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Biomedical subjects

R D Utiger

Publications and source records attributed to R D Utiger.

At least 55 records · Page 3Linked to original sources
PubMed1985

Caloric restriction does not alter thyrotropin secretion in hypothyroidism.

The effect of caloric restriction, as a model of nonthyroid illness, on serum thyroid hormone and TSH concentrations in hypothyroid patients was studied to determine if pituitary-thyroid function is altered in such patients, as it is in euthyroid subjects. Serum T4, T3, and TSH concentrations and serum TSH responses to TRH were measured in 5 untreated hypothyroid patients and 10 hypothyroid patients receiving T4 replacement therapy before and after restriction of caloric intake to 500 cal daily for 7 days. In 5 untreated hypothyroid patients, the mean serum T3 concentration declined 17%, from 75 +/- 14 (+/- SE) to 62 +/- 11 ng/dl. The mean basal serum TSH concentrations were 154 +/- 67 (+/- SE) microU/ml before and 161 +/- 75 microU/ml at the end of the period of caloric restriction, and the serum TSH responses to TRH were similar on both occasions. In 10 T4-treated hypothyroid patients, the mean serum T3 concentration declined 35%, from 110 +/- 8 to 71 +/- 8 ng/dl. In this group, mean basal serum TSH concentrations were 17 +/- 5.1 microU/ml before and 18.2 +/- 7.0 microU/ml at the end of the period of caloric restriction, and as in the untreated hypothyroid patients, the serum TSH responses to TRH were similar on both occasions. Mean serum T4 concentrations and serum free T4 index values did not change in either group. These results indicate that caloric restriction in both untreated and T4-treated hypothyroid patients is accompanied by 1) reduced serum T3 concentrations, as it is euthyroid subjects, and 2) no alterations in basal or TRH-stimulated TSH secretion.

Adult↗
PubMed1984

Myxedema coma during long-term amiodarone therapy.

Amiodarone is a potent new antiarrhythmic drug that has multiple effects on thyroid function, including inhibition of extrathyroidal triiodothyronine production and rarely, iodine-induced hypothyroidism. This report describes a man with recurrent ventricular tachycardia in whom hypothyroidism developed during amiodarone therapy and who died of probable myxedema coma. Parenteral and oral thyroxine therapy promptly reduced serum thyroid-stimulating hormone concentrations without increasing the patient's very low serum triiodothyronine concentration. This response to thyroxine suggests that thyroxine itself may have biologic activity and participate directly in regulation of thyrotropin secretion. Because amiodarone-induced hypothyroidism may be life-threatening, thyroid function should be monitored before and during amiodarone therapy, and the drug discontinued or appropriate therapy instituted if hypothyroidism develops.

Aged↗
PubMed1984

Triiodothyronine production by isolated rat hepatocytes: characterization and lack of glucoregulatory hormone effects.

Triiodothyronine (T3) production from thyroxine (T4) was studied in isolated rat hepatocytes. With an initial T4 concentration of 0.56 microM, hepatocyte T3 production was 0.029 +/- 0.003 (SEM) pmoles/min/mg protein. T3 production was greater in hepatocytes than in homogenates from the same liver prepared either before or after liver perfusion with collagenase. Most T3 produced remained within the cells under the conditions employed. Hepatocyte T3 production was dependent on cell number, medium bovine serum albumin concentration and temperature. It was stimulated by dithiothreitol, and inhibited by propylthiouracil, 3,3',5'-triiodothyronine and dinitrophenol; glutathione and ouabain had no effect. Alterations in medium glucose concentration and exposure to insulin or glucagon at several glucose concentrations in vitro did not alter T3 production. These results indicate that in hepatic tissue T3 production is enhanced when intact cellular organization is present and that insulin and glucagon do not acutely influence cell production of T3 in vitro.

2,4-Dinitrophenol↗
PubMed1984

Beta-adrenergic antagonist inhibition of hepatic 3,5,3'-triiodothyronine production.

beta-Adrenergic antagonists provide moderate symptomatic relief for most hyperthyroid patients, although these agents have no direct antithyroid effects. Propranolol administration results in modest declines in serum T3 concentrations in both hyperthyroid and normal subjects and also inhibits T4 to T3 conversion in various tissue preparations in vitro. Other beta-adrenergic antagonists have not been shown to consistently alter serum T3 concentrations in vivo or T3 production in vitro. To evaluate the ability of beta-adrenergic antagonists to inhibit T4-5'-deiodination, we measured T3 production from T4 in rat liver homogenates (10,000 X g supernatant) using 1 microM T4 in the presence of varying concentrations of the beta-adrenergic antagonists available in the United States. Each drug inhibited T3 production, and the dose-dependent responses were linear and parallel when plotted as percent inhibition vs. log dose concentration. The calculated drug concentrations required to produce 50% inhibition were: propranolol, 1.7 mM; pindolol, 6.7 mM; timolol, 11.5 mM; atenolol, 23.2 mM; metoprolol, 30.5 mM, and nadolol, 106.1 mM. The IC50 values were similar in the presence of 4 mM dithiothreitol. In separate studies, the ability of D- and L-propranolol to inhibit T3 production was compared with that of D,L-propranolol, the common form. Both D- and L-propranolol were as effective as the racemic mixture. The propranolol metabolites 4-hydroxypropranolol, 4-methylpropranolol, propranolol glycol, and N-desisopropyl propranolol were also effective inhibitors. Thus, beta-adrenergic antagonists inhibit T3 production in vitro. This inhibition is not related to beta-adrenergic antagonism per se, but is correlated with the lipid solubility of the drugs, which may explain the effects of propranolol on serum T3 in vivo.

Adrenergic beta-Agonists↗
PubMed1984

Reverse triiodothyronine does not alter pituitary-thyroid function in normal subjects.

Serum rT3 concentrations are often increased in patients with nonthyroid illness. Such elevations could be responsible for some of the alterations in pituitary-thyroid function that occur in such patients, particularly since rT3 is a potent inhibitor of extrathyroidal T3 production in vitro. To evaluate the role of serum rT3 elevations in the regulation of the hypothalamic-pituitary-thyroid axis, 10 normal subjects were given 3 mg rT3, orally, in divided doses for 4 days. Serum rT3 concentrations were elevated at least 10-fold by the end of the first day of treatment. Mean serum T4 and T3 concentrations did not change, nor was there any change in basal or TRH-stimulated serum TSH concentrations. There was, likewise, no change in serum binding of T3 or T4. These results show that rT3, given orally, has no detectable activity in normal subjects, and hence, elevations in serum rT3 concentrations per se do not contribute to other abnormalities in thyroid function found in patients with nonthyroid illness.

Adult↗
PubMed1984

Amenorrhea-galactorrhea, hyperprolactinemia, and suprasellar pituitary enlargement as presenting features of primary hypothyroidism.

Two women who presented with amenorrhea-galactorrhea and hyperprolactinemia associated with x-ray evidence of pituitary enlargement and suprasellar extension were found to have primary hypothyroidism. Resolution of the pituitary enlargement and galactorrhea occurred after thyroid hormone replacement. Both women spontaneously ovulated and conceived, and normal pregnancies resulted. Amenorrhea, galactorrhea, and/or pituitary enlargement may be the principal manifestations of primary hypothyroidism. In such patients, it is imperative that primary hypothyroidism be excluded before drug or surgical therapy for presumed prolactinoma is undertaken. When these findings are due to primary hypothyroidism, thyroid hormone replacement alone is adequate therapy.

Adult↗
PubMed1983

Hypothalamic portal blood immunoreactive TRH in the rat: lack of effect of hypothyroidism and thyroid hormone treatment.

Possible thyroid hormone regulation of hypothalamic thyrotropin-releasing hormone (TRH) secretion was studied by measurement of hypophyseal portal blood TRH concentrations in normal, hypothyroid and thyroid hormone treated rats. TRH was measured by radioimmunoassay of methanol extracts of blood. Extraction recovery was good. Endogenous TRH immunoreactivity (IR-TRH) was destroyed by incubation with normal human serum and it co-migrated with synthetic TRH in a thin layer electrophoresis and chromatography system. Mean portal blood IR-TRH concentrations ranged from 1041 to 2834 pg/ml in the various groups of rats studied. No consistent differences were found in portal blood IR-TRH concentrations in normal, hypothyroid or thyroid hormone treated rats. Peripheral blood IR-TRH concentrations were similar in normal rats and rats subjected to forebrain and hypothalamic removal. These results indicate that TRH secretion into the hypothalamic-pituitary portal system is not regulated by thyroid hormone and that forebrain and hypothalamic secretion do not contribute importantly to peripheral blood TRH.

Animals↗
PubMed1983

Growth hormone secretion and plasma somatomedin-C in primary hypothyroidism.

The effect of thyroid hormone deficiency on plasma immunoreactive somatomedin-C concentrations, growth hormone (GH) secretion in response to provocative stimuli, and the plasma somatomedin-C response to exogenous GH was studied in patients with primary hypothyroidism. Plasma Somatomedin-C concentrations were below the 95% confidence interval in 11 of 12 hypothyroid patients (mean +/- SD = 0.27 +/- 0.14 U/ml). With thyroid hormone therapy the mean plasma somatomedin-C level increased four-fold (1.00 +/- 0.43 U/ml). The capacity to secrete GH in response to pharmacological agents was impaired in 3 of the 6 hypothyroid patients tested and normal in the remainder. When the same 6 patients were given a single intramuscular injection of GH (0.1 U/kg) plasma somatomedin-C concentrations increased four-fold by 28 h after the injection. The magnitude of the somatomedin-C response was equal to or greater than that reported for euthyroid GH deficient subjects treated similarly. This study shows that plasma somatomedin-C concentrations are diminished by hypothyroidism. The decreased somatomedin-C levels do not appear to result from resistance to the stimulatory effect of GH, but may be either a result of diminished GH secretion or may be due to direct effects of hypothyroidism upon somatomedin production.

Adolescent↗
PubMed1983

Preincubation of thyroxine with sulfhydryl-reducing agents does not stimulate thyroxine inner or outer ring deiodination.

Sulfhydryl reagents stimulate enzymatic conversion of T4 to T3 and rT3. A recent study suggested that such reagents stimulated T4 5'-deiodination by a direct interaction with T4. We therefore tested the ability of dithiothreitol (DTT) and other sulfhydryl reagents to enhance the susceptibility of T4 and rT3 to 5'-deiodination by liver homogenates and of T4 to 5-deiodination by placental homogenates. Preincubation of T4 with DTT in concentrations ranging from 0.5-80 mM did not result in increased T3 production from T4 in rat liver homogenates, nor was T3 production increased by preincubation of T4 with reduced glutathione or mercaptoethanol. Preincubation of rT3 with DTT also did not result in increased rT3 degradation by liver homogenates. T4 5-deiodination to rT3 by rat and human placental homogenates was not consistently increased by preincubation of T4 with DTT in concentrations ranging from 2.25-450 mM. These results do not support the hypothesis that sulfhydryl stimulation of T4 deiodination occurs as a result of sulfhydryl-T4 interaction.

Animals↗
PubMed1982

Differing thyrotropin responses to increased serum triiodothyronine concentrations produced by overfeeding and by triiodothyronine administration.

The effects of overfeeding and triiodothyronine (T3) administration on basal serum thyrotropin (TRH) concentrations and the TSH response to thyrotropin-releasing hormone (TRH) was studied in normal subjects. Eight normal volunteers were fed their usual diet plus 2,000 kcal carbohydrate daily for 7 days. Their mean serum T3 concentrations increased from 102 +/- 6 (SEM) ng/dl to 126 +/- 10 ng/dl; there were no changes in serum thyroxine (T4) and basal serum TSh concentrations or the TSh response to TRH. Five of these subjects were fed their usual diet plus 10 micrograms T3 for 3 days and 20 micrograms T3 for 4 days divided doses. Their mean serum T3 concentrations increased from 104 +/- 6 ng/dl to 140 +/- 8 ng/dl. Mean serum T4 and basal serum TSH concentrations declined and serum TSH responses to TRH were significantly reduced. In both instances serum T3 concentrations remained within the normal range. These results indicate that increases in serum T3 concentrations of similar magnitude induced by augmented extrathyroidal T3 production and T3 administration have different effects on thyrotroph function.

Adult↗
PubMed1982

Thyroid function tests in patients with acute and resolved hepatitis B virus infection.

Serum thyroid hormones and thyroid hormone binding were sequentially measured in 20 patients with acute hepatitis B infection. Criteria to select patients consisted of a positive test for hepatitis B surface antigen, aspartate aminotransferase (AsAT) concentration greater than 400 U/L during the acute illness, and available serum specimens after recovery. The mean serum thyroxine (T4) concentration (+/- SE) was 12.5 +/- 0.6 microgram/dL during acute infection and 7.4 +/- 0.3 microgram/dL after recovery (p less than 0.001), whereas mean free T4 index values did not significantly differ. The mean serum thyroxine-binding globulin (TBG) concentration was significantly increased (p less than 0.001) during acute illness and accounted for the reversible of serum and the increased serum T4 concentrations. The rise in serum TBG correlated with the rise in AsAT during the acute illness (p less than 0.04) suggesting nonspecific release of these proteins from injured hepatocytes. The mean free triiodothyronine (T3) index was decreased during acute hepatitis (p less than 0.001) and returned to normal after recovery, indicating that acute hepatitis B infection, like other nonthyroidal illnesses, is associated with decreased T4 to T3 conversion in peripheral tissues.

Acute Disease↗
PubMed1982

Abnormalities in thyroid function tests in patients admitted to medical service.

Serum thyroid hormone, thyrotropin (TSH) and thyroxine-binding globulin (TBG) concentrations, free thyroxine index values, and free thyroxine concentrations were measured at the time of admission in all 77 patients hospitalized on a medical service on four separate days. Serum thyroxine (T4) concentrations and serum free T4 index values were decreased in 19.5% and 11.7%, respectively, and increased in 3.9% and 11.7%, respectively; serum free T4 concentrations were decreased in 6.8% and increased in 5.4%. Six patients (7.8%) had increased serum TSH concentrations. Serum triiodothyronine (T3) concentrations were decreased in 26.0% and reverse triiodothyronine (rT3) concentrations were increased in 29.9%. None had manifestations of thyroid disease. These results indicate that available thyroid function tests may give misleading results in patients with nonthyroid illness and suggest that caution be exercised in diagnosing thyroid disease in hospitalized patients.

Adolescent↗
PubMed1981

Peripheral resistance to thyroid hormone in an infant.

Peripheral resistance to thyroid hormone, a syndrome characterized by elevated serum total and free thyroid hormone levels and abnormal TSH suppression without manifestations of hyperthyroidism, was studied in a clinically euthyroid 6-month-old infant. Initial serum concentrations of T4, T3, and TSH were 22.1 micrograms/dl, 334 ng/dl, and 7.6 microunits/ml, respectively; infusion of synthetic TRH increased the serum TSH to 47.4 microunits/ml, an exaggerated response. Pituitary insensitivity to T3 was investigated by measuring these parameters in response to consecutive 7-day courses of increasing doses of T3. Four times the calculated replacement dose of T3 (40 micrograms/day) was required to normalize the serum T4 and the serum TSH response to TRH. After administration of 80 micrograms/day T3, the serum TSH response to TRH was virtually abolished, but no clinical signs of thyroid hormone excess were observed. High doses of T4 blunted the serum TSH response to TRH in a manner similar to T3. Prednisone also decreased the TSH response to TRH but had no effect on serum thyroid hormone concentrations. In an attempt to determine the mechanism of thyroid hormone resistance, specific nuclear T3 binding was compared in cultured skin fibroblasts from the patient and a normal infant. Normal fibroblast nuclei had a single binding site with a Ka of 3.1 X 10(9) M-1. In contrast, the Scatchard plot of the patient's T3 binding was curvilinear, compatible with a high affinity site that had a Ka (4.2 X 10(9) M-1) similar to that of the normal fibroblasts and a second low affinity site (Ka = 2.7 X 10(8) M-1). Supraphysiological concentrations of T3 elicited a dose-related increase in fibroblast glucose consumption, which was similar in cells from both the patient and from a normal infant. In conclusion, pituitary and peripheral resistance to thyroid hormone has been demonstrated in this infant, but despite the abnormality of nuclear T3 binding, the cellular mechanisms remain unclear.

Adolescent↗