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PubMed2001

Plasma cortisol response to 1 microgram adrenocorticotropin at 0800 h & 1600 h in healthy subjects.

BACKGROUND & OBJECTIVES: Cortisol response to 250 micrograms adrenocorticotropin (ACTH) exhibits no circadian variation. Information on the circadian variation, if any, in cortisol response to 1 microgram ACTH, which is considered as a physiological dose is not available. As the 1 microgram ACTH stimulation test is projected as an outpatients procedure with no time constraint, this information is very important. Hence, this study was designed to assess whether any circadian variability exists in cortisol response to 1 microgram ACTH in healthy subjects. METHODS: Thirty six healthy volunteers (23 male and 13 female) with mean age of 32.2 +/- 9.0 yr were consecutively studied after obtaining informed consent. On day 1, prestimulated and stimulated plasma cortisol samples were collected at 0800 h and, at 30 and 60 min following an intravenous bolus of 1 microgram ACTH, and on day 3, plasma cortisol samples were similarly collected at 1600 h. Cortisol estimation was done by a sensitive and specific radioimmunoassay. Stimulated plasma cortisol of 500 nmol/1 or more was defined as a normal response. RESULTS: The prestimulated and peak cortisol levels at 0800 h (377.5 +/- 93.3 and 729.1 +/- 183.2 nmol/l) were higher (P < 0.001 and P < 0.01) than those at 1600 h (230.1 +/- 75.7 and 665.8 +/- 138.6 nmol/l). However, a stimulated cortisol response of 500 nmol/l or more was observed at both 0800 h and 1600 h in all subjects at 30 min but not at 60 min. The [symbol: see text] (peak-basal) response was higher at 1600 h than that at 0800 h (432.8 +/- 136.8 vs 351.5 +/- 177.3, P < 0.01). INTERPRETATION & CONCLUSION: The demonstration of normal cortisol response to 1 microgram ACTH both at 0800 h and 1600 h suggests that the test can be performed at any time of the day.

Adrenal Cortex Function Tests↗
PubMed1997

Assessment of systemic corticosteroid activity.

The potency of the inhaled corticosteroid, dose, duration of treatment, and the study subject receiving treatment all play a role in the effects observed on the HPA axis. At low/medium doses of inhaled corticosteroids, where there is minimal/modest HPA axis suppression, there should be no risk of adrenal crisis even under stressful conditions (6). Thus, the risk of acute adrenal insufficiency, culminating in adrenal crisis, in patients taking inhaled steroids is extremely unlikely.

Administration, Inhalation↗
PubMed1976

Significance of 17alpha OH progesterone assay in the evaluation of ovarian and adrenal function.

Plasma 17alpha OH progesterone was assayed radioimmunologically, using an anti-17-OH-progesterone BSA antiserum as specific binding antigen. The method consisted in extracting steroids with ethyl ether from 1 ml plasm (to which 17alpha OH progesterone-1,2-3H had been added for the assessment of losses); the extract was then submitted to chromatography on a Sephadex LH-20 column, antiserum was added and the free steroid was separated from the bound form by Charcoal-dextran. Average recovery of 17alpha OH progesterone-1,2-3H was 75+/-5%. Minimum sensitivity of the method oscillated about 7-10 pg. MIF (Method Interfering Factors) were evaluated. The method was used for the assay of 17alpha OH progesterone plasma levels during normal menstrual cycles, in women undergoing ovarian stimulation with HMG and HCG in the follicular and luteal phase respectively. Finally, changes of plasma 17alpha OH progesterone levels were assessed during adrenal stimulation and suppression in various stages of the menstrual cycle.

Adrenal Cortex Function Tests↗
PubMedDate not supplied

[Study of the glucocorticoid function of the adrenals in patients with diabetes mellitus using a minor dexamethasone test].

The purpose of the paper is to define the state of glucocorticoid function in 37 male and female patients with types I and II diabetes mellitus of various degree of compensation before and after dexamethasone blockade of the hypothalamohypophyseoadrenal system (0.5 mg 4 times for 2 days). The level of cortisol in the plasma was determined by a radioimmunoassay using Sorin kits. Statistical data processing was performed using the d-3-28 computer. In patients with types I and II diabetes mellitus at the stage of compensation the level of plasma cortisol did not differ from that of persons without diabetes mellitus; in decompensation of types I and II diabetes mellitus its considerable increase was noted. After the dexamethasone test the more pronounced was a degree of decompensation of diabetes mellitus, the higher was the level of cortisol, i.e. there was resistance to dexamethasone inhibiting action, especially in type I which could be accounted for by deeper metabolic derangements in this type of diabetes mellitus and an increase in the threshold of sensitivity of the hypothalamic centers to dexamethasone. Therefore the minor dexamethasone test could be used for determination of a degree of metabolic compensation of patients with diabetes mellitus.

Adrenal Cortex↗
PubMed1996

Failure of the short ACTH test to unequivocally diagnose long-standing symptomatic secondary hypoadrenalism.

Recent guidelines propose that secondary hypoadrenalism can be reliably diagnosed, in the absence of acute ACTH deficiency or glucocorticoid use, by means of the short ACTH test (Synacthen). We report a patient who maintained a normal response to exogenous ACTH stimulation despite symptomatic chronic ACTH deficiency proven by the insulin tolerance and overnight metyrapone tests. It is suggested that partial ACTH deficiency may prevent involution of the adrenal cortex and preserve the cortisol response to ACTH stimulation. A normal cortisol response in the short ACTH test does not therefore exclude the possibility of clinically relevant ACTH deficiency.

Adrenal Cortex Function Tests↗
PubMed1984

Diagnosis of canine Cushing's syndrome based on multiple steroid analysis and dexamethasone turnover kinetics.

A comparison of cortisol concentrations, determined by high-performance liquid chromatography (HPLC) and radioimmunoassay, was made in healthy, mixed-breed dogs and in dogs with clinical signs of Cushing's syndrome. Absolute concentration of cortisol was less in resting, dexamethasone-suppressed, and ACTH-stimulated plasma samples, when measured by HPLC relative to cortisol concentrations determined by radioimmunoassay. Diagnosis of Cushing's syndrome could be made using either method. Plasma concentrations of cortisone and corticosterone were determined by HPLC. Cortisone and corticosterone concentrations alone were not diagnostic of Cushing's syndrome; but when used in conjunction with cortisol determinations, they provided additional criteria for laboratory confirmation of the clinical diagnosis of Cushing's syndrome. The clearance of exogenous dexamethasone used in the dexamethasone-suppression test was examined in the normal and cushingoid dogs. Plasma concentrations of exogenous dexamethasone were constant during the 3-hour test in the normal dogs. However, in 75% of the dogs with Cushing's syndrome, exogenous dexamethasone was cleared completely in the 3-hour test. Thus, dexamethasone clearance rates were excessively fast in most dogs with Cushing's syndrome.

Adrenal Cortex Function Tests↗
PubMed1988

Adrenal function in children with bronchial asthma treated with beclomethasone dipropionate or budesonide.

The effect of inhaled beclomethasone dipropionate and budesonide on the adrenal function was studied in 30 children (aged 7 to 15 years) with mild bronchial asthma. The trial was designed as a prospective double-blind parallel study of the effect of stepwise increase of either beclomethasone dipropionate or budesonide from 200 micrograms through 400 micrograms, to 800 micrograms daily in three consecutive periods of 4 weeks. At the end of each period, the adrenal stress response was evaluated by measurements of serum cortisol and androstenedione during a short adrenocorticotropic hormone test. The unstimulated diurnal production of glucocorticosteroids was assessed by measurements of free cortisol in 24-hour urine samples. Free cortisol in urine was found a valid measure of the total diurnal excretion of cortisol metabolites, since it exhibited a good correlation to the fractional cortisol metabolites measured by gas chromatography. The adrenal response to adrenocorticotropic hormone stimulation was unaffected by treatment or dose. The unstimulated diurnal production of glucocorticosteroids demonstrated a highly significant dose-related suppression in response to the inhaled steroids. No significant difference was found between the two topical steroids (probability value 5.3%), and yet the suppression was apparent in the group of children treated with beclomethasone dipropionate but not in the group of children treated with budesonide. Further studies are desirable in order to ascertain whether budesonide offers an improved ratio between beneficial anti-inflammatory effect and unwanted systemic activity.

Adolescent↗
PubMed1979

Genetic subtypes of unipolar primary depressive illness distinguished by hypothalamic-pituitary-adrenal axis activity.

Serum-cortisol response to the 1 mg overnight dexamethasone suppression test was investigated in 86 patients with unipolar primary depressive illness and 80 non-depressed controls (45 with mania and 35 with schizophrenia). The depressed patients were assigned to one of three genetic subtypes according to the family psychiatric history. Resistance to suppression of serum-cortisol by dexamethasone was found in 37 of 86 (43%) depressives and none of the 80 controls. Non-suppression distinguished the three genetic subtypes of depression, being found in 23 of 28 (82%) patients with familial pure depressive disease (F.P.D.D.), 13 of 35 (37%) patients with sporadic depressive disease (S.D.D.), and 1 of 23 (4%) patients with depression spectrum disease (D.S.D.). The three genetic subtypes were further distinguished by the age of onset, with S.D.D. the oldest, and by the number of previous depressive episodes, with F.P.D.D. the most. Severity of depression did not separate the three subtypes. This is the first report of a distinct neuroendocrine abnormality which supports an objectively defined classification of unipolar primary depressive illness. It is suggested that unipolar primary depressive illness is three or more separate illnesses, each with a potentially distinctive mode of inheritance, pathophysiology, neurochemistry, clinical course, and treatment response.

Adolescent↗
PubMed1993

Human corticotropin-releasing hormone (hCRH) test: sex and age differences in plasma ACTH and cortisol responses and their reproducibility in healthy adults.

The effectiveness and safety of MCI-028, a synthetic human corticotropin-releasing hormone (hCRH), as a diagnostic drug were examined in 65 healthy male and 24 healthy female adult volunteers. Mean maximum concentrations of plasma ACTH and cortisol after intravenous administration of 100 micrograms of MCI-028 were 3.0 and 2.0 times their basal concentrations, respectively, and there were no significant age or sex differences in the responses. Good reproducibility was observed in the responses in 59 male subjects who received a second administration after 1 to 2 weeks. Although slight adverse reactions such as mild and transient hot flushing were observed, these were not serious.

Adrenal Cortex Function Tests↗
PubMed1999

Effect of multiple courses of antenatal corticosteroids on pituitary-adrenal function in preterm infants.

AIM: To evaluate the pituitary-adrenal function of preterm infants whose mothers received multiple courses (8 or more doses) of antenatal dexamethasone. METHODS: The pituitary-adrenal function of 14 preterm infants whose mothers received eight or more doses of antenatal dexamethasone were assessed using the human corticotrophin releasing hormone (hCRH) stimulation test when 7 days (n = 14) and 14 days old (n = 12). During each test, blood samples were taken at 0 (baseline), 15, 30 and 60 minutes after an intravenous bolus dose of hCRH (1 microg/kg). The corresponding hormone concentrations were compared between days 7 and 14, and with various associated factors. RESULTS: The baseline (0 min) plasma adrenocorticotrophic hormone concentration was significantly higher at day 14 than at day 7 (p = 0.036). None of the corresponding poststimulation (15, 30, and 60 min) hormone concentrations was significantly different between the two time epochs. When the association between the hormone concentrations and the number of antenatal dexamethasone doses received by the mothers was assessed, a significant negative correlation was observed in serum cortisol concentrations at 15 and 30 min on day 14 (r = -0.59, p = 0.04 and r = -0.60, p = 0.039, respectively). CONCLUSIONS: The absence of a significant difference in poststimulation hormone concentrations between days 7 and 14 in this cohort of infants, and the similarity of their hormone responses with those of older children and adults, suggests that no severe pituitary-adrenal suppression had occurred. None the less there was evidence of mild adrenal suppression in some of the treated infants. Vigilance in monitoring blood pressure, electrolytes and signs of adrenal suppression in infants whose mothers receive multiple courses (8 or more doses) of antenatal dexamethasone is required, as some of them might have diminished adrenal reserve.

Adrenal Cortex Function Tests↗
PubMed1986

[Effect of biseptol on the adrenal cortex of the white rat in postoperative shock].

The study aimed to find out the effect of sulfonamide combined with Trimetaprim-Biseptol 480 on the adrenal cortex in post-operative shock after removal of SPIGELian lobe (lobectomy of the lobus caudatus and unilaterally of one kidney with its suprarenal gland. The study was performed on a material of white rats which were post-operatively administered Biseptol 480 in doses 5 times bigger than those given to men. It was attempted to determine histochemically the intensity of the adrenal cortex' function by testing the number of lipid droplets, activity of the main enzyme of steroidogenesis (beta-hydroxy steroid dehydrogenase) and the level of alpha-ketols (as the final stage of steroidogenesis). Pathomorphologic examinations were also performe. On the basis of the present study's results, it was observed that - in the case of liver-lobectomy - the zona fasciculata and zona reticularis are functionally stimulated but the zona glomerulosa becomes insufficient. In the case of nephrectomy plus suprarenal gland's removal, all the adrenal cortex becomes insufficient. Administration of Biseptol in the 1st case contributed to hormonal inactivation of the zone glomerulosa cells, but in the 2nd case, it caused an increased activity of steroid dehydrogenase and an increase of the alpha-ketol level in the zona fasciculata.

Adrenal Cortex↗
PubMed2002

Dehydroepiandrosterone, 17alpha-hydroxyprogesterone and aldosterone responses to the low-dose (1 micro g) ACTH test in subjects with preclinical adrenal autoimmunity.

OBJECTIVE: The appearance of 21-hydroxylase autoantibodies (21OHAbs) identifies subjects with preclinical adrenal insufficiency. In 21OHAb-positive subjects, the adrenocortical function is best evaluated by peak cortisol (F) levels after the low-dose (1 micro g) ACTH stimulation test (LDT). No information is currently available on the correlation between F and other adrenocortical hormone responses to the LDT in subjects with an ongoing autoimmune adrenal process. In this study, we tested the hypothesis that the dehydroepiandrosterone (DHEA), 17alpha-hydroxyprogesterone (17OHP) and aldosterone (A) responses to the LDT are consensual to that of F during the preclinical phase of autoimmune adrenal insufficiency. DESIGN AND PATIENTS: We studied 12 subjects positive for 21OHAb, in the absence of clinical signs of adrenal insufficiency. On the basis of peak F levels after the LDT, and according to the lower level of normal observed in 15 healthy volunteers (510.4 nmol/l), patients were subdivided into two groups: group A, n = 6 subjects with normal F response; and group B, n = 6 subjects with impaired F response. Results were expressed as absolute delta increase (Delta) between peak and basal levels. RESULTS: DeltaF was significantly higher in group A (314.5 +/- 115.8 nmol/l) than in group B (151.7 +/- 88.2 nmol/l) (P = 0.041). DeltaDHEA and Delta17OHP were also significantly higher in group A (17.0 +/- 13.5 nmol/l and 6.1 +/- 4.4 nmol/l, respectively) than in group B (0.69 +/- 2.25 nmol/l and 1.9 +/- 1.7 nmol/l, respectively) (P = 0.002 and P = 0.041). The difference in DeltaA between the two groups did not reach statistical significance (group A 321.8 +/- 272.0 pmol/l vs. group B 157.0 +/- 154.0 pmol/l). DeltaDHEA, Delta17OHP and DeltaA tended to correlate positively with DeltaF (P = 0.039, P = 0.039 and P = 0.044, respectively), but the correlations did not reach significance after correction of the P-value. CONCLUSIONS: Our study demonstrates a high concordance between F and DHEA, 17OHP and A responses to the LDT in subjects with preclinical adrenal autoimmunity, thus strengthening the concept that the LDT is an accurate test to identify early adrenal dysfunction.

17-alpha-Hydroxyprogesterone↗
PubMed1979

Assessment of adrenocortical function in asthmatic patients on long-term triamcinolone acetonide treatment.

The adrenocortical function of 48 adult asthmatic patients on long-term corticoid therapy was studied. All were treated with triamcinolone acetonide (TA) for from two to six (average 3.5 years). The adrenocortical function was assessed using a short Synacthen test as a screening procedure and a five-hour Synacthen test for TA exclusively treated patients with abnormal response in the short test. Among patients on long-term TA were nine with abnormally short Synacthen tests. The five-hour test revealed six abnormal responses (12% of the entire group of TA treated patients). Contrary to previously expressed opinions the authors feel that TA long-term treatment only occasionally causes steady adrenal suppression.

Adrenal Cortex Function Tests↗
PubMed1982

Adrenocortical function and responsiveness to tetracosactrin infusions after intra-articular treatment with triamcinolone acetonide and hydrocortisone acetate.

The urinary free cortisol (UFC) output, considered a parameter of the action of the exogenous corticosteroid on the hypothalamo-pituitary axis, was followed in five patients who received a total of 12 intra-articular (i.a.) injections of 40 mg of triamcinolone acetonide (TCA) distributed over eight treatment sessions. The effect of intra-articular TCA injections on UFC output was null after three treatment sessions, transient (48 hr) after another three, and more prolonged (6 days), although slight, after the remaining two sessions. These results contrast with the lasting and profound inhibition of the UFC output induced either by the same TCA dose given intramuscularly, or by oral administration of dexamethasone to 30 normal subjects, 0.75 mg at 8-hourly periods for 48 hours. Adrenocortical reactivity, as measured by the response to synthetic ACTH (tetracosactrin) of both plasma cortisol levels and UFC output, was studied in another five patients prior to and after eight i.a. injections of 40 mg of TCA, and in three patients after six i.a. injections of 25-100 mg of hydrocortisone acetate. No decrease was observed after the i.a. injections of HCA. Considered as a group the response to tetracosactrin after TCA injections was not significantly altered. Two patients showed a decreased response of both UFC and plasma cortisol, although their values remained within the limits of those obtained in 44 normal control subjects. In contrast, profound inhibition of the tetracosactrin induced response occurred in a control group of 30 subjects given 0.75 mg of dexamethasone orally at 8-hourly periods for 48 hours.

Adolescent↗
PubMed2004

Social suppression of cortisol in female marmoset monkeys: role of circulating ACTH levels and glucocorticoid negative feedback.

Behaviorally subordinate female common marmoset monkeys (Callithrix jacchus) exhibit pronounced, chronic reductions of circulating cortisol levels. Cortisol suppression in these animals is mediated in part by adrenocortical hyporesponsiveness to adrenocorticotropic hormone (ACTH). In addition, we hypothesized that social subordination may activate a central, neurally mediated mechanism to further inhibit hypothalamo-pituitary-adrenal function. In this study, therefore, we evaluated basal plasma cortisol and ACTH concentrations, as well as cortisol and ACTH responses to dexamethasone (DEX), in dominant and subordinate females to initially characterize such a mechanism. Morning plasma cortisol and ACTH levels were determined before, and 1, 2, and 3 days following administration of DEX (0.5, 1.0, or 5.0 mg/kg, IM) or saline. Baseline cortisol concentrations prior to DEX treatment were significantly lower in subordinate females than in dominants, as previously reported. However, ACTH concentrations in the same blood samples did not differ between the two groups. Furthermore, dominant and subordinate females showed similar cortisol and ACTH responses to DEX. These results indicate that reduced circulating cortisol levels in subordinate females are not associated with either altered circulating ACTH concentrations or enhanced responsiveness to glucocorticoid negative feedback. However, the finding that basal ACTH levels are not elevated in subordinate females as compared to dominants, in spite of low circulating cortisol concentrations, suggests that ACTH secretion in subordinate females is restrained by a steroid-independent inhibitory mechanism operating at the level of the brain or pituitary.

Adaptation, Physiological↗
PubMed1997

Diagnosis of canine hyperadrenocorticism.

Diagnosis of canine hyperadrenocorticism can only be made when a suspicion of the disorder persists after completion of a thorough history and physical examination. The first diagnostic testing steps include a complete blood count, serum biochemical tests, and urinalysis with urine culture. Radiography or ultrasonography may also be necessary, depending on physical findings. Screening tests are next applied to support or exclude the clinical diagnosis of hyperadrenocorticism. After the diagnosis has been made, discrimination tests are applied to determine whether the cause is pituitary or adrenal. The limitations of screening tests, particularly in the presence of nonadrenal diseases, cannot be overemphasized. We recommend that neither screening tests nor discrimination tests for hyperadrenocorticism be used in dogs with concurrent nonadrenal disease.

Abdomen↗
PubMed2003

Impaired adrenocortical function in very low birth weight infants after multiple pregnancies.

OBJECTIVE: To evaluate the differences in adrenal function between very low birth weight (VLBW) infants from singleton and multiple pregnancies. DESIGN AND METHODS: Forty infants of birth weights less than 1500 g underwent an ACTH test. Thirty infants born from singleton pregnancies (singleton group) and ten born from multiple pregnancies (multiple group) were enrolled. A baseline blood sample was drawn for cortisol measurement and thereafter serum cortisol was measured 1 and 2 h after an i.v. injection of ACTH. RESULTS: In multiple pregnancies, the median basal cortisol level of the infants was significantly lower than that in the singletons. The median cortisol level at 1 and 2 h after administration of ACTH was significantly lower in infants from multiple gestations than in singletons. Of infants from the multiple gestation group six, and of the singleton infants 12, had baseline cortisol levels lower than the reference values (P=0.48). One hour after ACTH stimulation all multiple and 53% of the singleton group infants showed a subnormal (<500 nmol/l, P=0.007) cortisol response. Two hours after ACTH, nine multiple group patients and 43% of the singletons had subnormal (<500 nmol/l, P=0.01) stimulated cortisol levels. CONCLUSIONS: We have concluded that VLBW infants from multiple gestations seem to be at an increased risk of insufficient postnatal adrenocortical function. In the future, specific attention should be paid to evaluate further newborn infants from multiple pregnancies with regard to a possible benefit of hydrocortisone substitution in stressful clinical situations.

Adrenal Cortex↗