Cortisol Secretion Rate Research Articles

Determination of pregnane-17,21-diol-20-ones in human urine.

Treatment of urine or of a urine extract with periodate followed by treatment of the acidic oxidation products with sodium bismuthate gave a mixture of neutral end products consisting only or predominantly of 17-oxoandrostanes derived from the corresponding urinary pregnane-17,21-diol-20-ones. The mixture of end products was resolved by gas-liquid or paper chromatography. The latter technique was used to determine cortisol secretion rates and the results were found to be in reasonable agreement with those obtained by a double-isotope method. Gas-liquid-chromatographic characterization of steroidal 4-en-3-ones is described.

Male pseudohermaphroditism due to 17 alpha-hydroxylase deficiency.

This is the first report of a male with 17alpha-hydroxylase deficiency resulting in male pseudohermaphroditism, ambiguous external genitalia, absence of male secondary sexual characteristics, and gynecomastia at puberty. Diagnosis was based on extensive studies of steroid metabolism including the following: low urinary excretion of 17-ketosteroids and 17-hydroxycorticoids which did not increase after ACTH; no response of very low plasma testosterone and dehydroepiandrosterone to adrenocorticotropin (ACTH) or chorionic gonadotropin; and low urinary aldosterone and plasma renin which increased after dexamethasone. Secretion rates of 17-hydroxylated steroids, cortisol (F) and 11-desoxycortisol (S), were very low while desoxycorticosterone (DOC) and corticosterone (B) secretion rates were increased sevenfold. Results expressed as milligrams per meter squared per day were as follows: F, 1.3; S, 0.023; DOC, 0.35; and B, 16 (mean normal values were F, 7.5; S, 0.26; DOC, 0.055, and B, 2.2). Plasma gonadotropins were markedly increased (FSH, 106; LH, 364 mIU/ml). Testicular biopsies revealed interstitial-cell hyperplasia and early spermatogenesis. Karyotype was 46/XY. Pedigree showed no other affected member. At laparotomy ovaries, uterus, and fallopian tubes were absent, vas deferens was incomplete, and prostate was present. External genitalia consisted of small phallus, bifid scrotum, third-degree hypospadias, and small vagina. At puberty there was no growth of body hair or phallic enlargement. Biopsy of marked gynecomastia showed both ducts and acini. Testosterone administration produced virilization. Sexual ambiguity demonstrates strong dependence of external genitalia on androgens for male differentiation. Suppression of Müllerian structures occurred despite female levels of testosterone indicating this step in male differentiation is not testosterone dependent. Pubertal breast development in this male supports the concept of femaleness during ontogeny unless counteracted by male factors. Diagnosis of other adrenocortical enzymatic deficiencies is excluded by the steroidal studies. The clinical response to testosterone excludes testicular feminization. Deficiency of 17-hydroxylation must be added to the cause of male pseudohermaphroditism.

Simultaneous metabolism of cortisol sulfate and cortisol in normal human adults.

Tracer doses of cortisol and of cortisol sulfate, each bearing a different radioactive label (isotope ratio = 1), were administered intravenously to 4 subjects. Unconjugated steroids, steroids released following β-glucuronidase hydrolysis, and steroid sulfates were sequentially extracted from the urine voided within 48 hr after the injection. Following purification from the glucuronide fraction, the isotope ratios of 11β-hydroxy- and 11-ketoetiocholanolone ranged from .13 to .99, while cortolone, tetrahydrocortisol and tetrahydrocortisone contained negligible amounts of the radioactivity originally associated with cortisol alcohol. From the specific activity of the latter 2 metabolites, cortisol secretion rates of 8–21 mg/day were calculated. Sulfation of cortisol did not occur to any appreciable extent. From the specific activity of cortisol sulfate, which was the main component of the sulfate fraction, secretion rates of this conjugate ranging from .04 to 0.1 mg/day were obtained. The data demonstrate that in adult subjects cortisol sulfate is in part metabolized through a pathway yielding 11/3-hydroxy- and ll-oxo-17-ketosteroids, which are subsequently excreted as glucuronide esters, and that the secretion rate of cortisol sulfate represents but a fraction of that of cortisol.

Effect of aminoglutehimide and reserpine on the human pituitary-adrenal axis: Remission of a case of Cushing's disease

A patient is presented with a documented five-year history of untreated pituitary ACTH-dependent hypercortisolism (Cushing's disease) who had a sudden remission while receiving aminoglutethimide and reserpine. Although aminoglutethimide is known to block adrenocortical steroidogenesis, the remission was not the result of primary adrenocortical or pituitary failure. Following the remission, the urine 17-OHCS were suppressible with 2 mg./day of dexamethasone, were responsive to synthetic vasopressin and ACTH, but were unresponsive to metyrapone. These data suggest that the remission was the result of a change in the abnormal force controlling the release of ACTH from the pituitary. Apparently the force controlling the inhibition of ACTH release was left intact, but the force responsible for stimulating ACTH release was impaired. The responses to tests of pituitary-adrenal function of euadrenal subjects receiving these drugs are described. The histological changes in the adrenal cortex of these subjects demonstrated atrophy of the zona glomerulosa and hyperplasia of the zona fasciculata. These morphological changes in the adrenal cortex of individuals receiving aminoglutethimide are consistent with the chemical findings of a decreased aldosterone secretion rate and a compensated, unchanged cortisol secretion rate.

Adrenocortical and Thyroid Function in the Deprivation Syndrome

The role of emotional factors in the growth failure of the deprivation syndrome was investigated by measuring adrenocortical and thyroid functions; three control groups had growth failure from other causes. Cortisol secretion rate was elevated in 50% of cases, but not in controls. Excessive appetites and a significantly higher weight gain per unit of nitrogen retention during ad libitum feeding were evidence of increased biological activity. Plasma cortisol was higher on admission than after weight gain; standard deviations decreased with recovery, suggesting establishment of a diurnal rhythm. Serum thyroxine (T 4 ) was decreased in patients with the deprivation syndrome and in controls with growth failure due to undernutrition, but the basal metabolic rate was normal. The low T 4 thus seems to reflect a decrease in thyroxine binding proteins, apparently on the basis of undernutrition.

Adrenal blood flow dependence of cortisol secretion rate in unanesthetized dogs.

ARTICLESAdrenal blood flow dependence of cortisol secretion rate in unanesthetized dogsM L'age, A Gonzalez-Luque, and FE YatesM L'age, A Gonzalez-Luque, and FE YatesPublished Online:01 Aug 1970https://doi.org/10.1152/ajplegacy.1970.219.2.281MoreSectionsPDF (2 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByEffect of Angiotensin II and ACTH on Adrenal Blood Flow in the Male Rat Adrenal Gland In Vivo13 November 2017 | Endocrinology, Vol. 159, No. 1Aldosterone Secretagogues Increase Adrenal Blood Flow in Male RatsEndocrinology, Vol. 155, No. 1Diurnal ACTH and plasma cortisol variations in healthy dogs and in those with pituitary-dependent Cushing’s syndrome before and after treatment with retinoic acidResearch in Veterinary Science, Vol. 86, No. 2Steroid-Producing Cells Regulate Arterial Tone of Adrenal Cortical ArteriesEndocrinology, Vol. 148, No. 8Hormone multifunctionalities: a theory of endocrine signaling, command and controlProgress in Biophysics and Molecular Biology, Vol. 86, No. 3Corticosterone-dependent driving influence of the suprachiasmatic nucleus on adrenal sensitivity to ACTHDominique Sage, Daniel Maurel, and Olivier Bosler1 February 2002 | American Journal of Physiology-Endocrinology and Metabolism, Vol. 282, No. 2Vasodilator response to exogenous adrenocorticotropic hormone in fetal adrenal cortex precedes increased steroidogenesis in sheep at 105–112 days gestationEuropean Journal of Obstetrics & Gynecology and Reproductive Biology, Vol. 81, No. 1Development of the hypothalamus-pituitary-adrenal axis of the equine fetus: A comparative review10 June 2010 | Equine Veterinary Journal, Vol. 29, No. S24The relationship between adrenal vascular events and steroid secretion: The role of mast cells and endothelinThe Journal of Steroid Biochemistry and Molecular Biology, Vol. 40, No. 1-3Effects of acute stress, (1–24)ACTH administration and changes in superfusion temperature and flow rate on the in vitro secretion of glucocorticosteroids and aldosterone from the mongolian gerbil (Meriones unguiculatus) adrenal glandComparative Biochemistry and Physiology Part A: Physiology, Vol. 82, No. 4Effect of histamine on blood flow to the adrenal glands of pigsVeterinary Research Communications, Vol. 5, No. 1REGULATION OF FETOPLACENTAL STEROIDOGENESIS IN RHESUS MACAQUES,Regulation of Myocardial ContractilityAnalysis of the Adrenocortical Steady-State CharacteristicsIEEE Transactions on Biomedical Engineering, Vol. BME-24, No. 4Static gain and dynamics of cortisol secretory response to intravenous corticotropin (ACTH) in unanesthetized dogs analysis by a linear mean-squared estimatorAnnals of Biomedical Engineering, Vol. 4, No. 4Models of Adrenal Cortical Control More from this issue > Volume 219Issue 2August 1970Pages 281-287 Copyright & PermissionsCopyright © 1970 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1970.219.2.281PubMed4317596History Published online 1 August 1970 Published in print 1 August 1970 Metrics

The secretion rate of cortisol in patients with rheumatoid arthritis

The secretion rate of cortisol was determined in patients with rheumatoid arthritis by a known isotope dilution technique which was slightly modified. In 24 patients not previously treated with corticosteroids or corticotrophin, 3 patients had cortisol secretion rates on the low side of the normal range and the remaining patients had normal values; also among 14 patients who had been receiving prolonged oral prednisolone treatment for varying periods (from 2 years 7 months to 7 years 2 months) and from whom steroid treatment was gradually withdrawn (0.5 mg/month) only 2 patients had cortisol secretion rates in the low normal range and the values of the remaining 12 patients were within normal limits. There was good correlation between the cortisol secretion rate and the total 17-oxogenic steroid values. From the results presented here it cannot be significantly concluded that patients with rheumatoid arthritis present low secretion rates of cortisol.

Cortisol metabolism in the morning and evening; relation to cortisol secretion rate measurements

The question was studied whether the discrepancies observed in cortisol secretion rate determinations from several metabolites were due to changes in metabolic pathway of cortisol during the course of the day. Cortisol-4- 14C was administered to two subjects in the morning at about 0800 hr. The studies were repeated in the same subjects twice in the evening at about 1800 hr and one subject received cortisol-4- 14C at 1415 hr as well. The specific activities of 6 metabolites were determined and the apparent cortisol secretion rates were calculated. The production rates from the various metabolites were not in precise agreement at any of the times of day studied; the disagreement was apparently greatest when the tracer was given in the evening. That the time of day at which labeled cortisol is injected is not the factor responsible for the different estimates was shown in an adrenalectomized subject maintained on dexamethasone. Tracer cortisol-4- 14C was given to this patient at 1750 hr and 36 hours later another tracer of cortisol 1,2- 3H was given at 0900 hr. Complete urine collections were obtained from the time of administration of the first tracer until 36 hours after the second. The urine was processed as a single collection. The 3H/ 14C ratios of all the metabolites were identical demonstrating that the labeled cortisol followed identical metabolic pathway in the morning and in the evening. It thus appears that a diurnal variation in cortisol metabolizing enzymes is not responsible for the demonstrated discrepancies between metabolites when secretion rate is measured by the isotope dilution method from urinary metabolites.

Cortisol responses to diazoxide in man and their possible relationship to effective blood volume

In previously reported studies, oral salt loading resulted in increases in urinary cortisol and the cortisol secretion rate, and, conversely, the potent diuretics, hydrochlorothiazide or ethacrynic acid, resulted in decreased cortisol excretion. Because of its structural similarity to hydrochlorothiazide and also because it reduces the effective blood volume without inducing sodium depletion it seemed that diazoxide would be useful in further studies of the cortisol responses noted above. The administration of oral diazoxide, 200–400 mg./day, to five normal subjects resulted in evidences of diminished cortisol secretion in every instance; mild sodium retention was noted, although aldosterone excretion did not increase significantly except in one subject. The results of all these studies are consistent with the proposition that cortisol production increases with factors tending toward volume hyperexpansion and decreases with those tending to reduce the effective blood volume. It is tempting to speculate that these cortisol responses reflect another mechanism involved in the maintenance of volume homeostasis.

The assessment of adrenal-cortical function in patients receiving corticotrophin therapy.

ABSTRACT Plasma cortisol and urinary 17-hydroxycorticosteroids and cortisol secretion rates have been measured on patients with multiple sclerosis taking part in a therapeutic trial of corticotrophin. Patients who had not received corticotrophin showed no evidence of abnormal adrenal function, although the combination of normal levels of plasma cortisol with somewhat low concentrations of urinary cortisol metabolites suggested an abnormal steroid metabolism. Patients who had been treated continuously with corticotrophin (for at least 1 year) showed elevated plasma cortisol concentrations and an even greater disparity between plasma and urine concentrations than the untreated controls. Thus, the urinary steroid measurements did not give a useful measure of the degree of adrenal response and should not be used to monitor prolonged corticotrophin therapy.

Stimulation of corticotropin release by corticotropin-releasing factor (CRF) or by vasopressin following intrapituitary infusions in unanesthetized dogs: inhibition of the responses by dexamethasone.

A new technique was developed for intrapituitary infusion of test substances into trained, unanesthetized. dogs. Blood from one adrenal was collected intermittently by a modification of the method of Hume and Nelson. Adrenal secretion rate of cortisol was variably increased by intrapituitary infusion of vehicle solutions at the rate of 40 μl/25 min. In contrast, infusions of crude ovine CRF at a rate of 170 μg in 40 μl/25 min into the pituitary provoked a rapid but submaximal increase in cortisol secretion rate. Similarly, lysine vasopressin infused into the pituitary of these unanesthetized dogs without pharmacological pretreatment had potent ACTH-releasing properties: at a dose of approximately 212 mU/25 min it also provoked rapid but submaximal increases in cortisol secretion rate in every case. The corticotropinreleasing properties of ovine CRF and of lysine vasopressin were completely suppressed by systemic dexamethasone (4 mg/og sc) if the dexamethasone was administered 2–8 hr before the ip injectio...

Secretion rates of cortisol and aldosterone precursors in various forms of congenital adrenal hyperplasia.

Using a previously described method for the simultaneous determination of the secretion rates of cortisol and aldosterone precursors, the specific enzyme deficiency in various form? of congenital adrenal hyperplasia was elucidated. Secretion rates of cortisol (F), 11-desoxycortisol (S), corticosterone (B), 11-desoxycorticosterone (DOC) and aldosterone (aldo) were determined in 10 normal subjects, 2 children with simple virilizing adrenal hyperplasia (21-hydroxylase defect) and 1 child with hypertensive virilizing adrenal hyperplasia (11-hydroxylase defect) under the following conditions: normal, low and high sodium (Na) diets, administration of metyrapone, dexamethasone and intravenous ACTH. The mean daily normal secretion rates were: F—7.5 mg/m2; S—0.26 mg/m2; B—2.2 mg/m2; DOC—0.055 mg/m2; aldo—0.13 mg/m2. Changes in dietary Na altered only aldo secretion. ACTH administration raised B and F secretion significantly. Metyrapone increased S and DOC secretion more than ACTH but decreased B, F and aldo secretion. In 21- hydroxylase defect the secretion rates of B, F, DOC and S did not increase appropriately with ACTH and aldo secretion showed a blunted increase with low Na diet. Secretion of B and F was below normal under all conditions. In the 11-hydroxylase defect the secretion rates of B and F were very low and did not increase with ACTH, while the secretion rates of DOC and S were 100 times normal and increased further with ACTH and metyrapone. Aldosterone secretion was very low and did not increase with Na deprivation. Results confirmed a deficiency of 21-hydroxylase in the simple form and a deficiency of 11-hydroxylase in the hypertensive form of adrenal hyperplasia.

Hypothalamic-pituitary-adrenal function in obesity and the cortisol secretion rate following prolonged starvation.

ABSTRACT Evaluation of the hypothalamic-pituitary-adrenal axis was undertaken in obesity. Abnormality of diurnal rhythm of plasma cortisol, elevated cortisol secretion rate (CSR) and, to a lesser extent, excessive response to adrenal stimulation, were found in a proportion of cases. Adequate hypoglycaemia invariably produced a significant cortisol rise and 80% of cases responded to L.8 vasopressin at 5 units im. A significant fall in CSR, urinary 17-OHCS and 17-KS occurred with starvation. The significance of these findings in relation to Cushing's syndrome is discussed.

Exchangeable sodium and aldosterone secretion in children with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

Extract: Aldosterone secterion rates(ASR) and exchangeable body sodium (Nae) have been measured simultaneously in 25 cases of congenital adrenal hyperplasia (CAH) with and without salt loss, both during normal and during low salt intake. The degree of 21-hydroxylase deficiency was assessed from the cortisol secretion rate (CSR) and urinary excretion of pregnanetriol and 11-ketopregnanetriol.

Fetal and maternal secretion rate of cortisol in sheep: diffusion resistance of the placenta.

Extract Three pregnant ewes and their fetuses, in utero, were infused constantly with 14C-cortisol and 3H-cortisol. The maternal concentrations of cortisol in plasma were 5.24f1.16 ,ug/100 ml and the fetal concentrations in plasma were 2.39%0.25 pg1100 ml. Metabolic clearance rates were estimated to have a mean of 1,397 liters124 h in the ewes and 92 liters124 h in the fetuses. The mean rates of blood production for the ewe and the fetus were 73.6 and 2.14 mg/24 h, respectively, while the mean rates of cortisol secretion for the ewe and fetus were 73.5 and 1.64 mg/24 h, respectively. Application of the theoretical model presented, allowed us to calculate the contribution the mother was making to the cortisol concentration in the plasma of the fetus and vice versa. We also calculated the ratio of relative resistance for transplacental passage of cortisol. S'eculation From the model proposed, it was calculated that the fetus contributed very little to the maternal cortisol levels. In two experiments, more than 60 % of the fetal levels of plasma cortisol were of fetal origin, while in another experiment, almost all the cortisol was produced by the fetus. We speculate, therefore, that a 'placental barrier' exists in sheep during pregnancy. The physiological role of this barrier remains to be determined.

EMBRYO MORTALITY IN THE HEAT STRESSED EWE

Summary. The possible roles were examined of the corpus luteum, thyroid and adrenal cortex in the embryo mortality experienced by heat stressed Merino ewes. Heat stress during early pregnancy did not significantly affect the histology, size or weight of the corpus luteum, and progesterone therapy did not enhance embryo survival in heated ewes. Heat stress did depress (P<0-001) thyroid epithelial cell height and hence, presumably, thyroxine secretion rate. However, thyroxine therapy was without effect on embryo survival in both heated and unheated ewes. Raised cortisol secretion rates were not indicated in heated ewes. Cortisol administered to unheated ewes did not affect embryo survival, although it did depress embryo growth rate ( <0·10). Changes in the luminal fluids of the Fallopian tubes and uterus are proposed as the most likely mechanism of heat-induced embryo mor¬ tality in the ewe.

Problems related to the determination of cortisol secretion rate in man when using "urinary" methods.

Problems related to the determination of cortisol secretion rate in man when using "urinary" methods.

THE SECRETION, INTERCONVERSION AND CATABOLISM OF CORTISOL, CORTISONE AND SOME OF THEIR METABOLITES IN MAN

ABSTRACT Trace doses of one or more of the following radioactive steroids were given to 2 normal and 4 rheumatoid arthritic men: cortisol, cortisone, 20α-dihydrocortisol, 20β-dihydrocortisol and tetrahydrocortisol. The specific activities of the given steroids and some of their unconjugated and conjugated metabolites in urine were measured. The secretion rates of cortisol and cortisone for the 2 normal men, deduced from their specific activities in urine, were found to be approximately equal and in sum approximately equal to the secretion rate of cortisol deduced from the specific activities of their conjugated metabolites. Evidence of the speed of interconversion of cortisol and cortisone was obtained by giving [4-14C] cortisol and [1,2-3H] cortisone simultaneously to the 2 normal subjects and measuring the specific activities of the cortisol and cortisone in urine; also by measuring, in one subject, the proportion of 14C and 3H in plasma cortisol and cortisone at intervals after administration. The specific activities were similar, the plasma cortisone was approximately 50 % derived from cortisol at 30 min and the plasma cortisol 40 % derived from cortisone at 40 min. For both the normal subjects given 14C-cortisol and 3H-cortisone the specific activities of the urinary unconjugated metabolites were consistently and markedly higher than those of the hydrolysed conjugated metabolites. The combined secretion rate of 20α- and 20β-dihydrocortisol and tetrahydrocortisol, for one normal subject, was estimated to be approximately 4 mg/24 h. It is suggested that the findings are consistent with the hypotheses that under basal unstressed conditions, 1, cortisol and cortisone are secreted by the adrenal in approximately equal amount; 2, cortisol and cortisone are interconverted at a speed that precludes the liver from being the main site of the interconversion; 3, the major fractions of the unconjugated and conjugated cortisol and cortisone metabolites are formed at different sites.

The diagnosis of hypercortisolism. Biochemical criteria differentiating patients from lean and obese normal subjects and from females on oral contraceptives.

ABSTRACT Hypercortisolism may be difficult to diagnose because the clinical features are sometimes unimpressive, or because current laboratory determinations may furnish misleading results. Studies have been performed on 40 lean subjects, 28 obese subjects, 15 females on oral contraceptives, 23 patients with long-standing paraplegia, 17 patients with undoubted features of Cushing's syndrome and chemical evidence of hypercortisolism, and 28 individuals with questionable hypercortisolism. The overlap between obese normal subjects and patients with hypercortisolism in urinary 17-OHCS excretion and cortisol secretion rates has been eliminated by expressing these measurements per gram of excreted creatinine. Patients with hypercortisolism invariably excreted more than the normal amounts of 17-OHCS (2.0–6.5 mg/day/g creatinine) and secreted more than normal amounts of cortisol (4.4–19.0 mg/day/g creatinine). Plasma 17-OHCS in patients with hypercortisolism was sometimes normal between 8 and 9 am [normal =19.2 ±...

Metabolism of cortisol in cushing's syndrome

The urinary output of 6β,11β, 17∞, 21, tetrahydroxypregn-4-ene-3, 20-dione (6β-OH-F) and its 20 dihydro metabolites 6β,11β,17∞, 20∞, 21 pentahydroxypregn-4-ene-3-one (6β, 20∞-OH-F) and 6β,11β,17∞,20β-21 pentahydroxypregn-4-ene-3-one (6β, 20β-OH-F) have been determined in patients with Cushing's syndrome. Following the administration of tritiated Cortisol, the specific activities of cortisol (F) and tetrahydrocortisol (THF) were compared with the specific activity of 6β-OH-F to demonstrate that adrenal secretion of 6β-OH-F occured, in addition to its formation by the peripheral metabolism of circulating F. Contrary to earlier findings, the production of 6β-OH-F in Cushing's syndrome expressed as a percentage of the cortisol secretion rate (CSR) was found to be lower than normal. This would appear to indicate a possible derangement of cortisol metabolism in this syndrome. A tentative explanation of this phenomenon is discussed. When compared with normal excretion values, the excretion rate of both' 20 dihydro metabolites of 6β-OH-F expressed as a percentage of the CSR were found to be elevated. A possible explanation for this phenomenon is given.