Insulin and glucagon infusion in the treatment of liver failure.

In an attempt to improve liver function and promote hepatic regeneration in a patient with severe liver injury, insulin alone or insulin and glucagon were administered by constant peripheral venous infusion during a 61-day period. The response, as assessed by a broad spectrum of hepato-cellular function tests, including synthetic, detoxification, bile metabolism, and microsomal enzyme function, and also histological evidence, indicated a beneficial effect. Continuous insulin and glucagon infusion merits further evaluation in the treatment of some forms of hepatic failure.

Oral-contraceptive-induced hypertension after adrenalectomy and hypophysectomy.

The cause of oral-contraceptive-induced hypertension in certain susceptible subjects is obscure. We describe a woman who was receiving replacement doses of fludrocortisone acetate after adrenalectomy and hypophysectomy who developed high blood pressure while ingesting an estrogen-containing oral contraceptive. Renin substrate level was increased, but renin activity was suppressed and unresponsive to tilting. The patient developed a markedly exaggerated natriuresis when infused with saline. Both blood pressure and her responses to infused sodium and tilting normalized after discontinuance of the oral contraceptive medication. In this adrenalectomized patient, the estrogenic component of the pill acting synergistically with a fixed ("nonsuppressible") replacement dose of mineralocorticoid seems to have caused a volume-related hypertension.

Enhancement of adrenal cortisol secretion after intravenous high dose dexamethasone.

To assess the possible existence of a short loop feedback mechanism of direct glucocorticoid suppression on the adrenal glands, we performed a series of tests employing insulin hypoglycemia or ACTH infusions to obtain adrenal stimulation by ACTH levels that remained within the physiological range. Although the rapidity of glucocorticoid suppression of the pituitary thwarted efforts to use endogenous ACTH as a stimulus, we were able to mimic the stressed state by very low dose ACTH infusions (0.05 microgram/kg BW). No inhibition of cortisol secretion in response to ACTH infusions was detected in tests done after administration of dexamethasone compared to placebo [mean integrated response, 29.37 +/- 1.91 (+/- SE) vs. 29.12 +/- 1.12 microgram . h/dl, respectively]. Furthermore, when high doses of dexamethasone were administered iv, a small paradoxical increase in cortisol secretion was found (33.82 +/- 1.44 microgram . h/dl) without a difference in ACTH levels. These data do not support the concept of significant direct glucocorticoid inhibition of adrenal secretion. Non-ACTH factors that may enhance cortisol secretion in the presence of ACTH may exist.

Direct inhibition of Leydig cell function by estradiol.

Suppression of plasma testosterone levels from a mean of 760 ng/dl to a mean of 295 ng/dl could be induced in normal young adult men 24 h after a single injection of 2 mg aqueous 17 beta-estradiol. Maximum suppression to 123 ng/dl was noted 36 h after estradiol administration. Neither LH nor FSH levels were similarly affected. After administration of 5000 IU hCG to a similar group of subjects, daily blood samples were obtained for testosterone and estrogen. Maximum testosterone levels of 2060 ng/dl (basal, 784 ng/dl) were seen 96 h after hCG administration. Maximum estrogen levels of 13 pg/ml (basal 73 pg/ml) were seen 36 h after hCG administration. The testosterone response to hCG could be attenuated by preceding hCG administration with an injection of 17 beta-estradiol. These results can be explained by the concept of enzyme inhibition; estrogen acts directly on the Leydig cell to effect changes in the activities of certain enzymes important for testosterone synthesis. Whether endogenous estrogen production by the Leydig cell may be important in this postulated short loop feedback is as yet unclear.

The effect of dexamethasone on the 24-hour profiles of adrenocorticotropin and cortisol in Cushing's syndrome.

ACTH and cortisol are normally secreted episodically rather than continuously. This characteristic of episodic secretion is preserved in patients with Cushing's syndrome. To determine whether exogenous glucocorticoids modulate this pulsatility and to study its possible etiological implications, we obtained 24-h plasma cortisol profiles in seven patients with Cushing's syndrome (five Cushing's disease, one adrenal adenoma, and one bilateral adrenal cortical macronodular hyperplasia) before and during suppression with various doses of dexamethasone [low (0.5 mg, every 6 h), high (2 mg, every 6 h), and very high (4 mg, every 6 h)]. Simultaneous 24-h plasma ACTH profiles were obtained in two patients with Cushing's disease. Blood was drawn at 30-min intervals for 25 h. Individual profiles were analyzed to determine the 24-h mean level, the presence of a circadian component and its amplitude, and the number and magnitude of significant secretory pulses over the 24-h span. The concordance between significant ACTH and cortisol pulses also was quantified. Baseline values in patients were compared to those in seven normal subjects. Under basal conditions, the 24-h mean cortisol level was 3- to 4-fold higher than normal in all patients with Cushing's syndrome. In contrast, the basal 24-h mean ACTH level was normal in one, and slightly elevated in the other of the two patients with Cushing's disease in whom plasma ACTH concentrations were measured. However, in contrast to the normal subjects, all ACTH values were above 10 pg/ml even during the period of minimal secretion. Basal circadian variation in adrenocortical activity, albeit of reduced amplitude, was found in four of five patients with Cushing's disease; it was absent in the patient with adrenal adenoma. Low dose dexamethasone reduced the 24-h mean cortisol level and increased the amplitude of the circadian rhythm, unmasking a diurnal rhythm in the single patient with Cushing's disease in whom no significant circadian periodicity was present in the basal condition. This effect was further increased with the high dose of dexamethasone, which concomitantly reduced the number and increments of the secretory pulses. A lesser effect was found in the patient with bilateral nodular hyperplasia, and no effect was seen in the patient with adrenal adenoma. ACTH pulsatility, but not diurnal rhythm, also was dampened by dexamethasone. Reduction in the magnitude, but not the number, of ACTH secretory pulses by dexamethasone produced a reduced concordance ratio of ACTH with cortisol pulses of 0.39, compared to 0.64 in the basal state.(ABSTRACT TRUNCATED AT 400 WORDS)

The effects of fluoxymesterone administration on testicular function.

Long term daily administration of fluoxymesterone (9alpha-fluoro-17alpha-methyl-11beta, 17beta-dihydroxyandrost-4-en-3-one) was associated with a modest suppression of sperm production and a profound suppression of testosterone levels in the absence of significant effects on plasma gonadotropin levels. Nine normal male volunteers took either 10, 20, or 30 mg of fluoxymesterone daily for twelve weeks. Plasma samples were obtained for testosterone, estrogen, LH and FSH levels at biweekly intervals before, during and for up to 12 weeks after fluoxymesterone treatment. Samples were obtained for dehydroepiandrosterone sulfate, testosterone binding globulin and free testosterone assays at representative times before, during and after treatment. Although lower sperm counts were observed at several points during both the treatment and follow up periods, significant consistent suppression of spermatogenesis could not be demonstrated. Reduced plasma testosterone levels were seen within 24 h after beginning fluoxymesterone, and further reductions were noted throughout the treatment period. Changes in plasma estrogen levels did not correlate with fluoxymesterone administration. Neither plasma LH nor plasma FSH levels were significantly altered by fluoxymesterone. A short term study utilizing a single dose of fluoxymesterone yielded similar findings. It is proposed that fluoxymesterone has a local effect on the Leydig cell which is not mediated by gonadotropins.

The protein-sparing action of protein feeding: absence of relationship to insulin secretion.

The influence of a 2-day fast was compared with that of a modified fast (1.5 g beef protein hydrolysate per kg body wt) on nitrogen metabolism and insulin secretion in three normal young men. During the fast urinary urea excretion indicated a negative nitrogen balance of 10 to 12 g daily in each subjects. With protein feeding nitrogen equilibrium was approached in each instance. Insulin secretion as indicated by the urinary excretion of C-peptide dropped profoundly with fasting to levels which averaged just 13 to 22% of the control base-lines and remained at about these levels during the protein feeding. The fact that this sensitive indicator of insulin secretion disclosed no significant difference during fasting and protein feeding provides strong evidence that the protein-sparing influence of protein feeding cannot be ascribed to the decline in insulin secretion.

Functioning lipoadenoma of the parathyroid gland.

Lipoadenoma is a rare tumor of the parathyroid gland composed of adult adipose tissue and irregular trabeculae of parathyroid cells. This variant of adenoma is poorly documented. Similar lesions that have been either functional or apparently nonfunctional have been reported as adenoma with unusual stromal development and as parathyroid hamartoma, respectively. In this report, the second case of a functional lipoadenoma of the parathyroid gland is described.

Death is not the enemy.

KIE: The authors, who are associated respectively with the University of Chicago's Department of Medicine and its Divinity School, reflect on the current intense preoccupation with the preservation of physical life and the denial of death as an integral aspect of human life. They question the development of technologies with the prime aim of prolonging life when the result is a "grotesque, fragmented, or inordinately expensive existence." They remind physicians that their major role is to improve the quality of life of their patients, which includes guiding them to a perspective in which the preservation of life does not become their "God."^ieng

The metabolic influence of progestins.

PIP: Information concerning the general metabolic, or what might be termed the systemic, effects of progesterone and synthetic progestins is reviewed. Included in the review, are sections on: 1) electrolyte metabolism, 2) protein metabolism, 3) growth hormone secretion, 4) carbohydrate metabolism, 5) fat metabolism, 6) respiratory effects, 7) the influence of synthetic progestins on electrolyte metabolism, and 8) the effect of synthetic progestins on electrolyte metabolism, and 8) the effect of synthetic progestins on protein metabolism. It appears that aldosterone and progesterone are the dominate endocrine factors regulating salt excretion during pregnancy. As 1 of the sex hormones, progesterone has a distinct growth-promoting influence on selected tissues of the accessory sex apparatus. Progesterone induces protein wasting which can be compensated for by the comsumption of added calories. It appears that progesterone is partially responsible for maintaining the positive energy balance in pregnant women, the appetite stimulus arising from the catabolic process which it initiates. Recent interest in the influence of progesterone and synthetic progestins on pituitary growth hormone secretion has come about both as a by-product of studies done on the effects of progestins on protein and carbohydrate metabolism and because of the known effects of other sex steroids on the output of this hormone. Progestins whether derived from testosterone or 17-alpha-hydroxyprogesterone when employed in the usual antiovulatory doses, and progesterone in amounts comparable to the levels achieved in the first half of pregnancy have no adverse effect on carbohydrate metabolism in normal men or women. However, in diabetics and perhaps in potential or prediabetics, 17-alpha-hydroxyprogesterone derivatives may cause slight deterioration in glucose tolerance. Circumstantial evidence has provided much support for the idea that some relationship exists between sex hormones and serum lipid content. A great number of synthetic and few natural derivatives of testosterone have ben evaluated with the purpose of developing a pharmacologically effective steroid with the full general protein anabolic activity of the male hormone but with minimal androgenic or virilizing potential.^ieng

Serum cortisol appearance-disappearance in adrenal insufficiency after oral cortisone acetate.

Six patients with long-standing idiopathic primary adrenal insufficiency were given 25 mg of cortisone acetate orally on two occasions. Circulating serum cortisol levels were determined hourly for five hours after ingestion. Two patients were additionally studied with an oral dose of 20 mg of cortisol. Marked patient to patient variation in peak hormone and in fifth hour hormone levels was observed. Both values were lowest in the two chronically symptomatic patients who had been maintained on empiric glucocorticoid replacement. Specific information on blood cortisol levels in treated Addisonian individuals has not been previously reported.

Changes in plasma apolipoproteins A-I, A-II, and B, and lipoprotein cholesterol after jejunoileal bypass.

In view of the role of the small intestine in lipoprotein synthesis and bile salt reabsorption, we have determined plasma lipid fractions and apolipoproteins A-I, A-II, and B at regular intervals in 26 patients who underwent jejunoileal bypass surgery for morbid obesity. After surgery, no change in plasma triglycerides was noted, but there was a prompt and significant fall in total plasma cholesterol and low density lipoprotein cholesterol, which persisted beyond 2 yr. Plasma apolipoprotein B levels did not fall concurrently, and hence the protein/lipid composition of low density lipoprotein was permanently altered by the surgery. Levels of high density lipoprotein cholesterol were low before bypass surgery, decreased after surgery, and rose thereafter toward the normal range. Similar changes in apolipoprotein A-I and A-II values were noted. These postoperative alterations in plasma lipid and apoprotein levels demonstrate the importance of intestinal absorptive integrity in the regulation of lipoprotein metabolism.

Experimental cryptorchidism in adult male rats: histological and hormonal sequelae.

Mature male rats were rendered cryptorchid and followed for up to nine weeks during which serial blood specimens were obtained for multiple hormonal analyses; serial testicular samples were obtained as well. In contrast with control animals, cryptorchid rats showed transient rises in FSH which returned to normal at the end of the study; estrogen levels were high in the final weeks. Plasma testosterone levels were unchanged and LH levels changed little. Light and electron microscopic studies of testicular biopsy specimens showed prompt disruption of spermatogenesis which became more extensive with time. Sertoli cells underwent multiple changes including increased lipid storage and phagocytosis of spermatozoa. Comparisons are made between the sequence of hormonal changes and that of histological changes. In addition, questions are raised concerning the ways in which Sertoli cells are affected by experimental cryptorchidism.