John W. Kendall

The primary empty sella syndrome: Analysis of the clinical characteristics, radiographic features, pituitary function and cerebrospinal fluid adenohypophysial hormone concentrations

Twelve cases of the primary empty sella syndrome were analyzed in regard to clinical findings, roentgenographic features, pituitary function and cerebrospinal fluid adenohypophysial hormone concentration. The findings were compared with those in 247 cases of the primary empty sella syndrome reviewed from the literature in order to determine the major characteristics of this disorder. The majority of patients are obese, multiparous women with normal pituitary reserve, normal visual fields and undetectable adenohypophysiol hormone concentrations in cerebrospinal fluid. In addition occasional patients witll have hypertension, pseudotumor cerebri and cerebrospinal fluid rhinorrhea. Patients who present with the typical features of the primary empty sella syndrome should be evaluated periodically with pituitary function testing, visual field examinations and cerebrospinal fluid adenohypophysial hormone determinations. If these parameters remain normal during careful follow-up studies, the patient is likely to have an empty sella, and pneumoencephalographic and angiographic studies can be avoided.

Kinetic, hormonal and clinical studies with aminoglutethimide in breast cancer

Approximately one‐third of patients with metastatic breast carcinoma respond to surgical ablative therapy but the morbidity associated with these procedures has limited their use to highly selected patients. Consequently, a chemical method of adrenal suppression was developed using a potent inhibitor of adrenal steroid synthesis, aminoglutethimide, in combination with a synthetic glucocorticoid, dexamethasone. While this regimen effectively blocked adrenal function, it was complicated by a drug interaction in which aminoglutethimide accelerated the metabolism and reduced the bioavailability of dexamethasone. To overcome this problem, a new regime using aminoglutethimide and hydro‐cortisone, a glucocorticoid less susceptible to altered metabolism, was developed. Kinetic studies confirmed that aminoglutethimide does not interact with hydrocortisone to alter its rate of metabolism. Hormone measurements established that 1000 mg of aminoglutethimide and 40 mg of hydrocortisone daily suppressed DHA‐sulfate, androstenedione, estrone, estradiol and aldosterone to a greater extent than the prior protocol using aminoglutethimide and 2–3 mg of dexamethasone. Patients experienced objective tumor regression with equal frequency while receiving the aminoglutethimide‐hydrocortisone regimen or aminoglutethimide and dexamethasone and the overall rate of response in 50 evaluable patients was 38%. Side effects occurred frequently in the first few weeks of treatment but disappeared nearly uniformly thereafter. The present aminoglutethimide‐hydrocortisone regimen is simple, non‐toxic, effective in inhibiting estradiol synthesis and capable of inducing tumor regression as frequently as previously reported with adrenalectomy.

Dexamethasone stimulation of running activity in the male rat

Abstract The effect of the synthetic glucocorticoid, dexamethasone-21-phosphate, added to the drinking water (0.1–20 μg/ml), on running wheel activity was studied in male rats. The rats were maintained in standard activity cages in a controlled environment with 12 hr light, 12 hr dark. After 2 weeks of equilibration in the activity cages, dexamethasone was started. One to three days later running activity increased. Peak activity (up to 10 times basal levels) was reached 5–7 days after the onset of dexamethasone. The increase in activity occurred entirely in the nocturnal phase. After stopping dexamethasone, activity continued at levels above the pre-treatment base line for 1–2 weeks if the dose was small (one μg/ml) and duration of dexamethasone administration was short. Selective depression of pituitary-adrenocortical function was produced in other rats by implantation of a cortisol acetate pellet in the median eminence of the hypothalamus. Activity was markedly reduced following implantation and was restored promptly by dexamethasone in the drinking water. It was concluded that dexamethasone markedly stimulates running activity in the rat. Since the increased activity occurs at night, it appears that glucocorticoids affect the magnitude of running activity but not its rhythmicity.

Quantitative and Temporal Studies on Effect of Dexamethasone on Corticosterone Secretion in the Rat.

Summary The rat corticosterone secretion rate determined fluorimetrically from 3-minute samples of adrenal effluent (123 ± 5.3 μg/kg/adrenal/hr) agrees well with values reported for more extended collection periods and analyzed by other methods. Dexamethasone-21-phosphate, a non-fluorescing, corticotropin-suppressing, synthetic steroid was found to produce maximal suppression of the corticosterone secretion rate 4 to 8 hours following a single dose. The technic described may be applied to assays of corticotropin itself or assays of corticotropin suppressing activity of other non-fluorescing agents.

The half-life of endogenous immunoreactive ACTH in rat plasma.

Summary A radioimmunoassay for ACTH in the rat, which has previously been shown to provide close agreement with bioassay, was used to determine the disappearance rate of ACTH from the plasma of male rats following hypophysectomy under ether anesthesia. The calculated half-life of the immunoreactive ACTH was 5 min.

Brain-Dependent ACTH Secretion from Multiple Heterotopic Pituitaries.

Summary Hypophysectomized rats with multiple heterotopic pituitaries have nearly normal adrenal weight and significant, though subnormal, corticosterone secretion. Removal of the entire forebrain, but not decortication, in these animals reduced corticosterone secretion nearly to values found in hypophysectomized control animals. These results indicate that heterotopic pituitary ACTH secretion is dependent on some subcortical portion of the forebrain.

Uterine concentration of thyroxine during the estrous cycle.

Summary Uterine ability to concentrate 131I-thyroxine in female rats during various stages of the estrous cycle was studied. Uteri from metestrous rats had the highest concentration of radioactivity. Uptake during diestrus although less than metestrus was significantly greater than during proestrus or estrus.