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Biomedical subjects

L Wartofsky

Publications and source records attributed to L Wartofsky.

At least 145 records · Page 8Linked to original sources
PubMed1978

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↗
PubMed1978

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↗
PubMed1978

Quantitative thyroid fluorescent scanning: technique and clinical experience.

A method for quantifying thyroid gland iodine content using a modified fluorescence scanning system is described. The technique does not require a computer. Two single channel analyzers and digital scalers are used to determine net counts from iodine k-alpha x-rays and system response in counts per milligram is calibrated from studies of known quantities of iodine placed in thyroid phantoms. Fluorescence quantification of thyroid gland iodine content was performed in 250 patients with a wide variety of thyroid disorders. Thirty euthyroid patients judged to have no evidence of thyroid disease averaged 10.1 +/- 3.9 mg glandular iodine. Results for several major diagnostic categories were: untreated Graves' disease, 28 patients, 24.4 +/- 9.9 mg; diffuse euthyroid goiter, 14 patients, 16.1 +/- 7.4 mg; primary hypothyroidism, seven patients, 0.5 mg; and nontoxic multinodular goiter, 28 patients, 7.3 +/- 4.1 mg. Follow-up studies on patients treated for Graves' disease both medically and with 131I generally revealed elevated iodine contents in persistently hyperthyroid patients, lower than normal average amounts in euthyroid patients, and only trace amounts in hypothyroid patients. Although the clinical role of fluorescence iodine quantification remains to be fully established, the technique provides information not otherwise available on an important parameter of thyroid status.

Fluorescence↗
PubMed1977

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↗
PubMed1977

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↗
PubMed1977

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↗
PubMed1977

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↗
PubMed1976

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↗
PubMed1976

Effect of acute increases in serum triiodothyronine on TSH and prolactin responses to TRH, and estimates of pituitary stores of TSH and prolactin in normal subjects and in patients with primary hypothyroidism.

Previous investigators have shown that daily administration of TRH to normal individuals leads to diminishing TSH responses which were believed due to rising serum T3 with subsequent feedback inhibition of the pituitary. Patients with primary hypothyroidism were examined in the present study to test this hypothesis, since their T3 cannot increase after TRH. Bi-daily TRH (100 mug) was given to 4 patients for 3 consecutive days, and repeated on a 4th day following oral T3 (50 mug). TSH and PRL responses were unchanged during these 3days of serial TRH and were unaltered by T3 administration on the fouth day. In 5 other hypothyroid subjects studied before and during 3 consecutive days of T3 administration, TSH but not PRL responses to TRH appeared to decrease slowly but progressively. These observations led us to re-examine TRH responses in normal subjects given T3, since other workers had reported that 50 mug T3 completely abolished TSH response. Responses to TRH in 11 normals on a control day were compared to those observed 1 hour after oral T3. In spite of marked increases in serum T3, there was no significant difference between the mean TSH responses of the two studies.

Clinical Trials as Topic↗
PubMed1976

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↗
PubMed1976

Isolated thyrotropin deficiency with thyrotropin-releasing-hormone induced TSH secretion and thyroidal release.

A patient with isolated thyrotropin (TSH) deficiency was studied. Prior to treatment with thyroid hormone, administration of thyrotropin releasing hormone (TRH) produced no increment in serum TSH and a normal increase in plasma prolactin (PRL). In order to explore whether physiologic increases in serum TSH might be occurring below the limits of detectability of TSH by radioimmunoassay, a double isotope technique of assessing thyroidal secretion secondary to release of TSH was employed. The patient was restudied seven months later, after discontinuing thyroid hormone replacement therapy for two months, and on this occasion repeat TRH administration produced small increments in serum TSH. After administration of 125I and 131I-T4 to assess thyroid hormone secretion, TRH was infused continuously for 6 h. Small increases in serum TSH were again observed, along with significant increases in PG125I/PB131I and urinary 125I/131I, reflecting increased thyroidal iodine secretion, although serum T3 and T4 did not change. These studies indicate that: 1) isolated TSH deficiency need not be complete and may be associated with detectable levels of immunoassayable TSH; 2) the TSH released possesses in vivo biological activity; and 3) therapy with thyroid hormone may have facilitated TSH release.

Adult↗
PubMed1976

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↗
PubMed1976

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↗
PubMed1976

Hypothyroidism after x irradiation to the neck: three case reports and a brief review of the literature.

Three patients who developed hypothyroidism after x irradiation to the neck are presented. The first two cases demonstrate that patients can develop clinical and chemical hypothyroidism after a very short interval following radiotherapy. Hypothyroidism developed in the first patient in the absence of surgical manipulation of the neck, or a large iodine load 4 months after receiving 6800 rad of x-ray therapy to his neck for carcinoma of the larynx. The second patient developed hypothyroidism approximately 6 months after his radiotherapy for carcinoma of the esophagus. Both of these patients demonstrated high titers of serum antithyroid antibodies. A third patient with Hodgkin's disease did not manifest clinical symptoms and signs of hypothyroidism until 6 years after radiation therapy. These cases demonstrate the variability of onset of hypothyroidism after radiotherapy and emphasize the need for careful evaluation of thyroid function before and after neck irradiation.

Adult↗
PubMed1975

Acromegaly. Treatment by transsphenoidal microsurgery.

Serum growth hormone levels, thyroid function, and adrenal function were measured before and after surgery in 16 of 17 acromegalic patients undergoing undergoing transnasal transsphenoidal microsurgery of the pituitary. Thirteen patients have been followed up for 12 to 24 months; three patients have been followed up for three to six months. Serum growth hormone levels decreased to less than 5 ng/ml in seven of nine previously untreated patients; thyroid and adrenal function were preserved in eight of these nine patients. In seven patients treated previously by other modes of therapy, growth hormone levels after transsphenoidal surgery decreased to less than 5 ng/ml in three, to between 5 and 10 ng/ml in three, and from 98 to 41 ng/ml in one. Preoperative adrenal function was normal in six of these seven patients and was preserved in four; thyroid function was normal in five patients preoperatively and was preserved in three. Transsphenoidal microsurgery appears to offer an effective means of lowering growth hormone levels and a possiblity of preserving any remaining normal pituitary function. It may be considered for initial treatment in selected patients in whom more rapid arrest of acromegaly is indicated.

Acromegaly↗