolism or possible deterioration in preexisting ischemic heart disease: From a clinical point of view, most of non-thyroidal illness-induced changes in ITH-metabolism seem to implicate a pitfall in physician's diagnosis of the thyroid state rather than a therapeutic question.

Topics: Body Temperature Regulation; Catecholamines; Glucose; Humans; Infant, Newborn; Iodide Peroxidase; Ketone Bodies; Models, Biological; Respiratory Distress Syndrome, Newborn; Shock, Septic; Syndrome; Thyroglobulin; Thyroid Diseases; Thyroid Gland; Thyronines; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Topics: Animals; Fetus; Humans; Hyperthyroidism; Hypothyroidism; Syndrome; Thyroid Hormones; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Non-thyroidal illnesses, such as surgical stress, are associated with abnormal metabolism of thyroid hormones. However, the potential impact of variable surgical procedures remain to be elucidated. In order to evaluate the effect of mild surgical stress upon thyroid function, TT4, TT3, rT3 and TSH were measured in twenty-two patients undergoing laparoscopic cholecystectomy before (Stage 1), during (Stages 2-5), at the recovery room (Stage 6) and 24h postoperatively (Stage 7). The values of TSH remained within the normal limits with transient changes during the study period. Similarly, TT4 values displayed normal variations within the normal range without reaching a statistically significant difference during the study period. A decrease of TT3 values was detected early at stage 2 during induction of anaesthesia. TT3 remained at low levels during the perioperative period, and a further decrease was observed 24 h postoperatively. The above profile of thyroid hormone metabolism, reflects a low-T3 syndrome in patients undergoing laparoscopic cholecystectomy. Interestingly, there was a tendency for rT3 to increase and it reach its highest value 24h postoperatively with the difference being statistically significant (p<0.05). The asynchronous distribution of rT3 and TT3 might be attributed to multifactorial influences.

Topics: Adult; Aged; Anesthesia; Cholecystectomy, Laparoscopic; Female; Humans; Intraoperative Period; Middle Aged; Postoperative Period; Radioimmunoassay; Stress, Physiological; Syndrome; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Interleukin-6 (IL-6) administration to human subjects or experimental animals induces changes in thyroid hormone metabolism resembling those in the sick euthyroid syndrome. Furthermore, the decrease in serum T3 during illness is significantly related to serum IL-6 concentrations. These findings suggest, but do not prove, a causal role for IL-6 in the development of the low T3 syndrome. The aim of the present study was to evaluate the role of IL-6 in the development of the sick euthyroid syndrome in IL-6 knock-out (IL-6(-/-)) mice compared to that in wild-type mice (IL-6(+/+)). Illness was induced in IL-6(-/-) and IL-6(+/+) mice by 1) administration of bacterial endotoxin (LPS), 2) infection with Listeria monocytogenes, and 3) turpentine injection in both hind limbs. Food intake was kept similar in both groups in all three experiments. Serial measurements were made of serum IL-6, tumor necrosis factor-alpha, T3, T4, corticosterone, and liver 5'-deiodinase (5'-DI) messenger RNA (mRNA) for 24 h (LPS), 96 h (L. monocytogenes), and 48 h (turpentine). Serum IL-6 increased in response to all stimuli in IL-6(+/+) mice, but not in IL-6(-/-) mice. Serum tumor necrosis factor-alpha was induced by LPS in both groups to a similar extent, but did not rise after L. monocytogenes or turpentine administration. Serum T3 and T4 decreased after all three stimuli. The decrease in serum T4 in IL-6(-/-) was similar to that in IL-6(+/+) mice. The decrease in serum T3, however, was smaller in the IL-6(-/-) mice than in the IL-6(+/+) mice; T3 levels were 1.56 +/- 0.29 and 0.99 +/- 0.15 nmol/liter, respectively, 24 h after LPS treatment (P < 0.01), 2.39 +/- 0.17 and 1.75 +/- 0.24 nmol/liter 96 h after L. monocytogenes treatment (P < 0.01), and 1.46 +/- 0.18 and 1.10 +/- 0.25 nmol/liter 48 h after turpentine treatment (P < 0.05). The smaller fall in serum T3 in IL-6(-/-) mice could not be attributed to differences in the severity of the induced illness, food intake, or corticosterone response, which were all similar in IL-6(-/-) mice and IL-6(+/+) mice. Liver 5'-deiodinase mRNA decreased after all three stimuli; the decrease after LPS and L. monocytogenes infection was smaller in the IL-6(-/-) mice, but the difference in IL-6(+/+) mice just failed to reached statistical significance. Liver 5'-deiodinase activity after turpentine injection administration decreased in the wild-type animals by 36%, but did not change in the knock-out mice. In conclusion, acutely induced illness generat

Topics: Animals; Corticosterone; Female; Interleukin-6; Iodide Peroxidase; Liver; Mice; Mice, Knockout; RNA, Messenger; Syndrome; Triiodothyronine, Reverse; Tumor Necrosis Factor-alpha

Changes in thyroid hormone metabolism in the low-3,5,3'-triiodothyronine (T3) syndrome cannot be fully explained in all conditions by a decrease in 5'-deiodinase activity. Recent observations showed that in rat hepatocytes iodothyronines are taken up by an active transport mechanism. To investigate whether regulation, i.e., inhibition of active transmembraneous transport for iodothyronines in humans may contribute to the generation of the low-T3 syndrome, tracer thyroxine (T4) and T3 kinetic studies were performed in 10 obese subjects before and after 7 days on a 240 kcal diet. Kinetics analyses were performed according to a three-pool model of distribution and metabolism for both T4 and T3. For T4 kinetics, during caloric deprivation serum total T4 and plasma pool did not change and production rate and metabolic clearance rate (MCR) were significantly lower. Despite a significantly higher serum free T4, the mass transfer rate to the rapidly equilibrating pool (REP) and the slowly equilibrating pool (SEP) diminished significantly, leading to smaller tissue pools. For T3 kinetics, both serum total T3, free T3, plasma pool, and production rate diminished significantly, while MCR remained unchanged. Mass transfer rates to the REP and the SEP were lowered by approximately 50%, leading to smaller tissue pools. These changes cannot be fully explained by a similar decrease of serum free T3 (only 25%), indicating a diminished transport efficiency for T3. In conclusion, during caloric restriction, transport of T4 and T3 into tissues is diminished, and this phenomenon is much more pronounced for T4 than for T3.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Diet, Reducing; Energy Intake; Female; Humans; Iodide Peroxidase; Iodine Radioisotopes; Kinetics; Male; Obesity; Syndrome; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Time sequence and specificity of thyroid hormones and biochemical parameters were investigated in patients following major surgery. Serum concentration of triiodothyronine decreases significantly following operation, with a biphasic regression. There is a reciprocal change in serum reverse triiodothyronine levels, but serum thyroxine levels show no significant change after operation. The significant decrease in serum concentration of alpha-2-macroglobulin and antithrombin III during and after surgery is the result of consumption of these inhibitors because the reciprocal change in serum concentration of elastase-like protease has been recognized. According to the change of curvilinear regression of serum triiodothyronine levels, 14 patients were grouped into 3. The patients for whom the curvilinear regression resembled a polynomial of degree 3 and 2 had a good prognosis, but the remaining 4 with no significant curvilinear regression had major complications and 2 died. It is meaningful that the postoperative change of triiodothyronine levels relates to the clinical outcome, to some degree.

Topics: Adolescent; Adult; Female; Humans; Male; Middle Aged; Prognosis; Surgical Procedures, Operative; Syndrome; Thyroxine; Time Factors; Triiodothyronine; Triiodothyronine, Reverse

Topics: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Male; Syndrome; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Two patients, a boy of 8 and a women of 60 years of age, had higher than normal levels of serum total thyroxine (T4), free T4, (FT4), FT4 index, and reverse triiodothyronine, but normal serum triiodothyronine (T3) levels. The pituitary-thyroid axis could be normally stimulated by thyrotropin-releasing hormone, suggesting euthyroidism at the pituitary level. High levels of serum T4-binding globulin decreased during T3 treatment in the boy. Studies show that in these patients a raised serum FT4 is necessary to produce in the peripheral tissues sufficient amounts of T3 for biological action. Two possible mechanisms for a basic defect underlying this newly recognised syndrome are proposed: inhibition of T4 transport into tissue cells and reduced intracellular 5'-deiodinase activity catalysing T4 to T3 conversion.

Topics: Child; Extracellular Space; Female; Humans; Hypothyroidism; Intracellular Membranes; Iodide Peroxidase; Male; Middle Aged; Syndrome; Thyroid Function Tests; Thyrotropin; Thyroxine; Thyroxine-Binding Proteins; Triiodothyronine; Triiodothyronine, Reverse

Thyroid and pituitary function was studied in 10 male and 6 patients female during critical non-endocrine disease. Low concentrations of TT3 were observed in each case. Seven patients out of whom 3 survived, presented with low levels of TT4 due to deficiency in TBG in the presence of normal values of FTI and FT4, whereas a 'low T4-syndrome', characterized by low concentrations of both TT4 and FT4 was seen in 9 patients, 8 of whom died 1 to 16 days after evaluation of pituitary function. A diminished response of TSH to iv TRH (400 micrograms), as observed in 4 patients with normal FT4 and in all patients with 'low T4-syndrome', was not accompanied by a concomitant lack in stimulated release of LH, FSH and Pr1 in the majority of cases. However, the secretory maximum of LH and FSH following stimulation by LRH (100 micrograms iv) was delayed in 10 and in 9 patients, respectively, including patients both with normal and subnormal concentrations of FT4. From the above it appears that low stimulated concentrations of TSH in the presence of subnormal concentrations of FT4 indicate an extremely poor prognosis in critically ill patients. The abnormal behaviour of TSH in this group of patients cannot be explained by generalized pituitary insufficiency or by an increase in FT4.

Topics: Adult; Aged; Bacterial Infections; Female; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Male; Middle Aged; Pituitary Gland; Prolactin; Sepsis; Syndrome; Thyroglobulin; Thyroid Gland; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse; Virus Diseases

Topics: Diagnosis, Differential; Humans; Hypothyroidism; Male; Middle Aged; Syndrome; Thyroid Function Tests; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

The thyroid function of patients with three different types of organification defect was studied. All patients were characterized by a high thyroidal 131I uptake and a positive perchlorate discharge. Patients with Pendred's syndrome who had goitre and congenital nerve deafness were mostly euthyroid with normal circulating thyroid hormone levels. Only two of them had compensated euthyroidism with elevated total T3, high basal TSH and delayed return to basal value with TRH. The patients who were euthyroid with large goitres and normal hearing had elevated total T3 and an exaggerated TSH response to TRH. The thyroid function of these two groups of patients contrasted with that of goitrous cretins, who were clinically hypothyroid with low circulating total T4, increased T3 and decreased rT3 levels. The data suggest that in patients with intrathyroidal iodine deficiency secondary to organification defect, there is preferential T3 production in an effort to maintain euthyroid state, and this is further substantiated in the case of gross thyroid insufficiency either by enhanced peripheral conversion of T4 to T3, or reduced metabolic clearance of T3 and increased clearance of rT3, resulting in elevated T3 and decreased rT3 levels.

Topics: Adolescent; Adult; Congenital Hypothyroidism; Deafness; Female; Goiter; Humans; Iodine; Male; Pedigree; Syndrome; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse