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Biomedical subjects

J M Earll

Publications and source records attributed to J M Earll.

At least 37 records · Page 2Linked to original sources

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↗

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↗

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↗

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↗

Prolactin, thyrotropin, and growth hormone release during stress associated with parachute jumping.

Prolactin, growth hormone, and thyrotropin (TSH) release during the stress of parachute jumping has been evaluated in 14 male subjects. Subjects were studied at several times before and immediately after their first military parachute jump. All three hormones had risen significantly 1 to 14 min after the jump, compared to mean levels measured immediately beforehand. Earlier studies of physical exercise by ourselves and others would suggest that emotional stress played a role in producing changes of this magnitude. We conclude that prolactin, TSH, and growth hormone are released in physiologically significant amounts in association with the stress of parachute jumping.

Adolescent↗

Effect of ethyl alcohol on lonic calcium and prolactin in man.

Earlier animal studies suggested that there might be physiologically significant changes in serum calcium following administration of ethyl alcohol. Ionized and total calcium were measured in five normal male subjects following the oral ingestion of 200cm3 of 50% ethyl alcohol. Although blood alcohols reached intoxication levels in all subjects, no significant change in ionized calcium or total calcium occurred. It is unlikely that alcohol contributes to the risks of hypocalcemia or hyperventilation and anxiety in individuals performing in adverse environments, although there is little question it contributes to other risks. Even though two-fold elevations in plasma prolactin have been described in men with chronic alcoholism, no significant changes in plasma prolactin occurred during acute alcohol ingestion. Awareness of the significant increase in plasma osmolality, which has been demonstrated with alcohol, is important to avoid inappropriate therapy, since individuals performing in adverse environments are at risk of becoming dehydrated.

Adult↗

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↗

Localization of hyperfunctioning parathyroid tissue. Radioimmunoassay of parathyroid hormone on samples from the large veins of the neck and thorax and selectively catheterized thyroid veins.

Radioimmunoassay of parathyroid hormone on samples obtained from the large veins of the neck and thorax was utilized for localization in twenty-one patients with hyperparathyroidism. In seventeen of these patients, as many of the thyroid and mediastinal veins as possible were also sampled. This study reveals that sampling of the large veins of the neck and thorax is an insensitive means of adenoma from hyperplasia. Anatomic variations in the drainage of the inferior thyroid veins and dilution of the parathyroid venous effluent by the large veins of the neck and thorax seem to explain this insensitivity and the occasionally misleading results of large vein sampling. Sampling of the small thyroid veins, however, is a sensitive and specific means of localization and permitted preoperative differentiation of adenoma from hyperplasia in fourteen of our seventeen patients. Communications between the inferior thyroid and thymic veins and the fact that mediastinal adenomas frequently bring their blood supply down from the cerevical area suggest that sampling of the small thyroid veins may be of only limited value in identifying a mediastinal adenoma.

Adenoma↗

Failure of propranolol to alter thyroid iodine release, thyroxine turnover, or the TSH and PRL responses to thyrotropin-releasing hormone in patients with thyrotoxicosis.

A dual isotope method allowing simultaneous analysis of both endogenous thyroidal release and peripheral thyroxine disposal was employed in four patients with thyrotoxicosis before and during propranolol therapy (160 mg/day) to determine whether beta adrenergic blockade with this agent affected the secretion or metabolism of thyroid hormone. Since catecholamines may be involved in the regulation of both thyrotropin (TSH) and prolactin (PRL) release from the pituitary, the effect of propranolol on the TSH and PRL responses to thyrotropin-releasing hormone (TRH) was also examined. In the dosage employed in these patients, propranolol had no demonstrable effect on either thyroid hormone secretion, the peripheral disposal of T4, or the TSH and prl responses to TRH.

Humans↗

Effect of an oral water load on serum TSH in normal subjects, and on TSH and prolactin response to thyrotropin-releasing hormone (TRH) in patients with primary hypothyroidism.

Reports of suppression of plasma prolactin (PRL) in humans by water loading led us to examine the effect of a 20 cc/kg water load on serum TSH in 21 normal volunteers. In addition, the effects of a water load on basal and TRH-stimulated TSH and PRL levels were evaluated in seven patients with primary hypothyroidism. The water load had no effect on pasal serum TSH levels in either normal or hypothyroid subjects, and did not alter the TSH response to TRH in hypothyroid subjects. Basal or TRH-stimulated plasma PRL was also unaffected by water loading in the hypothyrpid subjects. These data suggest that a water load of 20 cc/kg does not significantly affect TSH release by the anterior pituitary, and also provide further evidence that water loading does not consistently suppress PRL secretion.

Administration, Oral↗

Klinefelter's syndrome: examination of thyroid function, and the TSH and PRL responses to thyrotropin-releasing hormone prior to and after testosterone administration.

Thyroid function and prolactin (PRL) responsiveness to thyrotropin-releasing hormone (TRH) were examined in 6 patients with Klinefelter's syndrome prior to and after therapy with testosterone. The thyroid function tests, including serum triiodothyronine (T3), thyroxine (T4), thyroxine binding globulin (TBG), resin T3 uptake (RT3U), radioactive iodine uptake (RAIU), thyrotropin (TSH) stimulation and the TSH response to TRH were normal during both periods of study. Testosterone treatment had no significant effect on any of these parameters with the exception of the RT3U which increased. PRL response to TRH were significantly higher than those observed in normal men (P less than 0.05). Despite the fact that mean plasma PRL responses to TRH were decreased when the patients were restudied during testosterone therapy, they remained greater than those of normal men. Mean serum estradiol concentrations were normal and did not increase significantly during testosterone therapy. These studies suggest that: (1) thyroid function may be normal in patients with Klinefelter's syndrome more often than previously reported, and (2) patients with Klinefelter's syndrome may manifest PRL hyper-responsiveness to TRH that is decreased but not normalized during testosterone therapy. Because estradiol levels failed to increase despite a marked rise in testosterone, further studies are warranted to examine testosterone and estradiol clearance and conversion rates in patients with Klinefelter's syndrome.

Adolescent↗

Evaluation of a rapid and simple technique for the radioimmunoassay of triiodothyronine (T3).

This report compares T3 measurements obtained on the same serum samples by a resinstrip technique and by another existing radioimmunoassay method. The samples analyzed were obtained from a total of 90 subjects who were clinically categorized as hypothyroid, normal, hyperthyroid, or euthyroid while taking estrogen-containing compounds or while pregnant. The correlation coefficient for all 90 sera with these two different techniques was 0.94. All subjects who were clinically euthyroid (32) had a normal serum T3 concentration by the resin-strip technique. Similarly, 23 clinically hyperthyroid patients had elevated serum T3 concentrations and 15 of 17 clinically hypothyroid patients had decreased serum T3 levels.

Contraceptive Agents, Female↗