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Biomedical subjects

K D Burman

Publications and source records attributed to K D Burman.

At least 109 records · Page 6Linked to original sources
PubMed1986

Radioiodine treatment of Graves' disease. An assessment of its potential risks.

Concern about the side effects of radiation exposure has deterred physicians from using radioiodine treatment for Graves' disease, although the efficacy and safety of this treatment have been established in the 35 years since its introduction. In that time, no significant side effects have been discovered. We believe iodine-131 should be considered the treatment of choice in most patients with Graves' disease. This article reviews the current understanding of the risks in radioiodine treatment of Graves' disease, including the risks for teratogenicity, genetic damage, carcinogenesis, and cellular dysfunction.

Abnormalities, Radiation-Induced↗
PubMed1985

Angiotensin-converting enzyme activity. A potential marker of tissue hypothyroidism in critical illness.

We measured serum angiotensin-converting enzyme (ACE) activity radiometrically as a possible indicator of reduced thyroid function in 57 euthyroid controls, 27 patients in a noncardiac intensive care unit (13 with medical and 14 with surgical disorders), and 29 patients having coronary artery bypass grafting. In the last group, blood was obtained preoperatively and one day and one month after surgery (group 1; n = 18) or preoperatively and six hours and one day after surgery (group 2; n = 11). Patients in group 1 had significant reductions in levels of serum thyroxine (T4), triiodothyronine (T3), and thyrotropin response to protirelin one day postoperatively. The ACE activity fell significantly. Patients in group 2 had low levels of T4, T3, thyrotropin, and ACE six hours postoperatively. All these levels remained low the next day, and free T4 and free T3 levels were also reduced; the reverse T3 level became elevated. Changes in ACE significantly paralleled changes in T3. The 27 patients without coronary artery bypass grafting also had significant reductions in serum T4, T3, and ACE levels. Dilution studies and dialysis of serum with low ACE activity failed to demonstrate an inhibitor to explain the reduced enzyme function.

Adult↗
PubMed1985

Stereospecific determination and in vivo monodeiodination of thyroxine enantiomers in euthyroid man.

To compare in man the absorption, serum disappearance, and peripheral monodeiodination of the thyroxine enantiomers, we studied six euthyroid subjects who, on separate occasions, orally ingested 3 mg of either dextrothyroxine (DT4) or levothyroxine (LT4). We measured the serum concentrations of total T4 (TT4), total T3, and reverse T3 (rT3) by nonstereospecific radioimmunoassay and we determined serum DT4 and LT4 by stereospecific chromatography. Mean serum TT4 levels from 4 hours were significantly greater after LT4 administration. After DT4 administration, stereospecific analysis of serum revealed two T4 peaks that persisted from 2 to 48 hours. The mean serum LT4 level did not significantly change during the 48 hours after DT4 administration. Increases in serum T3 and rT3 were seen from 2 hours after administration of either enantiomer. From 12 hours the levels of both triiodothyronines after LT4 were significantly higher than after DT4. In this short term study we found no evidence that in man DT4 is converted to LT4, nor is it preferentially deiodinated to rT3. The greater and more persistent increases in serum T4 and T3 observed after LT4 probably contribute to the known higher bioactivity of that enantiomer.

Absorption↗
PubMed1985

Effects of exercise and physical fitness on the pituitary-thyroid axis and on prolactin secretion in male runners.

The effects of acute exercise and thyrotropin-releasing hormone on the pituitary-thyroid axis were examined in men placed into three well-defined categories of physical fitness. There were 20 sedentary men, 22 joggers (running four to 20 miles per week) and 18 marathoners (running 30 to 100 miles per week) who participated. During treadmill exercise, the mean VO2 max differed among all groups, being 38.5, 45.0, and 60.3 mL/kg . min in the sedentary, jogger, and marathon groups, respectively. Serum was obtained before, immediately after, and one hour after exercise for measurement of thyroxine (T4), triiodothyronine (T3), reverse T3, thyrotropin (TSH), and prolactin. Basal values of all hormones did not differ among the groups. Maximal short-term treadmill exercise produced no change in serum T4, T3, reverse T3, or TSH. Prolactin rose significantly by a similar amount in all three subject groups. On a separate day, ten individuals from each group received thyrotropin releasing hormone (TRH; 500 micrograms IV). Neither the peak TSH response nor the total TSH secreted during two hours after TRH differed among groups. The mean total prolactin secretion in the joggers and marathoners was 48% and 45% greater, respectively, than in the sedentary men. Five subjects in each group also underwent a TRH test immediately postexercise. Similar to the results on the nonexercise day, the integrated TSH response to TRH was similar in all three groups, whereas the integrated PRL response to TRH was increased by 52% and 78% in the two conditioned groups. Post-TRH sera from one subject in each group were fractionated on a Sephadex G-100 column.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

A longitudinal evaluation of thyroid function in critically ill surgical patients.

Thyroid hormone alterations (known as the "sick-euthyroid syndrome") are common following major surgery, but the time course for appearance and recovery from these alterations has not previously been longitudinally studied in a large group of surgical patients. The authors prospectively studied 59 patients undergoing major surgery (coronary artery bypass grafting, pneumonectomy, or subtotal colectomy). Compared with preoperative values, the mean serum T4, T3, free T3, and TSH concentrations decreased significantly (p less than 0.05) following surgery. Serum reverse T3 and T3 resin uptake index increased, while free T4 levels remained unchanged. These changes were seen within 6 hours of surgery and normalized by 1 week after surgery. Although the serum TSH response to TRH was normal before and after surgery in 56 of the 59 patients, the maximal TRH-induced increase in serum TSH and the integrated serum TSH response to TRH were suppressed in the early perioperative period. This postoperative TSH suppression correlated with elevated postoperative plasma dopamine concentrations (r = 0.57, p less than 0.05). Three patients with compensated primary hypothyroidism were detected in the study and represent the first documentation of serial thyroid hormone and TSH levels in hypothyroid patients undergoing major surgery. These patients had similar changes in thyroid hormone values compared with euthyroid patients. The serum TSH response to TRH was suppressed into the normal range in two of these patients on the day following surgery. The authors conclude that the sick-euthyroid syndrome occurs within a few hours of major surgery and remits with convalescence. Postoperative decreases in serum TSH may mask the diagnosis of hypothyroidism. Surgical consultants should be aware of these rapid postoperative changes so that thyroid function tests are properly interpreted in patients who have undergone major surgery.

Adult↗
PubMed1985

Antithyrotropin antibodies in the sera of Graves' disease patients.

To determine the presence and potential importance of antiidiotypic antibodies (anti-id) in the immune regulation of Graves' disease, sera from 57 patients with Graves' disease were screened before or during antithyroid therapy by enzyme-linked immunoabsorbent assay (ELISA) for presumptive anti-id, as defined by the presence of immunoglobulins (Igs) directed against TSH. The mean optical density, indicating the presence of TSH-binding antibodies, was 0.34 +/- 0.28 (+/- SD) in the sera of Graves' disease patients and 0.19 +/- 0.12 in the sera of 24 normal subjects (P less than 0.004). Control antigens (hCG and albumin) did not bind significant amounts of serum Igs. In 8 Graves' patients whose sera bound TSH, 40-80% inhibition was obtained with the addition of TSH receptor-purified IgG (approximately 1 microgram/ml) derived from a single Graves' patient's serum; no inhibition was found with normal IgG (approximately 10 micrograms/ml). Presumptive anti-id was isolated from sera of 6 Graves' patients by affinity purification with a TSH affinity column; the resultant IgG blocked immunoglobulin binding to the TSH receptor when added to the serum of the same patient from whom it had been isolated. The presence of anti-id correlated inversely with the presence of TSH receptor antibodies (r = -0.76; P less than 0.01). These studies demonstrate that 1) significant TSH binding is present in sera from Graves' disease patients, and 2) this TSH binding is specifically inhibitable by Graves' IgG, but not by normal IgG. These data support the hypothesis that TSH-binding immunoglobulins may represent anti-id that are present in Graves' disease as part of the immunological response to TSH receptor or TSH receptor antibodies. Such anti-id could modulate the expression of disease activity in Graves' disease by altering TSH receptor antibody action or production.

Antibody Affinity↗
PubMed1985

The in vitro regulation of human thyrocyte HLA-DR antigen expression.

The ability of endocrine organs to express human immune response-associated antigens (Ia), such as HLA-DR, is a subject of intense current interest. In this study, the effects of various potential modulators of thyroid follicular cell HLA-DR expression were examined using in vitro cultures. A culture supernatant containing T-cell-derived lymphokines caused DR antigen expression on 13-18% of thyroid cells; more consistent effects were produced by recombinant gamma-interferon, which led to 46-100% of the thyroid cells becoming HLA-DR positive after 3 days in culture. This effect was both time and concentration dependent and occurred in thyroid cells derived from patients with Graves' disease (n = 7) and Hashimoto's thyroiditis (n = 2) as well as from three subjects with no autoimmune thyroid disease. Thyroid cells stained with the monoclonal antibodies 4F2 and 5E9, which recognize cell activation antigens, regardless of whether they were treated with gamma-interferon. The lectin phytohemagglutinin also induced HLA-DR antigen expression (21-91% of cells positive). This response was dependent on T cell contamination of thyroid cell suspensions, since the effect was inhibited by cyclosporin A. HLA-DQ antigen expression, identified by the Leu-10 monoclonal antibody, was also induced on thyroid cells by gamma-interferon and phytohemagglutinin. In contrast, neither recombinant alpha-interferon nor interleukin-2 induced HLA-DR antigens. Irradiation reduced the response of thyroid cells to gamma-interferon, but two of the known inhibitors of macrophage Ia expression, prostaglandin E2 and (Bu)2cAMP, did not affect gamma-interferon-induced thyroid cell HLA-DR expression. We were unable to detect interleukin-1 production by thyroid cells. These results suggest that 1) under normal circumstances, thyroid cells are 4F2 and 5E9 positive, but are incapable of expressing Ia antigens and, thus, of activating T cells to initiate autoimmune thyroiditis; and 2) once activated, for example by a virus, T cells could release gamma-interferon and induce thyroid cell HLA-DR and -DQ antigen expression; these Ia-positive thyroid cells could then have a role in maintaining or enhancing the autoimmune response.

Adult↗
PubMed1985

Beta receptors in peripheral mononuclear cells increase acutely during exercise.

Five healthy adult well trained men (averaging 49 miles running per week) were exercised to exhaustion on a treadmill. Plasma epinephrine increased from 168 +/- 37 pg/ml prior to exercise to 633 +/- 155 pg/ml immediately after exercise (P less than 0.025) and plasma norepinephrine increased from 1608 +/- 345 to 8576 +/- 1662 pg/ml (P less than 0.025) in the two respective periods. Beta receptor density increased from 53 +/- 18 fmol/mg protein before exercise, to 223 +/- 63 fmol/mg (P less than 0.05) protein immediately after exercise, and then decreased to 83 +/- 27 fmol/mg protein 1 h later (P less than 0.05 compared to post-exercise). The mean Kd value prior to exercise of 1.5 +/- 0.2 X 10(-11) M was unchanged statistically throughout the study. Following correction for haemodilution, serum total and free T4 and T3 concentrations were also unchanged during exercise, although reverse T3 levels did increase from 39 +/- 4 to 45 +/- 0 ng/dl (P less than 0.05). These findings suggest that: 1) plasma epinephrine, norepinephrine and beta receptor density, but not Kd, increase acutely during exercise and 2) total and free T4 and T3, after correction for haemodilution, do not change during acute exercise. Our data indicate that acute exercise represents an unusual condition during which 'down regulation' is not observed, but, rather, there appear to be parallel alterations in beta receptor density and plasma catecholamine levels.

Adult↗
PubMed1985

The equivalency of two L-thyroxine preparations.

Differences in blood levels of thyroid hormones have been reported when patients taking synthetic L-thyroxine were shifted from one manufactured form of the hormone to another. Because recent formulation changes have rendered these earlier data obsolete, we did a crossover study to determine differences in bioavailability of the two principal brands of thyroxine, Synthroid and Levothroid. Twenty patients received Synthroid and then Levothroid, and 14 received Levothroid and then Synthroid. Patients received each drug for 6 weeks. Although no significant differences were seen in routine thyroid hormone measurements, combined data from both groups showed a significantly higher free thyroxine level in the patients treated with Synthroid, as well as lower thyrotrophin values at 15 and 30 minutes after administration of thyrotrophin-releasing hormone. Equal doses of the currently manufactured forms of these two products are similar but not bioequivalent.

Female↗
PubMed1985

Activation, proliferation, and differentiation of circulating B cells in autoimmune thyroid disease.

Several studies of thyroid autoantibody production in vitro have been reported with the use of pokeweed mitogen, but the conclusions that have resulted regarding the immunoregulation of B cell function in thyroid disease are difficult to interpret due to the relatively nonphysiologic nature of pokeweed mitogen stimulation. We have therefore examined the responses of circulating B cells in Graves' disease and Hashimoto's thyroiditis by using a combination of lymphokines and other stimuli that act at various stages of the B cell cycle. In patients with autoimmune thyroid disease, nonspecific B cell proliferation and differentiation into IgG-secreting cells were both normal. However, a previously unsuspected heterogeneity among patients was found in their ability to produce autoantibodies in vitro. B cells of certain patients produced maximal autoantibody in response to pokeweed mitogen, some in response to Staphylococcus aureus Cowan strain I, and some in response to the lymphokines contained in the supernatants of stimulated T cell cultures. There was no correlation between serum autoantibody levels and those achieved in vitro. Attempts to stimulate antibody production by autoantigen (thyroglobulin) were unsuccessful, even when B cells were cultured with purified autologous OKT4+ T cells to avoid potential suppressor effects in the OKT8+ population. However, OKT4+ T cells enhanced pokeweed mitogen-driven autoantibody production. Our results show that several different functional stages of B cells exist in the circulation of patients with autoimmune thyroid disease, and that circulating B cells from such patients do not manifest a uniform response to B cell stimulators. This is presumably the result of differences in migration of circulating B cells and in their level of activation at the major sites of autoantibody production, such as the thyroid gland itself. In the light of these findings, caution is required in interpreting the results obtained from studies of circulating B cells as a means of elucidating the pathophysiology of autoimmune thyroid disease.

Autoantibodies↗
PubMed1985

A rapid, sensitive enzyme-linked immunoassay for human thyrotropin.

In this enzyme-linked immunoassay for human thyrotropin (TSH) in unextracted serum we use 96-well immunoenzymometric assay plates, first coated with polyclonal antibody to TSH, then incubated with the serum samples and reacted with mouse monoclonal antibody to human TSH. After incubation with alkaline phosphatase-labeled antibody against mouse IgG, disodium p-nitrophenyl phosphate is added and the color change is measured spectrophotometrically. Assay sensitivity is 0.1 milli-int. unit/L. Cross reactivity with lutropin, follitropin, or choriogonadotropin was negligible. TSH concentrations ranged from 0.4 to 4.1 milli-int. units/L in 43 normal subjects (mean 2.0, SD 1.0), and were uniformly less than 0.3 milli-int. unit/L in 23 patients with hyperthyroidism. Features which make this assay advantageous to the clinical laboratory include ease of set-up, ability to assay many samples at a time, high sensitivity, rapid turnaround time (8 h), and absence of requirements for radioactive materials.

Animals↗
PubMed1984

Immunohistochemical characterization of intrathyroid lymphocytes in Graves' disease. Interstitial and intraepithelial populations.

The phenotypic cell surface markers of the lymphocytes present in thyroid tissue from four patients with Graves' disease were quantitatively analyzed using the avidin-biotin immunoperoxidase technique. As control specimens, normal perinodular tissues from three patients who had benign thyroid nodules resected were also studied. In contrast to normal thyroid tissue, which contained very few T cells and no B cells, thyroid tissue of all four patients with Graves' disease contained a lymphocytic infiltrate, and this could be divided into two populations of lymphocytes. The first population was located in the follicular epithelium and expressed a cytotoxic-suppressor T cell marker (Leu2a). On the average, these cells were 4.2 times as numerous in Graves' tissues as in normal tissues (p less than 0.05). Most of these cells did not express Leu1, a pan-T cell marker. The second population was found in the interstitial tissues, often within lymphoid aggregates, and 70 to 83 percent of the cells expressed Leu1. The majority of these cells expressed a helper-inducer T cell marker, Leu3a; Leu3a/Leu2a ratios within aggregates ranged from 1.9 to 2.1. The number of B cells present was small, ranging from 5.8 to 12.1 percent of the interstitial lymphocytes. These findings are consistent with the involvement of both helper-inducer and suppressor-cytotoxic T cells in a localized autoimmune reaction directed, at least in part, against the thyroid follicular epithelial cells.

Autoimmune Diseases↗
PubMed1984

Thyrotropin secretion in starved rats is enhanced by somatostatin antiserum.

Previous studies have demonstrated that serum TSH and GH decrease during fasting. Taking advantage of the fact that somatostatin antiserum administration is an effective, specific method of blocking endogenous somatostatin activity, we performed the present investigation to explore whether known fasting-induced increases in somatostatin might underlie the mechanism(s) of this decrement. After a 48 hour fast, two groups of male rats were anesthetized and an indwelling right atrial catheter inserted. The control rats (n = 11) were injected with normal sheep serum and the experimental rats (n = 9) were injected with a specific antiserum to cyclic somatostatin; one and one-half hours later, blood was collected in a basal state after which 200 ng TRH was injected. The basal mean (+/- SE) T3 and T4 concentrations were 23 +/- 3 ng/dl and 1.9 +/- 0.1 ug/dl, respectively, in the fasted control group and 30 +/- 2 ng/dl and 2.3 +/- 0.2 ug/dl in the fasted somatostatin antiserum injected rats. While serum T4 and T3 levels were statistically unchanged between these two groups, basal TSH increased from 537 +/- 81 ng/ml in the control rats to 2913 +/- 742 ng/ml in the somatostatin antiserum-treated rats (P less than 0.05). Basal growth hormone levels were also higher in the somatostatin antiserum-injected rats (196 +/- 19 ng/ml vs 72 +/- 7 ng/ml (P less than 0.0025). TSH peak values following TRH injection were not different in the two study groups. In summary, the present study indicates that: (1) somatostatin antiserum increases both basal GH and TSH values in fasting rats; and (2) somatostatin and TRH may act through different pathways to modulate TSH secretion. By implication, therefore, it is suggested that enhanced somatostatin-like activity may represent one mechanism mediating the fasting-induced decrement observed in serum TSH and GH.

Animals↗
PubMed1984

Production, isolation, and characterization of rabbit anti-idiotypic antibodies directed against human antithyrotrophin receptor antibodies.

Previous studies have shown that anti-idiotypic antibodies can be developed in vivo through animal immunization with idiotype, and that these antibodies can be isolated from other anti-immunoglobulin antibodies by affinity purification. These techniques have relied on large amounts of idiotype, which were produced either by hyperimmunization or by monoclonal antibodies, to serve as the affinity adsorbent. In the present study, we produced anti-idiotypic antibodies to human anti-thyroid-stimulating hormone (TSH) receptor antibodies by first injecting rabbits with (TSH receptor purified) IgG from Graves' patients. The resulting antiserum was then adsorbed with Sepharose-coupled TSH in an attempt to specifically bind and isolate the anti-idiotype. The antibody obtained from this process was shown to bind specifically to TSH receptor-binding antibodies from Graves' patients, and this binding could be inhibited by 56% with the addition of 10(-4) M TSH but not by HCG (10(-2) M). The anti-idiotype also bound to TSH, and this binding could be specifically inhibited by receptor-purified Graves' IgG (60% inhibition at 10 micrograms/ml IgG), but not by IgG from normal subjects (no inhibition at 50 micrograms/ml IgG). In a TSH receptor binding assay, the anti-idiotype could inhibit TSH receptor binding in Graves' sera at a 1,000-fold lower concentration than could anti-kappa/lambda antiserum; the anti-idiotypic antiserum also inhibited in vitro TSH-mediated adenylate cyclase stimulation at an IgG concentration of 5 micrograms/ml, while heterologous anti-TSH antisera and normal IgG at similar concentrations had no effect. Finally, despite being generated against a single patient's TSH receptor binding antibody, the anti-idiotype was able to block TSH receptor binding in the serum of six other Graves' patients, thus suggesting that there may be conformational conservation in the antigen that is recognized by different individuals' TSH receptor-binding immunoglobulins.

Adipose Tissue↗
PubMed1984

Low serum thyroxine and high serum triiodothyronine in nephrotic rats: etiology and implications for bioavailability of protein-bound hormone.

Traditionally, it has been thought that the bioavailable fraction of circulating serum hormones, i.e. that which is available for cellular uptake and is physiologically active, is limited to the free (nonprotein bound) hormone. However, recent evidence, based on acute organ uptake of labeled hormone, suggests that the amount of hormone which is bioavailable in vivo may exceed that which is calculated to be free in vitro. To explore the bioavailability of circulating protein-bound thyroid hormones under steady state conditions in vivo, we altered serum thyroid hormone-binding proteins in rats by inducing nephrotic syndrome with puromycin aminonucleoside. Nephrotic rats (serum albumin, 1.1 g/dl) were found to have a marked reduction in serum T4 [2.1 +/- 0.2 (SEM) vs. 6.5 +/- 0.3 microgram/dl; P less than 0.01] and an elevation of serum T3 [141 +/- 8 vs. 51 +/- 2 ng/dl; P less than 0.01]. Estimated T4 production rate was normal in nephrotic rats, and the 3- to 4-fold increase in T4 MCR appeared to account for the marked reduction in serum T4. By contrast, increased serum T3 levels in nephrotic rats reflected both a reduction (55%) in T3 MCR and an increased rate of peripheral conversion of T4 to T3. A circulating inhibitor of T4 binding to serum proteins appeared to be present in nephrotic rats. The changes in the various serum components of thyroid hormone [T4-binding prealbumin (TBPA)-bound, albumin-bound, free] produced by nephrotic syndrome were compared with the corresponding changes in indices of thyroid hormone bioavailability (MCR, urinary excretion, hepatic content, TSH suppression, single pass extraction by liver). These comparisons suggested that nephrotic syndrome results in increased bioavailability of circulating T4 and decreased bioavailability of circulating T3. The bioavailable fraction of circulating T3 in vivo seemed to include both free T3 and that which is albumin bound in vitro. The bioavailable fraction of circulating T4 resembled free T4 more than non-TBPA-bound T4 (= albumin bound + free), although a nephrosis-induced increase in bioavailability of TBPA-bound T4 was also possible. We conclude that nephrotic rats have low serum T4, which is related to accelerated T4 clearance, and high serum T3, which is related both to decreased T3 clearance and increased peripheral conversion of T4 to T3. Under steady state conditions in vivo, bioavailable circulating T3 appears to include both free T3 and the T3 that is bound to albumin in vitro.

Animals↗