After Adrenocorticotropic Hormone Research Articles

Group housing in row cages: an alternative housing system for juvenile mink

We studied a group housing system as an alternative to the traditional pair housing of juvenile mink. The focus was on both the welfare and production of mink. The pairs were housed in standard mink cages, whereas the groups were in row cage systems consisting of three standard mink cages connected to each other. The welfare of the mink was evaluated by behavioural observations (stereotypies and social contacts), evaluation of the incidence of scars assumed to be caused by biting, and adrenal function (serum cortisol level after adrenocorticotropic hormone (ACTH) administration and adrenal mass). Feed consumption, pelt length, quality and price were used for comparing the two housing systems from the economic point of view. Although the incidence of scars showed that there might have been more aggressive behaviour among the group-housed than among the pair-housed mink, this was not observed unambiguously in behavioural observations, and, at least, aggression did not cause mortality or serious injuries to the animals as has been observed in some earlier studies. In addition, the housing system did not affect pelt size, and, although the quality of the pelts was slightly lower in the group than in pair-housed mink, there was only a tendency for lower pelt prices. The lower pelt prices in the group-housed mink might even be partially compensated for by the group-housed mink eating 10% to 20% less in the late autumn, due to thermoregulatory benefits, than their pair-housed conspecifics. The results on the frequency of stereotypic behaviour (but not adrenal function) suggest that the group-housed animals were possibly less stressed than the pair-housed animals. Group housing of juvenile farmed mink in a row cage system cannot be recommended before the effects on welfare and production are clarified in further studies.

Localization of Aldosterone-Producing Adrenocortical Adenomas: Significance of Adrenal Venous Sampling

Accurate localization of aldosterone-producing adenoma (APA) is essential for the treatment of primary aldosteronism (PA). In order to confirm the clinical usefulness of adrenal venous sampling (AVS), we retrospectively studied 87 cases of PA in whom AVS was conducted. We collected right and left adrenal venous effluents simultaneously before and after adrenocorticotropic hormone (ACTH) stimulation for measurements of aldosterone concentration (A) and cortisol concentration (C). Based on AVS results, we judged 66 cases as having unilateral aldosterone hypersecretion and the remaining 21 cases as having no apparent laterality. Of the above 66 subjects, 61 underwent laparoscopic removal of the adrenal gland through a retroperitoneal approach. The presence of APA was histopathologically confirmed, and blood pressure decreased significantly with normalization of plasma aldosterone concentration (PAC) in all cases. The receiver operator characteristics (ROC) curve analysis between the operated and no-apparent-laterality groups revealed that the ratio of A/C on the higher side to A/C on the lower side (A/C ratio) after ACTH stimulation is a useful index, with a cutoff value of 2.6, a sensitivity of 0.98 and a specificity of 1.0. The ROC curve analysis between the APA side and contralateral side within the operated patients revealed that the cutoff value of A was 1,340 ng/dL, with a sensitivity of 0.92 and a specificity of 1.00. Our results indicate the usefulness of simultaneous AVS and ACTH stimulation for localizing APA.

Hormonal disturbances associated with obesity in dogs

Obesity is associated with multiple endocrine alterations and changes in the concentration of circulating hormones. However, few studies have explored such alterations in dogs with naturally acquired excess weight. In the present study, we investigated the effect of naturally acquired obesity on cortisol, insulin-like growth factor (IGF)-1 and prolactin secretion in dogs. Thirty-one overweight dogs were enrolled in the trial. Blood samples were collected before and after adrenocorticotrophic hormone (ACTH) injection. Free thyroxine (fT4), cortisol, thyroid-stimulating hormone (TSH), IGF-1, prolactin and fructosamine were assayed. Body weight excess increased significantly with age and neutered dogs were more obese than entire ones. The ACTH stimulation test was within the normal range for 26 of 31 dogs. Prolactinaemia was increased in seven dogs and IGF-1 in six dogs. Twenty dogs had a fructosamine concentration >340 microm. Interestingly, 18 of 31 dogs showed disturbances of thyroid function based on high TSH and/or low fT4 baseline concentration, with 11 dogs showing both. According to these parameters only six of 31 dogs were free of hormonal disturbances. These results revealed the high incidence of such disturbances, especially thyroid dysfunction, in obese, but otherwise apparently healthy dogs. They demonstrate the importance of examining endocrine function during the initial evaluation of obese dogs to avoid failure of any nutritional treatment.

Effects of long-term inhaled corticosteroids on adrenal function in patients with asthma

Inhaled corticosteroids (ICSs) are effective asthma controllers, but long-term use could lead to adverse effects. To examine adrenal responsiveness of patients with persistent asthma treated with long-term ICSs. Morning plasma cortisol levels before and 30 minutes after adrenocorticotropic hormone (ACTH) (1 microg intravenously) stimulation were compared. Primary end points included mean prestimulation and poststimulation cortisol levels; secondary end points included morning cortisol level of 5 microg/dL or less, post-ACTH stimulation cortisol level of 18 microg/dL or less, and/or a net change of 7 microg/dL or less from baseline. A total of 103 asthmatic patients (29 in the triamcinolone acetonide group, 18 in the flunisolide group, 45 in the fluticasone propionate group, and 11 in the oral corticosteroids group [positive controls]) completed the study. Mean daily ICS doses and durations were as follows: triamcinolone acetonide: 448 microg for 36 months; flunisolide: 1,181 microg for 41 months; and fluticasone propionate: 745 microg for 19 months. Eleven of 30 patients taking high-dose ICSs (10 of 28 taking fluticasone propionate and 1 of 2 taking flunisolide) had both low morning cortisol levels and abnormal post-ACTH stimulation cortisol levels. Few patients taking lower doses of any ICS had abnormal results. Patients who require long-term treatment with high-dose ICSs may have abnormal morning plasma cortisol levels and reduced responsiveness to ACTH stimulation. Careful monitoring of adrenal function should be considered in such patients.

Effects of turning duration during incubation on embryo growth, utilization of albumen, and stress regulation

Eggs from Cobb broiler breeders were incubated for 18 d. Eggs were not turned (T0) or were turned until 9 (T9), 12 (T12), 15 (T15), or 18 (T18) d. First, the effects of turning on embryo and albumen weights were studied. Samples of eggs were opened at d 9, 12, 15, and 18 for embryo and albumen weighing. The results show that embryos from unturned eggs had lower weights and higher remaining albumen weights than those from turned eggs. At d 18, albumen utilization was completed in the T12, T15, and T18 groups only. Also, further turning until d 15 and 18 increased embryo weights. The responsiveness of the embryo after adrenocorticotropic hormone (ACTH) injection was studied to test stress control in embryos. Blood samples were collected from embryos at 60 and 150 min after injection at d 12, 15, and 18 and were analyzed for corticosterone concentrations. The results showed that basal corticosterone levels increased with embryo age. At 60 min after ACTH injection, corticosterone levels were lower at d 12 than at d 15 and 18. At 150 min after ACTH injection, corticosterone levels followed different trends according to incubation stage and turning duration. The highest basal corticosterone levels were obtained with the T15 group at d 15 and 18. Also at d 18, corticosterone levels in the T15 group were the highest at 150 min after ACTH injection. We concluded that egg turning was required during incubation until d 12, at least, and should not be stopped until after d 15.

17α-hydroxylase deficiency

To search for molecular changes in two Argentinian sisters with a clinical and biochemical diagnosis of 17alpha-hydroxylase deficiency. Both patients had 46 XX karyotype, with sexual infantilism, primary amenorrhea, and hypertension. Other member of the first degree family did not have this deficiency. HORMONAL RESULTS: The patients showed high levels of gonadotrophins and progesterone along with very low cortisol and androgen levels. Basal levels of corticosterone were very high, but aldosterone was normal. Both steroids had a high response after adrenocorticotropic hormone (ACTH) stimulation, with no changes in 17-hydroxyl progesterone and cortisol levels. Progesterone, corticosterone, and aldosterone decreased with the dexamethasone test, without modifications in 17-hydroxyl progesterone and cortisol levels. A corticosterone/aldosterone ratio was calculated from the results of the stimulation test; the ratios were similar in both patients. On administration of the ACTH test, both parents and one sister (S2) showed a marked response in corticosterone levels, their corticosterone/aldosterone ratios were also similar to each other and similar to the patients. MOLECULAR RESULTS: Molecular studies in the cytochrome P450 17 (CYP17) gene showed that exon 8 had a 4 bp duplication at codon 480 (CATC) in the two patients and their mother and in exon 1, a C to T transition at codon 96 was identified, changing CGG into TGG in the two patients, S2, and their father. Both patients were shown to be compound heterozygous, carrying different alleles in exon 1 and exon 8, inherited from their father and mother, respectively. The molecular results obtained on S2 confirmed the heterozygosity suggested by the stimulated hormonal test and corticosterone/aldosterone ratio.

Low 11-deoxycortisol to cortisol conversion reflects extra-adrenal factors in the majority of women with normo-gonadotrophic normo-estrogenic infertility.

Women with normogonadotrophic normo-estrogenic oligomenorrhoea often disclose a variety of clinical symptoms. Many of these individuals are obese with features of pseudo-hypercortisolism. In the current study, 11-deoxycortisol and cortisol concentrations were determined in this group and compared with ovulatory controls. Twenty-six women with clomiphene citrate-resistant infertility, 12 lean and 11 obese ovulatory controls were studied. Women with infertility had the highest 11-deoxycortisol concentrations (mean +/- SD: 4.1 +/- 1.5 ng/ml) compared with obese and lean controls (3.1 +/- 1.4 and 2.4 +/- 0.9 ng/ml) (P < 0.01), but similar morning cortisol concentrations (0.47 +/- 0.15, 0.45 +/- 0.16 and 0.47 +/- 0.18 nmol/l). Baseline 11-deoxycortisol/cortisol ratios (>90th percentile of ovulatory controls) were elevated in 23/26 infertile women (88%), and in 3/26 women (12%) after adrenocorticotrophic hormone (ACTH) stimulation. Three out of six lean infertile women had elevated baseline 11-deoxycortisol/cortisol ratios, but none of these women had elevated ratios after ACTH stimulation. Stepwise regression analysis, after exclusion of testosterone, revealed significant correlations between the groups (lean controls, obese controls, infertility) and ACTH-stimulated 11-deoxycortisol/cortisol ratio (P < 0.05), but not with fasting glucose, insulin, cortisol, 11-deoxycortisol and baseline 11-deoxycortisol/cortisol ratios. Congenital adrenal hyperplasia was not observed in the majority of infertile women. The data indicate that extra-adrenal factors were involved in most of the infertility syndromes that were studied.

Correlation between plasma and salivary cortisol levels in preterm infants

We sought to determine correlations between plasma and salivary cortisol levels in preterm infants in the basal state and after adrenocorticotropic hormone (ACTH) stimulation during the first week of life. Infants (n = 48) were given ACTH or saline solution; each injection was separated by 24 hours. Salivary and plasma cortisol levels correlated at baseline (r = 0.67, P < .0001) and 1 hour after ACTH stimulation (r = 0.40, P = .0047). ACTH increased cortisol levels in plasma from 12.3 ± 6.4 to 30.3 ± 13.2 μg/dL (P < .0001) and in saliva from 1.0 ± 0.8 to 2.6 ± 1.0 μg/dL (P < .0001). The adrenal response to ACTH can be detected in the saliva of premature newborns during the first week of life. (J Pediatr 2002;140:116-8)

Welfare of farmed silver foxes (Vulpes vulpes) housed in sibling groups in large outdoor enclosures

The aim of the present study was to evaluate the effects of housing farmed silver foxes in large outdoor enclosures with less abundant human contacts on some behavioural and physiological welfare parameters. Farmed silver fox cubs were housed either singly in traditional fox cages or in sibling groups in enclosures. Mass of adrenals, serum cortisol level after adrenocorticotrophic hormone (ACTH) administration and stress-induced hyperthermia, as well as 24-h activity measures and the number of bite scars, were used to draw conclusions on the welfare effects of housing farmed silver foxes in the two experimental housing systems. The housing system had significant effects neither on the serum cortisol level after ACTH administration nor on the mass of adrenals. This result shows that intra-group social tension and non-habituation to humans, both leading to increased long-term stress in foxes housed in large outdoor enclosures, can be partly overcome by, respectively, altering the group composition and keeping the cubs for a longer time in cage conditions with close human contact. However, a large number of bite scars and increased stress-induced hyperthermia (SIH) in the foxes housed in enclosures, indicating an acute stress response to the presence of humans, may not be overcome. Furthermore, the 24-h activity rhythm changed in the foxes housed in large enclosures resembling, especially in November, the nocturnal activity pattern of the wild red fox, indicating that the foxes in enclosures became at least to some extent feral. Key words: Activity rhythm, aggression, hypothalamic-pituitary-adrenal axis, human-animal relation, stress-induced hyperthermia, Vulpes vulpes

Dehydroepiandrosterone (DHEA) response to i.v. ACTH in patients with chronic fatigue syndrome.

Previous studies have demonstrated concentrating neuroendocrinological disturbances in chronic fatigue syndrome (CFS) patients, concentrating in particular on low cortisol levels and a hypothalamic deficiency. In order to investigate the dynamic response of the adrenal glands, we measured dehydroepiandrosterone (DHEA) in serum after adreno-corticotropic hormone (ACTH) stimulation during 60 minutes in 22 CFS-patients and 14 healthy controls. We found normal basal DHEA levels, but a blunted serum DHEA response curve to i.v. ACTH injection. This observation adds to the large amount of evidence of endocrinological abnormalities in CFS. Relative glucocorticoid deficiency might contribute to the overall clinical picture in CFS, and could explain some of the immunological disturbances observed in this syndrome.

A contribution to the classification of cases of non-classic 21-hydroxylase-deficient congenital adrenal hyperplasia.

The aim of this study was to classify the degree of 21 alpha-hydroxylase deficiency in patients suspected for non-classic 21-hydroxylase-deficient congenital adrenal hyperplasia (CAH). In 66 selected subjects (45 young women with polycystic ovary (PCO)-like symptoms and members of their families, of whom 12 were men), progesterone, 17-hydroxyprogesterone (17-OHP) and cortisol were measured at 0, 15, 30, 45 and 60 min after adrenocorticotropic hormone (ACTH) stimulation. The markers [(17-OHP at 30 min--17-OHP at 0 min) + (progesterone at 30 min--progesterone at 0 min)]/30 proposed by Gutai and the ratio of cortisol to 17-OHP at 30 min (cortisol30/17-OHP30) were calculated and cluster analysis was performed using the above two markers and 17-OHP at 60 min (17-OHP60). Our patients were grouped by cluster analysis into four Groups: I, II, III and IV (n = 3, 11, 35 and 16, respectively) with (1) Gutai (mean +/- SE) 107.0 +/- 21.7, 29.9 +/- 4.4, 10.5 +/- 0.54 and 4.0 +/- 0.37 ng/dl per min, respectively, (2) 17-OHP60 169.7 +/- 28.3, 10.8 +/- 1.3, 4.6 +/- 0.2 and 3.7 +/- 0.4 ng/ml, respectively, and (3) cortisol/17-OHP30 0.97 +/- 0.28, 38.5 +/- 6.9, 82.3 +/- 5.5 and 112.0 +/- 8.9, respectively. All three markers showed highly significant differences between the four groups (p < 0.0001). The patterns of 17-OHP, cortisol and cortisol/17-OHP ratio following ACTH testing revealed the degree of 21-hydroxylase deficiency in every group. HLA typing effected in 20 studied individuals confirmed the classification derived from cluster analysis. Thus, it seems that Groups I, II and III include, respectively, patients with severe, mild and minimal forms of non-classic 21-hydroxylase-deficient CAH, while in patients of Group IV the hyperandrogenemic symptoms are of different etiology. In conclusion, the concurrent evaluation of the three markers together with the variations of 17-OHP, cortisol and the cortisol/17-OHP ratio after ACTH testing enhance the accurate identification of a patient suspected for non-classic 21-hydroxylase-deficient CAH in relation to the severity of the enzymatic defect.

Hormonal characteristics of free-ranging female lions (Panthera leo) of the Serengeti Plains and Ngorongoro Crater

Pituitary responses to gonadotrophin-releasing hormone (GnRH) and prolactin and steroid secretory profiles were examined in two populations of adult, female lions in the Serengeti (one outbred in the Serengeti Plains and one inbred in the Ngorongoro Crater) to determine whether reductions in genetic variability adversely affected endocrine function. GnRH-induced gonadotrophin secretion was also examined after adrenocorticotrophic hormone (ACTH) treatment to determine whether acute increases in serum cortisol altered pituitary function. Anaesthetized lions were administered (i) saline i.v. after 10 and 100 min of blood sampling, (ii) saline at 10 min and GnRH (1 micrograms kg-1 body weight) after 100 min; or (iii) ACTH (3 micrograms kg-1) at 10 min and GnRH after 100 min of sampling. Basal serum cortisol and basal and GnRH-induced gonadotrophin secretion were similar (P > 0.05) between females of the Ngorongoro Crater and Serengeti Plains. After ACTH, serum cortisol increased two- to threefold over baseline values and the response was unaffected (P > 0.05) by location. ACTH-induced increases in serum cortisol had no effect on subsequent basal or GnRH-stimulated luteinizing hormone (LH) or follicle-stimulating hormone (FSH) secretion. Overall mean serum progesterone concentrations ranged from 0.2 to 5.4 ng ml-1 with the exception of four females (two in the Serengeti and two in the Crater; progesterone range, 18.4-46.5 ng ml-1) that were presumed pregnant (three of these females were observed nursing cubs several weeks later).(ABSTRACT TRUNCATED AT 250 WORDS)

Excess weight and precocious pubarche in children: alterations of the adrenocortical hormones.

In this paper we assess the qualitative and quantitative differences in adrenal function before and after adrenocorticotropic hormone (ACTH) stimulation between normal weight and overweight precocious pubarche (PP) patients. Twelve of the 22 PP patients had a normal body weight for height with linear growth and bone ages (BAs) that were appropriate for chronological age. The remaining 10 PP patients had body weights which were greater than 120% of ideal weight for height and body mass indices (BMIs), which were more than 125% of the ideal for age and sex. In six overweight patients, linear growth was accelerated and BAs were advanced beyond chronological age. All patients underwent an ACTH stimulation test where they received an intravenous bolus of 250 micrograms Cortrosyn. Blood samples were obtained at 0' and 60' for 17-OHProgesterone (17-OHP), 17-OHPregnenolone (17-OHPG), dehydroepiandrosterone (DHEA), androstenedione (A-dione), and cortisol levels. Results of the baseline and stimulated adrenal hormones in the normal weight children were found to be within reference range for normal Tanner I children. In contrast, two of the 10 overweight children were suspected of having congenital adrenal hyperplasia [one with 21-hydroxylase (21-OHase) deficiency, another with 3-betahydroxysteroid (3 beta ol) deficiency]. These two children were indistinguishable in their linear growth rate and degree of skeletal maturation from the other overweight children. In both patients the BA/chronological age and BA/height age (HA) ratios were within two standard deviations of the mean for the overweight patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative effects of proligestone and megestrol acetate on basal plasma glucose concentrations and cortisol responses to exogenous adrenocorticotrophic hormone in cats

Cats were given megestrol acetate (MA, 5 mg once daily for 14 days), subcutaneous proligestone (PRG, 100 mg on two occasions one week apart) or subcutaneous saline (1 ml as for PRG). In cats given saline (n = 6) basal cortical concentrations, cortisol concentrations after adrenocorticotrophic hormone (ACTH) administration and fasting blood glucose concentrations did not change significantly during the following seven weeks. Cats given MA (n = 7) developed suppression of basal and ACTH-stimulated cortisol concentrations and fasting hyperglycaemia during treatment. Effects on cortisol persisted for two weeks after MA dosage ceased. In cats given PRG (n = 7), basal cortisol concentrations were reduced overall, but only three cats had persistently suppressed post-ACTH cortisol concentrations. Adrenal suppression continued for 14 weeks in one of these and for at least 22 weeks in two cats. Fasting blood glucose concentrations were unchanged in PRG-treated cats.

A retrospective study of aldosterone secretion in normal and adrenopathic dogs.

A retrospective study on stored plasma from normal dogs and dogs with pituitary dependent hyperadrenocorticism (PDH), pituitary dependent hyperadrenocorticism controlled by mitotane (o,p'-DDD),* iatrogenic hyperadrenocorticism, and hypoadrenocorticism was conducted to determine if alterations in aldosterone production exist in these disorders. The plasma aldosterone concentration (PAC) was measured by radioimmunoassay immediately before and 1 hour after adrenocorticotropic hormone (ACTH) administration (0.5 IU/kg, intravenously [IV]). PACs increased significantly when ACTH was administered to normal dogs. Dogs with PDH had a lower baseline PAC, but their PAC increased to levels similar to that of normal dogs after ACTH administration. In dogs with PDH controlled by o,p'-DDD therapy, the response to ACTH was significantly less than that of normal dogs or dogs with untreated PDH. Dogs with iatrogenic hyperadrenocorticism had a lower baseline and post-ACTH PAC than normal dogs. Dogs with hypoadrenocorticism had a normal basal PAC, but showed no significant increase in PAC following ACTH administration. These findings suggest that PACs are significantly altered in a variety of adrenal diseases, and that the ACTH stimulation test may be useful when evaluating aldosterone secretion in adrenopathic disorders. In addition, at therapeutic dosages, o,p'-DDD treatment was associated with a decrease in basal and post-ACTH PACs in dogs with PDH.

Dehydroepiandrosterone-Sulphate Secretion and State of Adrenal Function in the Rat

This study was undertaken to gain better insight into dehydroepiandrosterone-sulphate (DHEA-S) secretion in rats, which is necessary for the subsequent investigation of the influence of nutritional status on DHEA-S secretion in this species (published as part II). DHEA-S as well as corticosterone (11-OHCS) blood levels were found to be markedly lower in dexamethasone-treated than in untreated rats. After adrenocorticotropic hormone (ACTH) administration DHEA-S and 11-OHCS increased significantly. A similar rise was seen for DHEA-S in metyrapone-treated rats. At the same time these animals exhibited a drastic elevation of 11-desoxycorticosterone (11-DOC). Furthermore DHEA-S levels of rats pretreated with ACTH prior to metyrapone application significantly exceeded the DHEA-S values measured in animals only given metyrapone. However, the DHEA-S level did not change clearly in rats treated with either a single or multiple doses of hCG, although the concentrations of DHEA, androstenedione, and testosterone were markedly elevated in these animals. These findings suggest that DHEA-S in rats is secreted chiefly (or exclusively) by the adrenal gland. Since a stimulative effect of ACTH pretreatment on the secretory DHEA-S response to subsequent metyrapone stimulation could be demonstrated, we conclude that stress (ACTH administration) associated with a stimulation of adrenal gland activity provokes an increase in the secretory capacity for DHEA-S.

Pathophysiology of epidemic St. Louis encephalitis. I. Inappropriate secretion of antidiuretic hormone. II. Pituitary-adrenal function. 3. Cerebral blood flow and metabolism.

Studies of pathophysiology in epidemic St. Louis encephalitis were undertaken during the 1966 Dallas epidemic. Eighteen of 52 patients were hyponatremic during their acute illness. Of this group, 13 patients appeared to have hyponatremia due to inappropriate secretion of antidiuretic hormone; the remaining patients were probably hyponatremic from salt depletion. Water loading in some of these patients showed that the defect (persistent elaboration of antidiuretic hormone) was only partial, allowing excretion of the water load with urine not maximally dilute. Severely ill patients tended to have 8 AM plasma 17-hydroxycorticoid (17-HOCS) values that were elevated or at the upper limit of normal. Normal diurnal variation in plasma 17-HOCS levels was absent. Plasma 17-HOCS rose after adrenocorticotrophic hormone (ACTH) administration but did not respond to dexamethasone suppression. An insulin-induced fall in blood sugar caused a rise in both plasma 17-HOCS and growth hormone. Patients had an increase in either urinary or plasma 11-deoxycorticoids (11-DOCS) after the administration of metyrapone. These findings probably represent the response to severe stress. The hypothalamic-pituitary-adrenal axis appeared to be functionally intact in these patients. Cerebral blood flow and metabolism were measured in five patients, one of whom was comatose when studied. In two of the conscious patients cerebral blood flow was normal despite normal arterial oxygen tension and systemic hypocapnia; inflammatory cerebral vasodilatation may have accounted for the findings. Inflammatory changes affecting the respiratory centers and an associated metabolic acidosis may have accounted, in part, for lowered carbon dioxide tensions found in at least two of the patients. In the comatose patient, although the cerebral blood flow was normal, the cerebral metabolic rate for oxygen was markedly depressed; this patient's findings represent what has been termed the "luxury-perfusion syndrome." Cerebral blood flow abnormalities per se were not responsible for the altered sensorium in these patients.

Estimation and identification of free and conjugated corticosteroids in human plasma.

SUMMARY 1. An examination has been made of the free and glucuronide-conjugated corticosteroids in the plasma of normal controls and of patients before and after hypophysectomy. Quantitative measure of the free plasma corticosteroid level 72 hr after withholding cortisone from a hypophysectomized patient (cortisone withdrawal test) is a useful index of completeness of hypophysectomy. Qualitative examination failed to detect corticosteroids in these patients. 2. In all plasmas examined (controls and patients in resting state and after adrenocorticotrophic hormone (ACTH)) the main component of the free corticosteroid fraction is cortisol. In 50% of the plasma samples cortisone was detected. Even after ACTH only occasional traces of corticosterone were detected by the method used in this study. 3. In the glucuronide-conjugated fraction of plasma from subjects in the resting state three compounds, concluded to be tetrahydrocortisol (THF)†, tetrahydrocortisone, and allo-THF†, were regularly seen. After ACTH other material was detected in this fraction which is considered to be tetrahydrocorticosterone (THB), tetrahydro 11-deoxycortisol (THS) and allo-THB. Administration of oral cortisone to hypophysectomized patients did not increase the amounts of THB, THS or allo-THB in the plasma.