17-OHCS Levels Research Articles

Psychophysiological correlation of 17-ketosteroids and 17-hydroxycorticosteroids in 21 pairs of monozygotic twins

Twenty-one pairs of healthy monozygotic male twins of college age have been observed in an attempt to correlate individual personality structure with characteristic and relatively enduring patterns of pituitary adrenocortical function. Ten pairs of comparable dizygotic male twins have been studied by the same methods. High levels of 17-OHCS excretion were found in individuals with forceful yearnings for close personal involvement or with active defenses against the threat of intimacy. Individuals with low 17-OHCS levels were more effectively isolated by well-organized neurotic defenses. High 17-KS levels were found in energetic, ambitious individuals with strong aggressive drives and equally strong defenses against them. Those with low 17-KS were over-controlled with apparently limited innate drive endowment. A one way analysis of variance was computed for both monozygotic and dizygotic. twins. The F ratio indicated that height, 17-KS mean values, and day-to-day variation in 17-KS might be influenced by genetic factors. The intra-class correlation in 17-OHCS means was just as great in dizygotic as in monozygotic pairs but the correlation in 17-KS means in monozygotic pairs was much higher than in dizygotic pairs. A contingency table was constructed by grouping the variation in 17-OHCS and 17-KS into quartiles. In 14 out of the 21 pairs of monozygotic twins both members of the pair were in the same quartile for 17-OHCS and 17-KS and both members of all the other pairs were in adjoining quartiles. The pyschological characteristics shared by all of the subjects in each contrasting quartile suggest meaningful correlations of steroid patterns with different but interrelated quantifiable ranges of psychological response corresponding respectively to the mean levels of the 17-OHCS and of the 17-KS.

Circadian rhythms of plasma 17-hydroxycorticosteroids in the infant monkey.

SummaryPlasma 17-hydroxycorticosteroids (17-OHCS) exhibited a significant circadian rhythm in rhesus monkeys (M. mulatta) in the first week of life. In two experiments, plasma 17-OHCS levels averaged 35 μg/100 ml at 8-9:00 am, and declined to levels of 29 μg/100 ml at 9:00 pm (Expt. I) and 24 μg/100 ml at 12:00 midnight (Expt. II). These changes were about half the magnitude reported by others in the adult monkey. Correlated with this steroid rhythm, the infant monkey, although having a polyphasic 24-hr sleep pattern, also exhibited a tendency to sleep more at 1:00 and 3:00 am than at other times of the day. This suggested a relationship between sleep–activity cycles and steroid cycles in the infant monkey similar to that in the adult monkey.

Influence of induced adrenal insufficiency and stress on porcine plasma and muscle characteristics.

Injecting 100 mg. prednisolone daily for days resulted in atrophy of the adrenal gland. The animals were stressed 48 hr. after recieving the last prednisolone injection and then sacrificed. Susceptibility to stress was increased in the partial adrenal insufficient pigs determined by their inability to withstand 5 min. of physical exercise before slaughter. Plasma lactate levels were increased significantly (P<.05) due to the effect of the physical exercise, and blood pH at death was significantly creased among the stressed adrenal insufficient group. Initial lactic acid content of the M. longissimus was significantly lower in group two pigs when compared to group three. No significant differences were noted among 24-hr, muscle lactate levels. The glycogen content of the M. longissimus was significantly increased because of prednisolone injections, but the level of initial muscle glycogen did not appear to influence the ultimate amount of lactic acid produced by postmortem anerobic glycolysis. No significant differences were noted among treatments when M. longissimus values and color scores were examined statistically. Low levels of plasma 17-OHCS per se did not serve to increase the rate of postmortem anerobic glycolysis. The partial adrenal insufficient pigs used in this study may be unable to adequately remove high levels of lactic acid from the blood and muscle during exhaustive exercise.

The diurnal variation of urinary and plasma 17-hydroxy-corticosteroid (17-OHCS) levels and the plasma 17-OHCS response to lysine-8-vasopressin in depressive patients.

Hyperactivity of the hypothalamic–pituitary–adrenal (HPA) axis is one of the key biological abnormalities described in major depressive disorder, occurring in 30–50% of depressed subjects. Corticotropin-releasing hormone (CRH) and vasopressin (AVP) are the main regulators of this stress system, with the two neuropeptides acting synergistically in bringing about adrenocorticotropin (ACTH) release from the anterior pituitary and cortisol from the adrenal gland. Based on the demonstration of elevated cerebrospinal fluid levels of CRH in depressives, and other evidence, it has been postulated that excess CRH and the resultant increased HPA forward drive form the basis of neuroendocrine dysregulation in depression. However, there is an accumulating body of evidence to support a significant role for AVP in the regulation of pituitary–adrenal activity in health and also in depressive disorder. This review, based on a Medline search from 1980 to 2001, focuses on the functional neuroanatomy, receptor pharmacology, VP synergism with CRH, and the data from clinical and pre-clinical studies that support an important role for AVP in the pathophysiology of major depression. We suggest that future antidepressants may target the vasopressinergic system.

Effect of coffee ingestion on adrenocortical secretion in young men and dogs

Studies performed in 13 young, normal, healthy subjects have shown that ingestion of moderate amounts of coffee results in a significant increase in urinary 11-OHCS which reflects a stimulation of the adrenocortical activity. This conclusion is supported by our experiments in dogs in which we found a significant increase in the plasma 11-OHCS level in the phrenico-abdominal vein after administration of caffeine. These findings in addition to the observations that caffeine results in significant elevations in FFA and catecholamines, are of particular interest in view of the possible relationship of these changes to an increase in certain lipid fractions, particularly triglycerides and cholesterol.

Pituitary-adrenal function in acute falciparum malaria.

Abstract Infection with Plasmodium falciparum is characterized by severe weakness, hypotension, vomiting, diarrhea, hyponatremia, and other clinical findings compatible with adrenal insufficiency. Previous investigators have correlated morphologic adrenocortical abnormalities in fatal cases with the clinical syndrome and suggested acute adrenal insufficiency as the mechanism of death. Standard methods were used to assess pituitary and adrenal function in 29 nonimmune patients with naturally acquired falciparum malaria. Symptoms and signs compatible with adrenal insufficiency were present in all patients during the acute illness. Levels of plasma 17-hydroxycorticosteroid (17-OHCS) were increased in all patients, and 12 of 14 patients tested had diurnal variation of abnormalities. In contrast to the increased plasma 17-OHCS, the urinary 17-OHCS and 17-ketosteroids were at the lower limit of normal in all patients. Administration of Metopirone® to 14 patients elicited a normal response. Excretion of urinary aldosterone, measured in 15 patients, was normal or increased. It is assumed that the observed depression of urinary-steroid excretion in association with increased plasma 17-OHCS levels reflects decreased hepatic conjugation during the acute illness, since hepatomegaly and increased serum glutamic oxalacetic transaminase levels were frequent and creatinine clearance was normal. We conclude that pituitary and adrenal function are normal during acute falciparum malaria despite clinical findings suggestive of adrenal insufficiency.

Assessment of a test of adrenocortical function using beta1-25 corticotrophin.

SUMMARY In ten patients with a variety of rheumatic disorders the changes in plasma corticosteroid (11-OHCS) levels have been studied after adrenocortical stimulation by a continuous 5 hr. infusion of Synacthen (Ciba) or by a single i.v. injection of 200 i.u. (320 μg.) Pentacosactride (Sandoz). Comparable increases were obtained using both synthetic polypeptides. It is suggested that administration of Pentacosactride intravenously is a simple method of obtaining prolonged maximal stimulation of the adrenal cortex. A normal range of values of plasma 11-OHCS, obtained from 28 subjects, is given, and it is shown that the results are reproducible. The results of tests in six subjects with secondary adrenal atrophy due to long-term corticosteroid therapy indicate that the test can discriminate between normal and subnormal adrenocortical function.

Plasma 11-hydroxycorticosteroid and growth hormone levels in acute medical illnesses.

Adrenal cortical response in acute medical illness has been studied by measuring the plasma 11-hydroxycorticosteroid (11-OHCS) concentration in 178 patients. Those with unbalanced diabetes, acute infections, and severe myocardial infarction had high levels. The results obtained suggest that in a patient with a severe infection and hypotension a plasma 11-OHCS level of less than 15 mug./100 ml. indicates an inadequate adrenal cortical response, and one patient with septicaemia and temporary adrenal cortical insufficiency is described. Growth hormone levels were increased in patients with severe diabetic ketosis but not in those with hyperosmolar non-ketotic diabetic coma.

Reversed action of acetylated corticotrophin: inhibition of adreno-cortical secretion.

ABSTRACT A derivative of corticotrophin with acetylated amino groups and hydroxyl groups in serine was used. Acetylated corticotrophin significantly decreased the 17-hydroxycorticosteroid (17-OHCS) level in the plasma of guineapigs 4 hours after the i. m. injection of the derivative in a dose equal to 2.5 USP units of the active hormone per 100 g of body weight. The mean plasma 17-OHCS concentration before the injection of the derivative was 44 ± 2.15 μg/100 ml. After the injection of acetylated corticotrophin, the fall in 17-OHCS content was highly significant, the average level being decreased to 61 %. However, in 12 out of 36 animals there was a fall to 30 % of the initial level. The derivative obtained may be considered as an »anahormone«, and probably has the ability to inhibit the secretion of endogenous corticotrophin.

Excretion of 17-hydroxycorticosteroids and vanillylmandelic acid during 205 hours of sleep deprivation in man.

Previous studies of adrenocortical activity during sleep deprivation revealed unchanged or lowered plasma 17-hydroxycorticosteroid (17-OHCS) levels and either unchanged, lowered, or elevated urine 17-OHCS values, depending on the subject and the length of the deprivation period. In the present study, plasma 17-OHCS, urine 17-OHCS, and urine vanillymandelic acid (VMA) were measured during 205 hr. of wakefulness, the rationale being that an extended period of sleep deprivation might result in more definitive physiological responses. Plasma 17-OHCS in all 4 subjects decreased to a low point at about 90 hr., then increased to peak values at about 170 hr. Urine 17-OHCS values tended to reflect changes in plasma 17-OHCS levels. Urine VMA excretion varied considerably among the 4 subjects. The results suggest that prolonged sleep deprivation per se results in only mild, if any, specific activation of the pituitary-adrenocortical axis and in variable increases of catecholamine biosynthesis. Differing patterns of physiological activity may occur among sleep-deprived subjects.

Antidepressive medication and diurnal variation of plasma 17-OHCS levels in depression

1. (1) Diurnal plasma 17-OHCS values were determined for 20 depressed female patients before treatment and after one fortnight and one month of drug therapy. Ten of the patients received monochlorimipramine and the other ten diazepam. 2. (2) There were no significant differences between the mean diurnal plasma 17-OHCS levels of the two patient groups either in the pre-treatment phase or after introducing the drug therapy. 3. (3) The diurnal plasma 17-OHCS values were higher in all depressive patients in the pre-treatment phase than in nonhospitalized healthy medical personnel ( p < 0.05). This is concluded to be due not to the depressive illness itself but rather reflects the adrenocortical response of the patients to admission to a psychiatric clinic. 4. (4) Patients with good remission did not have higher 17-OHCS values than patients with poor remission before drug therapy was initiated. After one month's treatment the values of the good remission group were higher, but only where levels at 9.00 p.m. were compared was the difference statistically significant ( p < 0.05). This is believed to be due to the greater chronic neuroticism in the depressive patients with poor remission.

A comparative study of endocrine tests in hypothalamic disease. Circadian periodicity of plasma 11-OHCS levels, plama 11-OHCS and growth hormone response to insulin hypoglycemia and metyrapone responsiveness.

Studies of circadian periodicity of plasma 11-oxysteroid (11-OHCS) levels, of the response of plasma 11-OHCS and plasma growth hormone to insulin hypoglycemia, and of metyrapone responsiveness have been carried out in 14 subjects with localized hypothalamic disease. None of the subjects had evidence of primary sellar involvement. The only evidence of hypopituitarism (utilizing tests of basal endocrine function) was undetectable urinary gonadotropin levels in one of these subjects. Abnormal circadian patterns of plasma 11- OHCS levels were observed in 7 of these 14 subjects. Adequate insulin hypoglycemia resulted in normal increases of plasma 11-OHCS levels in each of 11 subjects in whom this was studied, and in normal increases of growth hormone levels in 10 of 13 subjects. Normal urinary 17-OHCS responses to metyrapone administration were present in 9 of 10 subjects who were tested. These studies indicate that abnormalities in the circadian periodicity of plasma 11-OHCS levels may be the earliest endocrine abnormality to be detected in patients with delimited hypothalamic disease.

Stimulation and inhibition of ACTH release in patients with pituitary disease.

ABSTRACT The adrenocortical response to overnight dexamethasone suppression was determined in normal subjects, in patients with a variety of pituitary diseases other than Cushing's syndrome, and in patients with other disease states. Seventy-nine of 80 normal subjects suppressed 9 am plasma 17-OHCS levels to less than 11.2 μg/100 ml. Of 19 patients with pituitary disease who had one or more normal tests of ACTH reserve, 10 suppressed abnormally in response to dexamethasone. Eleven of 12 patients with deficient ACTH reserve had morning plasma 17-OHCS levels in the normal range after the administration of dexamethasone. However, the low plasma 17-OHCS levels in these patients may have been due to far advanced hormonal deficiency per se. Eight patients of a large group with non-endocrine diseases had impaired suppression of plasma 17-OHCS levels. On the basis of clinical and laboratory findings, there appears to be a spectrum of abnormalities involving ACTH regulation in patients with pituitary disease. Thes...

Interference of nalidixic acid in urinary 17-ketosteroid determinations.

A NUMBER of drugs have been shown to interfere with the determination of urinary 17-ketosteroids (17-KS), 17-ketogenic steroids (17-KGS) and 17-hydroxycorticosteroids (17-OHCS). Meprobamate,1 triacetyloleandomycin2 and spironolactone3 have been shown to produce false elevation of both 17-KS and 17-OHCS values. Phenaglycodol4 and penicillin5 cause increases in both urinary 17-KS and urinary 17-KGS levels. Chlordiazepoxide hydrochloride (Librium) and etryptamine acetate (Monase) increase urinary 17-OHCS and depress urinary 17-KS values, whereas chlorpromazine (Thorazine) decreases urinary 17-OHCS while increasing urinary 17-KS.6 Hydroxyzine (Atarax) increases urinary 17-OHCS, and ethinamate (Valmid) raises urinary 17-KS.6 Reserpine suppresses both urinary 17-OHCS and urinary 17-KS levels.6 This report demonstrates . . .

Abolition of circadian periodicity of plasma 17-OHCS levels in the cat.

Abolition of circadian periodicity of plasma 17-OHCS levels in the cat.

Plasma and urinary 17-hydroxycorticosteroid responses to 72-hr. avoidance sessions in the monkey.

Marked elevations in both mean urinary and mean 9 A.M. plasma 17-OHCS levels are associated with 72-hr. avoidance sessions in the monkey. The urinary 17-OHCS elevations persist also for several days in the recovery period. The 17-OHCS elevations, while substantial, do not appear to represent maximal adrenal cortical responses and no evidence of adrenal cortical exhaustion was observed. Indirect evidence suggests rather the hypothesis that neural suppressive or governing mechanisms may come into play as avoidance is sustained. Repetition of the 72-hr. avoidance experience is generally associated with both diminishing basal urinary 17-OHCS levels and urinary 17-OHCS response to avoidance. After 6 sessions at monthly intervals, however, a substantial urinary 17-OHCS response was obtained when the intensity of the emotional stimulus was increased. Substantial individual differences were observed between monkeys with respect to mean urinary 17-OHCS response to avoidance. Highly significant correlations were observed between these individual differences in 17-OHCS response and similar individual differences in mean lever response rate before, during, and after avoidance. Evidence is presented that, following temporary initial disruption, diurnal changes in plasma and urinary 17-OHCS levels persist throughout the stressful period. It is concluded that the 17-OHCS responses indicate that the stressful conditions in these experiments are of sufficient severity to provide a suitable test for the possible responsivity of other endocrine systems to a stressful situation in which predominantly psychological factors are involved.

Plasma Insulin Response to 72-Hr. Avoidance Sessions in the Monkey

Plasma immunoreactive insulin levels, determined by radioimmunoassay, show a biphasic pattern of response to avoidance sessions in the monkey. There is an initial drop in plasma immunoreactive insulin levels during the first hours of avoidance and a later prolonged elevation of levels above baseline--persisting often for many days following 72-hr. avoidance sessions. The fact that the plasma insulin changes in avoidance do not appear to be mediated by changes in plasma glucose levels suggests that other regulatory influences on insulin secretion may supersede blood sugar regulation of insulin levels under some conditions. Some possible mediating mechanisms underlying the observed suppression of plasma insulin levels are discussed. Some evidence is presented that emotional reactions to venipuncture may also elicit a decrease in plasma immuno-reactive insulin levels with associated elevations in plasma 17-OHCS and glucose levels.

Circadian rhythm of plasma 11-hydroxycorticosteroids in psychiatric disorders.

Studies of the circadian rhythm in plasma 11-O.H.C.S. levels showed that a subgroup of affective psychotics had higher plasma 11-OHCS values as compared with schizophrenic and other psychotic subgroups, and a somewhat less regular rhythm. One patient with depression who was studied over 48-hour periods showed a reduction in plasma 11-OHCS levels with clinical recovery. An accentuated fall and rise in plasma 11-OHCS values in the night and early morning samples, respectively, was observed in the schizophrenic subgroup.

Adrenocortical function related to methoxyflurane anaestheaia and surgery in man.

The effect of preanaesthetic medication, methoxyflurane anaesthesia, and surgery on free hydrocortisone (= 17-OHCS) concentrations in plasma were studied in eleven patients. The preanaesthetic medication significantly decreased plasma levels of free 17-OHCS, but the changes in concentration were variable after methoxyflurane anaesthesia for 30 minutes. Surgical stress evoked significant elevation of free 17-OHCS levels in plasma. These findings would imply that methoxyflurane anaesthesia is not a stressing agent for the adrenal cortex in man.

Correlation Between Clinical Pattern and Pathological Findings in Cushing's Syndrome

We reviewed 150 findings in 58 patients (14 males and 44 females) with adrenocortical tumors (26 with adenoma and 32 with carcinoma) admitted to Vanderbilt Hospital during 28 years. In general, our findings agree with those reported by others in multi-institutional series or literature reviews. Adenomas took longer to diagnose than carcinomas. Adenomas usually caused Cushing's syndrome, but two caused virilization and three caused no endocrine syndrome. There was no difference in time required for diagnosis of carcinoma in men or women or in those with Cushing's syndrome, virilization or no endocrine syndrome. Urinary 17-hydroxycorticoid (17-OHCS) levels were similar in those with adenoma and those with carcinoma, but 17-ketosteroid (17-KS) levels were usually less than 20 mg per day in patients with adenoma and greater than 20 mg per day in patients with carcinoma. Adenomas were uniformly independent of endogenous ACTH stimulation, but frequently responded to exogenous ACTH. As with adenomas, no carcinoma demonstrated normal suppression with dexamethasone or normal response to metyrapone, but only one responded to exogenous ACTH. Some patients had no clinical Cushing's syndrome despite high levels of plasma cortisol and urine 17-OHCS. “Nonfunctional” tumors probably merely secreted insufficient steroids to cause signs and symptoms. Patients with adenoma were uniformly cured by surgical tumor resection. Occasional patients with carcinoma enjoyed long survival despite incomplete resection of their tumors, but most patients died of recurrent or metastatic carcinoma within seven years, often within a year or two. Small tumor size and benign histologic features were insufficient to predict benign clinical behavior. The adrenocorticolytic drug, o,p′ DDD, offered objective remission for only an occasional patient.