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Biomedical subjects

S Refetoff

Publications and source records attributed to S Refetoff.

At least 181 records · Page 10Linked to original sources
PubMed1984

Reduced triiodothyronine content in liver but not pituitary of the uremic rat model: demonstration of changes compatible with thyroid hormone deficiency in liver only.

Intracellular thyroid hormone concentration and action were examined in the liver and the pituitary of a nephrectomized rat model (Nx); the results were compared with those obtained from control (C), thyroidectomized (Tx), and nephrectomized-thyroidectomized (NxTx) littermates. Based on the severity of the uremia, Nx rats were subdivided into Nx1 and Nx2 groups; the former included rats with serum urea nitrogen of less than 100 mg/dl and the latter rats with serum urea nitrogen greater than 100 mg/dl. A group of rats pair-fed to the Nx rats was also included (PF). In the liver, nuclear T3 content (picograms per g liver) and T3-receptor binding capacity (Cmax, picograms T3 per mg DNA) were measured. The respective results from all groups of rats were as follows (asterisks denote values differing from C with a P value less than 0.05): C, 308 +/- (SE) 45 and 121 +/- 11; Nx1, 245 +/- 43 and 85 +/- 15; Nx2, 163 +/- 19 and 74 +/- 7; Tx, 43 +/- 11 and 91 +/- 10; NxTx, 33 +/- 10 and 54 +/- 6; and PF, 237 +/- 20 and 121 +/- 9. T3 receptor binding affinity (Ka), ranging from 3.62-5.28 X 10(9) M-1, was not significantly different among the six groups of rats. In the pituitary, T3 content (picograms per mg pituitary) was reduced only in the Tx rats, being 3.13 +/- 0.89 as compared to 7.04 +/- 1.48 in the C rats (P less than 0.05). In the Nx1, Nx2, and PF rats, pituitary T3 contents were 9.81 +/- 3.22, 13.01 +/- 3.60, and 7.83 +/- 1.08, respectively, and were not different from the C rats. Serum TSH was reciprocally elevated only in the Tx rats. The reduction in hepatic nuclear T3 content and T3-Cmax in the Nx2 rats is consistent with the presence of selective tissue deficiency of thyroid hormone. This is in agreement with the observation of reduced activity of two liver enzymes known to be under thyroid hormone regulation. The pituitary, however, had normal T3 content, suggesting a dissociation in thyroid hormone-dependent metabolic status between a peripheral tissue (liver) and the pituitary. This explains the failure to observe an increase in the serum TSH level, a manifestation of reduced intracellular rather than serum T3 concentration. Decreased food intake appeared not to be the cause of thyroid hormone abnormalities observed in uremia, as PF rats failed to manifest the changes found in Nx rats.

Animals↗
PubMed1984

Radioimmunoassays specific for the tertiary and primary structures of thyroxine-binding globulin (TBG): measurement of denatured TBG in serum.

Antisera prepared by immunization of rabbits with human T4-binding globulin (TBG) contained two populations of antibodies: one directed against determinants of the native molecule, and the other directed against antigenic sites present only in denatured TBG. These two populations of antibodies were present in all nine antisera prepared in this or other laboratories that were tested. Exploiting this property of anti-TBG sera and using radioiodinated denatured TBG as a tracer, a RIA was developed which measures specifically denatured TBG in the presence of native TBG. The RIA for measuring denatured TBG used purified native TBG, which was denatured by reduction and pyridylethylation (RP-TBG) before labeling with 125I. Native TBG was measured using the same antiserum, but the 125I-labeled tracer was unmodified TBG. The sensitivity of the native TBG RIA was 0.25 ng purified native TBG. Equivalent amounts of native TBG in serum, desialylated TBG, and deglycosylated TBG produced superimposeable standard curves. The cross-reactivity with RP-TBG was less than 0.02%. The denatured TBG RIA had a sensitivity of 1 ng, and superimposeable curves were produced with equivalent concentrations of RP-TBG and heat-denatured native TBG. The cross-reactivity of 0.8% with native and deglycosylated TBG was, at least in part, due to denatured TBG in the purified preparations. The specificity of the two RIAs is due to the existence of distinct and exclusive antigenic determinants in native TBG and denatured TBG which are probably located on the surface of the tertiary structure and internally at the primary structure of the molecule, respectively. Heat and acid pH treatments of serum produced a progressive loss in immunoreactive native TBG, proportional to the loss of T4-binding capacity. A reciprocal and quantitative increase in denatured TBG, as measured in the denatured TBG RIA, was found. T4 partially protected the native TBG from denaturation. Denatured TBG was detected in sera from normal adults. The mean value was 6.05 +/- 2.25 (+/- SD) micrograms/dl (n = 11). Similar values were found in 8 pregnant women, 5 men with familial partial TBG deficiency, and 15 hypothyroid 7 hepatic, and 8 renal failure patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1983

The value of serum thyroglobulin measurement in clinical practice.

Thyroglobulin (TG) is a normal constituent of serum detectable by radioimmunoassay in 75% to 90% of healthy adults. Levels are altered in a number of physiological and pathological conditions. Although the indications for serum TG measurements have not been clearly established, it is simple, inexpensive, and presents no risk of radiation exposure. Problems include variable sensitivity and reproducibility of assays, interference by TG autoantibodies, and changes induced by certain diagnostic or therapeutic interventions. Serum TG measurements is primarily used as a tumor marker in thyroid carcinoma. Values are almost invariably high with disseminated metastases. After total ablation of thyroid tissue, serum TG determination is useful in separating patients in remission from those with residual metastatic disease. Serial measurements in the same patients are useful in monitoring the effect of treatment of nonfunctioning thyroid metastases. It is of no proved value in the initial diagnosis of thyroid carcinoma. Controversy still exists regarding the advantages of measuring TG during hormonal therapy. The assay may aid in the diagnosis of thyrotoxicosis factitia, painless subacute thyroiditis, and neonatal hypothyroidism.

Adult↗
PubMed1983

The influence of percutaneous fine needle aspiration on serum thyroglobulin.

To determine whether percutaneous needle aspiration of the thyroid affects tests of thyroid function, in particular thyroglobulin (TG), serum TG, T4, free T4 index, T3, and TSH were measured before and after percutaneous needle aspiration biopsy of the thyroid in 25 subjects. Seven control subjects were tested before and after vigorous external manual palpation of the thyroid. Serial measurements were made additionally in 3 subjects undergoing thyroid surgery to assess how quickly serum TG increases after injury. The results were analyzed, and statistically significant differences between paired results were defined if the differences were greater than the maximum interassay variation in 11 consecutive assays. Eleven out of 25 patients had statistically significant elevations of serum TG after aspiration. None of the seven who underwent external manual palpation of the thyroid gland had elevation of serum TG. With three exceptions, there were no significant changes in serum T4, free T4 index, T3, and TSH in either group. Marked elevations in serum TG occurred within 2 min after open manual palpation, diathermy, and excision. The results were analyzed and correlated with factors that might lead to release of TG from the thyroid during needle aspiration. No positive correlation was observed with the apparent degree of trauma, the size of nodule, the TG content, volume or character of aspirate, or the time elapsed from aspiration to withdrawal of the blood sample. Correlation of serum TG elevation with final diagnosis did not show a significant trend; however, the existence of a possible relationship needs further studies. We conclude that serum for TG measurement should be obtained before percutaneous thyroid aspiration biopsy.

Adolescent↗
PubMed1983

Effects of "jet lag" on hormonal patterns. IV. Time shifts increase growth hormone release.

Twenty-four-hour GH profiles were obtained in five normal male volunteers before travel, 1, 11, and 21 days after the Brussels-Chicago flight (time shift, 7 h); and 1, 11, and 21 days after the return flight. The westward and eastward travels involved, respectively, periods of 23 and 33 h of sleep deprivation. One year later, two of the five volunteers were submitted, in the laboratory, to an investigation mimicking the conditions of sleep deprivation undergone in the course of the eastward travel and involving two 24-h periods of blood sampling. Blood samples were drawn every 15 min, and sleep was polygraphically monitored. The amounts of GH secreted were quantified, and their relationship with the different sleep stages was analyzed. Time shifts, whether caused by "jet lag" or by sleep deprivation in the laboratory, had two effects on GH secretory patterns. First, a marked increase in GH release, due to an augmentation of the magnitude, rather than the number, of secretory spikes was observed, independently of sleep disturbances. Return to basal levels was slower after westward than after eastward travel and took at least 11 days. Second, 1 day after the eastward transportation as well as immediately after 33 h of sleep deprivation, the major GH spike, which occurred in early sleep in the other studies, was shifted to late sleep. In these investigations, the only consistent alteration of sleep was a reduction in the amount of rapid eye movement (REM) stage. The occurrence of GH spikes in sleep was significantly associated with slow wave (SW) stage. However, total amounts of GH secreted during sleep were negatively correlated with the total duration of REM stages rather than positively correlated with the total duration of SW stages. A spike by spike analysis showed that the amount of GH secreted correlates best with the ratio (SW - REM) to (SW + REM), which relates the amount of REM preceding the spike to the amount of SW during the spike and thus constitutes an indicator of the status of the REM-non-REM oscillation.

Adaptation, Physiological↗
PubMed1983

Elevated serum thyroglobulin level in congenital thyroxine-binding globulin deficiency.

Serum thyroglobulin (TG) is normally under TSH control. Serum TG levels are elevated during increased thyroid gland stimulation and suppressed by exogenous thyroid hormone. High serum TG levels are also found with thyroid gland damage and in patients with differentiated thyroid neoplasms. Congenital T4-binding globulin deficiency was found in this study to be an additional condition in which serum TG levels may be elevated. Elevated TG levels were found in 13 of 36 patients (36%) with congenital TBG deficiency compared to 1 of 27 unaffected relatives (4%). Mean TSH and free T4 index values were not significantly different. A postulated mechanism involves transient TSH stimulation of the thyroid after transient small declines in circulating free hormone levels due to the decreased extrathyroidal pool of thyroid hormone associated with T4-binding globulin deficiency.

Adolescent↗
PubMed1983

Hormonal regulation of glycosaminoglycan accumulation in fibroblasts from patients with resistance to thyroid hormone.

We have previously shown that physiological concentrations of T3 added to thyroid hormone-deficient media decreased the incorporation of [3H]acetate and [3H]glucosamine into glycosaminoglycans (GAG) in confluent cultures of skin fibroblasts obtained from normal individuals. This inhibitory effect of T3 on [3H]GAG accumulation was due to a decrease in GAG synthesis, was independent of the substrate pool size or number of transfers in culture, and could be reversed by removal of hormone from the medium. As shown in the current communication, it was also independent of the site of biopsy and age and sex of the donor. Fibroblast cultures were grown to confluence in medium containing 10% fetal calf serum and then exposed for 3 days to medium deprived of thyroid hormone (10% bovine serum from a thyroidectomized animal) without or with the addition of T3, T4, or dexamethasone (DEX). After exposure to labeled substrate [(3H]acetate or [3H]glucosamine) for the last 24 h, their incorporation into GAG was determined. The mean +/- SD maximal inhibition of [3H]GAG accumulation in fibroblasts from 14 normal subjects was 38.3 +/- 14.4% compared to 22.4 +/- 13.0% in fibroblasts from 8 patients with generalized resistance to thyroid hormone (GRTH). Although the difference was significant at the group level (P less than 0.05), there was a considerable overlap between the results obtained from normal subjects and those from patients with GRTH. Furthermore, fibroblasts from 2 normal subjects failed to respond to T3 in several trials. The specificity of the effect of T3 was examined in fibroblast cultures from eight normal subjects and six patients with GRTH by comparing their responsiveness to T3 and to DEX. All fibroblasts obtained from normal subjects that responded to T3 also responded to DEX. Fibroblasts from the two normal individuals that did not respond to T3 also failed to respond to T4 and to DEX. In contrast, fibroblasts from four of the six patients with GRTH had an attenuated response to T3, but not to DEX. Fibroblasts from a patient with Marfan's syndrome responded normally to T3 despite increased incorporation of the substrate into GAG. The maximal inhibitory effect of T4 on [3H]GAG accumulation was identical to that of T3. However, a 100-fold higher concentration of T4 was required.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1983

Coexisting thyroid and parathyroid disease--are they related?

A high prevalence of non-C cell, thyroid gland disease associated with primary hyperparathyroidism (HPT) has been reported in 11 uncontrolled studies. Yet experimental evidence linking these thyroid and parathyroid gland lesions is lacking. To test the hypothesis that the coexistence of these lesions is significant, we analyzed 124 consecutive cases of parathyroidectomy (110 women, mean age 53.5 +/- 12.7 years). Patients in the group with HPT who had visible or palpable thyroid disease at the time of operation were age-, sex-, and race-matched with autopsy controls. There was no statistical difference in the prevalence of total macroscopic thyroid lesions between the autopsy control group (46.4%) and the group of patients with HPT (54%, P = 0.8). Microscopic lesions in the absence of macroscopic abnormalities were found in an additional 26% of the autopsy control patients. Since in the surgical group, only those with macroscopic abnormalities underwent thyroid biopsy, no accurate calculation can be made of the microscopic lesions in those 55 patients with HPT who did not have macroscopic abnormalities. There was no difference in the prevalence of autoimmune or thyroid nodular disease between the two groups except for the presence of seven macroscopic nonmedullary thyroid carcinomas in the HPT group and none in the autopsy control group (P less than 0.001). One microscopic carcinoma was found in the autopsy group, however. An increased prevalence of parathyroid adenomas in nonmedullary thyroid disease has been suggested by other studies. We were unable to confirm this association. In fact, the incidence of parathyroid adenomas found unsuspectedly in 229 consecutive thyroidectomies was 0.43%. Thus with the exception of macroscopic, nonmedullary carcinomas, there was no evidence that thyroid disease accompanies HPT. Furthermore, parathyroid adenomas were not more frequent in surgical thyroid disease. Lesions of the thyroid and parathyroid glands are prevalent in middle-age women. This probably is the major factor that accounts for their coexistence.

Biopsy↗
PubMed1982

Syndromes of thyroid hormone resistance.

Resistance to the action of thyroid hormone can involve both peripheral tissues and the pituitary (global resistance), the pituitary only or peripheral tissues alone. Global resistance is of variable severity and has been observed in more than 60 individuals, the majority occurring in 17 families. Affected subjects are commonly eumetabolic and have goiters, elevated plasma levels of total and free thyroxine and triiodothyronine, normal thyroid hormone metabolism, and normal serum TSH levels (albeit high for the corresponding levels of thyroid hormone). A variable degree of delayed bone maturation, mental retardation, learning disabilities, and hearing defects have been reported; and a variety of treatment regimens, most of which are aimed at reducing the level of plasma hormones and/or goiter, have been attempted before the correct diagnosis has been reached. The clinical disorder is equally common in males and females and appears to be due to one or more autosomal gene mutations. The causes for the hormone resistance may be heterogeneous, either influencing the receptor for thyroid hormones or some unidentified steps in hormone action. At present, the diagnosis is one of exclusion; no effective therapy is available, and all measures designed to lower serum thyroid hormone levels should be avoided.

Adolescent↗
PubMed1982

Regulation of glycosaminoglycan synthesis by thyroid hormone in vitro.

Human skin fibroblasts synthesize and accumulate glycosaminoglycans (GAG). Recently, we reported that fibroblasts incubated in thyroid hormone-deficient media accumulate more GAG than do cultures incubated in the same media enriched with 0.1 muM triiodothyronine (T(3)) (1981. Endocrinology. 108: 2397). The current study characterizes that enhanced accumulation. Confluent cultures were maintained in thyroid hormone-deficient media without or with added T(3), labeled with [(3)H]acetate and analyzed for total [(3)H]GAG and [(3)H]hyaluronic acid content. Addition of T(3) to thyroid hormone-depleted media consistently inhibited the incorporation of [(3)H]acetate into GAG by 28-60% in fibroblast cultures from four different normal human donors. Maximal inhibitory effect was observed within 3 d after hormone addition at concentrations > 1 nM. 73% of the maximal inhibitory effect was observed in the presence of physiologic concentrations of T(3) (0.16 nM total T(3) or 1.4 pM free T(3)). The following observations indicated that T(3) inhibition of [(3)H]GAG accumulation is most likely due to a decrease in GAG synthesis rather than to changes in the acetate pool or GAG degradation: (a) Addition of 0, 100, 500, and 2,500 muM unlabeled acetate progressively decreased [(3)H]acetate incorporation into GAG, up to 80%, without altering the further inhibitory effect of T(3) (35-40%); (b). A similar effect of T(3) on GAG (32% inhibition) was observed using [(3)H]glucosamine as substrate; (c) T(3) decreased hyaluronate synthetase activity by 32%; and (d) There was no effect of T(3) on GAG degradation in a pulse-chase experiment. The effect of T(3) on [(3)H]GAG accumulation appears to be quite specific, since the hormone had no effect on the incorporation of [(3)H]leucine into trichloroacetic acid-precipitable material.Thus, thyroid hormone inhibits GAG accumulation in a dose-, time-dependent, and reversible manner. This inhibition is apparently due to specific effects on the rate of macromolecular synthesis.

Acetates↗
PubMed1982

The relationship between episodic variations of plasma prolactin and REM-non-REM cyclicity is an artifact.

The concept of concomitance between nadirs and peaks of plasma levels of PRL and, respectively, rapid eye movement (REM) and non-REM stages in sleep was reevaluated using 24 nighttime profiles of plasma PRL collected at 15-min intervals and the corresponding polygraphic recordings of sleep. The subjects were 5 healthy young male adults. Data were examined using the methodology described in the original report, consisting of averaging across individual nights PRL levels during REM and non-REM sleep stages as well as using a detailed spike by spike analysis of each individual pair of hormonal and sleep profiles. We showed that in our subjects, there was no relation, other than a purely random one, between episodic PRL fluctuations in plasma and REM-non-REM cycles.

Adult↗
PubMed1982

Radioimmunoassay detection of endorphins from long-term culture of human pituitary tumour cells.

Using a sensitive and precise radioimmunoassay for human beta-endorphin, we have demonstrated the sustained secretion of opioid peptides from human pituitary tumour cells. Pituitary tumour tissue obtained from a patient with Nelson's syndrome was maintained in continuous monolayer culture and secreted both beta-lipotropin and beta-endorphin, with predominance of the latter. This is compatible with the idea that the beta-endorphin in normal human serum is secreted as such despite the predominance of beta-lipotropin compared with beta-endorphin in the anterior pituitary.

Cells, Cultured↗
PubMed1982

Serum thyroglobulin in the management of patients with thyroid cancer.

We have reviewed our experience with the management of patients with thyroid cancer to assess the potential benefits of employing the serum thyroglobulin assay in patient management programs and to determine the optimal conditions for this application. Serum thyroglobulin levels were found to be more reliable when obtained from hypothyroid patients. Levels of thyroglobulin greater than 10 ng/mL appeared to be abnormally elevated in both thyroidectomized patients prior to radioactive iodine therapy (group 1) and in thyroidectomized patients after radioactive iodine therapy (group 2). Elevated thyroglobulin levels were found to be useful indicators of the presence of metastatic disease, whereas normal thyroglobulin levels were reliable indicators of the absence of metastases. In group 1 patients, elevated thyroglobulin levels reliably predicted the presence of important total body scan uptake. In group 2 patients, normal thyroglobulin levels reliably predicted the absence of total body scan uptake. The serum thyroglobulin assay can substantially reduce the need for repetitive total body scanning in the follow-up of group 2 patients with thyroid cancer.

Adenocarcinoma↗
PubMed1981

Radioautographic localization of prolactin messenger RNA on histological sections by in situ hybridization.

In situ hybridization of complementary [H3]DNA ([H3]cDNA) synthetized from purified rat prolactin messenger RNA (rPRL mRNA) was performed to specifically identify on histologic sections of rat hypophysis cells expressing the PRL gene. Radioautographic labelling occurred over weakly acidophilic cells, while other acidophils, with darker cytoplasm did not contain more silver grains than blood vessels.

Animals↗
PubMed1981

Dopaminergic control of prolactin mRNA accumulation in the pituitary of the male rat.

Dopaminergic control of the expression of the prolactin gene was investigated by administration of bromoergocryptine (CB154) to male rats. The effects of the drug on the following parameters were measured: (i) circulating levels of GH and PRL; (ii) synthesis of GH and PRl measured by pulse labeling pituitary fragments in vitro; (iii) GH and PRL mRNA activities; and (iv) content of PRL and mRNA. After 1 day of CB154 administration, serum PRL fell to undetectable levels whereas it took 3 days to observe a 50% reduction in PRL synthesis. This effect was accounted for by a parallel decrease in PRL mRNA activity and content. GH synthesis and GH mRNA were not affected by the treatment. Our results show that the dopaminergic inhibition of PRL production involves regulation at a pre-translational level.

Animals↗