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PubMed1996

The short Synacthen and insulin stress tests in the assessment of the hypothalamic-pituitary-adrenal axis.

OBJECTIVE: The best dynamic test for the assessment of the hypothalamic-pituitary-adrenal axis and the interpretation of the cortisol levels, remain a matter of controversy. We aimed to establish normal ranges with current assays, for both the short Synacthen (SST) and insulin stress tests (IST) and then to use these data to examine whether the SST can satisfactorily substitute for the IST in assessment of the hypothalamic-pituitary-adrenal axis. DESIGN: Thirty SSTs and 27 ISTs were performed on different healthy volunteers. The results of all paired tests performed on patients in the last three years are reviewed. SETTING: Programmed Investigation Unit. SUBJECTS: Fifty-seven healthy volunteers and 166 patients. MAIN OUTCOME MEASURES: Basal serum cortisol concentration and cortisol values obtained at 30 and 60 minutes during the SST compared to the maximum obtained with adequate hypoglycemia (plasma glucose < 2 mmol/l) during an IST. RESULTS: From normal data the mean-2SD 30-minute value during the SST was 392 nmol/l and 60-minute value was 497 nmol/l. The maximal cortisol response (mean - 2SD) during the IST was 519 nmol/l. Sixty patients failed the IST, none of whom had a basal cortisol > 450 nmol/l and only six (10%) had a 30-minute cortisol value > 600 nmol/l. The 30-minute value provided a better index than the 60-minute value. The basal, 30 and 60-minute values during the SST all correlated positively and significantly with the maximal cortisol on IST. The correlations persisted for all microadenomas and macroadenomas secreting prolactin, gonadotrophins or growth hormone, patients undergoing either pre or post-adenomectomy evaluation, and in those patients who had received long-term steroids provided that the medication had been reduced and stopped two days prior to admission. CONCLUSIONS: Using a 30-minute cortisol value > 600 nmol/l as a cut-off, the short Synacthen test provides a suitable substitute for the insulin stress test. Adopting this policy will decrease the number of insulin stress tests performed by one-quarter and thus provide a substantial saving without detriment to patient care.

Adrenal Cortex Function Tests↗
PubMed1984

Effects of single intravenous doses of dexamethasone on baseline plasma cortisol concentrations and responses to synthetic ACTH in healthy dogs.

The duration of adrenocortical suppression resulting from a single IV dose of dexamethasone or dexamethasone sodium phosphate was determined in dogs. At 0800 hours, 5 groups of dogs (n = 4/group) were treated with 0.01 or 0.1 mg of either agent/kg of body weight or saline solution (controls). Plasma cortisol concentrations were significantly (P less than 0.01) depressed in dogs given either dose of dexamethasone or dexamethasone sodium phosphate by posttreatment hour (PTH) 2 and concentrations remained suppressed for at least 16 hours. However, by PTH 24, plasma cortisol concentrations in all dogs, except those given 0.1 mg of dexamethasone/kg, returned to control values. Adrenocortical suppression was evident in dogs given 0.1 mg of dexamethasone/kg for up to 32 hours. The effect of dexamethasone pretreatment on the adrenocortical response to ACTH was studied in the same dogs 2 weeks later. Two groups of dogs (n = 10/group) were tested with 1 microgram of synthetic ACTH/kg given at 1000 hours or 1400 hours. One week later, half of the dogs in each group were given 0.01 mg of dexamethasone/kg at 0600 hours, whereas the remaining dogs were given 0.1 mg of dexamethasone/kg. The ACTH response test was then repeated so that the interval between dexamethasone treatment and ACTH injection was 4 hours (ACTH given at 1000 hours) or 8 hours (ACTH given at 1400 hours). Base-line plasma cortisol concentrations were reduced in all dogs given dexamethasone 4 or 8 hours previously.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗
PubMed1983

The relationship between the pineal gland and the pituitary--adrenal axis in health, endocrine and psychiatric conditions.

Evidence is reviewed in favour of a close relationship between the pineal hormone, melatonin and ACTH--cortisol in man. Subgroups of patients with Cushing's disease as well as with major depressive disorder have low levels of nocturnal serum melatonin. Depressed patients with an abnormal dexamethasone suppression test (DST) have lower melatonin levels than do patients with a normal DST. Low melatonin levels may be a genetic trait marker for vulnerability to depression. The mechanism may be related to increased corticotropin-releasing factor (CRF), secondary to hypofunction of a pineal factor which physiologically inhibits CRF.

Adenoma↗
PubMed1981

Recovery of plasma corticotrophin and cortisol levels after three-week course of prednisolone.

Patients with chronic airflow obstruction were given a three-week course of prednisolone 40 mg per day. The basal plasma cortisol level and response to tetracosactrin were depressed after such a course. Basal plasma cortisol and corticotrophin (ACTH) levels were measured on five consecutive days after three weeks of treatment with prednisolone and were found to rise simultaneously to control levels within three days. Pituitary and adrenal functions were depressed for four days after short high dose courses of corticosteroids and patients may be at risk if they encounter stress during this time.

Adrenal Cortex Function Tests↗
PubMedDate not supplied

Adrenal response to serial cosyntropin stimulation after repeated high-dose prednisone administration in patients with lymphoma.

To determine if repeated courses of high-dose prednisone given to patients with lymphoma as part of multiple-drug chemotherapy programs would lead to progressive adrenal suppression, serial cosyntropin stimulation tests were performed. Four patients with diffuse histiocytic lymphoma (group 1) received prednisone for 5 days every 3 weeks for five courses, and five patients with Hodgkin's disease (group 2) received prednisone for 14 days every 4 weeks for six courses. Testing was done on Day 1 of each treatment course prior to the administration of therapy and after the final course of chemotherapy. In group 1 patients, there was no evidence of adrenal suppression after any of the courses of prednisone. The plasma cortisol increments after cosyntropin injection were also normal. In the group 2 patients, significant depression of basal plasma cortisol concentrations was observed after the first and fifth courses of prednisone, compared to the pretreatment values. The depression reflected the previous course of prednisone administration only and was not progressive with subsequent courses. The plasma cortisol increments after cosyntropin injection were normal despite depressed basal plasma cortisol levels.

Adrenal Cortex Function Tests↗
PubMed1996

[Tests of adrenal gland and ovarian function in the hyperandrogenemia syndrome].

Androgen production in women is under the influence of pituitary hormones on ovaries and adrenal glands, or they originate from peripheral conversion of androgen precursor. Each of the three principal compartments of androgen production has a serum specific marker that may be clinically helpful. Serum testosterone signifies ovarian production, dehydroepiandrosterone sulfate (DHA-S) is an adrenal marker, and serum 3 alpha-diol glucuronide reflects androgen action in the peripheral compartment. Many physiologic and pathologic states affect transport proteins and enzyme systems which modulate androgenic activity. This fact makes the determination of mechanism and origin of hyperandrogenemia more difficult, as well as the choice of therapy. In the syndrome of hyperandrogenemia, the primary place of the disorder is determined by the tests of adrenal cortex and ovary functions. The correct response of androgens in dexamethasone test is manifested by free testosterone suppression to < 0.028 nmol/L, and by DHA-S and plasma cortisol suppression under the reference values. In the complex and controversial syndrome of hyperandrogenemia, the nafarelin test is used after insufficient free testosterone suppression in dexamethasone test. The significant diagnostic criterion is the rise of 17-hydroxyprogesterone (17-OHP) over 7 nmol/L, which aligns a great number of idiopathic hyperandrogenemias in the group of polycystic ovary syndrome. A good correlation was found between the rise of 17-OHP in nafarelin test and the suppression of free testosterone in dexamethasone test. This finding supports the conception that both tests determine the ovary function and that their sensitivity and specificity for ovary hyperandrogenemia is comparable.

Adrenal Cortex Function Tests↗
PubMed1987

Corticotropin-releasing hormone stimulation test before and after transsphenoidal selective microadenomectomy in 30 patients with Cushing's disease.

Thirty patients with ACTH-dependent Cushing's disease were tested with CRH before and 7-10 days and 3-6 months after selective transsphenoidal adenomectomy. In 28 of 30 patients an adenoma was found, and in 22 (79%) clinical and endocrinological remission occurred. Preoperatively, the majority of the patients had basal and CRH-stimulated plasma ACTH levels that were markedly increased compared to those in normal subjects. On the basis of the CRH stimulation test and low dose (2 mg) dexamethasone suppression test results 7-10 days after surgery, these 30 patients were divided into 4 groups. Groups I, II, and III were patients in remission, as defined by undetectable, subnormal, or normal basal plasma ACTH and cortisol levels in addition to sufficient suppression of cortisol (less than 2 micrograms/dL) during the low dose (2 mg) dexamethasone suppression test. Patients in group IV were not in remission. In group I (n = 6), CRH failed to raise undetectable basal ACTH levels in the early postoperative period; however, 3-6 months later plasma ACTH did increase in response to CRH. In group II (n = 11), undetectable or low basal ACTH levels increased after CRH, and the increase was similar to that in normal individuals. In group III (n = 5), basal ACTH levels were normal, and the response to CRH was exaggerated, but all patients responded normally to the dexamethasone suppression test. The CRH-induced ACTH increase in group III was significantly greater (P less than 0.003) than that in normal subjects, but was similar to that in patients not in remission in group IV (n = 6). Three to 6 months later, the ACTH response to CRH in group III was normal. In summary, the CRH test 7-10 days after surgery in patients with Cushing's disease indicated remission when there was no CRH-induced ACTH response or the response was normal (groups I and II). The test failed to predict remission in patients with an exaggerated CRH-induced ACTH response (groups III and IV). However, with regard to group II, the CRH-induced ACTH increase 1 week after selective adenomectomy indirectly supports the concept of CRH deficiency during hypercorticism and thus, in these patients as well as in group I, a pituitary origin of the disease.

Adenoma↗
PubMed2004

Free cortisol awakening responses are influenced by awakening time.

Psychobiological investigations on the hypothalamus-pituitary-adrenal (HPA) axis depend on markers that adequately describe the activity of this system. There is evidence that the free cortisol response to awakening, proposed as a marker for the HPA axis, can be influenced by time of awakening. To further investigate this possible confounder, 24 shift working nurses and 31 female students on a regular sleep-wake cycle collected saliva samples 0, 30, 45 and 60 minutes after awakening. Nurses were investigated on the first and second day of their early (awakening: 04:00-05:30 h), late (awakening: 06:00-09:00 h), and night shift (awakening: 11:00-14:00 h), respectively. Students were studied after taking a short nap on two consecutive weekdays (awakening: 18:45-20:30 h). Mean cortisol levels after awakening increased significantly under all three shift conditions (p<0.01), but decreased in the student sample (p<.05). Within the three shift conditions, cortisol responses following waking in the early shift were more pronounced than in late (p<.01) and night shift (p<.05). The present study shows that in a sample with a large range of awakening times, an impact of this variable on the cortisol awakening response can be observed. The data furthermore strongly suggest that waking up per se is insufficient for adrenocortical stimulation.

Adrenal Cortex Function Tests↗
PubMed2004

Nicotine withdrawal induces subsensitivity of hypothalamic-pituitary-adrenal axis to stress in rats: implications for precipitation of depression during smoking cessation.

Epidemiologic studies show that smokers with a past history of depression are more likely to relapse into depression after smoking cessation than those without a history of depression. These studies suggest the existence of a direct biological link between nicotine withdrawal and depression. To investigate the neuronal and hormonal mechanisms of the precipitation of depression during smoking cessation, we used an animal model of nicotine withdrawal and studied the function of the hypothalamic-pituitary-adrenal (HPA) axis, the abnormality of which is implicated in the pathogenesis of depression. Rats were implanted with a minipump delivering nicotine at 6.0 mg/kg/day for 12 days. The minipumps were removed in order to abruptly terminate nicotine infusion. The activity of the HPA axis was determined on day 2 of withdrawal using the stress-induced corticosterone response and the dexamethasone suppression test (DST). At the same time the expressions of glucocorticoid receptor (GR) mRNA in the hippocampus and paraventricular nucleus of hypothalamus (PVN) and corticotropin-releasing hormone (CRH) mRNA in PVN were determined by non-radioactive in situ hybridization. Nicotine withdrawal resulted in lower corticosterone levels during restraint stress, suggesting subsensitivity of the HPA axis to stress. The result of DST, however, did not show a significant difference between nicotine-withdrawal and control rats. These effects of nicotine withdrawal were not accompanied by any changes in the expressions of GR and CRH mRNA in either hippocampus or PVN. These results suggest that subsensitivity of the HPA axis to stress during nicotine withdrawal may be implicated in the precipitation of depression during smoking cessation, although GR and CRH in the HPA axis do not appear to play a significant role.

Adaptation, Physiological↗
PubMed2003

Comparison of 1-micro g and 250-micro g corticotropin stimulation tests for the evaluation of adrenal function in patients with acquired immunodeficiency syndrome.

Many patients with acquired immunodeficiency syndrome (AIDS) have symptoms suggestive of adrenal insufficiency, but a normal 250- micro g corticotropin (ACTH) stimulation test. We compared the results of 1- micro g and standard 250- micro g ACTH stimulation tests in patients with AIDS. Each patient was studied on 2 separate days. On day 1, 1 micro g ACTH was given intravenously at 8 am after an overnight fast and serum cortisol levels were measured at baseline, and 30 and 60 minutes after ACTH infusion. On day 2, the procedure was repeated with 250- micro g ACTH. An absolute peak cortisol value of > 18 micro g/dL and an increment of 7 micro g/dL or more from baseline constituted a normal response. Among 31 patients, 16 (52%) had discrepant results: 14 (45%) had subnormal responses to 1 micro g ACTH but normal responses to 250 micro g ACTH (group 1); 2 (6%) had normal responses to 1 micro g but subnormal responses to 250 micro g (group 2) ACTH; 6 patients (19%) had concordant abnormal responses (group 3); and 9 (30%) had concordant normal responses (group 4). Eight patients of group 1 underwent a confirmatory insulin tolerance test (ITT); 4 of these patients had abnormal responses to ITT. Kappa statistic and McNemar's test were used to evaluate the data. A kappa statistic value of 0.095 and a P value less than.003 for the McNemar test indicate only random level of agreement and significant differences in the probability of positive result between the 2 ACTH tests. We conclude that discrepancies between the 1- micro g and the 250- micro g ACTH stimulation tests are common in patients with AIDS, with the likelihood of agreement with the "gold standard" ITT of only 50% for each test in our sample of patients. Larger studies are needed to further evaluate the use of these tests in patients with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1987

ACTH deficiency: hypothalamic or pituitary in origin?

The level within the hypothalamic-pituitary axis at which isolated ACTH deficiency occurs, can be more clearly identified by assessing this axis with corticotrophin-releasing factor (CRF) and insulin induced hypoglycaemia. We report a case where lack of response to both tests, suggests a pituitary origin for this rare endocrine deficiency.

Adrenal Cortex Function Tests↗
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↗