No abstract

The 24-hour pattern of plasma cortisol concentration in four patients on the day before major elective surgery was compared with that of five similarly hospitalized control subjects to study the effect of the expectation of surgery on the secretion pattern. Using an indwelling venous catheter, which extended outside the patient's room, to collect blood samples every 20 minutes for 24 hours, it was found that cortisol was secreted episodically in both control subjects and presurgical patients. The nychthermal patterns of plasma cortisol concentration in the two groups were indistinguishable for most of the day despite the occurrence of intermittent events which appeared to cause anxiety in the presurgical patients. However, between 9 PM and 11 PM, while each presurgical patient was being preoperatively prepared (body shaving, wash, and enema), a major pulse of cortisol secretion occurred, raising the plasma cortisol concentration to between 6.9-10.5 standard deviations above that of the control subject mean for that time of day. We conclude that 1) expectation of a major surgical procedure for several weeks does not result in chronic activation of the pituitary-adrenocortical axis, 2) many discrete anxiety-provoking events do not evoke cortisol secretory episodes, 3) most episodes of cortisol secretion are part of an endogenous cyclical pattern with a circadian distribution and are not a direct result of environmental stimuli, and 4) preoperative preparation evokes a major cortisol secretory response in patients awaiting surgery. Whether that release of cortisol is a response to the physical manipulations or the psychological implications of that stimulus is presently unknown.

Cytokines, which include interferons (IFNs), interleukins (ILs), and tumor necrosis factor (TNF), are immunoregulatory proteins produced by lymphocytes and inflammatory cells. Several cytokines, most noteworthy IFNs and ILs, stimulate glucocorticoid secretion. In this study, the effects of variable doses and repetitive administration of IFNs and TNF on secretion of pituitary hormones and cortisol were measured. Patients were given for a period of 15 days on alternating days injections of IFN-beta (IFN-beta ser), 90 or 450 x 10(6) IU, IFN-gamma, 0.1-100 x 10(6) IU, or TNF 125-275 micrograms/m2. Sixty to 120 min after IFN-beta ser injection median levels of cortisol, adrenocorticotropin (ACTH), prolactin (PRL), and growth hormone (GH) rose two-fold. Urinary free cortisol excretion increased significantly during the day following IFN-beta ser administration. IFN-gamma > or = 30 x 10(6) IU caused a comparable rise in plasma cortisol. TNF induced two- to four-fold increases in ACTH and cortisol. The fact that increased cortisol secretion was associated with a rise in the level of ACTH as well as PRL and GH suggests that the cytokines increased cortisol by stimulating the anterior pituitary. The hormonal response induced by cytokines was unrelated to their pyrogenic effect, undiminished with repetitive treatment, and not dose-dependent above a threshold level. These observations reinforce the concept of a physiologic link between the immune system and the hypothalamic-pituitary-adrenal (HPA) axis.

1. The effect of progesterone on renal haemodynamics and intrarenal sodium handing was evaluated in thirteen normal men on a constant diet. Clearances were measured during maximal water diuresis and again 4-7 days later, this time 3 h after progesterone was given intramuscularly. Seven additional studies were performed 3 days after progesterone administration. Another four tests were performed on volunteers who had manifested renal 'escape' from the sodium-retaining effect of deoxycorticosterone acetate. 2. In acute progesterone studies glomerular filtration rate was unchanged, whereas effective renal plasma flow increased, so that filtration fraction decreased significantly. A similar in crease in urinary sodium occurred whether subjects received a low or high sodium diet. Indices which related to the distal delivery of filtrate (fractional urine flow and the sum of fractional free water and sodium clearances) increased significantly in both groups. The progesterone-induced increase in sodium excretion was not related to changes in plasma renin activity, renin substrate or urinary aldosterone. After 3 days of progesterone, the increase of sodium excretion was less than in the acute studies and urinary aldosterone increased tow- to four-fold. Progesterone failed to produce an acute increse in urinary sodium in subjects hyperexpanded by administration of exogenous mineralocorticoids. 3. Results suggest that the acute natriuretic action of progesterone is in part independent of aldosterone inhibition and that progesterone may inhibit sodium reabsorption at proximal as well as distal sites in the nephron.