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Biomedical subjects

K D Burman

Publications and source records attributed to K D Burman.

At least 127 records · Page 7Linked to original sources
PubMed1983

Adaptation to hypocaloric feeding: physiologic significance of the fall in serum T3 as measured by the pulse wave arrival time (QKd).

We have investigated the physiologic significance of the decline in serum triiodothyronine (T3) occurring during hypocaloric feeding by measurement of changes in cardiovascular function. The QKd interval, the interval between the Q wave of the electrocardiogram and the onset of Korotkoff sounds at diastolic pressure at the brachial artery, is the sum of the preejection period and pulsetransmission time, and has proven to be a sensitive and effective measure of the effect of thyroid hormones on the cardiovascular system. Fifteen euthyroid obese volunteers underwent successive 2 wk periods of hypocaloric feeding (200-400 calories per day) interspersed with periods of at least 2 wk of re-feeding on a weight-maintaining diet (1500 calories). In a later phase subjects received oral supplementation of triiodothyronine (T3) in addition to the diet to prevent the fall in serum T3. In the last study phase, subjects on the diet received supplementation with oral thyroxine (T4), which prevented the fall in serum T3 and resulted in a slight increase in serum T4. During the first 2 wk period of hypocaloric feeding, there was a statistically significant increase in QKd, and a decrease in pulse rate, compatible with a hypothyroid state relative to initial measurements. When oral T3 supplementation was given, the rise in QKd and fall in pulse rate were prevented. Likewise, with oral T4 supplementation, the changes in QKd and pulse were prevented. Thus, the fall in serum T3 occurring during hypocaloric feeding is associated with changes in the cardiovascular system which are qualitatively similar to those observed during hypothyroidism. The present data, taken with other data in the literature, suggest that the decline in serum T3 during hypocaloric feeding may be an adaptive mechanism to conserve energy during caloric deprivation.

Adaptation, Physiological↗
PubMed1983

T3 may be a better agent than T4 in the critically ill hypothyroid patient: evaluation of transport across the blood-brain barrier in a primate model.

Thyroid hormone transport across the blood brain barrier in hypothyroid patients is clinically important yet poorly understood. To study this question, 200 micrograms of thyroxine (T4), 100 micrograms of 3,5,3'-triiodothyronine (T3) and 100 micrograms of 3,3',5'-triiodothyronine (reverse T3) were administered separately to 3 baboons, first iv and at a later date intrathecally (IT). Six animals were used. Three received the iv injections and three received the IT injections. In each of the 18 experiments, cerebrospinal fluid (CSF) and serum specimens were collected serially for 6 h after injection. Mean maximal elevations from baseline in CSF iodothyronine levels were 100 +/- 10 ng/dl after iv T4, 3921 +/- 293 ng/dl after iv T3 and 31 +/- 17 ng/dl after iv reverse T3. When given IT in the same dosages, the mean maximal increases in serum iodothyronine concentrations were: 1670 +/- 600 ng/dl for T4, 806 +/- 405 ng/dl for T3, and 210 +/- 43 ng/dl for reverse T3. In every animal studied, rapid bidirectional transfer of T3 from serum to CSF and CSF to serum occurred, whereas iv T4 resulted in delayed minimal increments in CSF T4 concentration. Isotopic experiments were also performed and the results analyzed using a kinetic model. When 125I-T3 was given iv, the equilibrium point in CSF was observed within 90 min with 1.7% of the administered dose/L able to be counted in CSF at any moment in time. When labeled T4 was given iv, only 0.6% of the administered dose/L was counted in CSF and the equilibrium point was not reached until 360 min. These data suggest: (a) T4, T3, and reverse T3 are all capable of bidirectional transfer across the blood brain barrier, (b) T3 may be a better agent than T4 in treating patients with myxedema coma because T3 crosses more rapidly and more completely from serum to CSF.

Animals↗
PubMed1983

Partial characterization and clinical correlation of circulating human immunoglobulins directed against thyrotrophin binding sites in guinea pig fat cell membranes. Development of a direct enzyme immunoassay.

To obviate several problems inherent in indirect thyroid-stimulating hormone (TSH) receptor antibody assays, we developed an enzyme-linked immunosorbent assay (ELISA) that measures antibodies binding to guinea pig fat cell membrane, which contain high concentrations of TSH receptors. Solubilized guinea pig fat cell membranes were adsorbed to plastic microtiter plates and served as the solid-phase antigen. Test sera and affinity-purified alkaline phosphatase-conjugated anti-human IgG were co-incubated with membranes, after which p-nitrophenyl phosphate was added. Results were read when a positive control reached a standard color change (OD405nm). Specificity of this assay was demonstrated by the inability of albumin, insulin, TSH subunits, propranolol, or dexamethasone to block binding 30. normal subjects had a mean OD value of 0.080 +/- 0.050 (SD). 23 of 25 untreated Graves' patients had OD values at least 2 SD above the normal mean (Grave's mean +/- SD; 0.46 +/- 0.33, P less than 0.001) and in each case 10(-6) M TSH inhibited the binding by at least 60%, suggesting that the immunoglobulins were directed at the TSH receptor. Seven of 25 serum samples from patients with Hashimoto's disease, seven of 23 serum samples from patients with transient hyperthyroidism (subacute thyroiditis or painless thyrotoxic thyroiditis), and two of 10 samples from patients with thyroid carcinoma had significant elevations in the titers of membrane-directed immunoglobulins. Graves' patients who were treated with ablative therapy at least 6 mo earlier and who were euthyroid when restudied continued to have abnormally elevated membrane-directed immunoglobulins in six of eight samples studied. Further studies involved the substitution of affinity-purified alkaline phosphatase anti-IgM antisera for the anti-IgG antisera routinely used. Seven of 12 serum samples from patients with Graves' disease had significant elevations in binding which in every instance was inhibited by greater than 60% by 10(-6) M TSH. In sum, the present results indicate that (a) we have developed a sensitive, specific, reproducible, convenient ELISA for the measurement both of the total amount of circulating membrane-directed antibodies and of TSH-displaceable membrane-directed immunoglobulins. (b) This ELISA detected significant elevations in TSH-displaceable guinea pig membrane binding in 23 of 25 untreated Graves' patients as well as in approximately 30% of patients with Hashimoto's thyroiditis and subacute thyroiditis. (c) Elevated membrane directed antibodies may continue to be present many months or years after restoration of the euthyroid state. (d) Circulating membrane binding IgM immunoglobulins have been detected in patients with Graves' disease. Further studies using this ELISA should prove useful in a variety of investigative and clinical studies.

Adipose Tissue↗
PubMed1983

Fasting decreases thyrotropin responsiveness to thyrotropin-releasing hormone: a potential cause of misinterpretation of thyroid function tests in the critically ill.

We have previously reported that caloric deprivation inhibits peripheral T4 metabolism and blunts the TSH response to TRH in euthyroid obese subjects. To determine whether these phenomena also occur in hypothyroid subjects, T4, T3, rT3, and the TSH response to TRH were measured initially and after a 60-h fast in seven hypothyroid patients. Short term fasting caused a 29% decrement in the maximum serum TSH increment and a 32% decrement in the integrated TSH response to TRH (P less than 0.01). In two subjects with mild hypothyroidism, basal TSH as well as the TSH response to TRH were reduced to levels within the normal range. Specifically, basal TSH values decreased from 7.6 to 3.5 microU/ml and from 11 to 4.1 microU/ml. In the seven subjects, mean serum T3 decreased significantly from 88 to 60 ng/dl, (P less than 0.05) and rT3, initially undetectable in six of seven subjects, rose to detectable or low normal values in four of seven subjects, serum T4 remained at 2.7 micrograms/dl during both study periods. We conclude that 1) fasting induces changes in both peripheral thyroid hormone metabolism and the hypothalamic-pituitary axis in hypothyroid individuals which are qualitatively similar to those that occur in euthyroid subjects; and 2) in certain hypothyroid subjects, fasting alone can decrease basal TSH values to within the normal range. If these data can be extrapolated to critically ill subjects whose caloric intake may be diminished, they suggest that basal TSH concentrations in moderately and severely hypothyroid critically ill subjects will accurately reflect the biochemically hypothyroid state. However, mild degrees of hypothyroidism in critically ill subjects might be overlooked due to the lowering effect of fasting or poor caloric intake alone on basal TSH concentrations.

Adult↗
PubMed1983

Euthyroid hyperthyroxinemia.

An increasing number of disorders that may cause hyperthyroxinemia without thyrotoxicosis have been recognized in recent years. These include acquired and inherited abnormalities of serum thyroid-hormone-binding proteins, peripheral resistance to thyroid hormones, acute nonthyroidal illness, acute psychiatric illness, and some drug-induced conditions associated with nonthyrotoxic elevations of serum thyroxine. In addition to the laboratory finding of elevated serum thyroxine levels, many of these syndromes are also accompanied by abnormalities in triiodothyronine and free thyroid hormone levels, as well as unresponsiveness of thyroid-stimulating hormone to thyrotropin-releasing hormone, all of which further erroneously indicate a diagnosis of thyrotoxicosis. An awareness of these syndromes and alterations in the results of thyroid function tests that accompany them is important to prevent a misdiagnosis of hyperthyroidism and inappropriate therapy.

Amiodarone↗
PubMed1983

Familial resistance to thyroid hormone associated with decreased transport across the plasma membrane.

Resistance to thyroid hormone associated with a defect in hormone transport across the plasma membrane occurred in a 74-year-old eumetabolic woman. She had marked elevations in the serum levels of total thyroxine (T4), free T4, and reverse triiodothyronine (rT3). Levels of T3 were only minimally increased. The hyperthyroxinemia was thyrotrophin (TSH) dependent, but was not due to an alteration in the binding of T4 to serum proteins. Refractoriness to thyroxine was only partial, as indicated by the increase in the basal metabolic rate and suppression of the response of TSH to thyrotrophin-releasing hormone (TRH) after the administration of L-thyroxine, 600 micrograms daily, for 3 weeks. The basic abnormality involved a selective decrease of T4 plasma membrane transport shown by in-vitro studies of erythrocytes. Screening of family members showed similar biochemical abnormalities in two other relatives. In this familial syndrome characterized by eumetabolic hyperthyroxinemia, the alteration of thyroid hormone metabolism seems to involve primarily the partition of T4 between the intra- and extracellular spaces.

Adult↗
PubMed1982

Euthyroid familial hyperthyroxinemia due to abnormal thyroid hormone-binding protein.

A family is described in which three members had an elevated total serum thyroxine level and free thyroxine index. Each affected subject was clinically euthyroid and had a normal pulse wave arrival time (QKd), serum triiodothyronine and free thyroxine levels, and a normal serum thyroxine-binding globulin (TBG) concentration. Electrophoresis of their serum with 125I-labeled thyroxine revealed increased thyroxine binding in the albumin region. In addition, this abnormal protein, like thyroxine-binding globulin, bound 125I-labeled triiodothyronine and 125I-labeled reverse triiodothyronine. However, electrophoresis of serum treated by sialidase (neuraminidase) digestion suggested that this abnormal protein is not an anomalous form of thyroxine-binding globulin "buried" in the albumin area. These cases of euthyroid familial hyperthyroxinemia due to an abnormal thyroid hormone-binding protein show that an elevated serum thyroxine level or free thyroxine index is not always sufficient to confirm the presence of thyrotoxicosis.

Child↗
PubMed1982

Investigations into the etiology of elevated serum T3 levels in protein-malnourished rats.

Thyroid function studies and the peripheral metabolism of thyroid hormone were examined in rats fed a low protein diet (9% casein) for 4-8 wk. Compared to animals fed a normal protein diet ad libitum, both the low protein rats and a pair-fed control group weighed less at the end of the study. However, serum total T3 levels were significantly higher only in the protein deficient rats. The elevated serum T3 was not explainable by enhanced peripheral T4 to T3 conversion, as there was no evidence of any change in hepatic or renal 5'-deiodinase activity when homogenates were examined for conversion of T4 to T3, reverse T3 to 3,3'-diiodothyronine, or 3',5'-diiodothyronine to 3'-monoiodothyronine. Neither was there an effect on hepatic T3 receptor maximal binding capacity (204 +/- 24 versus 168 +/- 15 fmol/mg DNA control) or binding affinity (2.07 +/- 0.38 versus 2.49 +/- 0.24 x 10(-10) M control). In two separate experiments the dialyzable fraction of T3 was significantly lower in the low protein group while free T3 concentrations were unchanged or reduced. In contrast, serum total and free T4 were either normal or reduced and dialyzable T4 was unaffected by protein deficiency. We conclude that while serum total T3 is elevated in rats chronically fed a low protein diet, this elevation is not due to enhanced T4 to T3 conversion. Rather, the increased T3 levels can be accounted for by a striking alteration in protein binding to T3. Moreover, the failure to demonstrate similar changes in serum total and dialyzable T4 suggests that in the rat, protein deficiency has different effects on binding to the two major thyroid hormones. Dietary induced changes in serum thyroid hormone binding must be kept in mind in nutrition studies in the rat.

Animals↗
PubMed1982

Effects of thyroid hormone on the insulin receptor in rat liver membranes.

Although many studies have investigated the complex interrelationships between thyroid hormone levels and insulin-glucose secretion and action, there is at present a lack of information concerning the effects of various thyroid hormone levels on insulin receptors. In the present study, rat liver membranes were prepared from control, hyperthyroid [10 micrograms L-T4 (T4)/100 g BW for 14 days], and hypothyroid rats and the binding characteristics of [125I]iodoinsulin to these membranes were studied. In addition, serum T3, T4, glucose, and insulin levels were measured. The mean (+/- SD) serum T4 and T3 levels were higher (P less than 0.05) in the T4-injected rats than in the hypothyroid rats (T4, 9.1 +/- 0.6 vs. 1.7 +/- 0.4 microgram/dl; T3, 144 +/- 18 vs. 30 +/- 16 ng/dl). When compared to controls, glucose levels were higher in the hypothyroid rats (116 +/- 11 vs. 141 +/- 14 mg/dl; P less than 0.05) and were statistically unaltered in thyrotoxicosis. Plasma insulin levels were increased in hypothyroidism (6.5 +/- 0.8 vs. 10.8 +/- 2.9 microU/ml; P less than 0.05) and decreased in thyrotoxicosis (7.5 +/- 0.5 vs. 28.3 +/- 15 microU/ml; P less than 0.05). Despite these alterations, membrane binding and the derived Scatchard plots were not significantly different in the hyperthyroid or hypothyroid groups. In summary, the present studies indicate that plasma membrane insulin receptor number and affinity are unaltered regardless of the thyroid state of the rat.

Animals↗
PubMed1982

The effect of experimental hyperthyroidism and hypothyroidism on 5'-monodeiodination of 3,3',5'-triiodothyronine and 3',5'-diiodothyronine by rat liver and kidney.

To study the effect of alterations in thyroid status on 5'-monodeiodinase activity, conversions of rT3 to 3,3'-diiodothyronine and 3',5'-diiodothyronine (3',5'-T2) to 3'-monoiodothyronine were examined in vitro. Rats were injected either with T4 (10 micrograms/100 g BW, ip, daily for 12 days) to make them thyrotoxic or thyroidectomized to render them hypothyroid, and liver and kidney homogenates were prepared. Liver homogenates from hyperthyroid animals demonstrated a 2-fold increase in 5'-monodeiodination of both rT3 and 3',5'-T2; both reactions were also significantly increased in the kidneys of hyperthyroid rats. Hypothyroidism produced a significant decrease in 5'-deiodination of both rT3 and 3',5'-T2 in liver and kidney homogenates. These data indicate that the in vitro 5'-deiodination of both rT3 and 3',5'-T2 is increased in hyperthyroidism and decreased in hypothyroidism and suggest that these two iodothyronines are metabolized in a similar fashion in rat liver and kidney homogenates in states of altered thyroid function.

Animals↗
PubMed1982

Iodothyronine levels in human cerebrospinal fluid.

Iodothyronines were measured by RIA in concentrated human cerebrospinal fluid (CSF). In measurements performed in one laboratory at a 4-fold concentration of CSF, rT3 was detected in all 30 patients in whom the measurement was attempted and averaged 15.1 +/- 2.8 ng/dl (mean +/- SE). IN an independent laboratory, rT3 measurements at this 4-fold concentration were performed on 11 different samples and averaged 9.3 +/- 0.9 ng/dl, while at a 40-fold CSF concentration, rT3 averaged 13.1 +/- 0.72 ng/dl. CSF T3 values were detected in only 4 of 30 patients as a 4-fold concentration and averaged 8.2 +/- 3.1 ng/dl, while in pooled CSF at a 40-fold concentration, 4 of 4 samples were detectable and averaged 2.6 +/- 0.4 ng/dl. Levels of T4 could only be detected in CSF concentrated 40-fold and averaged 0.22 +/- 0.04 microgram/dl. Values for the percent dialyzable thyronines were 0.44 +/- 0.03% for T4, 4.39 +/- 0.29% for T3, and 0.91 +/- 0.04% for rT3. TSH was detected in CSF concentrated 4-fold, averaging 0.43 +/- 0.05 microunits/ml; in an independent assay with CSF concentrated 40-fold, TSH averaged 0.06 +/- 0.02 microunits/ml. Thyroid binding globulin was undetectable (less than 0.1 mg/dl). We have confirmed the presence of thyroid hormones (T4 and T3) in human CSF and have shown that rT3 is present as well. The role these hormones play in the development, function, and nourishment of the central nervous system and the role the CSF plays in the transport of these hormones into the central nervous system remains to be determined.

Humans↗
PubMed1982

Familial elevations of total and free thyroxine in healthy, euthyroid subjects without detectable binding protein abnormalities.

Elevations of serum thyroxine without thyrotoxicosis or binding protein abnormalities have been documented in 8 of 13 family members, representing 4 generations. This syndrome appears to represent an elevated threshold for the amount of free thyroxine substrate required to maintain adequate T3 production form the peripheral monodeiodination of T4. It reiterates the need for a prudent re-evaluation of all clinically euthyroid patients with elevated serum thyroxine concentrations before concluding that they are indeed thyrotoxic.

Adult↗
PubMed1982

"Hanging from the masthead": reflections on authorship.

Authorship of a scientific article should imply expertise on its content and thorough knowledge of the investigation reported. Because the number of authors per article has dramatically increased, I question whether these criteria for authorship are applied. Another explanation for this increase is that authors add names to the byline without reference to any set of criteria, resulting in the designation of coauthorship when not warranted. The medical community needs to redefine the proper procedure and criteria for deciding on authorship and to strictly abide by these procedures. Specific recommendations center around the protocol as the initial instrument of communication. Who should be designated as author, and the order of names, should be negotiated before and during the study, and written communication with other involved laboratories should result in more appropriate authorship attribution.

Authorship↗