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Biomedical subjects

C H Emerson

Publications and source records attributed to C H Emerson.

At least 19 recordsLinked to original sources
PubMed1991

Age, sex, and serum thyrotropin concentrations in primary hypothyroidism.

We studied the relationship between age, sex, serum thyroxine concentrations, and serum thyrotropin concentrations in 202 patients with primary hypothyroidism whose ages ranged from 10 to 89 years. The results from two groups of patients were analysed, both combined and separately, by multiple linear regression analysis of the factors age, sex, group, and serum free T4 index or serum T4 concentration, to predict serum TSH. The serum free T4 index or T4 values and age were negatively correlated with the serum TSH concentrations (p less than 0.001) for all comparisons. In contrast, there was no significant relationship between sex and serum TSH concentrations in these hypothyroid patients. The age-related decline in serum TSH concentrations in hypothyroidism was apparent during adolescence and early adult life (ages 10 to 39 years) and in elderly subjects (ages 61 to 89 years). We conclude that age is a determinant of TSH secretion independent of the level of thyroid secretion.

Adolescent↗
PubMed1990

Androstenedione and estrone dynamics in hypothyroid women.

To examine the effects of hypothyroidism on androstenedione (A) and estrone (E1) metabolism, we infused eight women with [3H]androstenedione and [14C]estrone when they were hypothyroid and again when they were euthyroid after levo-T4 administration. MCRs and conversion ratios were measured using concentrations of radioactivity in the blood pools of A and E1. Peripheral aromatization was measured from the concentrations of radioactivity in the E1 glucuronide pool in the urine. After the women were euthyroid, the MCR of A had increased in seven of eight, the MCR of E1 increased in all eight, and peripheral aromatization had decreased in seven of eight. These findings indicate that hypothyroidism results in a decrease in the MCRs of A and E1 and, in most subjects, an increase in peripheral aromatization of A to E1.

Adult↗
PubMed1990

Gender-related differences of serum thyroxine-binding proteins in the rat.

Because little information is available, studies were performed to determine the relationship between gender and sex steroid status on serum T4 binding proteins in the rat. The binding capacity of serum thyroxine-binding globulin was greater in female rats than in male rats (27 +/- 1.3 vs 18.0 +/- 1.3 nmol/l, p less than 0.01) and in fasted female rats than in fasted male rats (64.4 +/- 2.6 vs 30.8 +/- 2.7 nmol/l, p less than 0.01). The binding capacity of serum transthyretin was lower in female rats than in male rats (2.1 +/- 0.1 vs 3.1 +/- 0.1 mumol/l, p less than 0.01). Neither ovariectomy or orchidectomy affected the binding capacity of serum thyroxine-binding globulin and it was not increased in ovariectomized rats treated with estrogen. Orchidectomy did not cause a decrease in the binding capacity of serum transthyretin and testosterone administration did not increase it. In contrast, ovariectomy caused an increase in the binding capacity of serum transthyretin (Intact = 2.2 +/- 0.1 vs ovariectomized = 2.8 +/- 0.1 mumol/l, p less than 0.01) and estrogen administration caused a decrease (ovariectomized = 2.8 +/- 0.1 vs ovariectomized + E2 = 1.9 +/- 0.1 mumol/l, p less than 0.05). The results indicate that the binding capacity of serum thyroxine-binding globulin is higher in female rats than in male rats but this difference is not due to differences in the secretion of gonadal hormones. The binding capacity of transthyretin is lower in female rats than in male rats. This is probably due to the higher circulating levels of estrogen in the female compared to the male.

Animals↗
PubMed1989

Thyrotropin-secreting pituitary adenomas: clinical and biochemical heterogeneity. Case reports and follow-up of nine patients.

STUDY OBJECTIVE: To evaluate the clinical and biochemical features of patients with TSH (thyroid-stimulating hormone, thyrotropin)-secreting pituitary tumors; to measure the biologic activity in vitro of circulating TSH from selected patients before and after pituitary surgery. DESIGN: Case series. SETTING: Patients in an endocrinology unit. PATIENTS: Nine patients with TSH-secreting pituitary tumors. MEASUREMENTS AND MAIN RESULTS: All patients had hyperthyroidism, elevated free thyroxine and triiodothyronine levels, and detected levels of TSH. The free alpha subunit, a tumor marker for neoplasms of gonadotropic or thyrotropic cell origin, was elevated in all nine patients. Seven of the nine patients had been treated with thionamides, radioactive iodine, or thyroidectomy for presumed primary hyperthyroidism. The delay from the initial treatment of hyperthyroidism to the correct diagnosis of a pituitary neoplasm was 6.2 +/- 4.8 (mean +/- SD) years. Two of the seven patients with macroadenomas died in the perioperative period (one at NIH, one at a referring hospital). Of the remaining five patients with macroadenomas, four have residual tumor and inappropriate TSH secretion, despite surgery and radiation therapy, at follow-up from 3.5 to 6 years. In contrast, the two patients with microadenomas are clinically cured 2.5 and 4 years after transsphenoidal adenomectomy. The biologic to immunologic (B/I) ratio of serum TSH, determined preoperatively in five patients with TSH-secreting tumors, was elevated compared with euthyroid subjects. In three patients the B/I ratio of serum TSH was also measured after pituitary surgery; in two the elevated B/I ratio returned to normal after successful pituitary adenomectomy, while in the third this ratio remained elevated after incomplete adenoma resection. CONCLUSIONS: With the routine availability of ultrasensitive TSH assays and their increasing use to confirm thyrotoxicosis from all causes, we expect that TSH-secreting pituitary tumors will be diagnosed earlier, before inappropriate antithyroid therapy, permitting an improved outcome.

Adenoma↗
PubMed1989

Thyrotropin (TSH)-releasing hormone-stimulated TSH release and TSH concentration in the guinea pig pituitary, as determined by a heterologous radioimmunoassay.

Little is known regarding how the guinea pig (GP) compares with the rat in terms of TSH economy. To develop a heterologous RIA for GP TSH, rabbits were injected with GP TSH. In one rabbit (anti-gpTSH-8), antibodies that bound 125I-labeled bovine (b) TSH and rat (r) TSH but not 125I-labeled bLH or rPRL were generated. The binding of anti-gpTSH-8 to [125I]bTSH was inhibited in a parallel manner by bTSH over a range of 0.047-5.42 ng, rTSH over a range of 0.24-25 ng, and dilutions of GP pituitary extracts. This system, with bTSH as the standard, was employed as the basis for a heterologous TSH RIA (GP TSH RIA). The cross-reactions of rTSH and bLH in the GP TSH RIA were 45% and 7%, respectively. Rat and bovine FSH, GH, and PRL had little or no cross-reaction. GP pituitaries were incubated in vitro and dosed with LHRH and TRH. The GP TSH RIA detected an 11-fold increase in TSH in the medium in response to TRH and no change in immunoreactivity in response to LHRH. In contrast, a RIA for bLH detected a 25-fold increase in LH in the medium in response to LHRH and no increase in response to TRH. The TSH content in GP pituitaries was significantly lower than that in the rat (GP, 16.8 +/- 1.6 ng/mg; rat, 80.3 +/- 6.2 ng/mg; P less than 0.05) as were serum TSH concentrations (GP, 0.8 +/- 0.4 ng/ml; rat, 4.5 +/- 1.1 ng/ml; P less than 0.05). Thyroid hormone administration (T4 Rx) in both GP and rat produced a significant reduction in pituitary TSH content (GP control, 4.8 +/- 0.4 ng/mg; T4 Rx, 2.1 ng/mg; P less than 0.05; rat control, 52.4 +/- 4.0 ng/mg; T4 Rx, 20.5 +/- 1.6 ng/mg; P less than 0.05) and TSH release (GP control, 9.4 +/- 2.3 ng/ml; T4 Rx, 4.3 +/- 1.5 ng/ml; P less than 0.05; rat control, 357 +/- 81 ng/ml; T4 Rx, 133 +/- 27 ng/ml; P less than 0.05) from incubated hemipituitaries. Thyroidectomy in the rat was associated with a decrease in pituitary TSH content, but no change in pituitary content was found in thyroidectomized GPs. These studies demonstrate the feasibility of estimating GP TSH with a heterologous RIA that employs polyvalent antiserum against GP TSH as the first antibody and bTSH as the tracer and standard.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Serum thyrotropin concentrations are more highly correlated with serum triiodothyronine concentrations than with serum thyroxine concentrations in thyroid hormone-infused thyroidectomized rats.

To assess the relative role of circulating T4 and T3 in the regulation of serum TSH, we have measured serum T4, T3, and TSH concentrations in normal and thyroidectomized rats, some of which were chronically infused with T3 or T4. Serum T3, T4, and TSH concentrations were measured 7 and 14 days after surgery. Some groups of infused rats were mildly hypothyroid, as judged by elevated serum TSH concentrations. At both 7 and 14 days, there was a significant inverse correlation between serum T3 and serum TSH concentrations (day 7, r = 0.65, P less than 0.01; day 14, r = 0.71, P less than 0.01). The coefficients for the inverse correlations between serum T4 and TSH concentrations were 0.37 on day 7 (P less than 0.05) and 0.37 (P less than 0.05) on day 14. Linear regression analysis was performed using TSH as the dependent variable for outcome and serum T3 and T4 concentrations as the independent predictor variables. This analysis revealed that after controlling for T3, TSH and T4 were no longer significantly correlated (P = 0.14). The correlation between T3 and TSH remained highly significant. These results suggest that in the euthyroid and mildly hypothyroid rat, serum T3 has a greater inhibitory effect on TSH secretion than does serum T4.

Animals↗
PubMed1989

Fasting-associated changes in serum thyrotropin in the rat are influenced by gender.

Studies in the male rat have demonstrated that fasting is associated with a decrease in serum TSH concentrations. The present studies were performed to determine if gender influenced the serum TSH changes associated with fasting. In 8 of 10 experiments in male rats, serum TSH concentrations were significantly reduced in fasted compared to fed groups. In contrast, in none of the 9 experiments in female rats were serum TSH concentrations significantly reduced in the fasted groups. When all experiments were pooled, the decrease in the serum TSH concentration in the fasted rats compared to that in the fed rats was 55 +/- 4% (mean +/- SE) in males and 10 +/- 7% in females (P less than 0.001). In female rats ovariectomy did not result in a pattern in which fasting was associated with a decrease in serum TSH concentrations. Testosterone (T) was administered to male rats during fasting, but this treatment did not prevent the fasting-induced decrease in serum TSH concentrations. In gonadectomized male rats serum TSH concentrations were unchanged by fasting. However, if T was administered to gonadectomized male rats before and during fasting, serum TSH concentrations were significantly decreased in the fasted compared to the fed rats. These studies indicate that there is a sex difference in the serum TSH response to fasting in rats. The decline in serum TSH with fasting in the male rat is not mediated by a decline in serum T concentrations. Rather, T appears to maintain a process which increases the serum TSH concentration, and it is this process that is susceptible to inhibition by fasting.

Animals↗
PubMed1989

TRH pharmacokinetics and nerve stimulation evoked prostatic fluid secretion during TRH infusion in the dog.

The pharmacokinetics of TRH have been determined in man and the rat as well as other species whose serum contains TRH degrading enzymes, TRH pharmacokinetics have not been determined in the dog. This species is unusual in that its serum contains little or no TRH degrading activity. TRH pharmacokinetics were determined from measurements of plasma TRH concentrations during and following a 1-h infusion of TRH, 20 micrograms.kg-1.min-1, into dogs bearing prostatic urethral cannula. During TRH administration prostatic fluid secretion was evoked by hypogastric nerve stimulation and the content of TRH immunoreactive material in prostatic fluid was determined. Prostatic fluid was also collected after hypogastric nerve stimulation in dogs that did not receive TRH infusion. The TRH plasma profile in TRH-infused dogs exhibited two-compartment characteristics with an initial half-time of 10.4 +/- 5.4 (mean +/- SD) min, a terminal half-time of 69.4 +/- 24 min, and a metabolic clearance rate of 7.64 +/- 4.48 ml.min-1.kg-1. These findings suggest that the half-time of TRH is longer, and its metabolic clearance rate is less, in the dog than in humans or rats. TRH administration was not associated with altered nerve induced prostatic fluid secretion. Prostatic fluid samples contained TRH immunoreactive material regardless of whether they were collected after epithelial cell stimulation with pilocarpine, or after hypogastric nerve stimulation. In contrast to previous results with vasoactive intestinal peptide, TRH does not acutely alter prostatic fluid secretion. As has been reported for prostatic tissue extracts, immunoreactive material is present in prostatic fluid and appears to arise from epithelial cells.

Animals↗
PubMed1988

The effect of thyroid dysfunction and fasting on placenta inner ring deiodinase activity in the rat.

The placenta contains iodothyronine 5-deiodinase activity (P5-Dase) that probably acts on iodothyronines in the fetal circulation to convert T4 to rT3 and T3 to 3,3'-T2. Since thyroid status and fasting have profound effects on iodothyronine deiodinases in other tissues, the present studies were performed to determine if these perturbations affected P5-Dase. Control and treated rats were mated and killed near term on the 20th day of gestation. P5-Dase was determined in placenta homogenates enriched with dithiothreitol by measuring the conversion of T4 to rT3. In four of five studies, P5-Dase was similar in dams that underwent thyroidectomy (Tx) on day 7 of gestation and sham Tx dams. P5-Dase was not altered in dams that were treated with methimazole (MMI) to induce maternal and fetal hypothyroidism. Treatment of dams with supraphysiological doses of T4, beginning on the seventh day of gestation, did not significantly affect P5-Dase. In three of four studies, P5-Dase was similar in fed dams to values in dams fasted for the last 5 days of pregnancy. Placenta iodothyronine 5'-deiodinase activity (P5'-Dase) was also measured in some studies. P5'-Dase was not decreased in Tx rats and was modestly decreased in MMI-treated rats. However, the effect of MMI was not reversed by the administration of supraphysiological doses of T4, Tx, MMI treatment, and fasting all decreased hepatic T4 5'-deiodinase activity in pregnant rats. These results strongly suggest that thyroid status and fasting do not alter P5-Dase activity.

Animals↗
PubMed1987

Thyroid status influences rat serum but not brain TRH pyroglutamyl aminopeptidase activities.

Serum and brain cytosol contains pyroglutamyl aminopeptidase activity that converts TRH to His-ProNH2 (TRH PAPase). Whereas serum TRH PAPase has specificity for TRH, this is not the case for brain cytosol PAPase. Recent reports indicate that a brain membrane fraction contains TRH PAPase that is specific for TRH and has a remarkable similarity to serum TRH PAPase. In the present studies, a method for measuring serum TRH PAPase activity and the activities of the membrane and cytosol brain TRH PAPase enzymes are described. The effect of thyroid status on these different TRH PAPase activities was determined. In hypothyroid rats serum TRH PAPase activity was decreased, whereas in rats treated with supraphysiological doses of T4 it was increased. In contrast, the cytosolic and the membrane TRH PAPase enzymes in brain were not affected by thyroid status. It is concluded that the membrane-associated brain TRH PAPase differs from the serum TRH PAPase in terms of its response to thyroid hormone. In addition, the previously reported effects of thyroid status on rat serum TRH degrading activity are explained by the finding that thyroid hormone increases serum TRH PAPase activity.

Aminopeptidases↗
PubMed1986

Total and free serum thyroid hormone concentrations in fetal and adult pregnant and nonpregnant guinea pigs.

Information on total and free serum thyroid hormone concentrations in the adult and fetal guinea pig (Cavia porcellus) is limited. These variables were studied in adult male and female guinea pigs and in pregnant guinea pigs and their fetuses at various times during gestation. Total serum T4 levels in adult males, nonpregnant females, and pregnant females did not differ significantly [range, 2.5 +/- 0.3 to 3.2 +/- 0.8 micrograms/dl (mean +/- SD)]. Similarly, there were no significant differences in the percent free T4 (0.046-0.068%), free T4 (1.26-2.03 ng/dl), total T3 (39-44 ng/dl), the percent free T3 (0.521-0.638%), and free T3 (0.221-0.260 ng/dl) among adult males, nonpregnant females, and pregnant females. rT3 was undetectable in adult male, nonpregnant female, and pregnant female guinea pig serum. T4 values were similar and those for T3 were lower in fetal compared to maternal serum at 45 days of gestation, whereas serum rT3 was detectable in fetal serum. Between 45 and 62 days of gestation, fetal serum T4 increased from 2.5 to 0.3 to 4.3 +/- 1.3 micrograms/dl (mean +/- SD, P less than 0.01), fetal serum T3 remained unchanged, and fetal serum rT3 increased from 5.2 +/- 3.3 to 25.0 +/- 11.4 ng/dl (P less than 0.01). Near term, fetal serum total and free T4 and total rT3 concentrations were significantly higher and total and free T3 concentrations were significantly lower than the corresponding values in maternal serum. Total serum T4 is higher in the guinea pig than in the rabbit, is similar to values in the rat, and is lower than values in man. The free T4 concentration in guinea pig serum is similar to those in humans and rats. The ontogenesis of thyroid hormones differs strikingly in the guinea pig fetus compared to that in the rat fetus and shares many similarities with sheep and human fetal thyroid development.

Animals↗
PubMed1986

A new class of propylthiouracil analogs: comparison of 5'-deiodinase inhibition and antithyroid activity.

After in vivo administration, propylthiouracil (PTU) inhibits not only thyroid iodide uptake and organification, but also T4 5'-deiodinase activity in most peripheral organs. The present report describes the effects of some previously untested 6-substituted 2-thiouracil derivatives on in vivo and in vitro iodide uptake and organification, and on T4 5'-deiodinase activity in liver and pituitary homogenates. When added to homogenates, many analogs were as potent or more potent than PTU in inhibiting hepatic T4 5'-deiodinase activity. Three derivatives, 6-anilino-2-thiouracil (A compound), 6-(p-ethylanilino)2-thiouracil (B compound), and 6-(p-n-butylanilino) 2-thiouracil (C compound), which were among the most potent inhibitors of hepatic T4 5'-deiodinase, when added in vitro inhibited T4 5'-deiodinase activity in liver homogenates after in vivo administration. When added to pituitary homogenates prepared from hypothyroid rats, these compounds also significantly inhibited pituitary T4 5'-deiodinase activity. In a concentration of 1 mM in the presence of 20 mM dithiothreitol, the percent inhibition of pituitary T4 5'-deiodinase activity was 19.7 +/- 7.4 (mean +/- SE), 34.0 +/- 3.2, 47.3 +/- 3.1, and 89.0 +/- 1.0 for PTU and the A, B, and C compounds, respectively (P less than 0.05 for all groups vs. one another and vehicle). Despite their ability to inhibit hepatic T4 5'-deiodinase activity, none of the 13 analogs tested altered thyroid iodide uptake or organification after administration of 0.1 mg/rat. PTU, in the same dose, inhibited thyroid iodide uptake by 78.2 +/- 2.4% (P less than 0.001) and thyroid iodide organification by 36.4 +/- 7.3% (P less than 0.01). Furthermore, the A, B, and C compounds did not inhibit thyroid iodide uptake or iodide organification when administered in higher doses of 5, 5, and 1 mg/rat, respectively. In contrast to these in vivo results, the A, B, and C compounds were more potent than PTU in inhibiting iodide organification in a purified thyroid peroxidase system and in porcine thyroid slices. The concentrations causing 50% inhibition of iodide organification in the purified thyroid peroxidase system were 30, 7, 8, and 14 microM for PTU and the A, B, and C compounds, respectively. However, PTU was far more potent in inhibiting iodide organification in intact incubated thyroid lobes compared to the A, B, and C compounds.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Concentration of free thyroxin in serum of a patient with euthyroid hyperthyroxinemia secondary to increased thyroxin-binding prealbumin: results by various methods compared.

We used various kits to measure free thyroxin (T4) in serum from a patient with the very rare syndrome of euthyroid hyperthyroxinemia secondary to increased thyroxin-binding prealbumin in serum. This patient's free T4 by equilibrium dialysis was 13 ng/L (normal 9-21), whereas the free-T4 index was 18.6 (normal 5.5-11.5). Using six different commercial methods, the last three listed being T4-analog methods, we measured the serum free T4 in this patient. The mean +/- SD (and normal range) free-T4 concentrations (ng/L) measured were: GammaCoat, Two-Step, 19.2 +/- 4.5 (6.9-26.9); Liquisol, 17.8 +/- 3.0 (12.4-20.8); Immo Phase, Two-Step 26.8 +/- 0.3 (12.4-21.2); GammaCoat, Single-Step, 19.7 +/- 5.7 (10.3-21.0); Immo Phase, Single-Step, 27.7 +/- 0.9 (8.6-25.0); and Amerlex, 14.1 +/- 0.6 (5.3-14.1). In four patients with familial dysalbuminemic hyperthyroidism, in whom the serum T4 by equilibrium dialysis was normal, all three T4-analog methods gave results far exceeding normal (greater than 50 ng/L).

Humans↗