Louis J. Soffer

Role of Mucopolysaccharides in Pathogenesis of Experimental Exophthalmos.

Summary The development of experimental exophthalmos in the guinea pig is dependent on the accumulation of large quantities of intercellular ground substance and water in the connective tissue of the orbital contents. This is evidenced by the presence of considerable amounts of metachromatic material, of which hyaluronic acid is an important component, and by an increase in the hexosamine and water content of these tissues. This is similar to the changes observed in localized myxedema in man, and suggests a common mechanism for the two conditions.

Role of adrenal in uptake of I131 by the thyroid following parenteral administration of epinephrine.

In a previous paper 1 we reported that the parenteral injection of epinephrine into both the intact and the totally thyroidectomized dog resulted in an increase in secretion of thyrotropin from the adenohypophysis. In the intact dog this was evidenced by the development of hyperplastic changes in the thyroid following the daily injection of adrenalin-in-oil. Serum obtained from similarly treated totally thyroidectomized animals, when injected subcutaneously into young guinea pigs not exceeding 200 g in weight, resulted in hyperplastic changes in the thyroids of the treated guinea pigs. It was further reported that the increase in circulating thyrotropic factor resulting from the injection of epinephrine in totally thyroidectomized dogs reached its peak approximately 4 to 6 days following the beginning of treatment, and thereafter began to diminish despite the continued injection of epinephrine. The present report is concerned with a study of the role of the adrenals in the above described phenomena. In place of the biological assay method previously employed for the determination of circulating thyrotropin, we used the percentage uptake of parentally administered I131 as an index of thyroid activity. This technique has the relative advantages of simplicity and a higher degree of accuracy over the biological assay method. Methods. Male rats of the Wistar strain (Carworth Farms) weighing approximately 125 g were employed. They were placed on a low iodine, minimally goitrogenic (Steenboch) diet∗ for at least 3 weeks before being used experimentally in order to insure an adequate uptake by the thyroid gland of I131. 2 In the adrenalectomy experiments, rats of the Sprague-Dawley strain were also employed because of the reported lesser frequency of accessory adrenal tissue. The experiments were planned to study the 24-hour percentage uptake of parenterally administered I131 by the thyroid gland after the administration of epinephrine in the intact and in the adrenalectomized animals.

Metabolism of Corticotropin in Man.

Summary Synthetic beta1-24 corticotropin has been labeled with I131 and intravenously administered to normal subjects. Analysis of the blood radioactivity following intravenous administration of beta1-24 corticotropin-I131 revealed that this substance has an apparent space of distribution of 43% of the body weight and a plasma half-life of 7 minutes.

Effect of Iodine and Adrenalin on Thyrotropin in Graves'Disease and in Normal and Thyroidectomized Dogs

This study deals with (1) the evaluation of the amount of circulating thyrotropic factor in clinical hyperthyroidism, (2) the effect of iodine on such circulating thyrotropic factor, and (3) the influence of the parenteral injection of adrenalin on thyrotropic discharge from the anterior pituitary in the intact and the totally thyroidectomized experimental animals. Method. Biological assay was used for the determination of thyrotropic factor. This technic involves histological examination of the thyroids of young guinea pigs not exceeding 200 g in weight, following subcutaneous injection of 5 cc of serum from the patient or experimental animals. The guinea pigs were injected on 2 successive days and were killed with ether 24 hours after the last injection. The thyroid lobes were then removed, fixed in 10% formalin, and stained with hematoxylin-eosin. The thyroids were then examined for hyperplastic changes. Following the injection of varying amounts of pure thyrotropic factor there occur changes in the thyroid characterized by a decrease in the amount of colloid in the follicles an increase in the height of the cells lining the acini, a decrease in the size of the alveoli, and not infrequently mitosis may be observed.1-4 These findings are not dissimilar to those observed in the thyroids of patients with Gravesdisease. The amount of circulating thyrotropic factor in the serum of our patients and experimental animals was determined on the basis of the criteria just outlined. Specimens of blood were obtained from patients with Gravesdisease before treatment and again on the 2nd, 4th, 6th, 8th, and 11th days after lugolization was started. Five cc of the serum was injected into the guinea pigs on 2 successive days. The animals were killed 24 hours later and their thyroids promptly removed. On several patients samples of blood were also obtained on the 2nd, 4th, and 6th days, after subtotal thyroidectomy.

Effect of Adrenocorticotropin on Thyroidal Collection of I131 in the Adrenalectomized and Intact Rat.

Summary The administration of adrenocorticotropin results in a decreased collection of I131 by the thyroid gland of both the intact and adrenalectomized rat, suggesting that adrenocorticotropin inhibits the adenohypophyseal secretion of thyrotropin.

Urinary gonadotropin-inhibiting substance in Stein-Leventhal syndrome and other anovulatory states

Abstract Gonadotropin-inhibiting substance has been demonstrated in the urine of normal children and adults. It specifically inhibits gonadotropins with primarily LH-like effect while exercising no inhibition against FSH, estrone, or testosterone. “Inhibitor” has been detected in varying concentrations throughout the normal menstrual cycle, with the exception of days 7 to 9 where no inhibition could be demonstrated. In a total of 14 patients with classical Stein-Leventhal syndrome, low to nondetectable levels of “inhibitor” were consistently demonstrated. These findings are in contrast to those obtained in patients with other anovulatory conditions where significant inhibition was consistently observed.

Gonadal influences on erythrocyte reducing capacity in the adult male.

Summary The effect of an intravenous infusion of sodium thiosulfate on erythrocyte reducing capacity was determined in 8 male patients with disturbances of gonadal function. A reductivity index was then determined for each patient which is inversely proportional to the erythrocyte reducing capacity. In 5 patients with reduced urinary gonadotrophin titers, the reductivity index was significantly higher than that of normal males. In the 3 remaining patients with normal or elevated urinary gonadotrophins, there was a normal or equivocally elevated reductivity index. These results indicate that hypogonadism in the human male may be associated with a decrease in reducing capacity of the red blood cell. This probably reflects an inadequate activity of reduced glutathione in the erythrocyte.

Influence of Sodium Thiosulfate on Reducing Capacity of Human Erythrocytes in vivo.

Summary Reducing capacity of erythrocytes has been measured. Followng intravenous infusion of sodium thiosulfate, there occurs a significant diminution in this capacity. A reductivity index (R.I.) was established relating diminution in this capacity with amount of sodium thiosulfate infused. R. I. of erythrocytes of women is more than double that of normal men. Preliminary studies suggest that estrogen and androgen may influence R.I.

Medical Problems Associated With Pituitary Surgery

The main medical problems associated with pituitary lesions or pituitary surgery are hypopituitarism and diabetes insipidus. Hypopituitarism is manifested by hypogonadism, hypothyroidism and, in some cases, hypoadrenocorticism. Replacement therapy is necessary to correct the hormonal deficiencies arising from dysfunction of the three target glands. Management of diabetes insipidus consists primarily of administration of antidiuretic hormone.

Gas Chromatographic Method for the Determination of Testosterone in Human Urine

Clinical evaluation of hyperandrogenic states and gonadal function has been facilitated with the development of techniques for the microquantitative determination of testosterone in plasma and urine. Recently, we have devised a GLC method for analysis of testosterone glucuronide in urine and have utilized it as an ancillary test for the study of normal gonadal function and in patients with various endocrinopathies (1, 2).