Frank H. Tyler

Circadian rhythm in serum parathyroid hormone concentration in human subjects: correlation with serum calcium, phosphate, albumin, and growth hormone levels

A circadian variation in serum calcium, albumin and PTH concentration in normal subjects has been demonstrated. The levels of the three blood constituents were remarkably constant during the day, but striking night and early morning changes occurred. Serum calcium levels were highest at 8:00 p.m. and reached a nadir between 2:00 and 4:00 a.m. Serum albumin levels were parallel to those of serum calcium. PTH levels began to rise after 8:00 p.m., reached the highest levels between 2:00 and 4:00 a.m., and fell to baseline values by 8:00 a.m. The nocturnal fall in serum calcium levels appears to be secondary to dilution of serum proteins by increasing blood volume. The nocturnal rise in PTH levels appears to be independent of serum calcium levels within the normal range but it can be abolished by induced hypercalcemia. Serum phosphate levels were lowest between 8:00 a.m. and 10:00 a.m. and highest between 2:00 a.m. and 4:00 a.m. The data presented suggest that circadian changes in serum phosphate levels are not mediated in toto by parathyroid hormone but they are exaggerated when the secretion of this hormone is inhibited. They are independent of growth hormone levels and activity but they are greatly modified during a prolonged fast.

Potency and duration of action of glucocorticoids: Effects of hydrocortisone, prednisone and dexamethasone on human pituitary-adrenal function

Abstract This study was designed to quantitate the relative potencies of orally administered glucocorticoids and to investigate some of the factors affecting their relative potency in normal subjects. Corticosterone was measured in plasma samples obtained at 8 A.M. from eight normal adult subjects, three women and five men, following oral doses of dexamethasone, prednisone and hydrocortisone on the preceding midnight, at 6 P.M. and at 8 A.M. The half-time of disappearance of prednisolone and dexamethasone from plasma and their free concentrations in plasma were also determined. Concentrations of plasma corticosterone and cortisol showed a significant correlation (r = 0.68 to 0.99, p Our data indicate that relative intrinsic biologic potency and relative rates of disappearance from plasma are two of the most important factors in determining the relative glucocorticoid potency of orally administered glucocorticoids.

Studies in disorders of muscle: XII. Myopathy due to the administration of therapeutic amounts of 17-hydroxycorticosteroids

Abstract 1.1. Severe muscular weakness, which occurred during adrenocortical hormone therapy in seven patients, is reported. 2.2. After variable but relatively prolonged periods of administration of 17-hydroxycorticosteroids in comparatively large doses, deep pelvic and lower extremity muscle weakness and muscle atrophy occurred. After therapy was discontinued, muscle strength returned to normal. 3.3. Minimal histologic changes, consisting of scattered areas of muscle vacuolization and proliferation of sarcolemmal nuclei, were found in biopsy specimens of the muscle. 4.4. Increased serum creatine levels and creatinuria accompanied the muscle disorder. 5.5. The effects on creatine excretion of ACTH and 17-hydroxycorticosteroid therapy in patients with progressive muscular dystrophy and inflammatory muscle disease suggest that increased creatine synthesis together with decreased ability to store creatine may be responsible for the creatinuria observed in the patients with steroid myopathy. 6.6. Steroid myopathy may be the limiting factor in the quantity of 17-hydroxycorticosteroids which can be tolerated by certain patients.

Effect of Diphenylhydantoin on the Metabolism of Dexamethasone

Patients on chronic diphenylhydantoin therapy have abnormal plasma corticosteroid and urinary 17-hydroxycorticosteroid responses to low doses of dexamethasone (0.5 mg every six hours for eight dose...

BLOOD LEVELS OF 17-HYDROXYCORTICOSTEROIDS FOLLOWING THE ADMINISTRATION OF ADRENAL STEROIDS AND THEIR RELATION TO LEVELS OF CIRCULATING LEUKOCYTES'

occurrence of neutrophilia and lymphopenia following the administration of ACTH or adrenal cortical extracts to mice. In 1948 these findings were confirmed in man by Hills, Forsham and Finch (2), who noted, in addition, a pronounced fall in eosinophils. These changes in the blood have been used widely as an index of adrenal cortical activity. With the development of a method for the determination of 17-hydroxycorticosteroids in small quantities of blood or plasma (3) it has become possible to determine the relationship of the changes in blood steroid levels to the changes in leukocytes. In order to investigate this relationship, standard doses of various corticosteroids were administered to normal individuals and the alterations in blood 17-hydroxycorticosteroids and in leukocytes were observed at intervals thereafter.

Cushing's syndrome caused by bronchial adenomas

Abstract Two cases of Cushings syndrome caused by ACTH secreting bronchial adenomas are reported. In one ACTH was demonstrated in the tumor by bioassay and in the other by radioimmunoassay. In one patient the adenoma was found at autopsy, in the other the adenoma was discovered at the time Cushings syndrome was recognized. In this latter patient Cushings syndrome disappeared after resection of the tumor. Careful search for such a tumor should be made in every patient thought to have pituitary Cushings syndrome in order to select the most appropriate therapy. Presently available functional studies such as dexamethasone suppression and the response to metyrapone do not distinguish between these patients and those with Cushings syndrome due to excessive pituitary secretion of ACTH.

Electron Spin Resonance Studies of Erythrocytes from Patients with Duchenne Muscular Dystrophy

The membrane organization of the erythrocytes from patients with Duchenne muscular dystrophy was studied by means of electron spin resonance. The fluidity of the membrane near the polar region of Duchenne muscular dystrophy erythrocytes was similar to that of normal erythrocytes. The membrane environment in the nonpolar region, however, was quite different from that of normal erythrocytes, judged by the spectra with 2-(14-carboxytetradecyl) - 2 - ethyl - 4,4 - dimethyl - 3 - oxazolidinyloxyl as probe. The temperature dependence of the ratio of the line height of central field to that at the low field showed two inflection points in normal erythrocytes at pH 7.4 (13.5 degrees -16.5 degrees and 37.5 degrees -40.5 degrees C, respectively) but the inflection point in the lower temperature range was not detected in Duchenne muscular dystrophy erythrocytes. When pH was varied, an abrupt decrease in the ratio was observed at pH 5.9-5.6 in normal erythrocytes whereas there was a gradual decrease over the range of pH from 6.6 to 5.0 in Duchenne muscular dystrophy erythrocytes. The rate of reduction of the radical 2-(3-carboxypropyl)-4,4-dimethyl-2-tridecyl-3-oxazolidinyloxyl by ascorbate in normal erythrocytes was faster than that in Duchenne muscular dystrophy erythrocytes. Treatment of both erythrocytes with phloretin markedly reduced the rate of reduction by ascorbate and eliminated the difference in the two types of erythrocyte. These results indicate that in Duchenne muscular dystrophy the erythrocyte membrane is involved as well as the muscle cell.

Cushing's disease with cure by resection of a pituitary adenoma. Evidence against a primary hypothalamic defect.

Abstract A patient with Cushings disease was treated by transphenoidal resection of a pituitary adenoma. Pituitary-adrenal suppressibility, responsiveness to metyrapone and circadian rhythm were observed postoperatively. Reversion to physiologic regulation after resection of an adenoma implies that the lesion secreted ACTH autonomously (primary hyperpituitarism). Current evidence favors the pituitary adenoma, when present, as the primary etiologic factor in pituitary-dependent Cushings syndrome. Since adenomas occur in a majority of cases, initial therapy is best directed at the pituitary.

Thyroid disease in children. A survey of subjects potentially exposed to fallout radiation

Abstract We found no significant difference in any type of thyroid disease between children in Utah and Nevada exposed to fallout radiation in the 1950s and control groups living in Utah and Arizona at present. Of the 5,179 children surveyed, thyroid abnormalities were found in 201. Adolescent goiter was the most common disorder with a prevalence of 15 per 1,000 for boys and 20 per 1,000 for girls. There were seven cases of hyperthyroidism, and the rates for lymphocytic thyroiditis were 8 and 16 per 1,000 for boys and girls, respectively. Twenty benign neoplasms and two carcinomas of the thyroid were found. Only 6 of the 201 children with thyroid disease knew of their disease prior to our examination. The inapparent thyroid disease discovered in this group of children through meticulous examination may have its counterpart in other populations as well. This study demonstrates the need, therefore, for careful examination of thyroids even in apparently healthy children.

Steroid laboratory tests in the diagnosis of Cushing's syndrome☆

Abstract The best steroid tests currently available for identifying patients with Cushings syndrome are the low dose dexamethasone suppression test with determination of urinary 17-hydroxycorticosteroid (17-OHCS) excretion and the single dose dexamethasone suppression test with determination of plasma 17-OHCS concentration. The results of steroid laboratory tests may be helpful in suggesting the lesion responsible for Cushings syndrome but no single test can be used to identify the cause with great confidence. (1) The high dose dexamethasone suppression test is best for guiding the physician in selecting therapy. In 82 per cent of the patients with Cushings syndrome due to adrenal hyperplasia from excessive pituitary secretion of ACTH unassociated with a pituitary tumor, urinary 17-OHCS excretion decreased to less than half the control value with this test. Suppression of this degree is very uncommon in patients with adrenal tumors. (2) Urinary 17-OHCS excretion increased with metyrapone administration in patients with Cushings syndrome caused by adrenal hyperplasia not associated with tumors whereas this response was infrequent in patients with other causes of Cushings syndrome. (3) In patients with Cushings syndrome, urinary 17-ketosteroids (17-KS) were elevated to values at least four times the upper limit of normal in 52 per cent of the patients with adrenal carcinoma, in 15 per cent of the patients with extrapituitary ACTH-secreting tumors and in only 3 per cent of the patients with adrenal hyperplasia not associated with tumor. Urinary 17-KS levels were normal or low in 69 per cent of the patients with adrenal adenomas and in only 10 per cent of the patients with adrenal carcinomas.