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Biomedical subjects

K D Burman

Publications and source records attributed to K D Burman.

At least 163 records · Page 9Linked to original sources

Failure of 3,3'-diiodothyronine administration to alter TSH and prolactin responses to TRH stimulation.

In order to determine whether elevations in serum 3,3'-diiodothyronine (3,3'T2) concentrations influence the hypothalamic-pituitary--thyroid axis, thyrotropin (TSH) and prolactin responses to thyrotropin-releasing hormone (TRH) were assessed in five patients both prior to and during 3,3'T2 administration. Mean (+/- SE) peak TSH responses to TRH were 168 +/- 64 microU/ml during 3,3'T2 administration and 168 +/- 65 muU/ml during 3,3'T2 administration. Mean basal and peak prolactin concentrations after TRH were 6 +/- 3 ng/ml and 54 +/- 26 ng/ml, whereas during 3,3'T2 administration the basal and peak prolactin levels were 6 +/- 2 ng/ml and 55 +/- 28 ng/ml, respectively. Hypothyroid rats administered triiodothyronine (10 migrogram b.i.d.) for 5 days had a mean TSH response to TRH stimulation of 0.051 +/- 0.003 mU/ml, whereas rats to whom saline or 3,3'T2 (50 microgram b.i.d.) had been given for the same time interval had mean TRH-induced TSH responses of 1.127 +/- 0.179 mU/ml and 1.324 +/- 0.286 mU/ml, respectively. None of the TSH or prolactin responses to TRH, in either human or rat studies, were apparently altered by 3,3'T2. These observations suggest that elevation of serum 3,3'T2 levels are not associated with alterations in the hypothalamic--pituitary--thyroid axis in the experimental systems employed.

Animals↗

Recent developments in thyroid hormone metabolism: interpretation and significance of measurements of reverse T3, 3,3'T2, and thyroglobulin.

The development of specific radioimmunoassays has allowed measurements of 3,3',5'-triiodothyronine (reverse T3), 3,3'-diiodothyronine (3,3'T2), and thyroglobulin to be performed in serum and in various biological fluids both in normal and in altered states of thyroidal economy. The physiology, kinetics, and metabolic actions of reverse T3, 3,3'T2 and thyroglobulin are reviewed. Presently, it appears that reverse T3 and 3,3'T2 measurements in amniotic fluid and cord serum may potentially be useful in diagnosing fetal or neonatal thyroid dysfunction, and serum thyroglobulin measurements appear to be important as a measure of the efficacy of treatment of patients with differentiated thyroid carcinoma.

Amniotic Fluid↗

Parameters of thyroid function in patients with active acromegaly.

In order to determine if acromegaly per se may be associated with abnormalities in thyroidal economy, serum thyroxine-binding globulin (TBG), resin T3 uptake, total and free T4, T3, and reverse T3 concentrations were measured in 21 patients with active acromegaly. Mean (+/- SE) total T4, T3, and reverse T3 levels were 7.1 +/- 0.2 microgram/dl, 111 +/- 4 ng/dl, and 45 +/- 2 ng/dl, respectively, and the mean TBG concentration was 3.6 +/- 0.2 mg/dl. Similarly, mean free T4, T3, and reverse T3 concentrations were 2.4 +/- 0.09 ng/dl, 383 +/- 22 pg/dl, and 118 +/- 7 pg/dl, respectively. None of these values is significantly different from normal and the thyrotropin response to thyrotropin-releasing hormone was also normal. In contrast to several earlier reports, these data suggest that parameters of thyroid function are generally normal in patients with active acromegaly.

Acromegaly↗

Serum triiodothyronine in undernourished rats: dependence on dietary composition rather than total calorie or protein intake.

Serum triiodothyronine (T3) in rats did not change if food intake was restricted without altering the composition of the diet. Feeding a hypocaloric low-protein high-carbohydrate diet caused increases in serum T3, while feeding a hypocaloric high-protein low-carbohydrate diet caused decreases in serum T3. These changes were not related to reductions in intake of either calories or protein, and concomitant changes in serum thyroxine (T4) were not observed. Reduction in the dietary content of valine, without changes in the percentage of carbohydrate in the diet, caused increases in serum T3 when compared to growth-matched controls on a diet with normal valine concentration. Serum T3 in undernourished rats depends on the composition of the diet and not on total intake of calories or protein.

Animals↗

Metabolic clearance and production rates of 3,3',5-triiodothyronine in hyperthyroid, euthyroid, and hypothyroid subjects.

To further elucidate the peripheral metabolism of rT3 and to determine if rT3 production rates vary directly with thyroid function, we measured the disappearance of [125I]rT3 in thyrotoxic and hypothyroid subjects as well as in athyreotic patients maintained eumetabolic on exogenous T4. Kinetic parameters were determined by noncompartmental analysis, and serum concentrations of rT3 and T4 were determined by specific RIAs. In six hyperthyroid, seven euthyroid, and six hypothyroid subjects, the MCRs were 190.7 +/- 15.7, 111.7 +/- 13.2, and 71.8 +/- 7.0 liters/day kg, respectively (mean +/- SE). Production rates (PR) for these same groups were 271.3 +/- 40.5, 51.7 +/- 9.1, and 4.3 +/- 0.6 micrograms/day/70 kg. The observed differences in MCR and PR among the three study groups were highly significant (P less than 0.002). These data indicate that in comparison to euthyroid subjects, rT3 PR and MCR are increased in thyrotoxic and decreased in hypothyroid individuals.

Adult↗

A radioimmunoassay for 3',5'-diiodothyronine.

The present report describes a RIA for 3',5'-diiodothyronine (T2) that can be performed on unextracted serum and which has a lower limit of detectability of 2 ng/dl. Cross-reactivity with other iodothyronines was negligible, except for rT3 which began to demonstrate cross-reactivity when rT3 levels were elevated to 180 ng/dl. Employing this RIA for T2, we have determined that 83 healthy individuals had a mean (+/-SE) serum T2 concentration of 5.0 +/- 0.3 ng/dl, thyrotoxic subjects (n = 12) had a mean T2 level that was elevated to 10.8 +/- 0.8 ng/dl, and each of 6 hypothyroid subjects had undetectable (less than 2 ng/dl) concentrations. Athyreotic patients (n = 8), receiving 0.4 mg T4 daily, had serum T2 concentrations of 15.0 +/- 3.0 ng/dl. Fasting in obese subjects was associated with an increase in serum T2 to 6.9 +/- 0.6 ng/dl from a basal level of 4.4 +/- 0.4 ng/dl in the fed state (P less than 0.01). Despite the fact that rT3 levels may be elevated in amniotic fluid and that rT3 is expected to represent the major source from which extrathyroidal T2 arises, T2 levels were low in amniotic fluid, being undetectable (less than 2 ng/dl) in 9 of 19 samples; the mean (+/-SE) T2 concentration in the 10 detectable samples was 5.4 +/- 1 ng/dl. These data indicate T2 is a normal component of serum and that the majority of serum T2 is probably derived from peripheral conversion. Furthermore, these observations suggest that situations associated with elevated rT3 levels (e.g. thyrotoxicosis and fasting) may also have increased T2 values.

Amniotic Fluid↗

Reduction in hepatic triiodothyronine binding capacity induced by fasting.

Triiodothyronine (T3) receptor kinetics were determined in liver nuclei isolated from fasting and fed rats. The results indicate that although affinity equilibrium constants (Ka) did not differ in the two groups, mean (+/- SE) maximal binding capacity (MBC) was reduced significantly to .30 +/- .05 nM/mg DNA in fasting compared to .46 +/- .07 nM/mg DNA (p less than .01) in the fed state. This observed decrease in MBC during fasting apparently could not be accounted for by a differential rates of loss of either DNA or of the receptor during the period of incubation.

Animals↗

Studies on the nature of thyroidal suppression during acute falciparum malaria: integrity of pituitary response to TRH and alterations in serum T3 and reverse T3.

The nature of the suppression of the pituitary-thyroid axis during infection was studied by testing the integrity of thyrotropin (TSH) and prolactin (PRL) responses to thyrotropin-releasing hormone (TRH) during acute falciparum malaria in human volunteers. During infection, TSH responses to TRH were found to be intact while PRL secretion was slightly increased. That serum T3 levels abruptly declined during infection while serum T4 was stable or increasing suggested an alteration in peripheral degradative pathways and prompted the measuremnt of reverse T3. Changes in serum T3 concentration were found to be accompanied by reciprocal changes in reverse T3. These observations allow some clarification of previously unknown aspects of thyroidal economy during infection.

Humans↗

A radioimmunoassay for 3,3',5'-L-triiodothyronine (reverse T3): assessment of thyroid gland content and serum measurements in conditions of normal and altered thyroidal economy and following administration of thyrotropin releasing hormone (TRH) and thyrotropin (TSH).

The present report describes the development of a radioimmunoassay for 3,3',5'-L-triiodothyronine (reverse T3) which is performed on unextracted serum. Utilizing this radioimmunoassay, 21 normal subjects had a mean (+/-SD) serum reverse T3 level of 60 +/- 12 ng/100 ml, 17 of 19 hyperthyroid patients had elevated serum reverse T3 levels, and 10 of 11 hypothyroid subjects had decreased serum reverse T3 concentrations. Thyroidal secretion of reverse T3 was assessed by measurements in samples obtained from the internal carotid artery and jugular vein of sheep following the administration of thyrotropin releasing hormone (TRH) or bovine thyrotropin (TSH). Reverse T3 levels were increased 45-60 min after TRH administration, but TSH administration produced inconsistent alterations in reverse T3, although 18 of 27 samples obtained after TSH injection were higher than their average respective baseline concentration and the mean peak reverse T3 level was 14% higher than baseline. Following TRH administration to 10 normal human subjects, mean serum reverse T3 levels significantly increased from 53.6 ng/100 ml to 56.3ng/100 ml (P less than .05). The thyroid gland content of reverse T3 in human autopsy material was 6.5 +/- 1.5 microng/g tissue. Both pregnancy and estrogen administration were associated with increases in serum reverse T3 concentrations presumably because of their ability to augment thyroxine binding globulin synthesis.

Adult↗

Solitary autonomous thyroid nodules: comparison of fluorescent and pertechnetate imaging.

Twelve patients with solitary autonomous thyroid nodules were scanned with [99mTc] pertechnetate and by fluorescent imaging. Nodular dimensions were essentially identical on the two types of scans, but the relative scan densities in the nodular versus extranodular areas demonstrated striking differences. In 11 of the 12 patients, the ratio of nodular-to-extranodular radiotracer accumulation was significantly higher than the ratio of nodular-to-extranodular iodine content. In two patients with no demonstrable extranodular radiotracer accumulation by initial pertechnetate scan, extra-nodular tissue was demonstrated by fluorescent imaging. In such cases, fluorescent scanning may eliminate the need for a second radionuclide scan following TSH stimulation to visualize the extranodular tissue. Fluorescent scanning offers a unique new method for aiding the evaluation of patients with suspected autonomous nodules, and can facilitate the diagnosis in some cases. The maintenance of relatively uniform iodine concentration between nodular and extranodular tissues is an intriguing finding that bears further investigation.

Adolescent↗

Resin hemoperfusion: a method of removing circulating thyroid hormones.

The ability of an extracorporeal hemoperfusion system employing neutral Amberlite resin to bind thyroid hormone and to decrease circulating levels of triiodothyronine (T3), thyroxine (T4), and free thyroxine (FT4) was evaluated in dogs made thyrotoxic by the intramuscular administration of thyroid hormone. Since the resin column and tubing were charged with saline, the effects of hemodilution from this source on serum T3 and T4 was assessed by control perfusion through a column which did not contain any resin. After correction for hemodilution, the mean serum T3, T4 and FT4 decreased during 2 hours of resin hemoperfusion by 39%, 35%, and 46%, respectively. Hormonal clearance rates were calculated in two experiments and the estimated net hormone removed averaged 60.4 mug of T3 and 1990 mug of T4. Hematologic indices and routine chemistries did not change significantly in these dogs during the procedure except for a decrease in mean serum albumin concentration and an increase in mean serum glucose concentration. Hemoperfusion through this resin system seems to be a safe, effective means of decreasing serum T3, T4, and FT4 in thyrotoxic dogs and warrants evaluation for the treatment of thyroid storm in man.

Animals↗

Sensitivity to lithium in treated Graves' disease: effects on serum T4, T3 and reverse T3.

Seven patients judged to be euthyroid following treatment of diffuse toxic goiter were studied to determine if they were susceptible to lithium induced hypothyroidism. Lithium carbonate was administered for 4-7 weeks in a dosage (900 mg/day) which maintained serum lithium levels between 0.5-1.0 mEq/l. Blood was obtained weekly for the determination of serum 3,5,3'-triiodothyronine (T3), thyroxine (T4), 3,3',5'-TRIIODO-L-thyronine (reverse T3, rT3) and thyrotropin (TSH). Values observed during lithium therapy were compared to those obtained prior to, and approximately one week after discontinuing lithium. During the pretreatment preiod, mean (+/- SE) serum T3, T4, and rT3 concentrations were 130 +/- 21 ng/100 ml, 7.6 +/- 0.4 mug/100 ml and 48 +/- 8 ng/100 ml, respectively, and decreased during lithium administration with the lowest T3, T4 and reverse T3 concentrations of the lowest T3, T4 and reverse T3 concentrations of 92 +/- 8 ng/100 ml, 4.9 +/- 0.6mug/100 ml, and 33 +/- 6 ng/100, ml, respectively, being reached between the fourth and sixth weeks of study. Thereafter, and in spite of continued treatment with lithium, values for serum concentrations of T3, T4, and rT3 plateaued, or actually increased in 4, 6, and 5 subjects, respectively. Serum TSH concentrations remained 3.0 muU/ml or less throughout the study in 6 patients; 2 of these subjects had no TSH response to thyrotropin-releasing hormone (TRH), even though they had been euthyroid for 3 and 10 months. These data suggest that patients euthyroid following treatment of diffuse toxic goiter display sensitivity to the antithyroid effects of lithium. Furthermore, these observations support the thesis that the inhibitory effects of lithium and iodine upon thyroid hormone synthesis or secretion may involve a similar mechanism of action since increased thyroidal iodine content may be a consequence of therapy with either agent.

Adult↗

Measurement of 3,3',5'-Triiodothyroinine (reverse T3), 3,3'-L-diiodothyronine, T3 and T4 in human amniotic fluid and in cord and maternal serum.

In order to assess fetal function at term, we have investigated parameters of thyroid hormone secretion and degradation in human amniotic fluid and in cord and maternal sera at delivery. The parameters measured included 3,3' L-diiodothyronine (3,3'T2), 3,3',5'-triiodothyronine (reverse T3), 3,3',5'-triiodothyronine (T3), thyroxine (T4), dialyzable T3 and T4, thyroxine binding globulin (TBG),and total iodine. The mean (+/- SE) 3,3'T2 concentrations in cord sera, amniotic fluid, and maternal sera were 20 +/- 1 ng/100 ml, 20 +/- 2 ng/100 ml,and 27 +/- 3 ng/100 ml, respectively. The normal range of this metabolite in the sera of non-pregnant adult subjects was 7 to 29 ng/100 ml. The mean (+/- SE) concentration of reverse T3 was higher in cord sera (315 +/- 16 ng/100 ml), amniotic fluid (82 +/- 25 ng/100 ml) and maternal sera (79 +/- 5 ng/100 ml) than in the sera of normal subjects (mean +/- 2 SD; 60 +/- 12 ng/100 ml). In amniotic fluid, T3, T4, and TBG were low, per cent dialyzable T3 and T4 were increased, and iodine concentrations were relatively normal in comparison to their respective serum levels in euthyroid adults. Since T3 and T4 were low in amniotic fluid our data indicate that measurements of 3,3'T2, reverse T3, or per cent dialyzable T3 and T4 in amniotic fluid would be the potentially most useful in establishing the diagnosis of congenital hypothyroidism before birth. In addition, these studies demonstrate that 3,3'T2 is normally present in the peripheral circulation and suggest that reverse T3 is the major source of 3,3'T2 in both amniotic fluid and cord blood.

Amniotic Fluid↗

Ionized and total serum calcium and parathyroid hormone in hyperthyroidism.

Total and ionized calcium concentrations as well as parathyroid hormone levels were measured in a group of hyperthyroid persons. Ionized and total calcium levels were elevated in 21 of 45 (47%) and in 12 of 45 (27%) thyrotoxic patients, respectively. Mean ionized and total calcium levels were higher in these 45 patients than in normal persons. Using two different radioimmunoassay systems for a total of 44 determinations, mean parathyroid hormone levels were lower in thyrotoxic patients than in subjects with proved hyperparathyroidism. These data suggest that [1] elevations of both ionized and total calcium concentrations occur frequently in thyrotoxic patients; [2] ionized calcium concentrations may be elevated in a higher percentage of hyperthyroid subjects than are total calcium concentrations; and [3] the hypercalcemia associated with thyrotoxicosis is not associated with elevated parathyroid hormone levels.

Calcium↗

Hemiagenesis of the thyroid gland.

Three patients with hemiagenesis of the typhoid gland are described. One was clinically euthyroid, whereas the other two were more unusual in that one had coincident Graves' disease with thyrotoxicosis, and one had primary myxodema. In all three cases diagnosis of hemiagenesis was established by the administration of thyroid-stimulating hormone (TSH). The literature on hemiagenetic thyroid glands with and without associated thyroid disease is reviewed. Although the anomaly is uncommon, awareness and recogniton of its existence may clarify an otherwise puzzling clinical thyroid evaluation, and thus possible avert an unnecessary surgical procedure.

Adult↗