Affect Thyroid Hormone Metabolism Research Articles

Effect of nicotine on type 2 deiodinase activity in cultured rat glial cells.

Intracellular generation of triiodothyronine (T3) from thyroxine (T4) by type 2 deiodinase (D2) in the mammalian brain, plays a key role in thyroid hormone action. The presence of D2 in rat astrocytes suggests the importance of glial cells in the regulation of intracellular T3 levels in the rat central nervous system (CNS). To analyze further the factors that regulate D2 activity in the CNS, we investigated the effects of nicotine and of mecamylamine, which inhibits the binding of nicotine with nicotinic acetylcholine receptors, on D2 activity in cultured mixed glial cells of the rat brain. We incubated cultured mixed glial cells obtained from neonatal Wistar rats in the presence of 10 mM dithiothreitol, 2 nM [125I] reverse T3 and 1 mM 6-N-propyl-2-thiouracil for 2 h at 37 degrees C, and the released 125I- was counted in a gamma counter. D2 activity of cultured cells was dependent on the temperature and the amount of protein. The basal D2 activity of rat mixed glial cells was 1.9 +/- 0.2 fmol of I- released/mg protein/h (mean +/- SEM). The addition of 10(-11), 2 x 10(-11), 10(-10), and 10(-9) M nicotine significantly increased D2 activity to approximately 2.2-, 2.4, 3.5- and 2.9-fold the basal level, respectively. D2 activity stimulated by 10(-8) M nicotine (2.5-fold) reached a peak after 9 h incubation. The stimulatory effect of nicotine was completely blocked by 10(-6) M mecamylamine. In conclusion, nicotine increases D2 activity probably via nicotinic acetylcholine receptors, and may influence brain function, at least in part, by affecting thyroid hormone metabolism.

Thyroid function.

Normal thyroid status is dependent on the presence of many trace elements for both the synthesis and metabolism of thyroid hormones. Iodine is most important as a component of the hormones, thyroxine and 3,3',5-tri-iodothyronine (T3) and iodine deficiency may affect approximately one billion people throughout the world. Selenium is essential for normal thyroid hormone metabolism being involved with selenium-containing iodothyronine de-iodinases that control the synthesis and degradation of the biologically active thyroid hormone, T3. Additionally, selenoperoxidases and thioredoxin reductase protect the thyroid gland from peroxides produced during the synthesis of hormones. The roles of iron, zinc and copper in the thyroid are less well defined but sub- or supraoptimal dietary intakes of all these elements can adversely affect thyroid hormone metabolism.

Thyroid gland function in lithium treatment

Lithium is widely used in the acute and prophylactic treatment of affective disorders. Lithium affects thyroid hormone metabolism via different mechanisms. In patients this leads to a compensatory increase in pituitary thyroid stimulating hormone (TSH) which usually maintains the euthyroid status. This is probably the reason for the relatively high prevalence of goitre in lithium-treated patients; however, the enlargement of the gland is only moderate in most cases. Due to its immunostimulating effects lithium may support the appearance of thyroid auto-antibodies and the development of thyroiditis, which may be the reason for a higher prevalence of hypothyroidism in patients receiving lithium. However, also cases of hyperthyroidism in such patients have been reported repeatedly. Therapeutic recommendations for the treatment of disturbances of thyroid function during lithium treatment are given.

Thyroid hormone alterations during and after cardiopulmonary bypass

The haemodynamic effects of thyroid hormones are well known and include those on heart rate, contractility and myocardial oxygen consumption. Cardiopulmonary bypass produces various alterations in endocrine homoeostasis and may exert important haemodynamic effects postoperatively. The purpose of this prospective study was to determine the relation of cardiopulmonary bypass to changes in thyroid function. Blood samples were obtained from 20 patients preoperatively, at specific times before, during and after cardiopulmonary bypass. Total thyroxin (TT 4), total triiodothyronine (TT 3), free thyroxin (fT 4), free triiodothyronine (fT 3), thyroid-stimulating hormone (TSH), thyroid-binding globulin (TBG) and albumin were measured by radioimmunoassay and competitive immunoassay. Values of TT 4, TT 3 and fT 3 were significantly depressed up to 24 h after cardiopulmonary bypass ( P < 0.05). TSH and fT 4 levels remained within normal ranges at all sampling times. It is increasingly evident that cardiopulmonary bypass affects thyroid hormone metabolism, leading to a transient depression characterized by low levels of circulating TT 4, TT 3 and fT 3. Copyright © 1996 The International Society for Cardiovascular Surgery.

Thyroid Hormone Alterations during and after Cardiopulmonary Bypass

The haemodynamic effects of thyroid hormones are well known and include those on heart rate, contractility and myocardial oxygen consumption. Cardiopulmonary bypass produces various alterations in endocrine homoeostasis and may exert important haemodynamic effects postoperatively. The purpose of this prospective study was to determine the relation of cardiopulmonary bypass to changes in thyroid function. Blood samples were obtained from 20 patients preoperatively, at specific times before, during and after cardiopulmonary bypass. Total thyroxin (TT4), total triiodothyronine (TT3), free thyroxin (fT4), free triiodothyronine (fT3), thyroid-stimulating hormone (TSH), thyroid-binding globulin (TBG) and albumin were measured by radioimmunoassay and competitive immunoassay. Values of TT4, TT3 and fT3 were significantly depressed up to 24 h after cardiopulmonary bypass ( P &lt; 0.05). TSH and fT4 levels remained within normal ranges at all sampling times. It is increasingly evident that cardiopulmonary bypass affects thyroid hormone metabolism, leading to a transient depression characterized by low levels of circulating TT4, TT3 and fT3.

Relationship between serum 3,5,3'-triiodothyronine and serum interleukin-8, interleukin-10 or interferon gamma in patients with nonthyroidal illness.

In order to further delineate the role of cytokines in the pathogenesis of the low T3 syndrome, we studied the association between serum T3 and serum interferon gamma (IFN gamma), interleukin-8 (IL-8) and interleukin-10 (IL-10) in 99 consecutive patients hospitalised because of a wide variety of nonthyroidal diseases; none used drugs affecting thyroid hormone metabolism. Patients were divided in group A (normal serum T3 and T4), group B (subnormal serum T3 and normal T4) and group C (subnormal T3 and T4). Serum IFN gamma, IL-8 and IL-10 were not different between group A, B and C (with the exception of a small increase of IFN gamma in group B). Serum T3 was slightly related to serum IL-8 (r = 0.25, p < 0.05), but not to IFN gamma and IL-10. Stepwise multiple regression indicated that these serum cytokines were not independent determinants of the variability in serum T3. The results do not support any role of circulating IFN gamma, IL-8 or IL-10 in the pathogenesis of the low T3 syndrome during illness.

Thyroid Hormone Metabolism and Thyroid Diseases in Chronic Renal Failure

Patients with ESRD have multiple alterations of thyroid hormone metabolism in the absence of concurrent thyroid disease. These may include elevated basal TSH values, which may transiently increase to greater than 10 mU/liter, blunted TSH response to TRH, diminished or absent TSH diurnal rhythm, altered TSH glycosylation, and impaired TSH and TRH clearance rates. In addition, serum total and free T3 and T4 values may be reduced, free rT3 levels are elevated while total values are normal, serum binding protein concentrations may be altered, and disease-specific inhibitors reduce serum T4 binding. Changes in T4 and T3 transfer, distribution, and metabolism resemble those of other nonthyroidal illnesses, while changes in rT3 metabolism are disease specific. Dialysis therapy minimally affects thyroid hormone metabolism, while zinc and erythropoietin administration may partially reverse thyroid hormone abnormalities. Thyroid hormone metabolism normalizes with renal transplantation; however, glucocorticoid therapy may induce additional changes. ESRD patients may have an increased frequency of goiter, thyroid nodules, thyroid carcinoma, and hypothyroidism. Goiter and hypothyroidism may be induced by iodide excess, due to reduced renal iodide excretion, and may be reversed with iodide restriction in some patients. The increased frequency of thyroid nodules and malignancies in ESRD may relate to secondary hyperparathyroidism. After renal transplantation, the higher frequency of thyroid malignancies may relate to the immunosuppressed state. Clinical symptoms and signs and biochemical features of hypothyroidism and hyperthyroidism may be altered by concurrent ESRD. ESRD patients with hyperthyroidism or follicular neoplasms require reduced dosages of Na 131-I depending upon type, frequency, and duration of dialysis therapy.

Sodium ipodate in the preparation of Graves' hyperthyroid patients for thyroidectomy.

Sodium ipodate (SI) is an oral cholecystographic agent that also affects thyroid hormone metabolism. It inhibits the peripheral T4 to T3 conversion and the thyroidal hormone release. We investigated the safety and efficacy of SI (500 mg daily during 5 days) in the preparation for subtotal thyroidectomy of 7 Graves' hyperthyroid patients in whom treatment with thionamides was unsuccessful due to allergy or noncompliance. Plasma T3 levels (mean +/- SD) decreased from 4.90 +/- 1.80 nmol/l on day 0 to 1.70 +/- 0.30 nmol/l on day 4 of treatment. Thyroidectomy performed on day 5 of treatment was uneventful. In comparison with 14 Graves' hyperthyroid patients who underwent thyroidectomy during the same period after conventional preparation with thionamides and potassium iodide, the therapeutic outcome 1 year postoperatively was similar in both groups. However, in the mildly hypothyroid patients prepared with SI, the plasma thyroid-stimulating hormone level was transiently higher 3 and 6 months postoperatively. It is concluded (1) that SI is a safe and efficacious drug in the preparation of Graves' hyperthyroid patients for thyroidectomy; (2) the therapeutic outcome 12 months postoperatively is similar in SI and in conventionally prepared Graves' hyperthyroid patients, and (3) postoperative mild or subclinical hypothyroidism is more pronounced in SI than in conventionally prepared patients.

Rat Assay of a Simulated Human Diet for Antithyrotoxic Substances

Since certain dietary substances markedly alter the turnover and utilization of thyroid hormone in the rat, it is important to determine whether the same substances also affect thyroid hormone metabolism in the human. To conduct such a study, it is necessary to devise a diet that is very low in antithyrotoxic substances, and to find suitable foodstuffs that are high in antithyrotoxic activity. To this end, a simulated human diet was prepared and fed to rats given exogenous thyroxine (T4). The diet was very low in antithyrotoxic activity, and the inclusion of liver, milk, beef and fish into the diet afforded the same protection against the physiological effectiveness of T4 as liver residue, a commercial liver preparation, known to have high antithyrotoxic substance activity. Based on these results, it should be possible to prepare human diets both low and high in antithyrotoxic substance activity, and to determine the importance of these substances in human thyroid hormone metabolism and economy.