Cortisol Increment Research Articles

Regulation of the pituitary-adrenal axis and corticosteroid-binding globulin-cortisol interaction in the guinea pig.

Adult male guinea pigs were used to examine pituitary-adrenal function and corticosteroid-binding globulin (CBG)-cortisol interaction. A biphasic pattern in the circadian rhythm of plasma cortisol was observed, with nadirs occurring at 0800 and 2400 h and peaks and 1600 and 0400 h. An excellent correlation was noted between total and free plasma cortisol levels. In contrast, no correlation was noted between CBG binding capacity and either the total or free plasma cortisol level. The free plasma cortisol concentration ranged from 0.6-5.8 micrograms/dl, representing 6.1-14.5% of the total cortisol concentration. The CBG binding capacity ranged from 12.2-161.7 micrograms/dl, and the binding affinity was 1.3-2.2 x 10(7) M-1 at 22 C, which is 20-fold lower than that of human CBG. These results suggest that CBG in the guinea pig has a relatively minor effect on the plasma distribution of cortisol, and that free plasma cortisol is dependent on cortisol binding to nonspecific plasma proteins as well as on the total plasma cortisol concentration. It was found that the guinea pig was relatively resistant to dexamethasone suppression, requiring at least 1 mg/kg BW to obtain essentially complete suppression of the pituitary-adrenal axis. In addition, it was found that administering dexamethasone 6 h before the time that the animals were killed led to suppression, whereas giving the steroid 12 h before killing the animals was totally ineffective. Stress induced by both ether vapor and histamine injection significantly increased plasma cortisol levels. When the guinea pigs were treated with a 1 mg/kg BW dose of dexamethasone 6 h before the stimulus, however, a marked suppression of the plasma cortisol increment secondary to application of the stressful stimulus occurred.

Evaluation of the Hypothalamic Hypophyseal Adrenal Axis in Patients Receiving Long-term Hemodialysis

Several alterations are present in the hypothalamic hypophyseal regulation of many hormones in patients with chronic renal failure. Evaluation of the hypothalamic hypophyseal adrenal axis in these groups of patients demonstrated normal levels of plasma cortisol. Dexamethasone suppression is abnormal after administration of 1 mg of oral dexamethasone, but normal after 3 mg. Dexamethasone blood levels were lower than the control after administration of 1 mg of oral dexamethasone. A dexamethasone metabolic clearance showed a similar half-life between the patients and controls. Oral absorption study showed poor absorption of the drug. Therefore, there is a problem of gastrointestinal absorption producing the abnormal dexamethasone suppression test in patients with renal failure. Results of metyrapone tests were normal. Corticotropin stimulation tests elicited a normal response. Insulin-induced hypoglycemia does not produce an increment in plasma cortisol or adrenocorticotropic hormone levels.

Hypothalamic-pituitary-adrenocortical function during long-term low-dose dexamethasone therapy in hyperandrogenized women

Hypothalamic-pituitary-adrenocortical (H-P-A) function was tested in 14 hyperandrogenized women, aged 17 to 32 years, who had been continuously treated with nightly single-dose oral dexamethasone, 0.25 to 1.00 mg, for 3.7 to 16.5 months. Daily am serum cortisol concentrations were measured in nine subjects after discontinuation of dexamethasone. Basal cortisol concentrations returned to normal (≥6.0 μg/dl) within 36 hours in 67%, within 60 hours in 89%, and within 84 hours in 100%. Median time to return to normal was between 12 and 36 hours. Rate of return correlated with both the dose-adjusted duration of dexamethasone therapy (p < 0.01) and the degree of adrenocortical suppression during treatment (p < 0.01). The H-P-A response to insulin-induced hypoglycemia and the adrenal response to an acute intravenous adrenocorticotropic hormone (ACTH) challenge were evaluated in eight subjects 12 to 36 hours after the final dexamethasone dose. Thirty-eight percent demonstrated normal cortisol increments to hypoglycemia, 25% had blunted or absent cortisol responses to hypoglycemia but normal cortisol increments to exogenous ACTH, and 38% had blunted or absent responses to both hypoglycemia and exogenous ACTH. The responsiveness of the H-P-A axis correlated with the degree of adrenocortical suppression (p < 0.05) but not with dose of dexamethasone or duration of treatment. Small doses of dexamethasone are not necessarily “physiologic,” but dexamethasone therapy with maintenance of serum cortisol levels ≥2.0 μg/dl was associated with rapid return to normal basal cortisol concentration and a normal cortisol response to insulin-induced hypoglycemia.

Adrenocortical steroids, bone mineral content and endometrial condition in post-menopausal women

In 23 post-menopausal women, serum levels of cortisol, unconjugated dehydroepiandrosterone (DHA), dehydroepiandrosterone sulphate (DHAS), testosterone, unconjugated and total oestrone and prolactin were measured before and during an ACTH test. Significant positive correlations were found between basal levels of DHA and DHAS; DHA and unconjugated oestrone; DHA and total oestrone; testosterone and total oestrone and between unconjugated and total oestrone. ACTH significantly raised the levels of the steroids but not of prolactin. Significant positive correlations were found between basal levels and ACTH induced increments in DHA; between basal DHAS and increments in DHA and between increments in DHA and DHAS. A significant negative correlation was found between basal levels and increments in cortisol. No significant correlations were found between other combinations of hormone basal levels and/or increments. Significant positive correlations were found between basal levels of DHAS and the DHA response to ACTH respectively, and trabecular bone mineral content of the distal forearm. A significant correlation was also found between bone mineral content and pre-cancerous/ cancerous state of the uterine epithelium. The results are a furtner support to the concept of a link between adrenal androgens and bone mineral density, and do also indicate a relation to endometrial pathology. The lack of correlation between cortisol and other steroids indicate different regulatory mechanisms. Prolactin doss not seem to be involved in the regulation of the adrenal androgen synthesis.

Effect of Adrenocorticotropin on Milk and Plasma Cortisol and Prolactin Concentrations

Milk cortisol and prolactin concentrations were measured in 12 lactating Holstein cows for 3 days (Experiment 1). On day 3, cows were divided randomly into groups; IV1, IV4, IM and control. Group IV1 received one intravenous injections of 40 IU adrenocorticotropin, group IV4, the same dosage four times at 2-h intervals, group IM 240 IU adrenocorticotropin intramuscularly, and control cows were injected with saline. Cortisol concentrations in blood plasma were increased in all groups following adrenocorticotropin injection, while milk cortisol concentrations increased fourfold in groups IV4 and IM and remained unchanged in group IV1.In Experiment 2, infusion of 18% saline into the mammary gland of three cows increased the somatic cell count in the infused quarter but had no effect on prolactin and cortisol of milk or plasma.In Experiment 3, six cows each were assigned to treatment groups of saline controls, IV2–0 (40 IU adrenocorticotropin intravenously at 0 and 2h post-milking) or IV2–8 (40 IU adrenocorticotropin intravenously at 8 to 10h post-milking). Half udders of each cow were milked before treatment and 4h later. Increases of cortisol in plasma increased cortisol concentrations of milk 4h after each treatment (IV2–0 and IV2–8). However, by 12h after treatment in IV2–0 cortisol concentrations of milk had returned to normal.Increases in adrenal cortisol secretion are followed rapidly (within 4h) by increased cortisol concentrations in milk. However, these rapidly in the absence of sustanined increments in blood cortisol. Increased cortisol concentrations in milk most likely represent sustained elevations in plasma cortisol.

Epinephrine, norepinephrine, glucagon, and growth hormone release in association with physiological decrements in the plasma glucose concentration in normal and diabetic man.

The release of potentially important glucose counter-regulatory factors (epinephrine, norepinephrine, glucagon, GH, and cortisol) was studied during Biostator-controlled reductions in the plasma glucose concentration from the high physiological level of 95 mg/dl to the low physiological level of 60 mg/dl in 10 subjects (5 normal subjects and 5 patients with insulin-dependent diabetes) and from the supraphysiological level of 200 to 100 mg/dl in 6 subjects (3 normal subjects and 3 patients with insulin-dependent diabetes). Reductions in the plasma glucose concentration from 95 to 60 mg/dl were associated with early (+30 to +40 min) increments [here with the maximal values expressed as the percent of the mean baseline (mean ± SE)] in plasma epinephrine (529 ± 144; P < 0.02), norepinephrine (146 ± 12; P < 0.01), and glucagon (123 ± 13; P < 0.05) and a late (+75 min) increment in plasma GH (2504 ± 1065; P < 0.05); an apparent late (+105 min) increment in plasma cortisol (132 ± 15) was not statistically signif...

Endocrine Effects of Naloxone-Induced Opiate Receptor Blockade

Morley, John E.; Baranetsky, Nicholas G.; Wingert, Terence D.; Carlson, Harold E.; Hershman, Jerome M.; Melmed, Shlomo; Levin, Seymour R.; Jamison, Kay R.; Weitzman, Richard; Chang, H. Jeffrey; Varner, Albert A. Author Information

Pituitary-adrenal function in women treated with low doses of prednisone

In order to assess whether long-term low-dose glucocorticoid administration results in suppression of the hypothalamic-pituitary-adrenal (H-P-A) axis, we examined the response of plasma cortisol to insulin-induced hypoglycemia in 23 women treated with prednisone (5 mg/day) compared with that in 19 untreated women. Basal AM levels of plasma cortisol were unaffected (mean +/- SE, 11.6 +/- 0.9 versus 11.2 +/- 0.7 microgram/dl). The plasma cortisol increment at 609 minutes after insulin-induced hypoglycemia was significantly smaller in the treated group than in the untreated group (6.7 +/- 1.0 versus 11.6 +/- 1.2 microgram/dl, p less than 0.005). Thirteen of 23 women (56.5%) in the steroid-treated group compared to one of 19 (5.3%) in the untreated group, showed a rise in plasma cortisol of less than 6 microgram/dl at 60 minutes. Furthermore, a similar reduction in the increment of plasma cortisol was also found in a subset of 10 women tested both before and during prednisone treatment. These results indicate that the concept that low doses of glucocorticoids are free of suppressive effects on H-P-A function is not justified.

Plasma catecholamines and pituitary adrenal hormones related to mental task demand under quiet and noise conditions

Plasma levels of catecholamines and pituitary adrenal hormones were measured in 20 min samples from eight subjects, in one control session and two experimental sessions, while they performed a short-term memory task under quiet or noise conditions. Performing the task led to significant increase in the plasma levels of cortisol, adrenaline and noradrenaline, whereas no variations in growth hormone and dopamine were observed. Similarly, significant changes occurred in urinary catecholamine excretion. A significant correlation was found between individual plasma cortisol increments and error-rates assessed from an accuracy of recall variable. For adrenaline and noradrenaline, an early response apparently linked with an anticipatory process preceded the task. Exposure to noise did slightly amplify cortisol response to the task, but during the first experimental session, with or without noise, the task elicited greater cortisol increases in all subjects than during the second session. These results provide evidence for a relationship between sympathoadrenocortical activity and attentional demand, whereas cortisol increments seem to be more specifically related to better coping with the task. Frequent hormone level measurements during a prolonged mental task might clarify the complex relationship between time-related bodily hormonal changes, performance and subjective feelings.

The influence of acute physiological increments of cortisol on fuel metabolism and insulin binding to monocytes in normal humans.

The role of physiological hypercortisolemia in the regulation of fuel metabolism in man was examined during a 5-h primed-continuous infusion of cortisol which raised plasma cortisol levels to 40 microgram/dl. Plasma glucose increased by 15--20 mg/dl (P less than 0.005) in spite of unchanged rates of glucose production. Glucose uptake and clearance, on the other hand, fell by 15% (P less than 0.05) and 30% (P less than 0.005), respectively, thereby accounting for cortisol-induced hyperglycemia. Total blood ketones during cortisol infusion increased 3-fold above saline control values (P less than 0.01) despite comparable FFA levels in the two groups. In addition, there was a selective 40% rise in total branched chain amino acids (P less than 0.005) during cortisol infusion. These effects of cortisol on glucose, ketone, and amino acid metabolism occurred in the absence of significant changes in the plasma insulin or glucagon concentration. Furthermore, cortisol infusion had no effect on [125I]insulin binding to circulating monocytes. Our data thus suggest that acute elevations of plasma cortisol have antiinsulin effects in man which may occur independent of alterations in insulin receptors.

Endocrine effects of naloxone-induced opiate receptor blockade.

To test the effect of opiate receptor blockade on hormone release in man, we administered 10 mg naloxone iv to eight normal subjects and compared the results with those found after saline infusion. Naloxone produced a rise in serum cortisol (P < 0.01), LH (P < 0.01), FSH (P < 0.05), and insulin (P < 0.05) levels but did not alter serum GH, PRL, TSH, arginine vasopressin, glucagon, T3, or T4. Naloxon e had no effect on GH levels in two subjects with active acromegaly or on TSH levels i n six subjects with primary hypothyroidism. In dynamic pituitary function testing, naloxone diminished the GH response to arginine (P < 0.05) without altering the PRL response; naloxone augmented the PRL response to TRH (P < 0.025) without affecting the TSH response. Naloxone did not significantly alter GH or PRL response to L-dopa. Naloxone enhanced the increment in serum cortisol induced by the stress of gastroscopy without changing the GH or PRL response. Naloxone increased glucose response areas (P < 0.05) after an iv glucose bolus and raised the maximum plasma glucose level (P < 0.05) without altering the rate of glucose disappearance. Glucagon and insulin responses to glucose and arginine were not altered by naloxone. Psychological testing showed that naloxone altered performance on the Graham-Kendall Memory for Designs test in half of the subjects studied. There were no significant differences between saline and naloxone trials on the Profile of Mood States questionnaire or the mood-anxiety scale. Together with subjective reports from two of the subjects that naloxone decreased their ability to concentrate, these data suggest that opiate receptors may play a role in short term memory. Specific opiate receptor blockade with naloxone has definite endocrine and metabolic effects, suggesting endogenous opioid modulation of secretion of some of these hormones. Since these effects of naloxone are not always complementary to those of opiates, exogenous opiates may also act on separate receptors which are not blocked by naloxone.

Hormonal responses to insulin infusion in diabetes mellitus.

Twenty diabetic patients and fourteen normal volunteers received infusion of 2.4 U neutral porcine insulin/h until either the blood glucose level was stable, or until hypoglycaemia occurred. As previously reported [1] in the normal group the blood glucose stabilised at 2.8±0.1 mmol/l without any hypoglycaemic symptoms. There was an increase in blood levels of glucagon, cortisol and growth hormone as the blood glucose level fell, the mean peak increments being 167±33 pg/ml, 400±71 nmol/l and 29±7 mU/l, respectively. In ten of the diabetic subjects (Group A) the blood glucose level stabilised at 3.6±0.2 mmol/l during the insulin infusion, with peak increments in plasma glucagon (110±24pg/ml), cortisol (411±71 nmol/l) and growth hormone (22±6 mU/l), not significantly different from those in the normal subjects. These rises in hormone levels occurred during the last hour of infusion after normoglycaemia was reached and maintained. The ten remaining diabetics (Group B) developed symptoms of hypoglycaemia during the infusion. The peak increments in plasma glucagon (19±7 pg/ml), cortisol (183±36 nmol/l) and growth hormone (6±2 mU/l) in this latter group were significantly less than those in the other diabetic group or the normals. The absence of counter-regulatory hormonal responses in the Group B diabetics was related to the development of hypoglycaemia and may be the result of a dysfunction of hypothalamic gluco-regulatory centres.

Desoxycorticosterone in normal pregnancy: II. Cortisol-dependent fluctuations in free plasma desoxycorticosterone

Desoxycorticosterone (DOC) secretion increases during pregnancy. Administration of adrenocorticotropic hormone (ACTH) to women during the third trimester of pregnancy was noted previously to result in marked sodium retention, while aldosterone excretion declined. Since urinary tetrahydrodesoxycorticosterone increased substantially, sodium retention resulting from ACTH was ascribed to enhanced DOC secretion. Surprisingly, the elevated plasma DOC in late pregnancy failed to respond consistently to ACTH. Effects of ACTH upon total plasma concentrations and free indexes of DOC and cortisol were studied in pregnant women in the third trimester. As a result of ACTH, plasma cortisol and the free cortisol index increased strikingly; the plasma free DOC index rose markedly in those subjects in whom the total plasma DOC level was not altered appreciably and was unchanged or even increased slightly in the few subjects in whom the total DOC level decreased. The results support the proposition that the plasma free DOC fraction is increased because of displacement from corticosteroid-binding globulin by the ACTH-induced increment in cortisol. Resultant elevations of free DOC would not be evident from customary measurements of the total DOC concentration but, nonetheless, could contribute to sodium retention and also would be available for hepatic metabolism.

Synergistic Interactions of Physiologic Increments of Glucagon, Epinephrine, and Cortisol in the Dog

To evaluate the role of anti-insulin hormone actions and interactions in the pathogenesis of stress-induced hyperglycemia, the counterregulatory hormones, glucagon, epinephrine, and cortisol were infused alone as well as in double and triple combinations into normal conscious dogs in doses that were designed to simulate changes observed in severe stress. Infusion of glucagon, epinephrine, or cortisol alone produced only mild or insignificant elevations in plasma glucose concentration. In contrast, the rise in plasma glucose produced by combined infusion of any two counterregulatory hormones was 50-215% greater (P < 0.005-0.001) than the sum of the respective individual infusions. Furthermore, when all three hormones were infused simultaneously, the increment in plasma glucose concentration (144+/-2 mg/dl) was two- to fourfold greater than the sum of the responses to the individual hormone infusions or the sum of any combination of double plus single hormone infusion (P < 0.001). Infusion of glucagon or epinephrine alone resulted in a transient rise in glucose production (as measured by [3-(3)H]glucose). While glucagon infusion was accompanied by a rise in glucose clearance, with epinephrine there was a sustained, 20% fall in glucose clearance. When epinephrine was infused together with glucagon, the rise in glucose production was additive, albeit transient. However, the inhibitory effect of epinephrine on glucose clearance predominated, thereby accounting for the exaggerated glycemic response to combined infusion of glucagon and epinephrine. Although infusion of cortisol alone had no effect on glucose production, the addition of cortisol markedly accentuated hyperglycemia produced by glucagon and(or) epinephrine primarily by sustaining the increases in glucose production produced by these hormones. The combined hormonal infusions had no effect on beta-hydroxybutyrate concentration. It is concluded that (a) physiologic increments in glucagon, epinephrine, and cortisol interact synergistically in the normal dog so as to rapidly produce marked fasting hyperglycemia; (b) in this interaction, epinephrine enhances glucagon-stimulated glucose output and interferes with glucose uptake while cortisol sustains elevations in glucose production produced by epinephrine and glucagon; and (c) these data indicate that changes in glucose metabolism in circumstances in which several counterregulatory hormones are elevated (e.g., "stress hyperglycemia") are a consequence of synergistic interactions among these hormones.

Determination of serum cortisol fractions by isocolloidosmolar equilibrium dialysis. Changes during pregnancy.

A modified equilibrium dialysis method to determine the percentage of protein-unbound cortisol in the total serum cortisol (unbound cortisol %) was devised. When serum was dialyzed against an ordinary buffer solution, unbound cortisol% increased with the time of dialysis, accompanying a progressive decrease in serum protein concentration. These changes seemed to be due to the difference of colloidal osmotic pressure between the serum and the buffer. An addition of3% dextran in the buffer resulted in a stable equilibrium and both the unbound cortisol% and the protein concentration stayed unchanged after12hr of the dialysis. Therefore, the determination of unbound cortisol % was carried out by dialyzing serum against 3% dextran buffer for18hr and the method was called an isocolloidosmolar equilibrium dialysis. Dextran did not bind cortisol at all. Additions of graded amounts of cortisol in the dialysate caused significant increases in unbound cortisol % of a pooled serum. The ratio of unbound cortisol to albumin-bound cortisol was determined by the same dialysis system using heat-treated serum in the presence of nonradioactive cortisol. A combination of these two determinations enables to assess concentrations of unbound, albumin-bound and transcortin-bound cortisol in serum. Both intra-assay and inter-assay precisions of these methods were excellent (at most±4.65%).In normal subjects (cortisol concentration: 7.1±2.5μg/100ml), 5.8±0.7% was present as unbound cortisol, 15.8±2.5% as albumin-bound and78.3±2.8% as transcortin-bound cortisol. Concentrations of all serum cortisol fractions increased with the course of pregnancy, however, relative increment of transcortin-bound cortisol was larger than that of total cortisol, while those of unbound and albumin-bound cortisol were far less. Percentages of transcortin-bound and albumin-bound cortisol changed in parallel to changes in concentrations of these cortisol-binding proteins during pregnancy.pregnancy. The method requires a small amount of serum and is applicable to determine three cortisol fractions in individual sera.

Plasma ACTH and Cortisol Responses to TRF, Vasopressin or Hypoglycemia in Cushing's Disease and Nelson′s Syndrome

The response of plasma ACTH and/or cortisol concentrations to thyrotropin-releasing-factor (TRF), vasopressin, and insulin administration was determined in 5 patients with Nelson's syndrome and 12 patients with untreated Cushing's disease. TRF administration was associated with a mean increment of 267 pg/ml in plasma ACTH concentrations in patients with Nelson's syndrome, and of 42 pg/ml in patients with Cushing's disease. The increment in plasma cortisol concentrations in the latter group was 12 mug%. No ACTH or cortisol response was observed in normal subjects. Patients with Cushing's disease or Nelson's syndrome exhibited significantly greater increments in plasma ACTH concentrations in response to vasopressin administration (P less than .05, P less than .02 respectively) than did normal subjects; the increment in cortisol concentration was also greater, (P less than .05), in patients with Cushing's disease than in normal subjects. No significant difference was present between patients with Cushing's disease and Nelson's syndrome with regard to the magnitude of the ACTH response to vasopressin administration. In contrast, the increment in plasma cortisol and plasma ACTH concentrations following insulin induced hypoglycemia was significantly less in patients with Cushing's disease than seen in normal subjects, (P less than .001, P less than .05 respectively); while this stimulus was associated with a significantly greater increment in plasma ACTH concentrations in patients with Nelson's syndrome as compared to that seen in normal subjects, (P less than .01) and in patients with Cushing's disease (P less than .01). These findings indicate that pituitary function in patients with Nelson's syndrome is not autonomous and suggest the possibility that altered central nervous regulatory mechanism might play a role in the etiology of the pituitary tumors which are frequently associated with this syndrome. The TRF induced rise in plasm cortisol and ACTH concentrations in patients with Cushing's disease and Nelson's syndrome suggests the possibility of altered hypothalamic or pituitary receptors in such patients.

Norepinephrine and epinephrine release and adrenergic mediation of smoking-associated hemodynamic and metabolic events.

We studied the effects of cigarette smoking, sham smoking and smoking during adrenergic blockade in 10 subjects to determine whether smoking released the sympathetic neurotransmitter norepinephrine, as well as the adrenomedullary hormone epinephrine, and whether smoking-associated hemodynamic and metabolic changes were mediated through adrenergic mechanisms. Smoking-associated increments in mean (+/- S.E.M.) plasma norepinephrine (227 +/- 23 to 324 +/- 39 pg per milliliter, P less than 0.01) and epinephrine (44 +/- to 113 +/- 27 pg per milliliter, P less than 0.05) were demonstrated. Smoking-associated increments in pulse rate, blood pressure, blood glycerol and blood lactate/pyruvate ratio were prevented by adrenergic blockade; increments in plasma growth hormone and cortisol were not. Since significant smoking-associated increments, in pulse rate, blood pressure and blood lactate/pyruvate ratio, preceded measurable increments in plasma catecholamine concentrations, but were adrenergically mediated, these changes should be attributed to norepinephrine released locally from adrenergic axon terminals within the tissues rather than to increments in circulating catecholamines.

Evaluation of pituitary-adrenal function in patients with chronic bronchial asthma following substitution of steroid treatment with disodium cromoglycate (Lomudal)

In a group of 32 steroid-dependent asthmatic patients an attempt was made to replace steroid treatment with disodium cromoglycate (Lomudal). Withdrawal of steroids was accompanied by a transitory stage of combined corticotropin-Lomudal treatment for 6 to 8 mo. Pituitary-adrenal function was assessed by ACTH and Metopirone test. Before treatment an impairment of pituitary-adrenal function was found in most of our patients, although in 26 patients a normal increment of plasma cortisol was found after ACTH stimulation. At the end of the combined treatment, 17 patients are now on Lomudal with normal pituitary-adrenal function, 9 patients need small quantities of steroids occasionally, and 6 patients are steroid-dependent.

The Plasma Cortisol and Corticotropin Response to Hypoglycemia Following Adrenal Steroid and ACTH Administration

The plasma cortisol response to hypoglycemia is widely used as a test of hypothalamic-pituitary-adrenal function. It was the aim of this study to determine whether this test gives a reliable indication of pituitary corticotropin (ACTH) release in patients recovering from adrenocortical suppression due to corticosteroid or ACTH therapy. The 16 patients who were studied (6 on more than one occasion) had received in excess of 5 mg predinisone or equivalent daily for over 12 months. The insulin tolerance tests were carried out 18 h after stopping steroid therapy. The tests were then repeated three to four days after adrenal function had been restored (as indicated by urinary oxogenic steroid excretion of greater than 35 mg/24 h) by zinc tetracosactrin administration. The ACTH response to hypoglycemia was significantly impaired in the steroid-treated group. However with the exception of one patient who had persistently elevated resting ACTH levels there was a significant correlation (P less than 0.01) between the maximum increments in plasma cortisol and ACTH during hypoglycemia. No significant difference in sensitivity to endogenous ACTH could be demonstrated between the steroid-treated group and 12 normal control subjects. Following ACTH administration the plasma ACTH and growth hormone responses to hypoglycemia were significantly reduced, but the response in plasma cortisol was not significantly affected. It is concluded that the plasma cortisol response to hypoglycemia gives a useful indication of ACTH release in steroid-treated patients provided that they have not recently received exogenous ACTH.

Adrenal response to tolbutamide-induced hypoglycemia in high altitude dwellers.

Adrenal response to tolbutamide-induced hypoglycemia was studied in 23 normal men born and living at high altitude (Morococha, Perú, 4,540 m) and compared to 23 men born and living near sea level. Fasting blood sugar was significantly lower in the high altitude dwellers (HAD) and this difference persisted throughout the test period. The blood glucose decrement at 30 min was significantly less in the HAD. Plasma cortisol response was significantly higher at 30 and 60 min in the HAD. Peak cortisol level occurred earlier in the HAD than in men living at sea level. The absolute cortisol increment at 30 min was significantly greater in the HAD.