Euthyroid Control Subjects Research Articles

Immunoreactive thyroglobulin in sera and saliva of patients with various thyroid disorders: role of autoantibodies.

The present study was designed to assess the transfer of thyroglobulin (Tg) and anti-Tg antibodies (TgAb) to saliva in subjects with positive TgAb in their sera. Group I consisted of normal euthyroid control subjects (n = 10). Group II were patients with various thyroid disorders and no TgAb in their sera (n = 6). Group III were patients with thyroid disorders and TgAb in their sera (n = 31). The mean serum Tg level (+/- SE) and mean TgAb level [mean % binding +/- SE (range)] were as follows: Group I, Tg: 22.0 ng/ml +/- 1.64 (n = 10); TgAb 1.91% +/- 0.34 (range 0.6% to 4%). Group II, Tg: 119.8 ng/ml +/- 28.0 (n = 6) TgAb 1.59% +/- 0.34 (0.64% to 2.7%). Group III Tg 167.9 ng/ml +/- 41.0 (n = 31) TgAb 23.2% +/- 3.87 (4.2% to 67.5%). The mean salivary Tg level (SaTg) and mean TgAb binding (% +/- SE range) in saliva were as follows: Group I SaTg 2.07 ng/ml +/- 0.39 (n = 10) SaTgAb 1.13% +/- 0.38 (0% to 3.1). Group II SaTg 3.41 ng/ml +/- 0.67 (n = 6), SaTgAb 0.55% +/- 0.29 (0-1.9%). Group III SaTg 5.22 ng/ml +/- 0.96 (n = 31), SaTgAb 3.1% +/- 1.58 (0 to 47.7%). Salivary TgAb were only present in 4 out of 31 cases of Group III. Mean serum Tg in group IV-A was 75.01 ng/ml +/- 52.1 (n = 11). Mean serum TgAb in group IV-A was 1.94% +/- 0.31 (n = 11).(ABSTRACT TRUNCATED AT 250 WORDS)

Biological activity of serum prolactin in patients with primary hypothyroidism.

Prolactin bioactivity was measured in sera from 22 patients with primary hypothyroidism and 13 euthyroid control subjects and compared with estimates of immunoactivity given by radioimmunoassay. The Nb2 rat lymphoma cell assay was modified to improve specificity for prolactin and used to measure bioactivity. Results of serum prolactin levels obtained using the bioassay were closely correlated with radioimmunoassay results in both hypothyroid patients and control subjects. Mean bioactivity/immunoactivity ratios in patients were not significantly different from those in control subjects. Mean prolactin concentration measured by both assays was significantly higher in patients than control subjects. Serum prolactin in patients with primary hypothyroidism appears to have essentially normal bioactivity as measured in the Nb2 assay, in contrast with a report of major differences between activity in radioreceptor assay and RIA in hypothyroid patients.

Graves' disease. Influence of age on clinical findings.

To determine the influence of age on the signs and symptoms of hyperthyroidism we prospectively examined 880 patients and matched them by age, sex, race, and visit date with similarly examined euthyroid control subjects. Many signs and symptoms showed little change with age until after the fifth decade of life when they began to decrease gradually. Findings that increased with age were weight loss and atrial fibrillation, while those that decreased most markedly with age were increased appetite and weight gain. The diagnosis is more difficult as age progresses because there are fewer findings and because the significance of those present may not be appreciated. Identification of the most sensitive and specific signs and symptoms in each age decade should improve the early detection of hyperthyroidism.

Graves' Disease

• To determine the influence of age on the signs and symptoms of hyperthyroidism we prospectively examined 880 patients and matched them by age, sex, race, and visit date with similarly examined euthyroid control subjects. Many signs and symptoms showed little change with age until after the fifth decade of life when they began to decrease gradually. Findings that increased with age were weight loss and atrial fibrillation, while those that decreased most markedly with age were increased appetite and weight gain. The diagnosis is more difficult as age progresses because there are fewer findings and because the significance of those present may not be appreciated. Identification of the most sensitive and specific signs and symptoms in each age decade should improve the early detection of hyperthyroidism. (<i>Arch Intern Med</i>1988;148:626-631)

Alterations in magnesium and zinc metabolism in thyroid disease

Alterations in magnesium and zinc metabolism in thyroid disease

The circadian variation of thyrotrophin in patients with primary thyroidal disease.

We have used a highly sensitive immunochemiluminometric assay (ICMA) for human TSH to study the effect of thyroid status on the circadian variation in TSH levels. Three subjects with Graves' disease, three with toxic multinodular goitre and three with euthyroid multinodular goitre were sampled every hour for 24 h. The results obtained were compared to those from five euthyroid control subjects. It was found that some patients with hyperthyroidism and suppressed basal TSH levels exhibited a 24 h secretory pattern similar to that seen in normal subjects with peak TSH levels occurring at night. In addition two subjects with a euthyroid multinodular goitre demonstrated levels of TSH below the normal range despite being clinically and biochemically euthyroid. TSH suppression in these subjects is probably related to some degree of thyroid autonomy and possible development of hyperthyroidism in the future.

Decreased insulin receptor binding in hyperthyroidism.

The binding of 125I-insulin to insulin receptors on circulating mononuclear leukocytes was studied in ten patients with hyperthyroidism and 20 euthyroid normal volunteers. The hyperthyroid patients demonstrated significantly elevated glucose levels following an oral glucose load, despite normal insulin secretion. The infusion of insulin resulted in a delayed hypoglycaemic effect in the hyperthyroid patients; however, the inhibition of the endogenous insulin secretion as indicated by suppression of C-peptide levels was not different from euthyroid control subjects. Insulin binding to monocytes was significantly decreased in the hyperthyroid patients. Scatchard analysis of binding data indicates that a decrease of receptor number rather than receptor affinity seems to be the cause of the lowered insulin binding in hyperthyroid patients with diffuse toxic goitre. The findings of decreased insulin receptor number, mild degree of glucose intolerance despite normal insulin secretion and the delayed hypoglycaemic effect following insulin infusion suggest that peripheral insulin resistance could be involved in the highly complex pathophysiology of glucose intolerance in hyperthyroidism.

Measurement of free thyroxine and free triiodothyronine in thyrotoxicosis and hypothyroidism.

Free T4 and free T3 concentrations in thyrotoxic and hypothyroid patients at presentation differentiated those with thyroid disease from euthyroid control subjects and were closely correlated with T4/TBG ratio. A further group of thyrotoxic patients was followed serially during treatment with carbimazole. Measurements of free T4 and free T3 against closely reflected thyroid status with changes in the hormone measurements being paralleled by changes in T4/TBG ratio.

Serum thyroxine, free T 4, triiodothyronine, and reverse-T 3 in diphenylhydantoin-treated patients

Serum thyroxine, free T 4, triiodothyronine, and reverse-T 3 in diphenylhydantoin-treated patients

Effect of endogenous thyroid stimulating hormone levels on the secretion of thyroid hormones in man.

The effect of endogenous thyroid stimulating hormone (TSH) on the thyroid secretion of triiodothyronine (T3) and thyroxine (T4) was evaluated by serial determinations of serum T3. T4 and TSH concentrations in the following groups of patients: a) three patients submitted to surgical removal of a solitary, autonomous thyroid nodule which had completely inhibited the extranodular tissue; b) five subjects, with the same disease, in whom functional recovery of the extranodular tissue was induced by increased circulating TSH levels, produced by treatment with methimazole; c) one patient submitted to hemithyroidectomy for multinodular goitre; d) two hyperthyroid patients who had been treated with methimazole. In all these patients serum T3 and T4 levels progressively decreased, with a consequent progressive increase in serum TSH concentrations, leading to stimulation of the thyroid gland. During this TSH-induced stimulation of thyroid tissue, a significant positive correlation was found between the serum TSH concentrations and the corresponding ratio between the serum levels of T3 and T4 (T3/T4), both within each patient group (P less than 0.001) and among all patients (P less than 0.001). The same correlation also governs the relationship between the TSH and the T3/T4 values of 34 euthyroid control subjects and one patient with incipient hypothyroidism. These data strongly suggest that endogenous TSH can induce a preferential secretion of T3 over T4 by the human thyroid.

β-Adrenergic Receptors of Human Lymphocytes Are Unaltered by Hyperthyroidism*

Lymphocytes from 12 patients with untreated hyperthyroidism were compared to lymphocytes from age- and sex-matched euthyroid control subjects to test the hypothesis that alterations in beta-adrenergic response mechanisms occur in human hyperthyroidism. The binding of (-)[3H]dihydroalprenolol, a compound previously shown in these cells to label binding sites having the characteristics of beta-adrenergic receptors, was assayed and no significant difference was found between the two groups. In addition, the accumulation of cAMP in response to isoproterenol was determined by RIA and, again, no difference was found.

Evaluation of triiodothyronine (T3) kinetics in normal subjects, in hypothyroid, and hyperthyroid patients using specific antiserum for the determination of labeled T3 in plasma.

Triiodothyronine (T3) kinetics was evaluated using [125I]T3 and the single injection technique; 5 hypothyroid, 6 hyperthyroid patients, and 10 euthyroid control subjects were studied. Plasma-labeled T3 concentration was measured by means of a new method based on extraction of the hormone on Sephadex G-25 columns followed by elution with the specific antiserum. This technique allows a far better separation of the hormonal radioactivity from the labeled iodide produced from T3 catabolism in comparison with the TCA-precipitation-butanol extraction method. The analysis of the experimental data has been performed using non-compartmental treatment (integral approach); results of mono-compartmental analysis of the same data are also reported for comparison. Average metabolic clearance was 15.3 +/- 0.6 (mean + SEM) liters/day/m2 body surface in normal subjects; it was significantly decreased in hypothyroid patients (11.4 +/- 1.1) and significantly increased (33.4 +/- 4.0) in hyperthyroidism. The total plasma equivalent distribution volume was found significantly enlarged in hyperthyroid patients (22.6 +/- 0.9 liters/m2) in respect to that measured in the control group (15.6 +/- 0.4), whereas it was not different from normal value in hypothyroid patients (17 +/- 1.7). Using plasma concentration of native T3, absolute turnover rate and extrathyroidal pool were also estimated; their values were 6.5, 23.7, and 131.7 micrograms/day/m2 and 10.1, 24.2, and 90.6 micrograms/m2, respectively, in hypothyroid, normal, and hyperthyroid groups.

Coagulation and Fibrinolysis in Thyroid Disease

The levels of components of the coagulation mechanism and fibrinolytic system in 20 hyperthyroid patients and 9 hypothyroid patients were compared with those of 20 euthyroid control subjects. The mean levels of fibrinolytic activity and plasminogen were significantly reduced in the hyperthyroid patients while mean levels of alpha1-antitrypsin and C1 inactivator were increased. Patients with hypothyroidism had significantly increased levels of fibrinolytic activity and alpha2-macroglobulin, a prolonged partial thromboplastin time, and reduced levels of factor XII and antithrombin III.

Thyroid hormone concentrations and inhibition of thyroid stimulating hormone secretion in euthyroid subjects with autonomous thyroid nodules

Abstract. Sixty‐four euthyroid patients with autonomous thyroid nodules and normal thyroxine (T4) concentrations and tri‐iodothyronine resin uptake have been studied. The serum tri‐iodothyronine (T3) concentration of the patients was 2.24 (±0.67) ng/ml, significantly higher than in a group of fifty‐seven euthyroid control subjects (1.58 ± 0.30 ng/ml). When no extranodular tissue was visible on the basal thyroid scan, the T3 was 2.31 (±0.63) ng/ml, significantly higher than in patients with some extranodular uptake on the basal scan (1.91 ± 0.42 ng/ml). There was no significant difference in the serum T4 concentrations of the patients (7.37 ± 2.10 μg/100 ml) compared to the control group (6.88 ± 1.89 μg/100 ml). The T4 concentrations were not correlated with total or partial inhibition of the extranodular tissue. The thyroid hormone concentrations were not directly correlated to the size of the nodule assessed by scan imaging. The thyroid stimulating hormone (TSH) concentration of the patients (1.52 ± 0.38 μU/ml) was significantly lower than in normals (2.49 ± 0.96 μU/ml). No significant difference was found in the TSH concentrations of patients with partial or total inhibition of extranodular tissue irrespective of the T3 concentration. A thyrotrophin releasing hormone stimulation test in twelve patients did not increase the serum TSH, irrespectively of the T3 concentration.These data show the high frequency of elevated serum T3 concentrations despite normal serum T4 concentration in euthyroid patients with autonomous thyroid nodules. They confirm that inhibition of TSH secretion can occur when thyroid hormone concentrations are in the normal range.

THE RELATIONSHIP BETWEEN THYROID FUNCTION AND THE RENAL RESPONSE TO PARATHYROID HORMONE

The effect of thyroid status on renal adenosine 3', 5'-cyclic monophosphate (cyclic AMP) metabolism was assessed by measuring the increase in plasma cyclic AMP concentration following the intravenous administration of parathyroid hormone (PTH) to five hypothyroid and six hyperthyroid patients and seven euthyroid control subjects. PTH caused a rapid, transient increase in the concentration of plasma cyclic AMP which was similar in magnitude and time course in the euthyroid and hyperthyroid groups, but reduced in magnitude in the hypothyroid patients. The magnitude of the plasma cyclic AMP response to PTH was positively related to the free thyroxine index. The results suggest that the development of hypothyroidism may impair the renal response to PTH by affecting the turnover of cyclic AMP in the renal cortex.

Effect of hyper- and hypothyroidism on platelet monoamine oxidase activity and serotonin metabolism

Effect of hyper- and hypothyroidism on platelet monoamine oxidase activity and serotonin metabolism

Low Serum Triiodothyronine (T3) and Hypothyroidism in Anorexia Nervosa

Measurements of serum thyroid hormones were compared in 22 patients with typical anorexia nervosa and 22 euthyroid control subjects. Serum total triiodothyronine (T3) was (mean +/- (SE) 62.1 +/- 7.1 ng/100 ml in anorexia patients and 115.2 +/- 8.4 ng/100 ml in control subjects (P less than 0.001). Serum adjusted thyroxine (T4Adj) was significantly different in the anorexia (7.1 +/- 0.4) and control (8.2 +/- 0.4) groups. Serum T3 was subnormal in 63% and T4Adj subnormal in 36% of the 22 anorexia patients. The mean serum T4/T3 in anorexia patients (158 +/- 19) was higher than that in the control subjects (88 +/- 5.5, P less than 0.005) or in 18 patients with hypothalamic or pituitary hypothyroidism (77.9 +/- 10.1, P less than 0.001). Following weight gain in 6 anorexia patients, there was a significant rise in serum T3 without change in T4Adj concentration. The Achilles reflex half-relaxation time (ART) in 38 anorexia patients was 348.6 +/- 10 msec compared with 280 +/- 30 msec in 168 normal age-matched subjects (P less than 0.001), and was prolonged (greater than 340 msec) in 65% of these 38 patients. In 18 anorexia patients with measured ART, T3 and T4Adj, the mean ART was longer 376.1 +/- 20 msec) in 10 with subnormal T3 than in 8 patients with a normal T3 (294.7 +/- 13.2 msec, P less than 0.01). There was no significant difference in the mean ART between patients with a normal or low serum T4Adj. Administeration of oral T3 40 mug/day for 4 weeks to 11 anorexia patients caused a significant reduction (P less than 0.001) in mean ART of 108.7 +/- 9.6 msec compared with 17.7 +/- 3.3 msec in 18 normal subjects. There was a normal peak serum TSH and a rise in mean total serum T3 of 47 +/- 12 ng/100 ml (range 11-100 ng/ml) in 7 of 8 patients following 200 mug of iv thyrotropin releasing hormone (TRH). The fall in serum TSH was delayed in 6 patients. Assessment of hypothalamic control of thyroid function in 3 patients using the method of thyroidal iodide release (TIR) showed impairment of the normal diurnal variation and response to administered glucocorticoids. In the absence of a space-occupying pituitary lesion, the TRH and TIR data suggest a central inhibition of thyroid function, possibly by impairment of hypothalamic TRH release. In addition, a probable decrease of peripheral T4 to T3 conversion leads to low serum T3 concentrations. The prolonged basal ART and the marked ART reduction in response to T3 administration is attributed to correction of tissue thyroid hormone deficiency in the anorexia patients.

Thyrotoxic periodic paralysis: Effect of propranolol

Thyrotoxic periodic paralysis: Effect of propranolol

Renal response to sodium restriction in myxedema.

SummaryThe renal response to dietary Na restriction after initial equilibration on a liberal salt intake was studied under carefully controlled conditions in 6 patients with myxedema and four euthyroid control subjects. In 4 patients with mild to moderate hypothyroidism, the time required to reduce Na excretion by 50% (Na t1/2) and the cumulative urinary Na losses were comparable to those of the euthyroid controls. In 2 patients with clinically severe myxedema, however, renal Na conservation was clearly abnormal, with delayed achievement of sodium balance, prolonged Na t1/2 and increased cumulative sodium losses. Improvement in the ability to conserve Na was demonstrated upon restudy of one patient after partial correction of his myxedema-tous state. Available evidence suggests that the basis for the impairment in sodium conservation in hypothyroidism is a decrease in renal tubular sodium reabsorption.The authors are grateful to Dr. Lawrence Fish-man for the many helpful suggestions and criticisms. The in...

Serum thyrotropin (TSH) in pituitary and-or hypothalamic hypothyroidism: normal or elevated basal levels and paradoxical responses to thyrotropin-releasing hormone.

ABSTRACT Using a highly sensitive and specific radioimmunoassay for thyroid-stimulating hormone (TSH), basal serum TSH levels and the response to synthetic thyrotropin-releasing hormone (TRH) were evaluated in 21 patients with unequivocal hypothyroidism resulting from pituitary or hypothalamic lesions. Baseline TSH concentrations were undetectable in only 2, being normal (n = 9) or slightly elevated (n = 10) in the rest. Three of those with elevated levels had evidence of associated primary thyroid disease. Excluding these, the mean serum TSH concentration in the remaining 18 patients (3.4 ± 0.8 (sem) μU/ml) was significantly higher (p < 0.0005) than the mean of 75 euthyroid control subjects (1.0 ± 0.1 μU/ml). Patients with hypothalamic lesions generally had higher basal TSH levels than those with pituitary lesions. Treatment with thyroxine 0.1–0.3 mg/day led to suppression of the measured TSH values. Dilutions of sera containing normal and elevated TSH levels, showed parallelism with the standard curve (...