cosyntropin and adrenocorticotropin-zinc

Standard dose synacthen stimulation test (SDSST) is a gold standard screening test for evaluating adrenal gland function. Despite studies using SDSST to identify heterozygosity in. PubMed and MEDLINE databases were searched. A total of 1215 subjects (heterozygous carriers n=669, mutation-free controls n=546) were included in the meta-analyses.. Basal 17-OHP median/mean levels were 4.156 (3.05-10.5)/5.241 (±2.59) nmol/L and 3.90 (2.20-9.74)/4.67 (±2.62) nmol/L in symptomatic heterozygous carriers and symptomatic mutation-free controls, respectively. Stimulated 17-OHP median/mean levels were 17.29 (14.22-37.2)/19.51 (±7.63) nmol/L and 9.27 (7.32-15.9)/10.77 (±3.48) nmol/L in symptomatic heterozygous carriers and symptomatic mutation-free controls, respectively. Basal 17-OHP median/mean levels were 3.21 (2.64-4.78)/3.33 (±0.84) nmol/L and 3.12 (1.82-3.6)/2.83 (±0.71) nmol/L in asymptomatic heterozygous carriers and asymptomatic mutation-free healthy controls, respectively. Stimulated 17-OHP median/mean levels were 14.16 (12.73-16.37)/14.16 (±1.37) nmol/L and 6.26 (4.9-8.23)/6.48 (±1.2) nmol/L in asymptomatic heterozygous carriers and asymptomatic mutation-free healthy controls, respectively. The cut-off levels for stimulated 17-OHP were 10.48 nmol/L and 13.48 nmol/L for asymptomatic heterozygous and symptomatic heterozygous, respectively.. The meta-analyses support the idea that stimulated 17-OHP level has potential for use in identifying

Topics: 17-alpha-Hydroxyprogesterone; Adrenal Hyperplasia, Congenital; Cosyntropin; Heterozygote; Humans; Reproducibility of Results; Steroid 21-Hydroxylase

The melanocortin system is a neuroimmunoendocrine hormone system that constitutes the fulcrum in the homeostatic control of a diverse array of physiological functions, including melanogenesis, inflammation, immunomodulation, adrenocortical steroidogenesis, hemodynamics, natriuresis, energy homeostasis, sexual function, and exocrine secretion. The kidney is a quintessential effector organ of the melanocortin hormone system with melanocortin receptors abundantly expressed by multiple kidney parenchymal cells, including podocytes, mesangial cells, glomerular endothelial cells, and renal tubular cells. Converging evidence unequivocally demonstrates that the melanocortin-based therapy using the melanocortin peptide adrenocorticotropic hormone (ACTH) is prominently effective in inducing remission of steroid-resistant nephrotic syndrome caused by various glomerular diseases, including membranous nephropathy, minimal change disease and focal segmental glomerulosclerosis, suggesting a steroidogenic-independent mechanism. Mechanistically, ACTH and other synthetic melanocortin analogues possess potent proteinuria-reducing and renoprotective activities that could be attributable to direct protection of glomerular cells and systemic immunomodulation. Thus, leveraging melanocortin signaling pathways using ACTH or novel synthetic melanocortin analogues represents a promising and pragmatic therapeutic strategy for glomerular diseases. This review article introduces the biophysiology of the melanocortin hormone system with an emphasis on the kidney as a target organ, discusses the existing data on melanocortin therapy for glomerular diseases, and elucidates the potential mechanisms of action.

Topics: Adrenocorticotropic Hormone; alpha-MSH; Cosyntropin; Endothelial Cells; Glomerulonephritis; Glomerulonephritis, Membranous; Glomerulosclerosis, Focal Segmental; Hormones; Humans; Kidney; Kidney Glomerulus; Melanocortins; Mesangial Cells; Nephrosis, Lipoid; Nephrotic Syndrome; Podocytes; Receptors, Melanocortin; Signal Transduction

The silent pheochromocytoma, a hidden form of pheochromocytoma, exposes the patient to an increased risk of mortality if the diagnosis is not established on time. Biological diagnosis of pheochromocytoma can be difficult. Catecholamine secretion is dependent on tumor size and a large number of physiological, pharmacological, lifestyle modifications and sampling conditions influence the measurement of urinary and plasma metanephrines. The prevalence of pheochromocytoma is 2% among adrenal incidentaloma smaller than 3 cm (2/3 of tumors). Recent studies suggest the almost zero risk of pheochromocytoma among these tumors if they are hypodense (<10 housefield units) on adrenal tomography. Addison's disease is a pathology affecting about 1 in 8000. Immunopathology is still unknown, but some elements advocated the hypothesis of a predominant cell-mediated immunity in particular Interferon-gamma production by CD4 T lymphocytes in the presence of an epitope from the 21-hydroxylase, as well as IgG1 subtype produced by activated B lymphocytes, autoantibodies do appear to be a simple marker of the disease. Subclinical Addison's disease is defined by the presence of anti-21-hydroxylase autoantibodies, without clinical symptoms. It evolves faster to the clinical phase in young subjects, male, having high levels of autoantibodies and with an initially impaired adrenal function. Dosage of ACTH, plasma renin active, and basal cortisol and after Synacthen allow to discriminate the subjects with low or high risk of evolution and establish an appropriate monitoring.

Topics: Addison Disease; Adrenal Gland Neoplasms; Adrenal Glands; Adrenocorticotropic Hormone; Autoantibodies; CD4-Positive T-Lymphocytes; Cosyntropin; Humans; Hydrocortisone; Immunity, Cellular; Interferon-gamma; Male; Metanephrine; Pheochromocytoma; Renin; Steroid 21-Hydroxylase

Topics: Acute Disease; Adrenal Cortex; Adrenal Insufficiency; Adrenalectomy; Chronic Disease; Cosyntropin; Delayed-Action Preparations; Hormones; Humans; Hydrocortisone; Prognosis

Topics: Buserelin; Castration; Chorionic Gonadotropin; Cosyntropin; Dexamethasone; Diethylstilbestrol; Estrogens; Goserelin; Hormones; Humans; Luteinizing Hormone; Male; Prostatic Neoplasms; Testosterone

The present study tested the hypothesis that overexposure to endogenous glucocorticoids in neonatal life alters the reactivity of the hypothalamic-pituitary-adrenal (HPA) axis in ponies at 1 and 2 yr of age. Newborn foals received saline (0.9% NaCl, n = 8, control) or long-acting adrenocorticotropic hormone (ACTH1-24) (Depot Synacthen 0.125 mg intramuscularly twice daily, n = 9) for 5 d after birth to raise cortisol concentrations 5- to 6-fold. At 1 and 2 yr of age, HPA axis function was assessed by bolus administration of short-acting ACTH1-24 (1 μg/kg intravenous) and insulin (0.5 U/kg intravenous) to induce hypoglycemic on separate days. Arterial blood samples were taken at 5 to 30-min intervals before and after drug administration to measure plasma ACTH and/or cortisol concentrations. There were no differences in the basal plasma ACTH or cortisol concentrations or in the cortisol response to exogenous ACTH1-24 with neonatal treatment or age. At 1 and 2 yr of age, the increment in plasma ACTH but not cortisol at 60 min in response to insulin-induced hypoglycemia was greater in ponies treated neonatally with ACTH than saline (P < 0.05). Neonatal cortisol overexposure induced by neonatal ACTH treatment, therefore, alters functioning of the HPA axis in adult ponies.

Topics: Adrenal Cortex; Adrenocorticotropic Hormone; Aging; Animals; Animals, Newborn; Cosyntropin; Glucocorticoids; Horses; Hydrocortisone; Pituitary-Adrenal System

To examine serum cortisol responses to a simplified low-dose short Synacthen test (LDSST) in children treated with inhaled corticosteroids (ICS) for asthma and to compare these to early morning salivary cortisol (EMSC) and cortisone (EMSCn) levels.. Early morning salivary cortisol and EMSCn samples were collected for three consecutive days. On day three, Synacthen 500 ng/1·73 m(2) was administered intravenously. Samples were collected at 0, 15, 25, 35 min.. A total of 269 subjects (160 M: 109 F), median (range) age 10·0 (5·1-15·2) years were studied. Peak cortisol in the LDSST was <500 nmol/l in 101 subjects (37·5%) and <350 nmol/l in 12 subjects (4·5%). Basal cortisol correlated with peak cortisol: r = 0·55, (95% CI: 0·46, 0·63, P < 0·0001). Time at which peak cortisol concentration was achieved was significantly related to the value of peak cortisol (P < 0·0001), with higher cortisol peaks occurring later in the test and lower cortisol peaks occurring earlier. EMSC and EMSCn had no predictive value for the identification of patients with a peak cortisol <500 nmol/l. EMSCn was superior to EMSC in identifying patients with a peak cortisol <350 nmol/l: a minimum EMSCn cut-off value of 12·5 nmol/l gave a negative predictive value of 99·2% and positive predictive value of 30·1%.. Our data illustrate that basal measures of cortisol are likely to be of value in screening populations for patients at greatest risk of adrenal crisis. EMSCn shows promise as a screening tool for the identification of patients with severe adrenal insufficiency.

Topics: Adolescent; Adrenal Glands; Adrenal Insufficiency; Androstadienes; Asthma; Bronchodilator Agents; Child; Child, Preschool; Circadian Rhythm; Cortisone; Cosyntropin; Dose-Response Relationship, Drug; Fluticasone; Humans; Hydrocortisone; Pituitary-Adrenal Function Tests; Saliva

Despite lifelong steroid hormone replacement, there is excess morbidity and mortality associated with autoimmune Addison's disease. In health, adrenocortical cells undergo continuous self-renewal from a population of subcapsular progenitor cells, under the influence of ACTH, suggesting a therapeutic possibility.. We aimed to determine whether tetracosactide (synthetic ACTH1-24) could revive adrenal steroidogenic function in autoimmune Addison's disease.. Thirteen patients (aged 16-65 y) with established autoimmune Addison's disease for more than 1 year were recruited at the Newcastle University Clinical Research Facility.. The intervention included a 20-week study of regular sc tetracosactide (ACTH1-24) therapy.. Serum and urine corticosteroids were measured during medication withdrawal at baseline and every 5 weeks during the study.. Serum cortisol levels remained less than 100 nmol/L in 11 of 13 participants throughout the study. However, two women achieved peak serum cortisol concentrations greater than 400 nmol/L after 10 and 29 weeks of tetracosactide therapy, respectively, allowing withdrawal of corticosteroid replacement. Concurrently, urine glucocorticoid and mineralocorticoid metabolite excretion increased from subnormal to above the median of healthy controls. One of these responders remains well with improving peak serum cortisol (672 nmol/L) 28 months after stopping all treatments. The other responder showed a gradual reduction in serum cortisol and aldosterone over time, and steroid therapy was recommenced after a 28-week period without glucocorticoid replacement.. This is the first study to demonstrate that established autoimmune Addison's disease is amenable to a regenerative medicine therapy approach.

Topics: Addison Disease; Adolescent; Adrenal Cortex Hormones; Adrenal Glands; Adult; Aged; Cosyntropin; Female; Humans; Infusion Pumps; Male; Middle Aged; Remission Induction; Treatment Outcome; Young Adult

The effects of overexposure to glucocorticoids during early life of the foal on the subsequent HPA programming of the hypothalamic-pituitary-adrenal axis are unknown.. To test the hypotheses that excess glucocorticoid exposure in early life subsequently increases both basal plasma concentrations of cortisol and the adrenocortical responsiveness to exogenous adrenocorticotropic hormone (ACTH).. Foals received either saline (0.9% NaCl, n = 9) or long-acting ACTH (0.125 mg i.m. b.i.d., n = 6) for 5 days from Day 1 to increase endogenous cortisol concentrations. Long-term indwelling catheters were inserted under local anaesthesia into the jugular veins of foals aged 2 and 12 weeks. After recovery, short-acting ACTH1-24 was given as a single i.v. injection (2 microg/kg bwt) and blood samples were taken at 5-30 min intervals before and after ACTH administration to measure plasma cortisol concentrations.. Basal plasma cortisol concentrations were higher in ACTH- than in saline-treated foals at age 3 weeks, but not at 13 weeks. There were no significant differences in either the time profile or the area under the cortisol curve in response to ACTH between the 2 groups.. These data suggest that ACTH-induced overexposure to glucocorticoids during early post natal life of the foal does not have a programming effect on HPA axis function at 13 weeks. In foals, the effects of ACTH-induced overexposure to glucocorticoids, if any, may not become apparent until much later in life in a long-lived species such as the horse.. These studies suggest that clinical and other stressful conditions that raise plasma cortisol concentrations during early life are unlikely to programme cardiovascular and metabolic function in horses in the short term.

Topics: Adrenal Glands; Animals; Animals, Newborn; Cosyntropin; Female; Horses; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Pituitary-Adrenal System

The occurrence of eight cases of adrenal deficit in children hospitalized for acute lymphoblastic leukemia (ALL) led us to conduct a prospective study from May 2006 to May 2007 to better characterize this corticoid-induced adrenal deficit. Forty of the 48 patients hospitalized for ALL were given a low-dose Synacthen test (1 μg), a mean 7 days after the induction phase. An adrenal deficit was diagnosed in 27 patients (67.5%). No significant clinical or hematological difference was identified between the "with deficit" (n = 27) and "without deficit" (n = 13) groups. The diagnosis of adrenal deficit was not more common for children who had received dexamethasone (13/19) or prednisone (14/21), or for those who had (19/29) or had not (8/11) experienced corticoid toxicity during induction. The clinical signs suggesting adrenal deficit were identical in the two groups and none of the children presented an acute episode. In biological terms, only hypoprotidemia was significantly more common in patients with adrenal deficit (p = 0.0004). Of 13 patients with a deficit at the end of the induction who had received a 2nd low-dose Synacthène(®) test before intensification no. 1, 3 weeks on average after the end of corticotherapy, only two still had a deficit. Thus, corticoid-induced adrenal deficit is a common complication in children treated for ALL, although it is not highly symptomatic. Most of these children recover normal adrenal function before intensification no. 1, but it does not eliminate the risk of a secondary deficit after other courses of corticotherapy. Systematic repeated Synacthène(®) tests in common practice among children treated for ALL does not seem justified. However, the results of this study encouraged us to propose a hydrocortisone substitution to children treated for ALL in the event of stress.

Topics: Adolescent; Adrenal Insufficiency; Child; Child, Preschool; Cosyntropin; Dexamethasone; Female; Glucocorticoids; Hormones; Humans; Infant; Inpatients; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisone; Prospective Studies; Risk; Treatment Outcome

Topics: Adult; Apolipoproteins B; Cholesterol, LDL; Cosyntropin; Drug Administration Schedule; Hormones; Humans; Injections, Intramuscular; Male; Young Adult

Interleukin 6 (IL6) has the ability to influence each level of the hypothalamo-pituitary-adrenocortical (HPA) axis. The aim of the study was to test whether IL6 concentration correlates with the adrenal cortex response to ACTH in healthy humans. We postulated that higher basal IL6 concentration would be associated with the higher cortisol response to the stimulation.. Basal IL6 concentration was measured and a low dose (1 microg) ACTH test was performed to assess cortisol response. Twenty-seven apparently healthy subjects (11 male, 16 female, mean age 31.1 years, age range 22-47 years) were included in the study.. Data are presented as mean+/-S.E.M. Basal IL6 level was 0.84+/-0.10 pg/ml. Basal cortisol was 351.9+/-18.3 nmol/l. Maximal cortisol during synacthen test was 653.0+/-20.6 nmol/l. Maximal cortisol increment was 301.1+/-20.0 nmol/l. IL6 concentration was not correlated with basal or maximal cortisol concentration, but correlated significantly with cortisol increment (r=0.63, 95% confidence interval) 0.42-0.83).. In our study, we found that higher basal IL6 concentration is associated with the higher cortisol response to ACTH stimulation. Based on previous research and our data, IL6, even in low concentrations and under physiologic conditions, modulates adrenal cortex responsivity to ACTH. Therefore, it seems that immune modulation of HPA axis is also present under physiologic and not only pathologic conditions.

Topics: Adrenal Cortex; Adult; Cosyntropin; Female; Hormones; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Interleukin-6; Male; Middle Aged; Stimulation, Chemical

Children with nephrotic syndrome (NS) are usually treated with long-term low dose alternate day prednisolone with or without glucocorticoid sparing therapy, such as levamisole or ciclosporin, to maintain remission. The degree of hypothalamic-pituitary-adrenal axis (HPA) suppression with such therapeutic strategies has not been studied systematically. HPA suppression could cause a relapse or adrenal crisis.. To study the risks of HPA suppression, a modified low dose synacthen test (0.5 mug) was administered to 32 patients (22 male,10 female) with a mean age of 9.7 years (range 3.8-17.6 years) with NS receiving long-term alternate day prednisolone for over 12 months. Twelve patients received alternate day prednisolone, 11 alternate prednisolone+levamisole and nine alternate prednisolone+ciclosporin. All patients were followed up for 3 years and the relapse rate noted.. 20/32 (62.5%) patients had a peak serum cortisol concentration of <500 nmol/l, which suggested suboptimal cortisol secretion and possible HPA suppression. 10/12 children in the prednisolone group and 8/11 in the levamisole group had a suboptimal cortisol response compared with 2/9 in the ciclosporin group. During follow-up, the 20 children who had a suboptimal cortisol response had significantly more relapses (95 relapses) compared to the 12 children with a normal cortisol response who had 24 relapses (p = 0.01).. Children with NS receiving long-term alternate day prednisolone therapy are at risk of developing HPA suppression and should be evaluated using the modified synacthen test. Children with evidence of HPA suppression are at a greater risk of relapse.

Topics: Adolescent; Child; Child, Preschool; Cosyntropin; Cyclosporine; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Glucocorticoids; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Levamisole; Male; Nephrotic Syndrome; Pituitary-Adrenal System; Prednisolone; Recurrence

Body fat mass and nutrition influence secretion of the adrenocortical hormones--aldosterone and cortisol--via several mechanisms. However, there are no data on adrenocortical function following widely prescribed mild diet-induced weight loss (10%) in obese subjects. In the present study, 25 healthy obese volunteers (BMI 32.9+/-4.3 kg/m (2)) followed a 30% calorie restricted diet over 12 weeks. Hypothalamic-pituitary-adrenal (HPA) axis function was assessed by 24-hour urine free cortisol/cortisone and a 1 mcg ACTH stimulation test with measurement of total and free cortisol and corticosteroid-binding globulin (CBG). The renin-angiotensin-aldosterone system (RAAS) was assessed by measurement of plasma aldosterone and renin under salt depleted (30 mmol/d) and loading (250 mmol/d) conditions. Volunteers' weight fell by 8.5+/-0.8 kg (8.9+/-0.7%) and seated systolic blood pressure fell by 8.7+/-2.7 mmHg and diastolic blood pressure by 7.0+/-1.4 mmHg (p<0.01). Plasma aldosterone and renin levels fell significantly with weight loss (aldosterone: 853+/-156-635+/-73 pmol/l; renin: 35.4+/-7-24+/-3 mU/l, both p<0.05). The volunteers were relatively salt insensitive (mean arterial pressure change with salt intake: 4 mmHg) and this was not affected by weight loss. Moderate weight loss had no effect on 24-hour urine free cortisol/cortisone, or on basal, or ACTH-stimulated free and total cortisol, or CBG. Hence this conventional weight loss program reduces blood pressure and activity of the RAAS via an effect on renin release. Despite various described influences of fat mass and energy restriction on HPA axis function, there were no changes in basal and stimulated HPA axis function with moderate weight loss. There may be a threshold effect of weight loss/energy restriction required to alter HPA axis function, or moderate weight loss may lead to a counterbalanced effect of stimulatory and inhibitory influences on HPA axis function.

Topics: Adult; Aged; Aldosterone; Blood Pressure; Body Weight; Caloric Restriction; Cosyntropin; Cross-Over Studies; Diet, Reducing; Female; Humans; Hydrocortisone; Male; Middle Aged; Obesity; Pituitary-Adrenal System; Renin; Renin-Angiotensin System; Sodium Chloride, Dietary; Transcortin; Weight Loss

We conducted a prospective, randomised, double-blind trial to study the effect of Synacthen Depot in 18 parturients with postdural puncture headache following deliberate or accidental dural puncture. Women were randomly allocated to receive either Synacthen Depot 1 mg (1 ml) or 0.9% saline 1 ml intramuscularly. Using a 10-cm visual analogue scale, severity of headache was measured before and at intervals until 48 h after injection. There was no difference in the severity of headache or requirement for epidural blood patch. We conclude that there is no advantage to the use of Synacthen Depot 1 mg for the treatment of postdural puncture headache.

Topics: Adult; Anesthesia, Epidural; Anesthesia, Obstetrical; Blood Patch, Epidural; Cosyntropin; Delayed-Action Preparations; Double-Blind Method; Dura Mater; Female; Headache; Humans; Injections, Epidural; Pain Measurement; Pregnancy; Prospective Studies

To explore the relationship between cholesterol levels and the adrenal cortisol response to synacthen in critically ill patients.. Prospective observational study.. Critically ill patients with multiple organ dysfunction syndrome (MODS) with possible adrenal dysfunction defined as unexplained hypotension, ongoing inotropic support, unexplained fever, unexplained hyponatraemia or a combination of these symptoms.. HDL-cholesterol levels (HDL), total cholesterol levels (TC), and triglycerides (TG) before administration of synacthen. LDL-cholesterol was calculated using the Friedewald formula. Basal cortisol and response to 250 microg synacthen intravenously was measured. A cortisol rise of 0.25 micromol/l in a 30-min or 60-min blood sample after synacthen infusion was defined as a proper adrenal response.. Patients with a proper response to synacthen showed higher HDL-cholesterol levels than patients without that response ( P=0.02). Severity of disease as measured by APACHE II or SOFA was not a confounder. LDL-cholesterol levels were extremely low in both responders and non-responders and were not associated with the absolute rise in cortisol. In linear and logistic regression analysis HDL-cholesterol was the sole predictor of cortisol response.. Adrenal cortisol response to a "classic" 250-microg synacthen test relates in critically ill patients to HDL-cholesterol levels. LDL and TC levels did not show such a relation. These findings are in concordance with known biochemical pathways of cortisol production.

Topics: Adult; Aged; Aged, 80 and over; Cholesterol, HDL; Cosyntropin; Critical Care; Humans; Hydrocortisone; Logistic Models; Middle Aged; Multiple Organ Failure; Prospective Studies; Severity of Illness Index; Treatment Outcome

To assess the hypothalamic-pituitary-adrenal (HPA) axis after long-term intranasal corticosteroid treatment in nasal polyposis.. A short synacthen test was performed in 24 patients who received the highest dose of inhaled beclomethasone among a population of 392 patients treated for nasal polyposis with inhaled corticosteroid therapy and short-term oral corticosteroids.. Mean yearly dose of oral prednisone administered in short-term treatment was 371 mg/year. The amount of short-term oral prednisone decreased during the treatment. Mean daily dose of inhaled beclomethasone was 2861 micrograms/day, decreasing during treatment. Morning plasma cortisol was normal in all patients before and after stimulation (163 +/- 44 and 1 +/- 60 micrograms/ml respectively). Nolomethasone dose and plasma cortisol level before or after stimulation.. The high dose of inhaled beclomethasone used to treat nasal polyposis does not affect the HPA axis. Some authors in the literature contest the validity of short synacthen test to detect HPA axis suppression. This test does however detect severe impairments of the HPA axis in outpatients.

Topics: Administration, Inhalation; Administration, Oral; Anti-Inflammatory Agents; Beclomethasone; Cosyntropin; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Nasal Polyps; Prednisone; Regression Analysis; Treatment Outcome

In suspected adrenal insufficiency, the ideal test for assessing the hypothalamo-pituitary-adrenal axis is controversial. Therefore, three tests were compared in patients presenting with symptoms suggestive of adrenal insufficiency.. Responses to the standard short Synacthen test (SSST), the low dose Synacthen test (LDST), and the 08:00 hour serum cortisol concentration were measured in 32 patients. A normal response to the synacthen test was defined as a peak serum cortisol of >/= 500 nmol/l and/or incremental concentration of >/= 200 nmol/l. The sensitivity and specificity of the 08:00 hour serum cortisol concentration compared with other tests was calculated.. Three patients had neither an adequate peak nor increment after the SSST and LDST. All had a serum 08:00 hour cortisol concentration of < 200 nmol/l. Eight patients had abnormal responses by both criteria to the LDST but had normal responses to the SSST. Three reported amelioration of their symptoms on hydrocortisone replacement. Twenty one patients had a normal response to both tests (of these, 14 achieved adequate peak and increment after both tests and seven did not have an adequate peak after the LDST but had a normal increment). The lowest 08:00 hour serum cortisol concentration above which patients achieved normal responses to both the LDST and SSST was 500 nmol/l. At this cut off value (compared with the LDST), the serum 08:00 hour cortisol concentration had a sensitivity of 100% but specificity was only 33%.. The LDST revealed mild degrees of adrenal insufficiency not detected by the SSST. The value of a single 08:00 hour serum cortisol concentration is limited.

Topics: Adolescent; Adrenal Cortex Function Tests; Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Biomarkers; Child; Child, Preschool; Circadian Rhythm; Cosyntropin; Female; Humans; Hydrocortisone; Male; Sensitivity and Specificity

To assess the additional benefit of synacthen depot over standard inpatient care for patients hospitalized with active rheumatoid arthritis (RA).. All patients admitted to our unit with active RA without exclusion criteria were invited to participate and randomized to subcutaneous synacthen depot 0.5 mg on alternate days for 2 injections or 2 injections of saline. Patients, staff, and assessors of response were blinded to the intervention. Assessment [OMERACT set, American College of Rheumatology (ACR) global improvement, dose of intraarticular (IA) or intramuscular (IM) methylprednisolone] was performed at admission to hospital, at discharge, and at 3 and 6 months. Oral prednisone use constituted a protocol violation.. Of 137 patients with RA admitted over the period of recruitment, 36 (26%) were enrolled; 31 completed followup. There were no between-group differences in the change from admission of any individual disease activity measure at any time point. However, using a rigorous global response measure (ACR 50%), a difference was detected in favor of synacthen depot at discharge (52.6% of the intervention group improved vs. 17.6% of controls; p = 0.029, number-needed-to-treat 2.86). Patients treated with synacthen depot showed a trend toward more IA or IM corticosteroid between discharge and 3 months (mean dose 56 vs. 31 mg; p = 0.19) and a trend toward more patients requiring a change in slow acting antirheumatic drug after discharge (4 vs. 1; p = 0.27).. There is some additional benefit of synacthen depot in the hospital treatment of RA, but the effect is lost by 3 months, with a suggestion of rebound worsening in these patients. We postulate that oversuppression of corticotrophin releasing hormone by exogenous adrenocorticotrophic hormone in patients who already have a hypothalamic deficit may contribute to the rebound worsening of disease activity seen in these patients.

Topics: Anti-Inflammatory Agents; Arthritis, Rheumatoid; Cosyntropin; Delayed-Action Preparations; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Inpatients; Male; Methylprednisolone; Middle Aged; Patient Selection; Placebos; Treatment Outcome

New therapeutic indications based on the antiprogesterone action of RU 486 (Mifepristone) are emerging which require long term administration and raise the question of its safety because of the antiglucocorticoid action of the drug. A trial was designed to assess the antiglucocorticoid effect of RU 486, possible manifestations of peripheral cortisol deprivation, and the adrenocortical and corticotroph reserves. Ten normal male volunteers (aged 21-29 yr) were given RU 486 (200 mg/day) or placebo between 0800-0900 h for 8 consecutive days in a randomized, double blind, cross-over design, with a 1-month interval between the two periods. RU 486 induced overactivation of the pituitary-adrenal axis; baseline values (mean +/- SEM) before and at end of treatment were, respectively: 0800 h plasma cortisol, 147.3 +/- 15.5 and 257.6 +/- 8.8 ng/mL; 0800 h salivary cortisol, 5.8 +/- 1.2 and 15.2 +/- 0.8 ng/mL; nocturnal (2200-0800 h) urinary cortisol, 8.4 +/- 1.5 and 33.7 +/- 11.1 micrograms; and 0800 h plasma ACTH, 29.2 +/- 3.7 and 60.2 +/- 8.4 pg/mL. All of these variations were significantly different from those during placebo treatment (0.0001 < P < 0.03) and disappeared within 4 days after the end of treatment. A daily record of subjective clinical symptoms, body weight and temperature, blood pressure, and heart rate showed neither side-effects nor any significant variation during treatment. Blood electrolyte and eosinophil counts were unchanged; fasting blood glucose was slightly higher at the end of treatment (5.0 +/- 0.2 vs. 4.7 +/- 0.1 mmol/L; P = 0.04). The adrenocortical response to Cortrosyn (0.25 mg, im) was exaggerated during RU 486 treatment (P < 0.006): peak values before and at the end of treatment were, respectively: plasma cortisol, 272.5 +/- 15.2 and 347.1 +/- 20.6 ng/mL; and salivary cortisol, 17.0 +/- 2.2 and 31.1 +/- 3.1 ng/mL. Direct pituitary stimulation (100 micrograms ovine CRH, followed by 1 IU lysine vasopressin over 15 min) also induced exaggerated corticotroph and adrenocortical responses (P < 0.005); peak values before and at the end of treatment were, respectively: plasma ACTH, 147.7 +/- 24.6 and 254.0 +/- 41.3 pg/mL; and plasma cortisol, 231.6 +/- 7.3 and 319.2 +/- 12.3 ng/mL. These data show that 8-day treatment with 200 mg RU 486 daily induces a hormonally detectable antiglucocorticoid effect without clinical symptoms. This state results from reversible cortisol overproduction with preservation of adrenocortical and pituitary reserv. At Cochin Hospital in Paris, France, ten 21-29 year old normal male volunteers received either 200 mg RU-486 per day or a placebo for 8 consecutive days between 8:00 and 9:00 in the morning, then went through a 28-day washout period before receiving what they did not receive the first time for 8 days. The researchers wanted to examine the antiglucocorticoid effect of RU-486, any evidence of peripheral cortisol deprivation, and the adrenocortical and corticotroph reserves. An assessment of potential risk of longterm administration of RU-486 is needed to determine whether it can be used to treat chronic diseases (e.g., meningioma and breast cancer). RU-486 was responsible for overreaction of the pituitary-adrenal axis (8:00 am plasma cortisol, 147.3 ng/mL vs. 257.6 ng/mL; 8:00 am salivary cortisol, 5.8 ng/mL vs. 15.2 ng/mL; nocturnal urinary cortisol, 8.4 mcg vs. 33.7 mcg; and 8:00 am plasma adrenocorticotropic hormone [ACTH] 29.2 pg/mL vs. 60.2 pg/mL). All these changes differed significantly from those during placebo treatment (0.0001 p 0.03). These changes no longer existed 4 days after the end of treatment. The men kept a daily record of subjective clinical symptoms, body weight and temperature, blood pressure, and heart rate, which did not indicate any side effects or any considerable variation during treatment. RU-486 did not affect blood electrolyte and eosinophil counts. Blood glucose levels during fasting were somewhat higher at the end of treatment (p = 0.04). During RU-486 treatment, the adrenocortical response to 0.25 mg of intramuscularly injected Cortrosyn was amplified (peak values before and after, plasma cortisol, 272.5 ng/mL vs. 347.1 ng/mL; 17 ng/mL vs. 31.1 ng/mL) (p 0.006). Direct stimulation of the pituitary resulted in exaggerated corticotroph and adrenocortical responses (p 0.005). These findings showed that a daily dose of 200 mg RU-486 causes a hormonally detectable antiglucocorticoid effect but no clinical symptoms.

Topics: Adrenocorticotropic Hormone; Adult; Circadian Rhythm; Corticotropin-Releasing Hormone; Cosyntropin; Delayed-Action Preparations; Double-Blind Method; Glucocorticoids; Humans; Hydrocortisone; Lypressin; Male; Mifepristone; Pituitary-Adrenal System; Receptors, Glucocorticoid; Time Factors

In a double-blind randomized clinical trial 18 patients with exacerbations of distal ulcerative colitis were treated for 4 weeks with enemas containing either prednisolone 21-phosphate 30 mg (PP) or beclomethasone dipropionate 1 mg (BDP) a surface-active corticosteroid. All 8 patients treated with PP showed clinical and endoscopic improvement in contrast with only 4 of 10 patients treated with BDP. Endocrinologic evaluation showed a significant decrease in morning plasma cortisol, in cortisol increase after synacthen, and in urinary free cortisol excretion after PP therapy, but no changes in these variables after BDP therapy. We conclude that PP enemas are more active in the treatment of ulcerative proctitis, but they cause a suppression of the adrenal cortex, in contrast to BDP.

Topics: Adult; Beclomethasone; Clinical Trials as Topic; Cosyntropin; Double-Blind Method; Enema; Female; Humans; Hydrocortisone; Male; Middle Aged; Prednisolone; Proctitis; Random Allocation; Ulcer

Topics: Adolescent; Adult; Aged; Clinical Trials as Topic; Cosyntropin; Double-Blind Method; Female; Herpes Zoster; Humans; Male; Middle Aged; Neuralgia; Prednisone

Topics: Adrenocorticotropic Hormone; Adult; Asthma; Clinical Trials as Topic; Cosyntropin; Humans; Male; Middle Aged; Placebos

Topics: Abortion, Threatened; Adrenocorticotropic Hormone; Clinical Trials as Topic; Cosyntropin; Delayed-Action Preparations; Female; Hormones; Humans; Pregnancy; Progesterone; Progesterone Congeners; Zinc

Cortisol levels in response to stress are highly variable. Baseline and stimulated cortisol levels are commonly used to determine adrenal function following unilateral adrenalectomy. We report the results of synacthen stimulation testing following unilateral adrenalectomy in a tertiary referral center.. Data were collected retrospectively for 36 patients who underwent synacthen stimulation testing one day post unilateral adrenalectomy. None of the patients had clinical signs of hypercortisolism preoperatively. No patient received pre- or intraoperative steroids. Patients with overt Cushing's syndrome were excluded.. The median age was 58 (31-79) years. Preoperatively, 16 (44%) patients had a diagnosis of pheochromocytoma, 12 (33%) patients had primary aldosteronism and 8 (22%) patients had non-functioning adenomas with indeterminate/atypical imaging characteristics necessitating surgery. Preoperative overnight dexamethasone suppression test results revealed that 6 of 29 patients failed to suppress cortisol to <50 nmol/L. Twenty (56%) patients achieved a stimulated cortisol ≥450 nmol/L at 30 minutes and 28 (78%) at 60 minutes. None of the patients developed clinical adrenal insufficiency necessitating steroid replacement.. Synacthen stimulation testing following unilateral adrenalectomy using standard stimulated cortisol cut-off values would wrongly label many patients adrenally insufficient and may lead to inappropriate prescriptions of steroids to patients who do not need them.

Topics: Adenoma; Adrenal Gland Neoplasms; Adrenal Insufficiency; Adrenalectomy; Adult; Aged; Cosyntropin; Cushing Syndrome; Dexamethasone; Endocrinology; Female; Humans; Hydrocortisone; Hyperaldosteronism; Male; Middle Aged; Pheochromocytoma; Postoperative Period; Retrospective Studies

In humans, approximately 95% of circulating cortisol is bound to corticosteroid-binding globulin and albumin. It is only the free fraction that is biologically active and can activate signaling pathways via glucocorticoid hormone receptors in cells. Microdialysis is a well-established technique that enables the sampling of molecules in different compartments of the body, including extracellular fluid. This is the first study validating a rapid sampling microdialysis method measuring free cortisol in the subcutaneous and blood compartments of healthy volunteers.. Healthy nonsmoking volunteers (42 men, aged 18-24 years; body mass index 18-25 kg/m2) received placebo (saline), 250 μg Synacthen, or 1 mg dexamethasone with 10-minute sampling to measure total and free cortisol (subcutaneous, intravenous, and saliva) for an hour before and 4 hours after administration.. Following stimulation by Synacthen, total serum cortisol and free cortisol in both compartments rose significantly, achieving and maintaining maximum levels between 2 and 3 hours following the stimulus. A decline in cortisol levels was evident after the administration of dexamethasone or placebo, but there was a clear pulsatile activity around lunchtime in the latter group, which was prominent in the blood compartment (total and free cortisol). There was good correlation between serum total and free cortisol (subcutaneous and intravenous) in the Synacthen and dexamethasone groups with no significant delay (less than 5 minutes) between total and free cortisol.. This seminal study demonstrated the dynamic responses of total blood cortisol and microdialysis derived free cortisol in blood, subcutaneous tissue, and saliva in men.

Topics: Adolescent; Adult; Anti-Inflammatory Agents; Cosyntropin; Dexamethasone; Follow-Up Studies; Healthy Volunteers; Hormones; Humans; Hydrocortisone; Male; Microdialysis; Time Factors; Young Adult

Background Peptide-derived drugs represent an emerging class of prohibited substances in professional sports and, thus, in modern doping controls. After parental administration (e.g. subcutaneous, intravenous), these drugs undergo various metabolic processes, which degrade them to biologically active or inactive peptides. Knowledge about these metabolic processes and the hereby produced metabolites plays a key role in successful doping controls due to the effective design of analytical assays under consideration of optimal analytical targets. Unfortunately, the complexity of biological matrix (e.g. blood or urine) complicates the immediate identification of relevant metabolites due to the enormous excess of naturally occurring peptides and their degradation products. Methods In this study, a strategy employing in-vitro metabolism of stable isotope-labeled peptides producing characteristic reporter ions derived from labeled immonium ions is shown. The in-vitro experiments were performed with human skin tissue microsomes (S9), and model drugs representing prohibited peptide hormones were synacthen, insulin, and corticorelin (respectively, their stable isotope-labeled analogs). After generic sample preparation, the metabolites were identified by means of liquid chromatography (LC) coupled to high-resolution mass spectrometry (MS) in an untargeted approach. Results and conclusions For all three model peptides, several metabolic products were readily identified. While insulin and corticorelin were found to be comparably stable, synacthen was fully degraded, yielding a plethora of metabolic products. A proof of concept concerning the transferability of the obtained data was accomplished by analyzing plasma samples collected post-administration of recombinant human insulin, corroborating the presence of a skin protease-indicative insulin metabolite in vivo.

Topics: Adrenocorticotropic Hormone; Chromatography, High Pressure Liquid; Cosyntropin; Doping in Sports; Humans; Insulin; Ions; Isotope Labeling; Mass Spectrometry; Microsomes; Peptides

The emotional impact of exposure to stressors has not been well quantified in animals. We hypothesised that exogenous induction of stress in sheep would induce a pessimistic judgement bias and increased attention towards a threatening stimulus, suggestive of a negative emotional state. Stress was induced pharmacologically by administering synthetic adrenocorticotropic hormone. Judgement bias was assessed using a spatial go/no-go task after exposure to acute stress (one injection), chronic stress (21 daily injections) and acute-on-chronic stress (2 min isolation after 28 daily injections). Attention bias was assessed during chronic stress only (22 daily injections). In contrast with our hypotheses, there was no strong evidence that Synacthen administration altered judgement bias or attention bias at any stage of the experiment. Stressed sheep were more likely to approach ambiguous locations than saline Control animals, however, statistical evidence for models fitting treatment group was very weak. Overall, our findings suggest that elevated levels of cortisol may not fully explain changes to judgement bias observed in previous studies after environmentally-induced stress. Further studies are required to better understand which aspects of environmentally-induced stress alter judgement bias and to further validate cognitive methods of assessing affect in sheep.

Topics: Animal Welfare; Animals; Attentional Bias; Behavior, Animal; Cosyntropin; Emotions; Female; Hydrocortisone; Judgment; Male; Pessimism; Sheep; Stress, Psychological

Topics: Adolescent; Adrenal Insufficiency; Child; Cosyntropin; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Female; Hormones; Humans; Hydrocortisone; Male

Salivary cortisone reflects serum cortisol levels, is more sensitive than salivary cortisol at lower values of serum cortisol and is noninvasive.. To investigate the relationship between serum cortisol and salivary cortisol and cortisone following low- and high-dose synacthen.. Prospective pharmacodynamic studies in clinical research facilities.. Thirty-five dexamethasone-suppressed, healthy adult males underwent an intravenous synacthen test: N = 23 low-dose (1 mcg), N = 12 high-dose (250 mcg). Paired serum and salivary samples were taken at 15 sampling points over 120 minutes.. Serum cortisol and salivary cortisol and cortisone were analysed for correlations and by a mixed-effects model.. At baseline, the correlation between serum cortisol and salivary cortisol was weak with many samples undetectable (r = .45, NS), but there was a strong correlation with salivary cortisone (r = .94, P < .001). Up to 50 minutes following synacthen, the correlation coefficient between serum cortisol and salivary cortisol and cortisone was <0.8, but both had a stronger correlation at 60 minutes (salivary cortisol r = .89, P < .001, salivary cortisone r = .85, P < .001). The relationship was examined excluding samples in the dynamic phase (baseline to 60 minutes). Salivary cortisol and cortisone showed a close relationship to serum cortisol. Salivary cortisone showed the stronger correlation: salivary cortisol r = .82, P < .001, salivary cortisone r = .96, P < .001.. Following synacthen, both salivary cortisol and cortisone reflect serum cortisol levels, but there is a lag in their rise up to 60 minutes. The results support further research for possible future use of a 60-minute salivary cortisone measurement during the synacthen test.

Topics: Adult; Cortisone; Cosyntropin; Humans; Hydrocortisone; Male; Middle Aged; Prospective Studies; Saliva; Young Adult

The short synacthen test (SST) is widely used to assess patients for adrenal insufficiency, but the frequency and protocols used across different centres for the low-dose test (LDT) are unknown. This study aimed to survey centres and test the accuracy of ten different synacthen preparation strategies used for the LDT.. Members of 6 international endocrine societies were surveyed regarding diagnostic tests used for adrenal insufficiency, and in particular the SST. Synacthen was diluted for the LDT and concentrations measured using a synacthen ELISA.. Survey responses were received from 766 individuals across 60 countries (52% adult, 45% paediatric endocrinologists). The SST is used by 98% of centres: 92% using high-dose (250 μg), 43% low-dose and 37% both. Ten low-dose dilution methods were assessed and variation in synacthen concentration was demonstrated with intramethod coefficients of variation (CV) ranging from 2.1% to 109%. The method using 5% dextrose as a diluent was the least variable (CV of 2.1%). The variation in dilution methods means that the dose of synacthen administered in a LDT may vary between 0.16 and 0.81 μg.. The high-dose SST is the most popular diagnostic test of adrenal insufficiency, but up to 72% of paediatric endocrinologists use a LDT. There is considerable variation observed both within and between low-dose synacthen dilution methods creating considerable risk of inaccurate dosing and thereby invalid results.

Topics: Adrenal Insufficiency; Adult; Cosyntropin; Enzyme-Linked Immunosorbent Assay; Female; Humans; Male; Surveys and Questionnaires

It is well known that adrenal insufficiency is common in septic shock or hemodynamically unstable patients. But, there is as yet no sufficient clinically significant data about the exact prevalence or differences in the cause of cirrhosis with adrenal insufficiency. To investigate adrenal insufficiency prevalence in hemodynamically stable patients with cirrhosis and determine differences based on cirrhosis severity or etiology.From July 2011 to December 2012, 69 hemodynamically stable patients with cirrhosis without infection admitted at Hallym University Medical Center were enrolled. Adrenal insufficiency was defined as a peak cortisol level < 18 μg/dL, 30 or 60 minutes after 250 μg Synacthen injection.The study included 55 male patients (79.7%), and the mean age was 57.9 ± 12.9 years. Cirrhosis etiology was alcohol consumption, HBV, HCV, both viral and alcohol related, and cryptogenic in 49, 15, 7, 11, 9 patients, respectively. Adrenal insufficiency occurred in 24 patients (34.8%). No differences were found in age, sex, mean arterial pressure, heart rate, HDL, cirrhosis etiology, degree of alcohol consumption, encephalopathy, variceal bleeding history, or hepatocellular carcinoma between patients with or without adrenal insufficiency. Serum albumin level was lower (P < .05), and INR was higher (P < .05) in patients with than in those without adrenal insufficiency. However, multivariate analysis revealed no independent adrenal insufficiency predictor. Significant negative correlations were found between Child-Pugh score and peak cortisol levels (γ=-0.365, P = .008).Adrenal insufficiency was frequent even in hemodynamically stable patients with cirrhosis and tended to be associated with only liver disease severity, being unrelated to cirrhosis etiology.

Topics: Adrenal Insufficiency; Aged; Alcohol Drinking; Cosyntropin; Female; Hemodynamic Monitoring; Hormones; Humans; Hydrocortisone; International Normalized Ratio; Liver; Liver Cirrhosis; Male; Middle Aged; Prevalence; Prospective Studies; Serum Albumin; Severity of Illness Index

The tendency of peptides to adsorb to surfaces can raise a concern in variety of analytical fields where the qualitative/quantitative measurement of low concentration analytes (ng/mL-pg/mL) is required. To demonstrate the importance of using the optimal glassware/plasticware, four doping relevant model peptides (GHRP 5, TB-500, Insulin Lispro, Synachten) were chosen and their recovery from various surfaces were evaluated. Our experiments showed that choosing expensive consumables with low-bind characteristics is not beneficial in all cases. A careful selection of the consumables based on the evaluation of the physico/chemical features of the peptide is recommended.

Topics: Adsorption; Animals; Chromatography, High Pressure Liquid; Cosyntropin; Doping in Sports; Glass; Humans; Insulin Lispro; Oligopeptides; Polypropylenes

Criteria for the evaluation of the insulin tolerance test (ITT) and Synacthen test are still a matter of debate. The objective of the study was to make a comparison of serum and salivary cortisol during four stimulation tests. Sixty four healthy volunteers underwent the ITT, the Synacthen test with 1 (LDST), 10 (MDST) and 250 (HDST) microg dose of ACTH. Maximum serum cortisol response was observed at the 90 min of the ITT (49 %), HDST (89 %) and MDST (56 %) and at the 40 min of the LDST (44 %). Results expressed as 95 % confidence intervals: 408.0-843.6 and 289.5-868.1 nmol/l in the IIT at 60 and 90 min. In the HDST and the MDST serum cortisol reached the maximum at 90 min 542.6-1245.5 and 444.2-871.3 nmol/l. Levels of salivary cortisol followed the same pattern as serum cortisol. Salivary cortisol reached the maximum response in the HDST and the MDST at 90 min and at 40 min in the LDST. We confirmed good reliability of all tests with respect to timing of response and maximum response compared to the ITT. We proved that the MDST test can provide the similar response in serum cortisol to the HDST. Measuring either salivary cortisol or ACTH levels did not provide any additional benefit then measuring serum cortisol by itself.

Topics: Adult; Cosyntropin; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Insulin; Insulin Resistance; Male; Pituitary-Adrenal System; Reference Standards; Reproducibility of Results; Saliva

Dried blood spot (DBS) sampling, a technique used for taking whole blood samples dried on a filter paper, was initially reported in 1963 by Robert Guthrie. While the diagnostic analysis of metabolic disorders in newborns was the focus of investigations at that time, the number of established applications for preclinical drug development, toxicological studies, and therapeutic drug monitoring increased enormously in the last decades. As a consequence of speed, simplicity, and minimal invasiveness, DBS recommends itself as the preferential technique in sports drug testing. The present approach highlights for the first time the development of a screening assay for the analysis of the synthetic human adrenocorticotropic hormone tetracosactide hexaacetate (Synacthen(®)) in DBS using liquid chromatography tandem mass spectrometry. Highly purified sample extracts were obtained by an advanced sample preparation procedure including the addition of an internal standard (d8-tetracosactide) and immunoaffinity purification. The method's overall recovery was 27.6 %, and the assay's imprecision was calculated between 8.1 and 17.9 % for intraday and 12.9 to 20.5 % for interday measurements. Stability of the synthetic peptide in DBS was shown for at least 10 days at room temperature and presents a major benefit, since a rapid degradation in conventionally applied matrices such as urine or plasma is well known. With a limit of detection of 50 pg/mL, a detection window of several hours is expected considering reported steady-state plasma levels of 300 pg/mL after intramuscular application of Synacthen(®) Depot (1 mg). The analysis of authentic DBS samples within the scope of an administration study with 250 μg Synacthen(®) (short stimulation test) demonstrated the great potential of the developed assay to simplify the analysis of Synacthen(®) for doping control purposes.

Topics: Blood Chemical Analysis; Chromatography, Liquid; Cosyntropin; Female; Humans; Limit of Detection; Male; Tandem Mass Spectrometry

The test with pharmaceutical "Synachten Depot", a synthetic analogue of corticotropine was carried out. The sampling consisted of 30 clinically healthy women aged from 20 to 30 years and residents of Arkhangelsk. The scheme of blood sampling provided basal sample, 30 and 60 minutes, I and 4 days after administration of pharmaceutical. After 30 minutes of testing, increase of level of cortisol (F), progesterone (Δ4 = p), testosterone, triiodothyronine (T3) and decreasing of level of insulin and follitropin were established After 60 minutes of testing maximal level of cortisol, high concentration of progesterone and triiodothyronine, increasing of levels of testosterone, estradiol and insulin and decrease of concentration of thyrotropin and prolactin were observed. Up to the first day, the tests registered decrease of level of cortisol, progesterone, testosterone, thyrotropin, thyroxine and triiodothyronine under increasing of content of follitropin, estradiol and insulin in comparison with basal test. Up to the fourth day, tendency of increasing of the level of progesterone and estradiol and decreasing of lutropin and testosterone as compared with initial levels were observed.

Topics: Adrenocorticotropic Hormone; Adult; Cosyntropin; Estradiol; Female; Humans; Insulin; Progesterone; Prolactin; Russia; Testosterone; Thyrotropin; Thyroxine; Triiodothyronine

Determination of response of cortisol and its metabolites to different stimuli may be important for adrenal gland disorders. To date, only one metabolite, cortisone, has been followed in stimulation tests of the adrenal gland. We aimed to describe a response of cortisol metabolites to the standard short Synacthen test (HDST), insulin tolerance test (ITT), low dose Synacthen test (LDST) and medium dose Synacthen test (MDST). Sixty healthy subjects were investigated: 30 men and 30 women. Plasma for measurements of cortisol and its metabolites was obtained before and 30th and 60th min after Synacthen and insulin administration. The cut-off 500 nmol/l of cortisol was reached after stimulation in all of tests, the maximal stimulation level was reached in 60th min in all of the tests except for LDST. The response of cortisol and its metabolites at 30th and 60th min strongly correlated in all of the tests except for LDST. Cortisol and its metabolites increased after stimulation; in contrast, cortisone and its metabolites decreased. We showed that the response of the cortisol metabolites during the Synacthen tests and ITT well correlated, and the MDST showed similar response compared to HDST. The decrease in cortisone metabolites may correspond to the regeneration of cortisol from cortisone in response to stimulation test.

Topics: Adult; Cortisone; Cosyntropin; Female; Humans; Hydrocortisone; Insulin; Insulin Resistance; Male; Middle Aged

Previous studies have demonstrated that a morning serum cortisol of <100 nmol/l makes further dynamic testing such as the Synacthen stimulation test (SST) unnecessary to confirm adrenal insufficiency. The morning cortisol level that reliably predicts adrenal sufficiency (AS) is less well established, and values ranging from 300 to 500 nmol/l have been proposed.. The aim of this study was to determine the ambulatory morning cortisol level that predicts adrenal sufficiency, as defined by an adequate response to SST, using a receiver operating characteristics (ROC) curve.. Observational retrospective cross-sectional study.. We conducted a retrospective audit of SST performed at PathWest Laboratory QEII from January 2006 to August 2008. A total of 761 results were obtained. Patients who were acutely ill or in intensive care, on glucocorticoid therapy, and those with inadequate data or multiple records were excluded from the analysis leaving 505 available for analysis. Baseline serum was obtained prior to intramuscular injection of 250 mcg Synacthen, and a second sample was obtained 30 min post-Synacthen. AS was defined as a 30-min post-Synacthen cortisol of >550 nmol/l; values ≤550 nmol/l were considered inadequate.. Based on SST criteria, of the 505 patients included in the study, 350 patients (69%) were adrenal sufficient and 155 (31%) had adrenal insufficiency. Using the minimum ROC distance criterion, a basal cortisol value of >236 nmol/l was identified to predict AS with sensitivity 84% and specificity 71%. However, to increase the specificity to 95%, we recommend a basal cortisol cut-off of >375 nmol/l. For patients with known pituitary disease (n = 152), basal cortisol of >214 nmol/l (sensitivity 85% and specificity 71%) may obviate the need for SST in the appropriate clinical context, although 330 nmol/l gives a specificity of 95%.. Basal morning cortisol is a viable first step in the evaluation of patients with suspected adrenal insufficiency.

Topics: Adolescent; Adrenal Insufficiency; Adult; Aged; Aged, 80 and over; Child; Cosyntropin; Cross-Sectional Studies; Female; Humans; Hydrocortisone; Injections, Intramuscular; Male; Middle Aged; Pituitary-Adrenal Function Tests; Retrospective Studies; Time Factors; Young Adult

The short Synacthen test (SST) is widely used as alternative test to the insulin tolerance test (ITT) to investigate central adrenal insufficiency (CAI), but the methodology and cut-off values of the SST are controversial. Our aim was to evaluate the cut-off value of the ITT in normal subjects and to assess the different cut-off values of the high-dose SST (250 μg, HDT) and the low-dose SST (1 μg, LDT) in subjects with suspected CAI.. We conducted ITTs in 208 normal subjects to establish the cut-off value for the ITT, and 28 of those subjects underwent the HDT and LDT. From 1999 to 2007, 182 patients with suspected CAI were recruited and underwent ITTs, LDTs and HDTs to establish cut-off values and compare the diagnostic accuracy between the LDT and HDT.. The 95th percentile of the peak cortisol level during the ITT in the normal control subjects was 14·8 μg/dl. Receiver operator characteristics (ROC) analysis revealed that the optimal cut-off values of peak cortisol in the LDT and HDT in patients with suspected CAI were 15·8 and 17·4 μg/dl, respectively. However, the cut-off values from normative data (mean - 2 SD) were 18·3 μg/dl for the LDT and 20·5 μg/dl for the HDT in normal control.. The optimal cut-off values of SSTs needed to be individualized according to the type of SST and tested patient population.

Topics: Adolescent; Adrenal Insufficiency; Adult; Aged; Cosyntropin; Female; Glucose Tolerance Test; Humans; Insulin; Male; Middle Aged; Sensitivity and Specificity; Young Adult

Despite the widespread use of the short synacthen test (SST), there remains no clear consensus on sampling times for the measurement of serum cortisol that best determines adrenal reserve. We set out to establish whether there is any value in measuring serum cortisol at 60 min following administration of synacthen.. Retrospective data analysis of 500 SST results measuring 0, 30 and 60 min cortisol levels after administration of 250 μg of synacthen at 2 large urban National Health Teaching Hospitals in the UK.. Individuals thought to have primary or secondary adrenal insufficiency given 250 μg of synacthen.. Serum cortisol levels measured at 0, 30 and 60 min, looking to see how many people who had adrenal insufficiency at the 30 min sample but in whom the 60 min sample showed adequate adrenal reserve.. The results from 384 people were analysed. A total of 276 had normal responses at 30 min and also at 60 min. A sum of 33 individuals had 'insufficient' (i.e., <550 nmol/l) 30 min cortisol levels, rising to ≥ 550 nmol/l at the 60 min test. All 75 individuals who were insufficient at 60 min were also insufficient at 30 min. No individuals passed (≥550 nmol/l) at 30 min and then failed (<550 nmol/l) at 60 min.. These results suggest that a significant proportion of people undergoing a SST may be inappropriately diagnosed as having adrenal insufficiency if the 60 min sample is not measured. We suggest that the 60 min sample is measured in all individuals having a SST to prevent unnecessary over-diagnosis of adrenal insufficiency.

Topics: Adrenal Insufficiency; Adult; Aged; Cosyntropin; Female; Hormones; Hospitals, Teaching; Humans; Hydrocortisone; Male; Middle Aged; Retrospective Studies; ROC Curve; Time Factors; United Kingdom

Child abuse and other early-life environmental stressors are known to affect the hypothalamic-pituitary-adrenal axis. We sought to compare synacthen-stimulated cortisol responses in children who suffered inflicted or accidental traumatic brain injury (TBI).. Children with a history of early-childhood TBI were recruited from the Starship Children's Hospital database (Auckland, New Zealand, 1992-2010). All underwent a low-dose ACTH(1-24) (synacthen 1 μg IV) test, and serum cortisol response was compared between inflicted (TBI(I) ) and accidental (TBI(A) ) groups.. We assessed 64 children with TBI(I) and 134 with TBI(A) . Boys were more likely than girls to suffer accidental (P < 0·001), but not inflicted TBI. TBI(I) children displayed a 14% reduction in peak stimulated cortisol in comparison with the TBI(A) group (P < 0·001), as well as reduced cortisol responses at + 30 (P < 0·01) and + 60 min (P < 0·001). Importantly, these differences were not associated with severity of injury. The odds ratio of TBI(I) children having a mother who suffered domestic violence during pregnancy was 6·2 times that of the TBI(A) group (P < 0·001). However, reported domestic violence during pregnancy or placement of child in foster care did not appear to affect cortisol responses.. Synacthen-stimulated cortisol response is attenuated following inflicted TBI in early childhood. This may reflect chronic exposure to environmental stress as opposed to pituitary injury or early-life programming.

Topics: Brain Injuries; Child; Child Abuse; Child, Preschool; Cosyntropin; Domestic Violence; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Infant; Male; Pituitary-Adrenal System; Pregnancy; Stress, Physiological

We investigated: (i) the association between severity of cirrhosis and serum levels of free cortisol (SFC) and total cortisol (STC), measured before and 30 min after (T(30)) the low-dose 1-µg short synacthen test (LD-SST); and (ii) the prognostic value of SFC and STC.. Consecutive, hemodynamically stable, cirrhotic patients (34 Child-Pugh class A, 29B, and 32C) underwent the LD-SST. Patients were followed for at least 12 months to assess non-transplant-related mortality.. Child-Pugh class C patients had significantly higher basal levels of SFC than Child-Pugh class A or B patients. Prevalence of suspected adrenal dysfunction ranged between 7.4% (T(0) STC < 138 nmol/L) and 49.4% (change in STC < 250 nmol/L) according to the threshold used. In receiver-operator curve analysis, the area-under-the-curve values were 0.67 for T(30) SFC (0.51-0.79), 0.81 for Child-Pugh score (0.70-0.88), and 0.79 for albumin level (0.63-0.88). During the follow-up period, 16 patients with high T(30) SFC (≥ 78.9 nmol/L) (26.2%) and one patient with low T(30) SFC (< 78.9 nmol/L) (3.4%) died (P = 0.027 for high vs low T(30) SFC, log-rank test). Albeit not statistically significant, the risk of death for patients with T(30) SFC ≥ 78.9 nmol/L was fivefold higher than for patients with lower levels after adjusting for cirrhosis severity and level of albumin.. One-year, non-transplant-related mortality is high among patients with T(30) levels of SFC ≥ 78.9 nmol/L (26.2%). These findings might result from latent inflammatory stress in hemodynamically stable cirrhotic patients, detected by adrenal testing.

Topics: Adrenal Cortex Function Tests; Adrenal Gland Diseases; Adult; Aged; Biomarkers; Cosyntropin; Female; Hemodynamics; Humans; Hydrocortisone; Kaplan-Meier Estimate; Liver Cirrhosis; Male; Middle Aged; Predictive Value of Tests; Prevalence; Prognosis; Proportional Hazards Models; Prospective Studies; Risk Assessment; Risk Factors; Severity of Illness Index; Time Factors; Up-Regulation

The objectives of this study were first to show adrenocortical response to a long-acting adrenocorticotropic hormone preparation (tetracosactide acetate zinc suspension) (ACTH-Z) and its effect on adrenocortical function in beef cows (Experiment 1) and second to apply the ACTH-Z challenge in dairy cows based on cortisol concentrations in milk collected at routine milking (Experiment 2). In Experiment 1, four beef cows in luteal phase were challenged with ACTH-Z, and plasma cortisol concentrations were determined for 48 h after the injection at 30-min to 2-h intervals. A rapid ACTH test was conducted 3 days before and 2 h after the completion of ACTH-Z injection for 48 h to investigate the effect on adrenocortical function. Plasma cortisol concentrations increased significantly 30 min after ACTH-Z injection (p < 0.001), and the high cortisol levels were maintained for approximately 10 h after the injection. In Experiment 2, eight dairy cows were subjected to ACTH-Z challenge 1-2 weeks and 4-5 weeks post-partum. Blood and milk samples were taken at morning and afternoon milking. All the cows showed a significant increase in cortisol concentrations in plasma as well as in skim milk 8 h after ACTH-Z injection 1-2 weeks and 4-5 weeks post-partum (p < 0.001). There was a significant correlation between plasma and skim milk cortisol concentrations 8 h after ACTH-Z challenge (r = 0.74, p < 0.001). The results obtained in this study suggest that elevated levels of plasma cortisol are maintained for approximately 10 h after ACTH-Z treatment without adverse effect on adrenocortical function and a long-acting ACTH-Z challenge based on cortisol concentrations in milk, which were collected at the morning and the afternoon milking, can be a useful tool to monitor adrenocortical function in cows.

Topics: Animals; Cattle; Cosyntropin; Delayed-Action Preparations; Female; Hydrocortisone; Injections, Intramuscular; Milk; Time Factors

Prader-Willi syndrome (PWS) is a genetic disease associated with hypogonadism and partial GH insufficiency, possibly explained in part by a hypothalamic dysfunction. Partial insufficiency of the hypothalamic-pituitary-adrenal (HPA) axis has recently been suggested.. The objective of the study was to further explore the HPA axis in PWS by use of routine tests.. Nonselected PWS patients were examined with a standard high-dose synacthen test or the insulin tolerance test (ITT). A random serum (s) cortisol was measured in case of acute illness.. The study was conducted at university hospitals in Denmark and Sweden.. Sixty-five PWS patients with a confirmed genetic diagnosis participated in the study.. A s-cortisol value above 500 nmol/liter as well as an increase of 250 nmol/liter or greater was considered a normal response.. Fifty-seven PWS patients (median age 22 yr, total range 0.5-48 yr) were examined with the high-dose synacthen test. The median s-cortisol at the time of 30 min was 699 (474-1578) nmol/liter. Only one patient had a s-cortisol level below 500 nmol/liter but an increase of 359 nmol/liter. This patient subsequently showed a normal ITT response. Two patients had increases less than 250 nmol/liter but a time of 30-min s-cortisol values of 600 nmol/liter or greater. These three patients were interpreted as normal responders. Eight patients [aged 26 (16-36) yr] examined with the ITT had a median peak s-cortisol of 668 (502-822) nmol/liter. Four children admitted for acute illnesses had s-cortisol values ranging from 680 to 1372 nmol/liter.. In this PWS cohort, the function of the HPA axis was normal, suggesting that clinically significant adrenal insufficiency in PWS is rare.

Topics: Adolescent; Adrenal Insufficiency; Adult; Child; Child, Preschool; Cosyntropin; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Immunoassay; Infant; Insulin; Male; Middle Aged; Pituitary Function Tests; Pituitary-Adrenal System; Prader-Willi Syndrome

Imatinib mesylate [tyrosine kinase (TK) inhibitor] is a novel medication in the treatment of chronic myelogenous leukaemia (CML). TK is also essential in hypothalamo-pituitary-adrenal (HPA) axis.. The aim of this study was to evaluate HPA axis in patients treated with imatinib. Twenty-five patients were included in this study.. Glucagon stimulation test (GST) and low-dose (1 microg) adrenocorticotropin test (LDSST) were used to assess the HPA gland axis.. Seventeen (68%) subjects had impaired peak response when a cortisol cut-off value is accepted as 500 nmol/L. Twelve (48%) out of 17 subjects also failed to show a response to LDSST. Therefore, 12 patients (48%) were defined as HPA deficient. Only two of these 25 patients had morning serum cortisol < 200 nmol/l (7.22 microg/dl), and failed the GST and/or LDSST, indicating that the majority had partial glucocorticoid deficiency. If the cut-off presume for LDSST is from 500 to 600 nmol/l, 16 patients (64%) would have failed both the GST and LDSST.. Our results indicate an increased prevalence of subclinical glucocorticoid deficiency in patients receiving imatinib mesylate for CML. Therefore under stressed conditions, such as intercurrent illness state, overt and untreated partial glucocorticoid deficiency in CML patients become life threatening.

Topics: Adrenocorticotropic Hormone; Adult; Aged; Antineoplastic Agents; Benzamides; Cosyntropin; Endocrine System Diseases; Female; Glucagon; Glucocorticoids; Hormones; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Imatinib Mesylate; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Middle Aged; Piperazines; Pituitary-Adrenal System; Protein Kinase Inhibitors; Pyrimidines

Topics: Adrenal Insufficiency; Aged, 80 and over; Cosyntropin; Female; Hormones; Humans; Hydrocortisone; Shock

Persistent symptoms after treatment for neuroborreliosis are common for reasons mainly unknown. These symptoms are often unspecific and could be caused by dysfunctions in endocrine systems, an issue that has not been previously addressed systematically. We therefore mapped hormone levels in patients with previous confirmed Lyme neuroborreliosis of different outcomes and compared them with a healthy control group.. Twenty patients of a retrospective cohort of patients treated for definite Lyme neuroborreliosis were recruited 2.3 to 3.7 years (median 2.7) after diagnosis, together with 23 healthy controls. Lyme neuroborreliosis patients were stratified into two groups according to a symptom/sign score. All participants underwent anthropometric and physiological investigation as well as an extensive biochemical endocrine investigation including a short high-dose adrenocorticotropic hormone stimulation (Synacthen) test. In addition to hormonal status, we also examined electrolytes, 25-hydroxy-vitamin D and interleukin-6.. Eight patients (40%) had pronounced symptoms 2-3 years after treatment. This group had a higher cortisol response to synacthen as compared with both controls and the Lyme neuroborreliosis patients without remaining symptoms (p < 0.001 for both comparisons). No other significant differences in the various baseline biochemical parameters, anthropometric or physiological data could be detected across groups.. Apart from a positive association between the occurrence of long-lasting complaints after Lyme neuroborreliosis and cortisol response to synacthen, no corticotropic insufficiency or other serious hormonal dysfunction was found to be associated with remaining symptoms after treatment for Lyme neuroborreliosis.

Topics: Adult; Aged; Aged, 80 and over; Anthropometry; Antibodies, Bacterial; Case-Control Studies; Cosyntropin; Female; Humans; Hydrocortisone; Interleukin-6; Lyme Neuroborreliosis; Male; Middle Aged; Retrospective Studies; Treatment Outcome; Young Adult

The frequency of adrenal insufficiency after a prolonged, continuous course of oral high-dose corticosteroids is poorly documented. We evaluated it retrospectively in our internal medicine department.. The patients were included between February 2000 and June 2007 and were administered a Synacthene 250 microg test (ST250) before tapering prednisone dose below 5mg per day. A non-responsive test was defined by a cortisol increase below 18 microg/dL, 60 min after stimulation. We also studied the risk factors associated with biological adrenal insufficiency by a multivariate logistic regression analysis.. Hundred patients were included (mean age: 61.5+/-16.3 years). Mean initial dose of corticosteroids was 65.5+/-112 mg/d. Forty-five patients failed to respond to the ST250. A normal ST250 was negatively associated with a duration of corticosteroids therapy longer than 19.5 months (OR=0.38 [0.15-0.94]; p=0.04) and positively with an age over 63.5 years (OR=2.5 [1.1-6.4]; p=0.05). Two patients experienced a clinical adrenal insufficiency crisis.. Biological adrenal insufficiency is very common after a prolonged course of oral high-dose corticosteroids. The risk does not seem to increase with age. The clinical benefit of a systematic ST250 at the time of corticosteroids withdrawal followed by hydrocortisone substitution if the test is non responsive remains unknown, and this practice is still a matter of debate.

Topics: Adrenal Insufficiency; Aged; Cohort Studies; Cosyntropin; Female; France; Glucocorticoids; Hormones; Humans; Incidence; Male; Middle Aged; Prednisone; Retrospective Studies; Risk Factors

Many spontaneous adrenal hematomas have been observed in patients being treated by Synacthène. The purpose of this study is to define how to take those patients in charge on a short-, mid- and long-term.. From January 2000 to December 2008, five patients (four males and one female), mean age 47, were taken in charge in our service for spontaneous adrenal hematomas. All those patients had been treated with Synacthène for a mid-sciatic pain for 72 hours. We associated a clinical, endocrine and radiologic staging to treat those patients.. Four patients underwent a watchful waiting, only one patient needed surgery. No adrenal tumor was ever found during the mean two years follow-up (one to four). Two patients suffered of the condition of the antiphospholipid syndrome.. Spontaneous adrenal hematomas are a most uncommon pathology. The clinical attitude has thus to be defined clearly. The patient must be under close clinical evaluation. Biological and morphological parameters have to be often repeated. An adrenal tumor has to be excluded by the evaluation, as that tumor could be secreting or could not be secreting. Antiphospholipid syndrome must also be excluded.

Topics: Adrenal Gland Diseases; Adult; Aged; Cosyntropin; Decision Trees; Female; Hematoma; Hemorrhage; Hormones; Humans; Male; Middle Aged; Retrospective Studies

Accurate assessment of adrenal function is essential in patients with hypothalamic-pituitary-adrenal (HPA) disease. The measurement of salivary cortisol (SaC) instead of serum cortisol (SeC) offers several advantages, such as the determination of the free hormone. We evaluated the diagnostic value of SeC and SaC both unstimulated and during a high-dose short synacthen test (HDT) in comparison to the insulin tolerance test (ITT).. Comparative study between 2005 and 2007.. Fifty-five patients with HPA impairment and 21 healthy controls were enrolled. Samples were collected in the early morning and over 120 min during the HDT. Receiver operating characteristic analysis revealed individual thresholds for four HDT periods (0-30, 0-60, 0-90, and 0-120 min).. The ITT identified 30 subjects as adrenal insufficient. With respect to the four HDT periods, sensitivity and specificity were 67-79% and 71-88% for SeC, compared with 63-72% and 72-86% for SaC. If upper and lower thresholds (with specificities >95%) were applied, patients were diagnosed in 40-45% by SeC and in 25-31% by SaC. The combination of basal cortisol and HDT allowed a diagnosis in 47-49% (SeC) and in 42-45% (SaC) respectively.. We suggest the determination of basal SeC or SaC as first-line test. In comparison to the ITT, the HDT has only limited value in screening for alterations of the HPA axis. If the HDT is performed, sampling may be limited to 30 min post-synacthen, using either SeC or SaC. Due to the ease of collection and the independence of binding proteins, SaC may be preferable.

Topics: Adrenal Insufficiency; Adult; Algorithms; Area Under Curve; Cosyntropin; Female; Humans; Hydrocortisone; Hypothalamic Diseases; Insulin; Male; Middle Aged; Pituitary Diseases; Random Allocation; ROC Curve; Saliva; Sensitivity and Specificity

In order to identify whether low-dose (1 microg) tetracosactide (Synacthen) testing may be preferable to high-dose (250 microg) testing in the diagnosis of adrenal insufficiency in traumatic brain injury (TBI), as suggested by studies in other forms of critical illness.. We retrospectively reviewed the results of modified tetracosactide tests (involving administration of both low-dose and high-dose tetracosactide) conducted for clinical indications in patients in a neurocritical care unit within 10 days of TBI. Sixty-three modified tests were included and cortisol concentrations before and after administration of tetracosactide were extracted from the hospital records. Data were also extracted regarding hemodynamic response to empirical corticosteroid therapy, based on rapid weaning from vasoactive drugs.. Cortisol increments at 30 and 60 min following tetracosactide correlated well in the low-dose test (r(2) = 0.875, P < 0.0001). The mean cortisol concentration was 581 nmol/l at 30 min and 556 nmol/l at 60 min in the low-dose test. Cortisol increments following low-dose and high-dose testing correlated well overall (r(2) = 0.839, P < 0.0001), but results were discordant in 27 of 63 cases (43%) when the same diagnostic threshold was used. ROC curve analysis showed that both tests performed poorly in identifying hemodynamic steroid responsiveness (AUC 0.553 and 0.502, respectively).. In the low-dose tetracosactide test, it is sufficient to determine cortisol concentrations at baseline and at 30 min. Low-dose and high-dose tests give discordant results in a significant proportion of cases when using the same diagnostic threshold. Neither test can be used to guide the initiation of corticosteroid therapy in acute TBI.

Topics: Acute Disease; Adrenal Cortex Hormones; Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Aged; Brain Injuries; Cosyntropin; Delayed-Action Preparations; Dose-Response Relationship, Drug; Female; Hemodynamics; Humans; Hydrocortisone; Kinetics; Male; Middle Aged; Predictive Value of Tests; Retrospective Studies; ROC Curve; Sensitivity and Specificity; Young Adult

To assess the repeatability of low-dose Synacthen test (LDST) in asthmatic children receiving high-dose fluticasone propionate (FP).. Low-dose Synacthen test was performed on 18 children with stable chronic asthma treated with FP at a constant daily dose of > or =500 microg and repeated 1 month later. Repeatability was assessed using the Kappa statistic for categorical variables.. Fifteen patients had consistent results (either two normal or two abnormal responses) and three patients had inconsistent results (one normal and one abnormal response). The Kappa statistic was 0.56 indicating fair to good agreement between the tests.. The results of adrenal function testing in patients on inhaled steroids can have major implications for patient management, making it important to use a test with excellent repeatability. The LDST conducted using our protocol does not fulfil this criterion.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Function Tests; Adrenal Cortex Hormones; Adrenal Insufficiency; Androstadienes; Anti-Asthmatic Agents; Asthma; Child; Cosyntropin; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fluticasone; Humans; Hydrocortisone; Male; Reproducibility of Results

This study investigates the hypothesis that an adrenocorticotropic hormone-analog therapy may ameliorate relative adrenal insufficiency in the early phase of acute necrotizing pancreatitis (NP) by boosting endogenous glucocorticoid production.. Forty Wistar rats with taurocholate-induced NP were divided into 5 groups: the first group received low-dose Synacthen (0.5 mg/kg); the second, high-dose Synacthen (5mg/kg); the third,low-dose cortisol (10 mg/kg); the fourth, high-dose cortisol (100 mg/kg); and the fifth, the control group, received no treatment. All animals were killed after 6 hours: concentrations of plasma corticosterone, interleukin 1 (IL-1), IL-6, IL-10, tumor necrosis factor alpha, amylase, and lipase in ascites, myeloperoxidase activity in the pancreas, and a histological score were evaluated.. Corticosterone increased neither in the low-dose nor in the high-dose Synacthen group. Synacthen did not improve the early course of NP in terms of laboratory and histological results. A reduction of pancreatic necrosis and inflammation was observed in the low-dose cortisol group.. Endogenous glucocorticoid release seemed to be at its maximum during the early stage of NP and could not be further increased by Synacthen. Low-dose exogenous cortisol ameliorated the disease. These findings support the existence of relative adrenal insufficiency in the early phase of acute NP.

Topics: Adrenal Insufficiency; Amylases; Animals; Cosyntropin; Cytokines; Disease Models, Animal; Disease Progression; Female; Hydrocortisone; Lipase; Pancreas; Pancreatitis, Acute Necrotizing; Peroxidase; Rats; Rats, Wistar; Taurocholic Acid; Time Factors

There are few data in the paediatric literature on the normal cortisol response to stimulation during the low dose synacthen test (LDST) (1 microg).. To examine the cortisol responses in children, subsequently presumed to be normal, who had an LDST during anterior pituitary function tests (APFTs).. A retrospective review of results in children with short stature and normal growth hormone levels.. Of 33 children tested, seven had suboptimal cortisol responses based on accepted criteria (peak <500 nmol/l)--a false positive rate of 21%. Only three of these children had a repeat LDST, which was normal in all cases. The peak cortisol response (median 633, range, 417-1052 nmol/l) was inversely correlated with age (r = -0.44, p < 0.05).. One in five tests did not meet normal criteria. This false positive rate (21%) should be borne in mind when interpreting synacthen tests to prevent overdiagnosis of adrenal insufficiency.

Topics: Adolescent; Adrenal Insufficiency; Child; Child, Preschool; Cosyntropin; Dose-Response Relationship, Drug; False Positive Reactions; Female; Humans; Hydrocortisone; Male; Pituitary Function Tests; Pituitary Gland, Anterior; Reproducibility of Results; Retrospective Studies

The insulin tolerance test (ITT) has become less popular in paediatrics because of the risks associated with hypoglycaemia. Human corticotrophin-releasing hormone (hCRH) test results correlate with the ITT and may be an acceptable method to test for central adrenal insufficiency (CAI). Simpler tests, such as the low dose Synacthen test (LDST) and 9am cortisol, have also been proposed.. To compare the ability of the hCRH test, LDST, 9am cortisol level and 24-h cortisol profiles to diagnose CAI in a paediatric population.. A cross-sectional study in a tertiary paediatric endocrine clinic.. Thirty-one children and adolescents (aged 2.3-18.3 years) with CAI risk factors had an hCRH test, LDST, 9am cortisol and 24-h cortisol profile performed.. Of 23 patients with confirmed CAI (hCRH peak cortisol < 400 nmol/), 19 failed the LDST (peak cortisol < 267 nmol/l, i.e. 10th percentile for controls). Nineteen would have failed based on the 10th percentile cut point for 9am cortisol (< 140 nmol/l). Using receiver operating characteristic (ROC) curve coordinates, a 9am cortisol < 108 nmol/l was sensitive (83%) and specific (99%) for CAI. The 9am cortisol levels measured on two occasions were repeatable (94%) and correlated (r = 0.83, P = 0.01). All eight adrenally sufficient patients (hCRH peak cortisol > or = 400 nmol/l) passed the LDST. Seven had normal 9am cortisol (> or = 140 nmol/l). The 24-h cortisol area under the curve (AUC) for these patients was within the 10th-90th percentiles for control subjects' AUC. The peak cortisol to hCRH and LDST were correlated (r = 0.88, P = 0.01), with no difference between the peaks (mean difference -5.3 nmol/l, P = 0.69).. In children with CAI risk factors, the diagnosis can be made if unstressed 9am cortisol is < 108 nmol/l. As cortisol levels > 381 nmol/l are highly suggestive of normal hypothalamic-pituitary-adrenal (HPA) function, stimulation testing need only be performed if 9am cortisol is 108-381 nmol/l. The LDST should be interpreted cautiously because mild CAI may be missed. When stimulation results are marginal, 24-h cortisol profiles can provide reassurance of normal cortisol status.

Topics: Adolescent; Adrenal Insufficiency; Child; Child, Preschool; Corticotropin-Releasing Hormone; Cosyntropin; Cross-Sectional Studies; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Pituitary-Adrenal System; Sensitivity and Specificity

Previous studies have indicated that most individuals reach peak cortisol levels in 60 minutes during the short Synacthen test (SST) done to exclude adrenal insufficiency. Therefore, measuring serum cortisol at only 60 minutes may suffice. This study was carried out to evaluate the significance of the 60-minute serum cortisol level in SST as a reliable and cost-effective screening test in comparison to the conventional SST.. A cross-sectional study was conducted from January 2000 to September 2004, in which data was collected by reviewing medical records of all patients who underwent SST at the Aga Khan University Hospital, Karachi. A total of 236 patients suspected of having adrenal insufficiency were included. Values of serum cortisol at baseline, 30 and 60 minutes post-250 ug-injection Synacthen were recorded. The cortisol level was measured through fluorescence polarisation immunoassay. The cut-off value of 20 ug/dL was used to differentiate normal individuals from hypoadrenal individuals.. Out of 236 study participants, 93 (39 percent) were males and 143 (61 percent) were females. The mean age and standard deviation was 44.4 +/- 21 years. Cortisol concentration increased significantly from baseline to 30 minutes and 60 minutes after injecting Synacthen (p-value is less than 0.001 for each). The majority of the patients reached the cortisol peak of greater than 20 ug/dL (555 nmol/L) at 60 minutes. Normal responses were found in 148 patients (63.1 percent) at both 30 and 60 minutes, while 27 participants (12 percent) reached a peak greater than 20 ug/dL (555 nmol/L) at 60 minutes but were less than 20 ug/dL (555 nmol/L) at 30 minutes. In the deficient cases, SST showed abnormal responses in 60 cases (25 percent) at both 30 and 60 minutes. However, there was only one patient who reached a peak value of 21 ug/dL (589 nmol/L) at 30 minutes, which reduced to 17 ug/dL (485 nmol/L) at 60 minutes.. This study showed that a 60-minute cortisol value during SST was reliable enough in identifying normal subjects for excluding adrenal insufficiency, and was equally effective in identifying abnormal cases, as compared to values at both 30 and 60 minutes. It is therefore suggested that a single 60-minute post-Synacthen serum cortisol level may suffice, as compared to the conventional SST. This is also significant as a cost-effective measure, especially in third world countries where cost is a major issue for diagnosing and treating patients.

Topics: Adrenal Insufficiency; Adult; Cost-Benefit Analysis; Cosyntropin; Female; Hormones; Humans; Hydrocortisone; Male; Mass Screening; Middle Aged; Time Factors

Clinical adrenal insufficiency has been reported with doses of inhaled fluticasone proprionate (FP) > 400 microg/day, the maximum dose licensed for use in children with asthma. Following two cases of serious adrenal insufficiency (one fatal) attributed to FP, adrenal function was evaluated in children receiving FP outwith the licensed dose.. Children recorded as prescribed FP > or = 500 microg/day were invited to attend for assessment. Adrenal function was measured using the low dose Synacthen test (500 ng/1.73 m2 intravenously) and was categorised as: biochemically normal (peak cortisol response > 500 nmol/l); impaired (peak cortisol < or = 500 nmol/l); or flat (peak cortisol < or = 500 nmol/l with increment of < 200 nmol/l and basal morning cortisol < 200 nmol/l).. A total of 422 children had been receiving FP alone or in combination with salmeterol; 202 were not investigated (137 FP within license; 24 FP discontinued); 220 attended and 217 (age 2.6-19.3 years) were successfully tested. Of 194 receiving FP > or = 500 microg/day, six had flat responses, 82 impaired responses, 104 were normal, and in 2 the LDST was unsuccessful. Apart from the index child, the other five with flat responses were asymptomatic; a further child with impairment (peak cortisol 296 nmol/l) had encephalopathic symptoms with borderline hypoglycaemia during an intercurrent illness. The six with flat responses and the symptomatic child were all receiving FP doses of > or = 1000 microg/day.. Overall, flat adrenal responses in association with FP occurred in 2.8% of children tested, all receiving > or = 1000 microg/day, while impaired responses were seen in 39.6%. Children on above licence FP doses should have adrenal function monitoring as well as a written plan for emergency steroid replacement.

Topics: Adolescent; Adrenal Cortex Function Tests; Adrenal Insufficiency; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Child; Child, Preschool; Cosyntropin; Dose-Response Relationship, Drug; Drug Administration Schedule; Fluticasone; Humans; Hydrocortisone

Synacthen is a synthetic analogue to human adrenocorticotropin, which plays an important physiological role by stimulating production of cortisol. In sports, corticosteroids as well as releasing factors (corticotropins) are prohibited according to the regulations of the World Anti-Doping Agency, and the misuse of Synacthen has been reported several times. Hence, an assay enabling the detection of Synacthen in doping control samples has been developed using immunoaffinity chromatographic isolation of Synacthen from human plasma combined with a concentration of collected fractions using solid-phase extraction. Unambiguous determination of the target analyte was accomplished using microbore liquid chromatography/electrospray ionization tandem mass spectrometry. Diagnostic product ions such as m/z 223 were characterized using high-resolution/high-accuracy Orbitrap mass spectrometry and employed for triple quadrupole MS/MS analysis. The established assay requiring 2 mL of plasma allowed a lower limit of detection (LLOD) at 100 fmol/mL, a recovery of 97% and a precision at the LLOD < 20%. Authentic plasma samples obtained from a patient undergoing a standard short Synacthen test were used to prove the applicability of the developed procedure.

Topics: Blood Chemical Analysis; Chromatography, Liquid; Cosyntropin; Humans; Hydrocortisone; Immunoassay; Spectrometry, Mass, Electrospray Ionization

West syndrome (WS) is one of the catastrophic epileptic syndromes in infancy characterized by a triad of infantile spasms, psychomotor deterioration and hypsarrhythmic EEG pattern. WS is commonly associated with poor long-term outcome, especially in symptomatic cases, with development of other seizure types, impaired cognitive and psychosocial functioning. The aim of our study was to evaluate the efficacy of the control of infantile spasms using synthetic ACTH or vigabatrin in newly diagnosed cases and to correlate it with the underlyning causes, outcome and adverse effects.. The database of children with WS seen at the Neuropediatric Unit and followed at outpatient clinics from January 1, 1994 until December 31, 2003 were reviewed. The diagnosis of WS following the criteria of ILAE was made in 32 patients.. Data were collected for 32 children (9 girls and 23 boys). According to the etiology, 5 (15.6%) were cryptogenic, and 1 (3.1%) was idiopathic. In 26 (81.2%) symptomatic cases, hypoxic-ischemic encephalopathy (69.2%) was the most common etiologic factor, followed by central nervous system anomaly including malformation of cortical development (11.5%), and Sturge Weber syndrome (3.8%), and chromosomal translocation with Down syndrome (11.5%). In 65.1% of symptomatic cases birth occurred prematurely. The mean age at spasm onset was 5.8 months, and mean age at diagnosis and treatment 7.2 months. Between 1994 and 1996 synthetic ACTH was used for treatment of WS in 7 patients (1 cryptogenic and 6 symptomatic), spasm control was achieved in 6, hypsarrhythmia disappeared in 5, and vigabatrin was added after synthetic ACTH in 3 patients. In one child synthetic ACTH was stopped because of arterial hypertension. All children had Cushing syndrome. After 1996, vigabatrin was administrated to 5 children with cryptogenic and 20 children with symptomatic WS. In 22/32 spasm control was achieved within 15 days. Synthetic ACTH was added in 3 children with spasms and hypsarrhythmia disappeared in 1 child. There was no recurrence of WS. The mean follow-up in 27 children was 4.6 (0.5 to 9.9 years) whereas 5 were lost from follow-up. Of 6/27 children with cryptogenic WS, 1 had idiopathic WS, 3 had normal psychomotor development and 2 had psychomotor retardation, without epileptic fits and still receiving AED. Of 21/27 children with symptomatic WS 76.2% had severe psychomotor retardation, 42.8% had epilepsy, 23.8% had intractable epileptic fits, and 2 children with Down syndrome were without epilepsy and without AED. Lennox-Gastaut syndrome developed in 14.2% (3/21 children); 1 of them died at the age of 3.5 years from acute gastric bleeding during the administration of synthetic ACTH, and an other child died at the age of 5.5 years from infection and respiratory insufficiency. The mortality rate was 7.4% (2/27 children).. The cryptogenic etiology is associated with a very low risk of poor outcome in WS. In children with normal development and regular school performance an idiopathic etiology can be presumed. The children with Down syndrome had a relatively benign outcome with regard to seizure control compared with symptomatic infantile spasms in the general population. In symptomatic WS caused by hypoxic-ischemic encephalopathy the outcome was linked with coexistence of other forms of epilepsy and neurologic deficit. The poor prognosis concerning intractable nature of the seizures and serious neurologic deficit is recorded in children with malformation of cortical development and Sturge Weber syndrome. The outcome of these children is determined by the brain damage other than by epilepsy itself. Regarding the treatment with synthetic ACTH or vigabatrin, the control of WS was the same for cryptogenic and symptomatic forms, one drug may be effective if the other drug fails. Synthetic ACTH can have many side effects, even death. The visual field defect is associated with vigabatrin, but can be avoided with careful funduscopic follow-up. Vigabatrin can be suggested as the first drug for WS; if spasms persist after 15 days with a dose of 150 mg/kg, synthetic ACTH should be considered.

Topics: Anticonvulsants; Cosyntropin; Delayed-Action Preparations; Female; Humans; Infant; Infant, Newborn; Male; Prognosis; Spasms, Infantile; Vigabatrin

Patients with organic growth hormone deficiency (GHD) or with structural hypothalamic-pituitary abnormalities may have additional anterior pituitary hormone deficits, and are at risk of developing complete or partial corticotropin (ACTH) deficiency. Evaluation of the integrity of the hypothalamic-pituitary-adrenal axis (HPA) is essential in these patients because, although clinically asymptomatic, their HPA cannot appropriately react to stressful stimuli with potentially life-threatening consequences.. In this study we evaluated the integrity of the HPA in 24 patients (age 4.2-31 years at the time of the study) with an established diagnosis of GHD and compared the reliability of the insulin tolerance test (ITT), short synacthen test (SST), low-dose SST (LDSST), and corticotropin releasing hormone (CRH) test in the diagnosis of adrenal insufficiency.. At a cortisol cut-off for a normal response of 550 nmol/l (20 microg/dl), the response to ITT was subnormal in 11 subjects, 6 with congenital and 5 with acquired GHD. Four patients had overt adrenal insufficiency, with morning cortisol concentrations ranging between 66.2-135.2 nmol/l (2.4-4.9 microg/dl) and typical clinical symptoms and laboratory findings. In all these patients, a subnormal cortisol response to ITT was confirmed by LDSST and by CRH tests. SST failed to identify one of the patients as adrenal insufficient. In the seven asymptomatic patients with a subnormal cortisol response to ITT, the diagnosis of adrenal insufficiency was confirmed in one by LDSST, in none by SST, and in five by CRH tests. The five patients with a normal cortisol response to ITT exhibited a normal response also after LDSST and SST. Only two of them had a normal response after a CRH test. In the seven patients with asymptomatic adrenal insufficiency mean morning cortisol concentration was significantly higher than in the patients with overt adrenal insufficiency. ITT was contraindicated in eight patients, and none of them had clinical symptoms of overt adrenal insufficiency. One of these patients had a subnormal cortisol response to LDSST, SST, and CRH, and three exhibited a subnormal response to CRH but normal responses to LDSST and to SST.. We conclude that none of these tests can be considered completely reliable for establishing or excluding the presence of secondary or tertiary adrenal insufficiency. Consequently, clinical judgment remains one of the most important issues for deciding which patients need assessment or re-assessment of adrenal function.

Topics: Adolescent; Adrenal Glands; Adrenal Insufficiency; Adrenocorticotropic Hormone; Child; Child, Preschool; Corticotropin-Releasing Hormone; Cosyntropin; Diagnostic Techniques, Endocrine; Female; Human Growth Hormone; Humans; Hypoglycemia; Hypoglycemic Agents; Hypothalamic Diseases; Hypothalamo-Hypophyseal System; Insulin; Male; Pituitary Diseases; Pituitary-Adrenal System; Reproducibility of Results

A 6 year-old Chinese boy with Kabuki syndrome presented with hypoglycemic seizure. He was diagnosed to have isolated adrenocorticotropin deficiency. To our knowledge, this is the first case of Kabuki syndrome with isolated adrenocorticotropin deficiency in the literature.

Topics: Abnormalities, Multiple; Adrenocorticotropic Hormone; Child; Corticotropin-Releasing Hormone; Cosyntropin; Dermatoglyphics; Fingers; Hormones; Humans; Hypoglycemia; Hyponatremia; Intellectual Disability; Male; Seizures; Syndrome; Water-Electrolyte Imbalance

Although excessive glucocorticoids are a well-recognized cause of osteoporosis, little is known about the role of endogenous glucocorticoids in determining skeletal mass. We have performed a detailed study of the hypothalamic-pituitary-adrenal (HPA) axis to explore the relationships between cortisol secretion and adult bone mass in 151 healthy men and 96 healthy women aged 61 to 73 years. At baseline and 4-year follow-up, bone mineral density (BMD) was measured by dual energy X-ray absorptiometry (DXA) at the lumbar spine and proximal femur; a lifestyle questionnaire was completed; and height, weight, and waist and hip circumferences were measured. At follow-up subjects underwent a very low-dose (0.25 mg) dexamethasone suppression test, a low-dose (1 microg) short synacthen test, and a 24-hour urine collection for measurement of cortisol and its metabolites. In men, elevated peak plasma cortisol was associated with accelerated loss of mineral density in the lumbar spine (r = 0.16, P = 0.05). This relationship remained significant after adjustment for testosterone, estradiol, 25-hydroxyvitamin D, and parathyroid hormone levels (r = 0.22, P = 0.01) and after additional adjustment for age, (BM), activity, cigarette and alcohol consumption, and Kellgren/Lawrence score (r = 0.19, P = 0.03). In contrast in women, elevated peak plasma cortisol was associated with lower baseline BMD at the femoral neck (r = -0.23, P = 0.03) and greater femoral neck loss rate (r = 0.24, P = 0.02). There was no association between plasma cortisol concentrations after dexamethasone or urinary total cortisol metabolite excretion and bone density or bone loss rate at any site. These data provide evidence that circulating endogenous glucocorticoids influence the rate of involutional bone loss in healthy individuals.

Topics: Absorptiometry, Photon; Aged; Bone Density; Cosyntropin; Dexamethasone; Female; Femur; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Life Style; Lumbar Vertebrae; Male; Middle Aged; Osteoporosis, Postmenopausal; Pituitary-Adrenal Function Tests; Pituitary-Adrenal System; Surveys and Questionnaires

The short Synacthen test (SST) is the most commonly used test for the assessment of adrenal suppression. We investigated the potential of a simpler and more cost-effective procedure [morning salivary cortisol (MSC)] as an outpatient screening tool to detect adrenal suppression in patients using topical intranasal corticosteroids for rhinosinusitis.. Forty-eight patients who were using topical corticosteroids underwent adrenal function assessment by way of SST and MSC measurement.. Sixteen of the 48 patients had impaired MSCs. Of these 16 patients, 15 had an impaired SST (sensitivity 100%) and one had a normal SST. All patients with normal MSCs also had normal SSTs (specificity 97%).. The morning salivary cortisol measurement is a useful screening tool for adrenal suppression in this setting.

Topics: Administration, Intranasal; Adrenal Cortex Hormones; Adrenal Glands; Circadian Rhythm; Cosyntropin; Humans; Hydrocortisone; Pituitary-Adrenal Function Tests; Pituitary-Adrenal System; Saliva

Topics: Aged; Cosyntropin; Female; Glomerulonephritis, Membranous; Humans; Male; Middle Aged; Nephrotic Syndrome

A pilot study to establish what constitutes a normal response to the low dose synacthen test (using 500 ng/1.73 m2 of ACTH) in well preterm infants was carried out on seven well preterm infants. Previous studies on preterm neonates (using a dose of ACTH of 36 microg/kg) suggest that a normal adrenal response is a peak serum cortisol level of > or =360 nmol/l(24). The minimum peak serum cortisol achieved by our cohort was 358 nmol/l with 6/7 infants achieving more than 360 nmol/l. 71% attained a serum cortisol increment from basal level of > or =200 nmol/l. This pilot study suggests that the criterion used to denote a normal adrenal response in preterm neonates using a dose of 36 microg/kg of ACTH (which is a peak serum cortisol of > or =360 nmol/l) can also be a applied when a physiological dose of ACTH (as used in the low dose synacthen test) is used.

Topics: Cohort Studies; Cosyntropin; Dose-Response Relationship, Drug; Humans; Hydrocortisone; Infant, Newborn; Infant, Premature

ACTH is known to act through the activation of cAMP/PKA in adrenocortical cells, but it has been suggested that it could also act via other pathways such as the ERK 1/2 cascade. To determine the effects of ACTH administration at sequential time points on the activation of ERKs 1/2, groups of rats (n = 6/group) were subjected to i.p. injections of either ACTH (Synacthen Depot-0.2 mg/Kg), or saline (Ct). The animals were sacrificed and the adrenal glands collected at different timings after ACTH injection (2 h, 18 h and 24 h). Two additional groups were injected daily until sacrifice (3 days and 15 days). Blood was collected for analysis and the adrenals were used for immunohistochemistry or Western Blot (WB) analysis. Immunoreactivity was scored by counting the mean number of zonae fasciculata (ZF) and reticularis (ZR) positive cells/section (mean +/- SEM). Adrenal weight was increased by ACTH in comparison with Ct. Corticosterone levels, as expected, were higher in ACTH treated animals than in Ct. The number of pERK positive cells increased in a time-dependent manner until 3d, and declined although not significantly in the 15 days animals (Control--48.13 +/- 9.0; ACTH 2 h--125.93 +/- 14.5; ACTH 18 h-139.46 +/- 10.0; ACTH 24 h--185.28 +/- 13.3; ACTH 3 days--198.47 +/- 18.6; ACTH 15 days--158.58 +/- 15.1). Comparable results were obtained with WB analysis. Our data shows that ACTH induces the activation of the MAPK/ERKs 1/2 cascade, especially in the ZF, consistent with this zone being more responsive to ACTH.

Topics: Adrenal Glands; Adrenocorticotropic Hormone; Animals; Blotting, Western; Cosyntropin; Enzyme Activation; Immunohistochemistry; Injections, Intraperitoneal; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Phosphorylation; Rats; Time Factors

To evaluate the ocular changes and medical and surgical therapy after high-dose systemic steroid treatment in babies with infantile spasm and hypsarrhythmia.. Retrospective, noncomparative, interventional case series.. In 5 of the 9 (55%) babies with infantile spasm exposed to systemic corticosteroid treatment, an increase in intraocular pressure (IOP) and optic disc cupping was observed.. Ophthalmic examination under mild sedation was conducted 3 to 4 weeks after initiation of systemic therapy. Antiglaucoma treatment was given to the patients found to have high IOPs and cup-to-disc ratio changes. Routine follow-up was continued until systemic therapy was completed.. Controlled IOP with a decrease in cupping damage after antiglaucoma therapy.. Five patients required antiglaucoma treatment; one also underwent augmented trabeculectomy. Mean IOP decreased in this subgroup from 30.1 +/- 9.5 mmHg to 15.4 +/- 4.2 mmHg in the right eye (P = 0.043) and from 32.6 +/- 7.4 mmHg to 15.2 +/- 1.8 mmHg in the left eye (P = 0.043). Mean cup-to-disc ratio improved from 0.53 +/- 0.2 to 0.37 +/- 0.04 in the right eye (P = 0.06) and from 0.57 +/- 0.12 to 0.35 +/- 0.05 in the left eye (P = 0.042).. The rapid onset of IOP and cup-to-disc ratio changes in patients with infantile spasm and hypsarrhythmia treated by high-dose corticosteroids necessitates early and intensive monitoring to prevent anatomic ocular damage and visual impairment in the future.

Topics: Administration, Oral; Antihypertensive Agents; Cosyntropin; Female; Glucocorticoids; Humans; Infant; Injections, Intramuscular; Intraocular Pressure; Male; Ocular Hypertension; Optic Disk; Optic Nerve Diseases; Prednisone; Retrospective Studies; Spasms, Infantile; Tonometry, Ocular

Since 1988, when a retrospective study of patients attending this unit was published, we have advocated the use of the short synacthen test (SST) as the primary screening investigation to detect ACTH deficiency. However, others have published comparisons of SST and insulin tolerance tests that suggest a significant false negative rate with SST, leading to concern that some patients who pass the SST are in danger from the clinical consequences of ACTH deficiency. To address this, we audited biochemical results and clinical outcome in 63 patients who did not have ACTH deficiency detected (i.e. who passed the test) by SST after pituitary surgery. Twelve of the 63 patients who passed a SST after pituitary surgery became ACTH-deficient later as diagnosed by SST: 4 within the first year, 2 of whom had received postoperative radiotherapy (3 had symptoms of tiredness and 1 was admitted to the hospital with a viral infection); 8 in yr 3-5, 7 of whom had received postoperative radiotherapy (all had either no symptoms or symptoms of tiredness alone). Thus, the predictive value of the SST in excluding ACTH deficiency is approximately 97% (2 of 63 patients who initially passed the SST were found to be ACTH-deficient within 12 months without having received postoperative radiotherapy). Only 1 patient was ill enough to require hospital admission. Setting the risk of false negatives with SST against the morbidity and manpower implications associated with insulin tolerance tests, SST remains the primary screening test for ACTH deficiency in our practice. However, a high index of clinical suspicion to detect false negative results must be maintained.

Topics: Acromegaly; Adenoma; Adolescent; Adrenocorticotropic Hormone; Adult; Aged; Aged, 80 and over; Cosyntropin; Craniopharyngioma; False Negative Reactions; Female; Humans; Hydrocortisone; Insulin; Male; Middle Aged; Pituitary Gland; Pituitary Neoplasms; Prolactinoma; Retrospective Studies; Sensitivity and Specificity

The aim was to reevaluate a group of adults treated for idiopathic childhood onset GH deficiency (GHD) after 18 yr without GH treatment. Twenty-six (11 females) patients participated. All but two had isolated GHD. Childhood diagnosis was established by insulin tolerance test (ITT). The patients were retested with an ITT to evaluate adult GH status. In five patients, an arginine and a synacthen test were performed instead of an ITT. Eleven of 25 patients had a subnormal cortisol response to ITT or synacthen. Ten patients had a GH peak less than 3.0 microg/liter (0.5. +/- 0.5 microg/liter), whereas 16 patients displayed a normal GH response (12.3 +/- 10.6 microg/liter) after ITT. IGF-I values were decreased in the patients with a pathological retest as well as in patients with a normal GH response compared with controls (P < 0.005). In 26 idiopathic childhood onset GHD patients, 44% of the patients had developed adrenal insufficiency; 38.5% had persistent GHD in adulthood, using the same test in both childhood and adulthood. Patients having a normal GH test had decreased IGF-I levels, compared with controls, indicating impaired function of a seemingly normal GH axis. It is imperative that pituitary axes other than the GH axis are tested at regular intervals, even in the absence of GHD in adulthood.

Topics: Adrenal Insufficiency; Adult; Cosyntropin; Cross-Sectional Studies; Female; Human Growth Hormone; Humans; Hydrocortisone; Insulin; Insulin-Like Growth Factor I; Male; Metabolism, Inborn Errors; Risk Assessment

In patients with inflammatory bowel disease (IBD), little is known about the effect of long term corticosteroid therapy (CT) on the hypothalamic-pituitary-adrenal (HPA) axis function. Our aim was to assess HPA axis function in IBD, before the end of CT, during the tapering phase.. HPA axis function was assessed with cortisol (ng/ml) measurement before (T0) (normal > 100) and 60 min (normal > 210) after 0.25 mg tetracosactide (Synacthen immédiat) injection (T60) in 55 consecutive cases of IBD attacks. Abnormal response was defined as a T60 <210. The attacks were separated into two groups according to the result of the Synacthen test (ST).. In all, 36 of 55 ST were abnormal. The time for recovery normal HPA axis function was 7.2+/-1.3 months. Duration of disease since onset, past history of surgical or immunosuppressive treatment, severity and extension of the attack, need for surgical or immunosuppressive treatment, total cumulative and mean daily corticosteroid dose, total duration of CT, and steroid dose at the time of ST were not significantly different in the two groups. In multivariate analysis a past history of CT was predictive of abnormal ST (OR = 8.4, 95% CI = 2.2-31.5, p = 0.0009). Among patients with a past history of CT, the time (months) elapsed between the last course of CT was significantly longer in those with normal ST than in those with abnormal ST (45.5+/-13.5 vs 15.4+/-6.0; p = 0.02), and in multivariate analysis a duration free of CT < 15 months was predictive of abnormal ST (OR = 15.00, CI = 1.23-183.00, p = 0.03).. In all, 65% of the ST were abnormal. These results suggest that ST should be performed before corticosteroid withdrawal, especially in patients with recent past history of CT.

Topics: Adult; Cosyntropin; Delayed-Action Preparations; Female; Humans; Hypothalamo-Hypophyseal System; Inflammatory Bowel Diseases; Male; Pituitary-Adrenal System; Retrospective Studies; Risk Factors

We present the cases of three women who, within a 6-month period, suffered post-partum generalized tonic-clonic seizures. All had received an epidural in labour for analgesia and were subsequently diagnosed as suffering from postdural puncture headache. All were treated for that headache with Synacthen and one also received sumatriptan before her seizures. All made satisfactory recoveries and were discharged home. None displayed classical patterns suggestive of pre-eclampsia, meningitis, cortical venous thrombosis or any other pathological process that might explain these events adequately, and the specific precipitating factors were left unidentified.

Topics: Adult; Analgesia, Epidural; Anesthesia, Obstetrical; Cosyntropin; Female; Headache; Humans; Seizures; Spinal Puncture; Sumatriptan

Assessment of the hypothalamic--pituitary--adrenal (HPA) axis relies on the interpretation of serum (total) cortisol in response to dynamic tests of the HPA axis. Most cortisol is bound to cortisol-binding globulin (CBG) and serum total cortisol levels are significantly affected by variation in CBG. We hypothesised that CBG variation significantly affects interpretation of dynamic tests of the HPA axis.. We investigated the effect of CBG variation on the outcome of the 250 microg short Synacthen test (SST) in 30 healthy adults.. Blood was sampled at time -30, 0 (at which point Synacthen was given) and +30 min. CBG and total cortisol were measured at each time-point. Integrity of the HPA axis was confirmed by measurement of urine cortisol.. We found that CBG varied significantly within individuals, falling from 51+/-3.4 to 43 +/-3.2 microg/ml (P<0.0001) on changing from standing to lying. Total cortisol levels strongly correlated with CBG (r=0.88, P<0.0001). Thirteen subjects had a +30 min total cortisol <550 nmol/l. In these subjects, the CBG levels at each time-point were significantly lower compared with subjects who had a +30 min total cortisol of >550 nmol/l (P<0.05). To correct for variation in CBG we calculated the total cortisol:CBG ratio and found no significant difference in the +30 min ratio between these two groups.. CBG varies significantly within and between individuals. This is accompanied by changes in serum total cortisol large enough to affect the outcome of an SST and, by implication, other tests of the HPA axis.

Topics: Adrenal Glands; Adult; Aged; Carrier Proteins; Cosyntropin; Female; Humans; Hydrocortisone; Hypothalamus; Male; Middle Aged; Pituitary Gland

Amyloidosis is a multisystem disease which may cause organ loss. Renal involvement is the most common clinical problem in amyloidosis, however involvement of endocrin organs is possible. In this study to assess adrenocortical function and to evaluate the usefulness of low dose ACTH test in patients with renal amyloidosis, we determined cortisol, 17-hydroxyprogesteron (17-OHP) and 11-deoxycortisol (11-DOC) responses to both 1 microg and 250 microg Synacthen. We also determined the size of adrenal glands radiologically by using computerized tomography. Twenty one patients with renal amyloidosis and 16 healthy subjects for hormonal evaluation, and 20 patients with renal amyloidosis and 22 healthy subjects for radiologic evaluation were included in the study. In four patients (19%) peak serum cortisol levels following stimulation with the low dose of Synacthen were less than 20 microg/dL (550 nmol/L). Two of them had also subnormal cortisol response to the 250 microg Synacthen stimulation test. Basal and stimulated levels of 11-DOC were lower than those of control values (p=0.000 and p<0.01 respectively). The mean 11-DOC responses to stimulation with 1 microg Synacthen were also significantly lower than the values obtained after the simulation with 250 microg Synacthen (p<0.01 and p=0.000). Cortisol responses to the stimulation with 250 microg Synacthen were also lower than the control responses (p<0.05). 17-OHP responses were similar to the control values in both tests. In the radiological evaluation the mean maximum width of right adrenal glands and the mean anterior and maximum width of left adrenal glands were significantly greater in the patient group (p<0.01). In conclusion, adrenal involvement and adrenal insufficiency is common in amyloidosis. Low 11-DOC levels in amyloidosis is a new finding and further detailed studies is required to explain its cause.

Topics: 17-alpha-Hydroxyprogesterone; Adolescent; Adrenal Glands; Adult; Amyloidosis; Child; Cortodoxone; Cosyntropin; Delayed-Action Preparations; Female; Humans; Hydrocortisone; Kidney Diseases; Male; Middle Aged; Radiography

Daily regeneration of rat adrenocortical cells were investigated in terms of circadian and zonal variations by following the cells at the DNA-synthesizing stage. An S-phase was assessed by 5-bromo-2'-deoxyuridine (BrdU) incorporation into the cell-nuclei and/or by visualizing proliferating cell nuclear antigen. The BrdU-positive cells were observed throughout the day mainly in two regions of the adrenal cortex, i.e. the innermost portion of the zona glomerulosa and the outermost portion of the zona fasciculata. Cells only in a latter region showed a distinct circadian rhythm of cell proliferation with a peak at 3-4 a.m. A remarkable rise in the plasma adrenocorticotropin (ACTH) concentration preceded such an increase in the cell proliferation by about 4 hours. This phenomenon could be mimicked by raising the plasma ACTH concentration by the administration of Cortrosyn Z or metyrapone. Angiotensin II-stimuli induced by Na-deficiency increased the proliferation of zona glomerulosa cells in the former region at 6-7p.m without significant effects on that of the zona fasciculata cells in the latter region. Thus at least two sites, which respond differentially to the day/night cycle and circulating hormone levels, exist in rat adrenal cortex being responsible for the cytogenesis in this endocrine organ.

Topics: Adrenal Cortex; Adrenocorticotropic Hormone; Angiotensin II; Animals; Bromodeoxyuridine; Cell Division; Circadian Rhythm; Cosyntropin; DNA; Male; Metyrapone; Rats; Rats, Sprague-Dawley; Regeneration; S Phase; Sodium; Time Factors; Zona Fasciculata; Zona Glomerulosa

Addison's disease may present with diverse and non-specific clinical and biochemical features. Contentious issues include the appropriate criteria for the interpretation of the ACTH stimulation test and the necessary extent of investigation to identify a specific aetiology for the hypoadrenalism. The experience of Addison's disease at a South African teaching hospital was reviewed to (1) record the aetiology and spectrum of presentation, (2) examine the performance of the ACTH stimulation test and (3) determine the utility of adrenal CT scan and biopsy.. Retrospective study of patients admitted to a South African teaching hospital from 1980 to 1997 with a diagnosis of acute Addison's disease.. Fifty patients presenting with acute Addison's disease were identified by a search of hospital records. Pretreatment biochemical and haematological parameters were recorded. The cortisol response at 20 and 60 min to an intravenous injection of 250 micrograms synacthen (Cortrosyn) was analysed. In a subgroup of affected subjects, the bone mineral density (BMD) in the lumbar spine and femoral neck was measured during long-term follow-up.. Presenting features included hyperpigmentation (86%), weight loss (67%), abdominal pain (20%) and diarrhoea (16%). Thirty-nine patients (78%) were hyponatraemic, while 26 (53%) were hyperkalaemic. Nine patients (18%) were hypoglycaemic and 21% had hypercalcaemia. The mean basal cortisol was 148 nmol/l (range 10-487) and 16 patients (40%) had a normal basal cortisol. The mean cortisol 20 min after ACTH stimulation was 172 nmol/l (range 19-588). There was no significant increase in serum cortisol following ACTH stimulation (P > 0.05). Adrenal CT scans were performed in only 24 patients (48%) and were normal in 10, while abnormalities were detected in 14 patients (bilateral enlargement in 11, calcification in two and atrophic adrenals in one). Eight patients had a DEXA scan performed during follow-up--four were osteopaenic in the lumbar spine and five at the femoral neck. The probable aetiology of Addison's was idiopathic in 42%, related to active TB in 18%, old TB in 16%, autoimmune in 12% and malignancy with metastases in 6%--single cases were due to sarcoid, iron overload and adrenoleukodystrophy. Adrenal biopsy was performed in two patients and was diagnostic of malignancy in both cases. The mortality within the first month after hospitalization was 12%.. In our experience, Addison's disease is frequently idiopathic, presents with protean manifestations and should be considered in patients with unexplained hyperpigmentation or gastrointestinal complaints, particularly when associated with hyponatraemia and hyperkalaemia. A normal basal cortisol does not exclude the diagnosis which requires ACTH stimulation testing.

Topics: Abdominal Pain; Acute Disease; Addison Disease; Adolescent; Adult; Aged; Bone Density; Child; Cosyntropin; Diarrhea; Female; Follow-Up Studies; Hospitals, Teaching; Humans; Hydrocortisone; Hyperpigmentation; Male; Middle Aged; Retrospective Studies; South Africa

Adrenal suppression has been noted in patients who are receiving medroxyprogesterone acetate (MPA). Megestrol acetate (MA) is used to treat patients with advanced breast carcinoma, cachaexia related to acquired immune deficiency syndrome, and disseminated carcinomatosis, and it is believed to have fewer side effects than MPA. The aim of this study was to test for secondary adrenal suppression in patients receiving MA therapy for advanced metastatic cancer.. Ten postmenopausal female patients receiving long term MA therapy, nine with advanced metastatic breast carcinoma and one with metastatic ovarian carcinoma, were recruited consecutively from the oncology outpatient clinic at Ninewells Hospital in Dundee, Scotland. A short synacthen test and a corticotrophin-releasing hormone (CRH) stimulation test were performed on two separate occasions. Urine collection for 24-hour urinary free cortisol was performed on 6 patients. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), and free thyroxine (T4) were measured in eight patients. An insulin stress test (IST) was performed on two patients.. Nine of 10 patients had a poor cortisol response to the short synacthen test. The CRH test had abnormal results in eight of nine patients. In all patients tested, 24-hour urinary free cortisol excretion was low, indicating adrenal suppression. Basal serum FSH, LH, TSH, and free T4 values indicated normal pituitary function. Adrenocorticotrophic hormone response in the CRH test varied and is discussed in this article.. MA causes secondary adrenal suppression that is thought to be due to its effect at the hypothalamic level. The authors recommend a short course of steroid replacement for patients receiving MA at times of acute illness.

Topics: Adrenal Glands; Adrenocorticotropic Hormone; Aged; Antineoplastic Agents; Breast Neoplasms; Corticotropin-Releasing Hormone; Cosyntropin; Female; Humans; Hydrocortisone; Hypoaldosteronism; Hypothalamo-Hypophyseal System; Megestrol Acetate; Middle Aged; Ovarian Neoplasms; Pituitary-Adrenal System

Forty two children with West's syndrome who had been treated in the Clinic of Paediatrics, Higher Medical Institute, Plovdiv in the last 10 years were entered into the present study. Analysis is made of the aetiology of the disease, the results of treatment and development of the children. All children were followed up from 6 months to 10 years. The West's syndrome was idiopathic in four children and symptomatic in 38 children (90.5%). It had perinatal aetiology in 76.5% of the patients, prenatal in 21%, and postnatal in 2.6%. Complete seizure control was achieved in 17 children (40.5%) treated only with antiepileptic drugs. Synacthen was included in the treatment of the remaining 22 children in three therapeutic doses--0.0125 mg/kg/day (n = 8), 0.025 mg/kg/day (n = 8), and > or = 0.05 mg/kg/day (n = 6). Treatment with different doses of Synacthen showed no statistically significant differences in the three groups. The side effects of the treatment occurred more frequently and were more severe in the groups with a high-dose Synacthen treatment. The follow-up established mental retardation and/or neurological deficit in 88.1% of the children. One infant died during the treatment with Synacthen and another two with severe mental retardation--one year after treatment. In about one third of the cases transition was observed to other epileptic syndromes. Synacthen is concluded to be efficacious in the treatment of West's syndrome. If antiepileptic drugs fail to produce any effect Synacthen should be included in the therapy in due time, preferably in small doses in order to avoid severe and unwanted side effects.

Topics: Cosyntropin; Delayed-Action Preparations; Dose-Response Relationship, Drug; Echoencephalography; Electroencephalography; Female; Follow-Up Studies; Humans; Infant; Male; Prognosis; Retrospective Studies; Spasms, Infantile; Tomography, X-Ray Computed; Treatment Outcome

The present work investigated the effects of Norplant implants on the pituitary-adrenal function among 15 users of Norplant implants prior to and 6 months after insertion of the implants. Serum cortisol levels and their diurnal variations, ACTH and 24-h urinary 17-ketosteroids, ketogenic steroids, 17-hydroxy steroids, and creatinine, were measured. Also, a dynamic test (the 5-h Synacthen depot = ACTH stimulation test) was done before and 6 months after implants insertion. The 9 a.m. cortisol levels were blunted (within the normal ranges) while the 6 p.m. values were unaltered. The 24-h urinary ketogenic, hydroxy, and ketosteroids were also unchanged after Norplant implants use. The ACTH stimulation test showed a decreased adrenal response which was also within normal ranges. These data should raise the question related to suprarenal response to acute or prolonged stresses, such as surgical operations or shock in women using Norplant implants.. To ensure that Norplant contraceptive implants are not associated with a risk of pituitary-adrenal suppression, a series of laboratory tests were conducted in 15 women both before and 6 months after Norplant insertion. Comparisons of hormonal profiles before and after Norplant insertion revealed a significant drop in morning serum cortisol levels (404.33 +or- 84.07 nmol/l vs. 353.67 +or- 56.65 nmol/l, p 0.05), but no significant change in evening readings. The observed changes in morning cortisol values were still within the normal range. Serum ACTH values and 24-hour urinary 17-hydroxy steroids, 17-ketogenic steroids, and 17-ketosteroids were not different after insertion compared to baseline. Before Norplant insertion, injection of synthetic ACTH resulted in a 259.59 +or- 169.53% increase in the mean level of serum cortisol 5 hours later; 6 months after Norplant insertion, the percent rise above baseline was 165.85 +or- 91.64%. The significantly lower adrenal response among Norplant users (although still within normal limits) is presumably due to a local inhibition of the adrenal itself and not of the hypothalamic-pituitary axis. Although these findings suggest a minimal suppressive effect of prolonged microdose release of levonorgestrel from Norplant implants, the suprarenal response to acute or prolonged stresses (e.g., surgical operations or shock) in Norplant users requires investigation.

Topics: Adult; Contraceptive Agents, Female; Cosyntropin; Delayed-Action Preparations; Drug Implants; Female; Humans; Hydrocortisone; Levonorgestrel; Pituitary-Adrenal System; Radioimmunoassay

To evaluate whether ovarian function might have an influence on the adrenal hyperandrogenism present in patients with functional ovarian hyperandrogenism.. Controlled clinical study.. Tertiary institutional hospital.. Twenty-nine hirsute women with functional ovarian hyperandrogenism and 12 normal controls.. The ACTH and GnRH tests were performed before and during triptorelin-induced ovarian suppression in patients. The normal women served as controls for the ACTH test.. Basal and ACTH-stimulated steroid values.. All patients presented elevated T and free androgen index, which normalized after triptorelin. Patients with functional ovarian hyperandrogenism and adrenal hyperandrogenism, defined by elevated basal DHEAS (n = 10), presented enhanced delta 4-17, 20-lyase activity, which persisted during ovarian suppression. delta 4-17,20-lyase activity was normal in the functional ovarian hyperandrogenism patients without adrenal hyperandrogenism (n = 19). No correlation was observed between the any of the indexes of the adrenal enzymatic activities evaluated and plasma E2 or T.. Increased adrenal delta 4-17,20-lyase activity is present in functional ovarian hyperandrogenism women with adrenal hyperandrogenism. No influence of the excess ovarian androgens or estrogens was found on any of the adrenal enzymatic pathways explored.

Topics: Adolescent; Adrenocortical Hyperfunction; Adult; Androgens; Cohort Studies; Cosyntropin; Delayed-Action Preparations; Female; Follicular Phase; Gonadotropin-Releasing Hormone; Humans; Hyperandrogenism; Luteolytic Agents; Ovarian Diseases; Reference Values; Steroid 17-alpha-Hydroxylase; Steroids; Triptorelin Pamoate

To analyse critically a protocol for the investigation of girls presenting with virilisation in childhood.. Twenty five girls aged 1.6-8.7 years with features of virilisation were evaluated. Twenty four had presented with pubic hair, eight with auxilliary hair, seven with facial acne, four with clitoromegaly, and 10 with tall stature. They underwent clinical assessment (height, weight, height velocity, staging of puberty, physical examination for acne, body odour, and clitoromegaly) and laboratory assessment comprising basal concentrations of cortisol, 17 OH-progesterone (17 OHP), androstenedione, dehydroepiandrosteronesulphate (DHEAS), testosterone, and oestradiol. The above steroids were also measured during the short synacthen test (0.25 mg intramuscularly) in 16 subjects and low dose dexamethasone suppression tests (0.5 mg at six hourly intervals over 48 hours). Pelvic ultrasound, computed tomography and magnetic resonance imaging of adrenals were carried out when the biochemical findings suggested that there might be an autonomous source of androgen secretion.. Clinical and laboratory assessments differentiated the patients into three diagnostic categories: adrenarche (18 cases), congenital adrenal hyperplasia (five cases), and adrenocortical tumour (two cases). The last had elevated concentrations of DHEAS, 1.5 and 19.1 mumol/l (normal value < 0.5 mumol/l), androstenedione, 24.6 and 21.8 nmol/l (normal < 1 nmol/l), and testosterone, 4.5 and 2.4 nmol/l (normal < 0.8 nmol/l), with none suppressing on dexamethasone suppression. Congenital adrenal hyperplasia subjects had elevated basal serum concentrations of 17 OHP (n = 4): 250, 140, 14, and 14.1 nmol/l (normal < 10 nmol/l) and elevated peak values of 17 OHP after synacthen (n = 3): 76, 179.5, and 175 nmol/l. Adrenarche patients had elevated basal concentrations of DHEAS (median: 2.3 mumol/l; n = 17) and androstenedione (median 2.6 nmol/l; n = 17). Nine patients also had elevated basal serum testosterone concentrations (median 0.9 nmol/l). Peak values of 17 OHP after synacthen were significantly different from baseline (n = 12) and were < 50% of the lowest value in congenital adrenal hyperplasia. Serum DHEAS, androstenedione, and testosterone suppressed following dexamethasone suppression (n = 16), thereby distinguishing adrenarche patients from adrenal tumour patients. Clinical details did not distinguish patients, except for clitoromegaly which was present only in the tumour and congenital adrenal hyperplasia patients.. This protocol proved useful and practical in cases of virilisation presenting particular diagnostic difficulty.

Topics: Adrenal Cortex Neoplasms; Adrenal Hyperplasia, Congenital; Androgens; Child; Child, Preschool; Clinical Protocols; Cosyntropin; Dehydroepiandrosterone; Dexamethasone; Diagnosis, Differential; Female; Humans; Infant; Virilism

Adrenal insufficiency (AI) is a well known complication of AIDS. However, the clinical and biochemical features of AI in HIV infected patients have not been extensively studied.. A retrospective clinical study.. We reviewed clinical records of 74 AIDS patients with clinical and/or biochemical indications of AI who underwent Synacthen testing in order to determine adrenocortical function during a 5-year period.. AI was diagnosed when cortisol levels failed to rise above 496 nmol/l at any time during the test. Cortisol was measured by RIA.. Sixteen patients (22%) were diagnosed with AI. Most were young males and all of them had a known risk factor, principally i.v. drug users. The main complaint was fatigue. Hyponatraemia or hyperkalaemia were uncommon. All of them were severely immunosuppressed, with AIDS-defining conditions from at least 6 months before the diagnosis of AI, and had been diagnosed with at least one disease that has been reported to produce AI in AIDS patients. Survival was poor. Thirteen of these patients (81%) died within 6 months. Basal cortisol levels were lower than 275 nmol/l in 75% of patients with AI but in only 2% of the group of 58 patients who had normal adrenal responses to Synacthen.. Adrenal insufficiency features in AIDS patients with advanced disease, without specific findings and with a history of previous opportunistic diseases. Basal cortisol values at 0830 h lower than 275 nmol/l are highly suggestive of adrenal insufficiency in patients with AIDS.

Topics: Acquired Immunodeficiency Syndrome; Adrenal Insufficiency; Adult; Cosyntropin; Female; Humans; Hydrocortisone; Male; Retrospective Studies; Substance Abuse, Intravenous

Prostaglandin (PG) E2 is secreted into the fetal circulation during late gestation in the sheep. Exogenous infusion of PGE2 is associated with robust increases in the circulating concentrations of ACTH and cortisol and it has therefore been proposed that endogenous PGE2 modulates the activity of the fetal HPA axis, which is the primary determinant of parturition and essential for the maturation of vital organ systems. The sites of action of PGE2 within the HPA axis have not been clearly established. We have compared the effects of PGE2 infusion on ACTH and cortisol concentrations in intact fetuses and in those whose pituitaries were surgically disconnected from hypothalamic control (hypothalamo-pituitary disconnected; HPD fetuses operated at 111-113 days gestational age). The effect of advancing gestational age on these responses was investigated by infusing PGE2 at 121, 131, 141 and 148 days of gestation. The functional integrity of the pituitary corticotrophs was tested by injecting CRH (1 microgram) into intact and HPD fetuses at day 125. This test was repeated for the HPD fetuses at 160 days. The responsiveness of the adrenal glands was also tested by injecting 2.5 micrograms/kg synthetic ACTH1-24 (Synacthen) into both groups of fetuses at day 135, with the HPD group retested at day 155. PGE2 infusion was associated with a robust increase (P < 0.001) in plasma immunoreactive (ir) ACTH in intact fetuses at all gestational ages while HPD fetuses did not respond, except at day 148 when the response was small. Similarly, cortisol concentrations were increased (P < 0.001) during PGE2 infusion in intact fetuses but not in HPD fetuses, except for a minor increase at 148 days. The response of irACTH to exogenous CRH was similar in intact and HPD fetuses at 125 days and this response was maintained in HPD fetuses at day 160. The cortisol response of intact fetuses to ACTH1-24 exceeded that of HPD fetuses at day 135 and, in HPD fetuses, this response was unchanged when they were retested at 155 days, indicating that their adrenal responsiveness did not wane with time. We conclude that the effects of PGE2 on the fetal HPA axis are exerted predominantly or exclusively at a level above the pituitary gland.

Topics: Adrenocorticotropic Hormone; Animals; Cosyntropin; Dinoprostone; Female; Hypothalamo-Hypophyseal System; Hypothalamus; Male; Pituitary-Adrenal System; Pregnancy; Sheep

Topics: ACTH Syndrome, Ectopic; Addison Disease; Adrenocorticotropic Hormone; Corticotropin-Releasing Hormone; Cosyntropin; Cushing Syndrome; Delayed-Action Preparations; Dexamethasone; Evaluation Studies as Topic; Humans; Hypopituitarism; Immunoradiometric Assay; Nelson Syndrome; Reagent Kits, Diagnostic; Reproducibility of Results; Sensitivity and Specificity

Neonatal administration of hydrocortisone decrease steroidogenesis in the rat adrenals in immature and mature animals production of progesterone and androstenedione reducing, at that. Primary long-term disturbance of central regulatory influences controlling steroidogenesis in adrenals, was proposed. The steroid production disturbance in the gonads was lesser than in the adrenals and was found only in mature rats.

Topics: Adrenal Cortex Hormones; Adrenal Glands; Aging; Animals; Animals, Newborn; Chorionic Gonadotropin; Cosyntropin; Female; Gonadal Steroid Hormones; Hydrocortisone; Male; Ovary; Rats; Testis

We report a patient who began to have clusters of seizures characterized by brief elevation of the right arm at 6 months of age. An interictal electroencephalogram (EEG) at 7 months revealed hypsarrhythmia without definite asymmetry. Simultaneous EEG and video recording disclosed that these focal spasms were associated with fast wave bursts superimposed on slow waves most markedly in the left centro-midtemporal region. The patient became seizure-free after synthetic ACTH therapy. The patient is developmentally normal at 3 years 5 months, but magnetic resonance imaging studies revealed findings suggestive of delayed myelination in the left frontal region. This patient is considered to have had an unusual variant of West syndrome associated with focal delayed myelination.

Topics: Adolescent; Child, Preschool; Cosyntropin; Delayed-Action Preparations; Dominance, Cerebral; Electroencephalography; Epilepsies, Partial; Evoked Potentials; Follow-Up Studies; Frontal Lobe; Humans; Infant; Magnetic Resonance Imaging; Nerve Fibers, Myelinated; Spasms, Infantile

We present the endocrine parameters of two adult patients with partial hypopituitarism documented at 6 and 8 months after chemotherapy, single fraction total body irradiation (10.5 Gy) and autologous bone marrow transplantation. The hormone profiles demonstrate severe somatotroph insufficiency and impaired adrenocorticotroph secretory capacity, despite sparing of the gonadotroph compartment. We recommend stimulatory testing of hypothalamic-pituitary function from 3 months post-transplant, as basal hormonal concentrations may be equivocal, and supplementation may significantly improve quality of life.

Topics: Adult; Bone Marrow Transplantation; Cosyntropin; Hormones; Humans; Hydrocortisone; Hypopituitarism; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Radioimmunoassay; Transplantation, Autologous; Whole-Body Irradiation

The adrenal glands may be involved in tuberculosis. The exact frequency and extent of adrenal involvement in tuberculosis are not well known. Although there are some studies regarding adrenal gland involvement, they are not sufficient because of inadequate endocrinological tests and radiological procedures. The aim of this study was to assess the adrenal gland in acute and chronic pulmonary tuberculosis and to compare it with the findings obtained in healthy subjects.. We studied 20 patients with acute pulmonary tuberculosis, 41 patients with chronic pulmonary tuberculosis and 20 healthy subjects. Involvement of the adrenal gland was assessed by basal cortisol level, cortisol response to Synacthen and adrenal computed tomography.. Cortisol levels were measured before, 30 and 60 minutes after Synacthen (250 micrograms i.v.) injection. Computerized tomography of the adrenals was carried out in 61 patients with tuberculosis and 20 healthy subjects.. Mean basal cortisol level and 60-minute cortisol response to Synacthen were significantly higher in acute pulmonary tuberculosis than in chronic pulmonary tuberculosis and healthy subjects. Two patients with Addison's disease were diagnosed among the chronic tuberculous patients. Both length and thickness of the right and left adrenal gland were greater in patients with acute tuberculosis.. Adrenal enlargement demonstrated by computerized tomography is common in patients with acute pulmonary tuberculosis, but our findings show that cortisol reserve is normal, in contrast to previous suggestions.

Topics: Acute Disease; Adolescent; Adrenal Glands; Adult; Aged; Chronic Disease; Cosyntropin; Female; Humans; Hydrocortisone; Male; Middle Aged; Prospective Studies; Tomography, X-Ray Computed; Tuberculosis, Pulmonary

A regional hospital in Hong Kong.. To evaluate adrenocortical function in older patients admitted to hospital with active pulmonary tuberculosis (TB) and to determine whether adrenal insufficiency contributes to mortality in this high risk group.. Adrenocortical function was assessed in 39 consecutive patients aged over 50 admitted to hospital with active pulmonary TB. Short Synacthen stimulation tests were performed before treatment and repeated at 2 months. In patients who died during treatment, a post-mortem examination was performed. Particular attention was paid to TB involvement of the adrenal glands.. None of the patients had a subnormal basal cortisol concentration before treatment. 7 (18%) had raised basal cortisol concentrations and 16 (41%) had suboptimal cortisol responses to Synacthen stimulation. 14 patients (36%) died during treatment. The basal cortisol concentrations were significantly higher in the non-survivors compared to the survivors (743.7 +/- 288.5 vs 460.5 +/- 123.2 nmol/L, P < 0.0001). Autopsies were performed in 9 patients who died during treatment. Tuberculous involvement of the adrenal glands was found in only 1 patient who had a high basal cortisol concentration. After 2 months of treatment, all patients had normal cortisol concentrations and only 4 had borderline suboptimal Synacthen responses. The basal cortisol concentrations were significantly higher at presentation compared to those at 2 months after treatment (570.4 +/- 243.8 vs 386.3 +/- 108.3 nmol/L, P = 0.0014).. Adrenal insufficiency is uncommon in patients with pulmonary TB. Suboptimal cortisol responses to Synacthen usually reflect a hyperstimulated basal state secondary to stress. Treatment with anti-TB drugs causes reduction in basal cortisol with associated improvement in the Synacthen response.

Topics: Adrenal Cortex; Aged; Aged, 80 and over; Antitubercular Agents; Cosyntropin; Female; Humans; Hydrocortisone; Male; Middle Aged; Prospective Studies; Retrospective Studies; Tuberculosis, Pulmonary

Two men with nervous anorexia were fully investigated and the results were compared with those of 15 healthy men and 19 women with the same disease. A similarity of the hormonal changes in both sexes concerning the somatotropic hormone, thyroid and cortico-suprarenal axis was established. A difference was found between the women and the two men concerning the gonadotropic hormones which in the men showed a well expressed reaction to gonadoliberin with an early maximum.

Topics: Adolescent; Adult; Anorexia Nervosa; Cosyntropin; Delayed-Action Preparations; Endocrine System Diseases; Female; Gonadotropin-Releasing Hormone; Humans; Male; Prolactin; Psychophysiologic Disorders; Thyrotropin; Weight Loss

CGS 16949A is a potent inhibitor of aromatase in vitro with an IC50 of 0.03 microM for the inhibition of LH-stimulated estrogen biosynthesis in hamster ovaries. In vivo, CGS 16949A leads to sequelae of estrogen deprivation (e.g. regression of DMBA-induced mammary tumors) without causing adrenal hypertrophy in adult rats. To complement these in vitro and in vivo findings, the effect of CGS 16949A on adrenal steroid biosynthesis in rats was investigated in vitro and in vivo. The surprising finding in vitro was that CGS 16949A inhibited aldosterone biosynthesis (IC50 = 1 microM) at concentrations 100 times lower than those for inhibition of corticosterone biosynthesis (IC50 = 100 microM). Moreover, deoxycorticosterone (DOC) concentrations were elevated at all concentrations of CGS 16949A which inhibited aldosterone synthesis. The classical biosynthetic pathway for aldosterone is DOC----corticosterone----18-OH-corticosterone----aldosterone. Thus inhibition of aldosterone biosynthesis, reflected in DOC accumulation, without affecting corticosterone concentrations, indicates that corticosterone is not an obligatory intermediate in the conversion of DOC to aldosterone in the rat. In vivo, CGS 16949A showed a suppression of plasma aldosterone in ACTH-stimulated male rats at doses which did not significantly affect plasma corticosterone. In conclusion, aldosterone measured both in vitro and in vivo must be derived primarily from a biosynthetic pathway in which corticosterone is not obligatory intermediate.

Topics: Adrenal Glands; Aldosterone; Aminoglutethimide; Animals; Aromatase Inhibitors; Corticosterone; Cosyntropin; Delayed-Action Preparations; Desoxycorticosterone; Fadrozole; Imidazoles; In Vitro Techniques; Male; Nitriles; Rats; Rats, Inbred Strains

Serum corticotropin and cortisol levels were measured in 20-40-year old healthy residents (144 males and 361 females) in the North. A functional Synacthen Depot test was performed in 5 volunteers. The adrenal glands from 56 males and 8 females of the same age who had died from accidents were pathohistologically and stereometrically examined. The signs of functional tension were established in the pituitary-adrenal cortex system. The Synacthen Depot test determined sufficient potentials of the organ to show responses to specific stimulation. Morphologically, a number of changes were found, which might be regarded as a prerequisite to the development of functional and pathological disturbances in the above-mentioned link of the endocrine system.

Topics: Adaptation, Physiological; Adrenal Cortex; Adrenocorticotropic Hormone; Adult; Arctic Regions; Cosyntropin; Female; Humans; Hydrocortisone; Male; Pituitary-Adrenal System; USSR

A 43-year-old woman with isolated ACTH deficiency in association with transient thyrotoxicosis is reported. The initial evaluation revealed that plasma ACTH and cortisol did not respond to corticotropin-releasing hormone (CRH) in the presence of hyperthyroxinemia and hyperprolactinemia. During the replacement therapy with dexamethasone, she developed transient hypothyroxinemia with persistent hyperprolactinemia. Although thyroid open biopsy did not show any evidence of autoimmune thyroiditis or subacute thyroiditis, the data appear to provide other evidence of a possible relationship between acute adrenal insufficiency and transient thyroid dysfunction.

Topics: Adrenocorticotropic Hormone; Adult; Corticotropin-Releasing Hormone; Cosyntropin; Dexamethasone; Female; Gonadotropin-Releasing Hormone; Humans; Hyperprolactinemia; Insulin; Lypressin; Thyroid Function Tests; Thyroid Gland; Thyrotoxicosis; Thyrotropin-Releasing Hormone; Time Factors

Serum cortisol, prolactin (PRL), TSH, GH, LH and FSH levels were measured before and immediately after daily ACTH-Z therapy (0.01 mg/kg/day, 1-2 weeks) for 5 patients with infantile spasms and one patient with myoclonus epilepsy. Total number of ACTH-Z therapy were 8 times, and all patients became seizure free after ACTH-Z therapy. In 6 occasions, TRH, LH-RH and insulin tolerance tests were performed before and after daily ACTH-Z therapy. Serum cortisol levels were significantly increased after daily ACTH-Z therapy but all other hormone levels were significantly decreased. In TRH and LH-RH tolerance tests, peak levels and increments of PRL, LH and FSH were significantly decreased after daily ACTH-Z therapy and those of TSH were mildly decreased. In one case insulin tolerance test revealed an adequate decrease of blood glucose before and after ACTH-Z therapy, and there was a poor GH response after ACTH-Z therapy. Daily ACTH-Z therapy was thought to suppress secretion of anterior pituitary hormones.

Topics: Child, Preschool; Cosyntropin; Female; Humans; Infant; Male; Pituitary Gland, Anterior; Spasms, Infantile

Topics: Adult; Arthritis; Chronic Disease; Cosyntropin; Delayed-Action Preparations; Drug Evaluation; Humans; Middle Aged; Psoriasis; Remission Induction; Time Factors

Adrenocortical function, as reflected by sequential analysis of plasma cortisol and adrenocorticotropin (ACTH) test, was investigated in elderly patients (greater than or equal to 65 years) with acute myocardial infarction (AMI), and compared to young patients (less than or equal to 55 years) with AMI. Further, age-matched subjects admitted with ischaemic chest pain, in whom AMI was not verified, served as controls. Following infarction, plasma cortisol peaked within 24 hours in both age groups, whereupon the cortisol level gradually decreased till day 12. Plasma cortisol during AMI disclosed no age-related difference, but was significantly correlated to the localization of infarction and lactate dehydrogenase (LDH). The development of complications, i.e. hypotension, congestive heart failure, and arrhythmia, calling for therapeutic intervention, was solely correlated to infarct size, as estimated by peak LDH. Young and elderly patients responded equally and normally to ACTH stimulation, and in both groups a significant, positive correlation between the basal and the 30-min plasma cortisol was observed. Thus, we may conclude that in patients with AMI, the hypothalamic-pituitary-adrenocortical (HPA) response to stress and ACTH test shows no repression due to age.

Topics: Adrenal Cortex Function Tests; Adult; Aged; Aged, 80 and over; Aging; Alanine Transaminase; Aspartate Aminotransferases; Cosyntropin; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; L-Lactate Dehydrogenase; Male; Middle Aged; Myocardial Infarction; Pituitary-Adrenal System

Topics: Adrenocorticotropic Hormone; Adult; Asthma; Bronchitis; Cosyntropin; Female; Humans; Hydrocortisone; Injections, Intramuscular; Injections, Intravenous; Male; Middle Aged; Respiration

Two infants developed hyperkalemia shortly after cessation of prolonged ACTH therapy for infantile spasms. We wish to call for cautious approach at time of cessation of prolonged ACTH therapy because of possible unexpected and only partially understood hazardous side effects such as hyperkalemia.

Topics: Cosyntropin; Electroencephalography; Female; Humans; Hyperkalemia; Infant; Long-Term Care; Male; Spasms, Infantile

Topics: Adrenal Cortex Diseases; Adrenal Cortex Function Tests; Animals; Cattle; Cattle Diseases; Cosyntropin; Female; Pituitary-Adrenal Function Tests

The influence of aging on the steroid secretory capacity of the adrenal gland was evaluated by comparing data on young (age 20 to 21 years) with elderly (age 77 to 86 years) healthy male subjects. After the administration of ACTH-Z (1 mg, im) during the treatment of dexamethasone (1 mg/day, for 2 days), blood samples were taken at time 0, 1, 2, 3, 6, 12 and 24 h. The mean basal levels of pregnenolone (P5), 17-hydroxypregnenolone (170HP5), dehydroepiandrosterone (DHEA), progesterone (P4), 17-hydroxyprogesterone (170HP4), androstenedione (A-dione) and aldosterone (Ald) gradually decreased with advance in age. Dexamethasone administration to the elderly men produced no significant fall in plasma P4 and Ald. Plasma ACTH levels after ACTH-Z administration were significantly higher in the elderly men than the comparable levels in the young men. The apparent half-life of ACTH-Z in plasma was prolonged in the elderly men. For 3 hours after ACTH-Z injection, the responses of all plasma steroids, such as P5, 170HP5, DHEA, P4, 170HP4, A-dione, Ald and cortisol (F), were significantly lower in the elderly men. When the 24-hour secretion rates of steroid hormones were compared by delta area, which indicated the increased area for 24 hours after ACTH-Z administration, the secretion rate of F showed no significant difference between the two groups, but that of DHEA was significantly low in the elderly men. The 24-hour secretion rates of P5 and P4 were not impaired and that of 170HP4 was significantly high in the elderly men. These results indicate that the steroidogenic response to ACTH decreases with aging, and that, in the elderly men, an apparent decrease in C17,20 lyase efficiency may be related in part to the decreased secretion of adrenal androgens.

Topics: 17-alpha-Hydroxypregnenolone; Adrenal Cortex; Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Adult; Aged; Aging; Cosyntropin; Dehydroepiandrosterone; Dexamethasone; Humans; Injections, Intramuscular; Male; Middle Aged; Pregnenolone; Progesterone; Radioimmunoassay

Topics: Adrenocorticotropic Hormone; Cosyntropin; Humans; Hydrocortisone; Infant; Prognosis; Spasms, Infantile

Topics: Adrenocorticotropic Hormone; Anticonvulsants; Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Cosyntropin; Drug Therapy, Combination; Epilepsies, Partial; Female; Humans; Infant; Liver Function Tests; Male

Topics: Adrenocorticotropic Hormone; Cosyntropin; Humans

Topics: Adrenal Cortex; Adrenal Cortex Function Tests; Adult; Aldosterone; Cosyntropin; Female; Humans; Hypopituitarism; Male; Metoclopramide; Middle Aged; Pituitary Gland, Anterior

Total (free plus protein-bound) and free cortisol concentrations in paired samples of serum and skim milk or colostrum were determined by specific radioimmunoassay after extraction or ultrafiltration. For 11 cows in established lactation mean total cortisol concentrations +/- SE in serum and milk were 4.5 +/- .7 ng/ml and .35 +/- .06 ng/ml, respectively. Concentrations of free cortisol in serum and milk were about .3 ng/ml, which is at the lower limit of the present assay. Following 200 IU Synacthen injection to 5 cows, total cortisol in serum and milk rose to 67 +/- 6.0 ng/ml and 11.4 +/- 1.5 ng/ml by 8 h postinjection, while free concentrations increased to 4.3 +/- .7 ng/ml and 6.5 +/- .8 ng/ml in serum and milk, respectively. Eight additional cows were sampled at 1 to 2 d after parturition, and total cortisol in serum and colostrum was 16.6 +/- 1.6 ng/ml and 4.4 +/- 1.3 ng/ml, and free cortisol was 2.4 +/- .4 ng/ml and 1.8 +/- .5 ng/ml, respectively. Free cortisol concentrations in colostrum or in milk from cows in established lactation, before or after adrenal stimulation, are directly related to free cortisol concentrations in the blood, while the bound cortisol in milk is more related to these two stages of lactation rather than the bound hormone in the blood. Measurement of free cortisol in milk should allow the monitoring of changes in plasma free cortisol in studies of stress in dairy cows.

Topics: Animals; Cattle; Colostrum; Cosyntropin; Female; Hydrocortisone; Lactation; Milk; Pregnancy; Radioimmunoassay

It is well documented that small basic peptides with lipophilic counterparts induce non-cytolytic histamine release particularly from rat peritoneal mast cells, and to a lesser extent from human leukocytes. Since pro-albumin hexapeptide with its lipophilic core also exhibits a high percentage of basic amino acid residues, it was thought valid to investigate its potential histamine releasing activity using the above-mentioned cell systems. Results show that the peptide failed in both cell types to induce histamine release, or to inhibit IgE mediated or anaphylatoxin induced histamine release up to concentrations of 10(-4) M.

Topics: Animals; Basophils; Cosyntropin; Histamine Release; Humans; Immunoglobulin E; Leukocytes; Mast Cells; Peptide Fragments; Prealbumin; Rabbits; Rats

Topics: Adrenocorticotropic Hormone; Cosyntropin; Humans; Skin Diseases

Serum 11-beta-hydroxy-androstenedione (11OHAD), androstenedione (AD) and cortisol (F) were estimated during an i.v. insulin test in 2 large groups of normal prepubertal children and in normal adults. The results revealed that the basal level and responsiveness of AD were much lower in both groups of children than in adults whereas the corresponding 11OHAD data were similar or superior to those of adults. This suggests that during childhood the limited amount of adrenal AD is preferentially switched to the 11-hydroxylation step. Comparison of hormonal data observed in adults after i.v. insulin (mild ACTH stimulation) and a maximal stimulating dose of synacthen showed that the sensitivity of delta 4-3 keto-androgens pathway is inferior to that of F.

Topics: Adrenal Glands; Androstenedione; Child; Child, Preschool; Cosyntropin; Female; Humans; Hydrocortisone; Infant; Insulin; Male

Topics: Animals; Antilymphocyte Serum; Child, Preschool; Cosyntropin; Drug Evaluation, Preclinical; Female; Guinea Pigs; Humans; Hypothalamo-Hypophyseal System; Infant; Lymphatic Diseases; Male; Pituitary-Adrenal System; Pneumonia; Suspensions; Thymus Gland; Thymus Hyperplasia; Time Factors

Topics: Aged; Coronary Disease; Cosyntropin; Epinephrine; Humans; Hypertension; Intracranial Arteriosclerosis; Middle Aged; Renin-Angiotensin System

Topics: Adrenal Glands; Adrenocorticotropic Hormone; Cosyntropin; Etomidate; Female; Humans; Hydrocortisone; Imidazoles; Infusions, Parenteral; Male

A possibility to use the larvae of ecaudate amphibia as a test model for the quantitative determination of certain hypophyseal hormones has been shown. The physiological reactions of the pigmentary cells in tadpoles of Rana temporaria can be used for a quick and exact testing of the adrenocorticotropic hormone preparations (ACTH): corticotropin and Zn-corticotropin. Evidently the method elaborated for the biological testing of hypophyseal hormones may be used in the production of the endocrinous preparations as a quick assessment of melanocyte-stimulating hormones in integral raw and sublimated hypophyses.

Topics: Adrenocorticotropic Hormone; Animals; Biological Assay; Cosyntropin; Larva; Melanophores; Pituitary Hormones; Rana temporaria

Topics: Adrenocorticotropic Hormone; Child; Child, Preschool; Cosyntropin; Epilepsy; Female; Humans; Hydrocortisone; Infant; Male

Topics: Adrenocorticotropic Hormone; Cosyntropin; Female; Humans; Hydrocortisone; Infant; Male; Spasms, Infantile

Steroidogenesis by zona reticularis (ZR) and zona fasciculata (ZF) cells from guinea-pig, macaque and human adrenals has been examined to establish the relative importance of the two cell types in the production of adrenal androgens. Microdissection and equilibrium density sedimentation of enzymically dispersed cells on Percoll gradients have been used to separate the two cell types with varying degrees of purity. Outputs of androstenedione and cortisol were measured for all the species studied and dehydroepiandrosterone sulphate (DHAS) for human adrenal cells. In all three species, the ZF cells produced more cortisol than the ZR cells. This production was stimulated to a greater extent in the ZF than the ZR cells in the guinea-pig, but to a similar extent in the macaque and human cells. Outputs of androstenedione were greater for ZF cells than ZR cells in the guinea-pig both basally and in response to an ACTH stimulus but basal production of this androgen was slightly greater from the ZR than the ZF in tissue incubations (1.6-fold), although cortisol output was still higher for ZF tissue by a factor of 2. Examination of androstenedione/cortisol ratios for all the species, both tissue and cells and in the presence or absence of ACTH, demonstrated clearly the inherent bias for ZR cells towards androgen synthesis by the fact that this ratio was always higher for ZR than for ZF cells or tissue. The most marked difference in this ratio was found in the human cells comparing the purest ZR and the purest ZF cell preparations even though the highest estimated purity of either cell type was only 80%. The difference in the ratio DHAS/cortisol was even greater comparing these human ZR and ZF cell preparations, ranging from 18- to 44-fold basally and in response to ACTH. The preliminary experiment on human adrenal cells indicates that the ZR cells are much more important than the ZF cells in the production of androgens even in the presence of ACTH, in contrast to the other species studied.

Topics: Adrenal Cortex; Adrenocorticotropic Hormone; Androgens; Androstenedione; Animals; Cell Separation; Centrifugation, Density Gradient; Cosyntropin; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Female; Guinea Pigs; Hydrocortisone; Macaca fascicularis

Hypercortisolism was induced in rats by the administration of a corticotrophin analogue (Synacthen depot). The effect of this treatment during different periods was studied in normally fed and overnight-fasted rats. The activity of liver-type lipases, i.e., of lipases similar to the heparin-releasable lipase of rat liver (liver lipase), was determined in the adrenal gland and in the liver. Short-term (16 h) treatment had no effect on the lipase activity in the adrenal gland. During prolonged treatment, however, the lipase activity rose to 600-700% of control values in 10 days and from then on remained constant. The effect was similar in fed and overnight-fasted rats. The lipase activity in the liver decreased upon Synacthen administration. In the fed rats a decrease of 25% of the initial value was found after 16 h, 40% after 3 days and 50% after 20 days of treatment. In overnight-fasted rats the lowering of the lipase activity was less marked than in fasted controls. Serum lipid levels and high-density lipoprotein (HDL) subclass concentrations were also measured. The cholesterol concentration in the lipoproteins with a density greater than 1.050 g/ml (HDL) was elevated in rats treated for 3-20 days. If the rats were treated for longer than 10 days, overnight fasting led to a normalization of the HDL-cholesterol levels. After separation of the HDL into two subfractions, a relatively 'light' apolipoprotein E-rich fraction and a more 'heavy' apolipoprotein A-I-rich fraction, in fed and fasted animals treated with Synacthen for 3 days both HDL subfractions were elevated. After 10 days treatment only the apolipoprotein A-I-rich HDL fraction was still enhanced in both fed and fasted rats.

Topics: Adrenal Glands; Adrenocorticotropic Hormone; Animals; Body Weight; Chemical Phenomena; Chemistry; Cholesterol; Cosyntropin; Fasting; Lipase; Lipoproteins, HDL; Liver; Male; Rats; Rats, Inbred Strains

Topics: Adrenocorticotropic Hormone; Cosyntropin; Female; Hormones; Humans; Hyaline Membrane Disease; Infant, Newborn; Maternal-Fetal Exchange; Obstetric Labor, Premature; Pregnancy

Salivary sampling regimens are non-invasive, and therefore facilitate dynamic tests of hormone function and assessment of biological rhythms. Concentrations of neutral steroids in saliva are independent of flow rate and appear to reflect the non-protein-bound, 'free' fraction. Comparison of replicate determinations of quality control pools with determinations of samples collected at 2 min intervals allows the significance of short-term fluctuations in cortisol and testosterone secretory activity to be estimated. Samples collected at 15 min intervals provide a convenient way to estimate circadian rhythms, particularly in young children. Determination of salivary progesterone concentrations in samples collected by women daily, over extended periods of time, provides a valuable means of assessing ovarian function. Such assays may be used to monitor ovulation-induction therapy.

Topics: Adult; Child; Child, Preschool; Circadian Rhythm; Cosyntropin; Humans; Hydrocortisone; Infant, Newborn; Infertility, Male; Kinetics; Male; Progesterone; Saliva; Testis; Testosterone

The metabolic response to pathophysiologic concentrations of glucagon, induced by glucagon infusion, has been examined in normal man before and after 36-60 hr hypercortisolaemia, induced by administration of tetracosactrin-depot. Glucagon alone increased serum insulin levels twofold but blood glucose was unaltered. Plasma NEFA and blood ketone body concentrations were decreased by glucagon infusion. Tetracosactrin produced a threefold rise in serum cortisol levels and caused mild fasting hyperglycemia and hyperinsulinaemia. Subsequent glucagon infusion had no effect on circulating insulin, glucose, NEFA or ketone body concentrations. Simultaneous infusion of somatostatin, to produce partial insulin-deficiency, unmasked a hyperglycemic action of glucagon (+ 3.8 +/- 0.2 mmol/l at 90 min, p less than 0.02). This glucagon-induced rise in blood glucose was diminished by prior tetracosactrin administration. Tetracosactrin revealed a mild lipolytic action of glucagon in partial insulin deficiency, not apparent in the euadrenal state. Glucagon was equally hyperketonemic during somatostatin infusion before and after tetracosactrin. Thus the hyperglycemic and hyperketonemic actions of glucagon at pathophysiologic levels are restricted to insulin deficiency. Hypercortisolaemia reveals a lipolytic action of glucagon in insulin-deficient man but does not potentiate the hyperglycemic or hyperketonemic effects.

Topics: Adult; Blood Glucose; Cosyntropin; Drug Synergism; Fatty Acids, Nonesterified; Glucagon; Humans; Hydrocortisone; Insulin; Ketone Bodies; Male; Somatostatin

The metabolic effects of chronic hypercortisolaemia were studied by administration of tetracosactrin-depot, 1 mg I.M. daily for 36-60 hr to normal subjects. Partial insulin and glucagon deficiency were induced at the end of the period by infusion of somatostatin, 100 micrograms/h for 210 min. Tetracosactrin alone induced a three fold rise in basal serum cortisol levels and fasting blood glucose concentration rose from 5.2 +/- 0.2 to 7.2 +/- 0.2 mmole/l (p less than 0.01) with a rise in fasting serum insulin from 5.2 +/- 1.2 to 13.1 +/- 1.9 mU/l (p less than 0.02). Concentrations of the gluconeogenic precursors lactate, pyruvate and alanine were also raised, but non-esterified fatty acid, glycerol and ketone body levels were unchanged. Somatostatin infusion caused a 30%-50% decrease in serum insulin and a 20%-60% decrease in plasma glucagon concentrations both before and after tetracosactrin administration. A similar rise in blood glucose concentration, relative to the saline control, occurred over the period of somatostatin infusion both with and without elevated cortisol levels. However, prior tetracosactrin administration caused a 100% greater rise in blood ketone body concentrations during infusion of somatostatin than was seen in the euadrenal state, despite similar plasma NEFA concentrations. Hypercortisolaemia causes hyperglycaemia and elevated gluconeogenic precursor concentrations but the associated rise in serum insulin concentrations limits lipolysis and ketosis. In insulin deficiency, a ketotic effort of glucocorticoid excess is evident which may be independent of lipolysis and occurs despite concurrent glucagon deficiency. These catabolic actions of cortisol are likely to be of major importance in the metabolic response to stress.

Topics: Adult; Blood Glucose; Cosyntropin; Fasting; Fatty Acids, Nonesterified; Glucagon; Gluconeogenesis; Humans; Hydrocortisone; Insulin; Ketone Bodies; Somatostatin

Topics: Adrenocorticotropic Hormone; Adult; Aged; Antineoplastic Agents; Cosyntropin; Female; Humans; Male; Middle Aged; Time Factors

The production of basophils in semisolid agar cultures form normal and chronic myeloid leukemia (CML) committed granulocyte-macrophage precursors was investigated using an original whole-dish staining technique with toluidine blue which produces a specific metachromasia in basophils. As additional proof of the basophilic nature of metachromatic cells, their degranulation after challenge with C5a anaphylotoxin and Synachten was observed. Our studies show that few basophils are produced in cultures form normal bone marrow. CML CFUc produce more basophils, their number being roughly correlated with the degree of basophilia. We observed only clusters composed by a pure basophilic population, while larger aggregates in which basophils could be detected were composed also by other granulocytic cells.

Topics: Agar; Anaphylatoxins; Basophils; Bone Marrow Cells; Cosyntropin; Culture Techniques; Cytoplasmic Granules; Humans; Leukemia, Myeloid; Staining and Labeling; Tolonium Chloride

Topics: Adolescent; Adrenocorticotropic Hormone; Adult; Airway Obstruction; Asthma; Cosyntropin; Drug Hypersensitivity; Female; Humans; Male

Gas chromatography was used to study both the relative composition and level of nonesterified fatty acids in the blood of pigs, following target-oriented deflection of two hormonal systems, hypothalamus-pituitary gland-thyroid and hypothalamus-pituitary gland-adrenal cortex. The findings originally expected were not made. Percentual C-18 was increased, following long-time application of tri-iodothyronine/thyroxine, while c-12 was percentually lowered, as compared to the perchlorate group. Deflection of the hypothalamus-pituitary gland-adrenocortical system caused slight alteration in both the composition and overall concentration of blood-borne non-esterified fatty acids.

Topics: Animals; Cosyntropin; Fatty Acids, Nonesterified; Hydrocortisone; Hypothalamo-Hypophyseal System; Metyrapone; Perchlorates; Pituitary-Adrenal System; Potassium; Potassium Compounds; Propranolol; Swine; Thyroid Gland; Thyroxine; Triiodothyronine

A case of subdural hematoma following ACTH-Z therapy for infantile spasms was presented. A female baby of 5 months old showed little clinical evidence of cerebral dysfunction associated with subdural hematoma. There have been several reports about the relationship between steroid treatment and apparent brain atrophy on the CT brain scans. Then, we studied the CT brain scans before and after ACTH-Z therapy for infantile spasms, atonic seizure or Lennox syndrome and showed some relationship between apparent brain atrophy on the CT brain scans and ACTH-Z treatment. We also discussed the possible etiology of apparent brain atrophy and subdural hematoma, and stressed the necessity of extreme caution with long-term ACTH-Z administration.

Topics: Adrenocorticotropic Hormone; Atrophy; Brain; Cosyntropin; Electroencephalography; Female; Hematoma, Subdural; Humans; Infant; Spasms, Infantile; Tomography, X-Ray Computed

Topics: Adrenal Cortex; Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Adult; Cosyntropin; Female; Humans; Hypertrichosis; Prolactin; Testosterone

Topics: Adrenal Cortex Function Tests; Adrenal Insufficiency; Cosyntropin; Humans; Hyperaldosteronism; Hypertension; Membrane Potentials; Pituitary-Adrenal Function Tests; Potassium; Spironolactone

Topics: Adrenocorticotropic Hormone; Animals; Cosyntropin; Glucagon; Lipids; Liver; Male; Pyruvate Kinase; Rats; Zinc

The responses of serum concentrations of TSH, thyroxine (T4), triiodothyronine (T3) and of reverse triiodothyronine (rT3) to i. v. administration of 0.4 mg THR were examined prior to (and after) i. m. administration of ACTH (2 mg Synacthen Depot) in 7 euthyroid women using estrogen-containing oral contraceptives and in 8 controls, with the following results: (1) an increase in endogenous glucocorticoid secretion is associated with a depression of the TSH response to TRH; (2) TSH formed in decreased amounts is still capable of stimulating thyroid secretion; (3) the increased serum corticoid levels fail to affect the secretory response of the thyroid to TSH; (4) control of the pituitary-thyroid axis remains normal in the presence of increased serum thyroxine-binding globulin (TBG) levels. In a further series the serum levels of TBG, T4, T3, rT3 and cortisol under the effect of ACTH-induced endogenous glucocorticoid hypersecretion were studied in 6 normal untreated controls, in 6 normal women using oral contraceptives and in 10 untreated hyperthyroid patients. During four days subsequent to treatment the serum TBG levels decreased, maximum decrease being found in the users of oral contraceptives, minimum decrease in the controls. Serum T4 was found to decrease during 2 to 4 days, serum T3 parallel with an increase in serum rT3, for 1 to 2 days, subsequent for ACTH loading. In the euthyroid cases also the serum TSH levels showed a transitory decline. It is concluded that in case of endogenous hyperproduction of glucocorticoids (1) T4 leads to T3 monodeiodination decreases and T4 leads to rT3 conversion increases parallel with the changes in the serum cortisol levels; (2) TBG synthesis is inhibited by endogenous glucocorticoids; (3) the changes in serum TBG levels are accompanied by a decrease in the serum T4 concentrations.

Topics: Adrenocorticotropic Hormone; Adult; Cosyntropin; Female; Humans; Hydrocortisone; Hyperthyroidism; Thyroid Hormones; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Thyroxine-Binding Proteins; Triiodothyronine; Triiodothyronine, Reverse; Zinc

The response of plasma testosterone (T), delta 4-androstenedione, and cortisol (F) to the administration of synthetic Zn beta 1-24 ACTH (0.5 mg/m2 im every 12 h for 3 days) was ascertained in 20 infants, 35 prepubertal children, 4 early pubertal boys, and 15 adults. At all ages and in both sexes, a significant rise in delta 4-androstenedione and F was observed (P less than 0.00001), whereas the response of T showed a sex difference: T levels increased in females (P less than 0.001) at all ages in response to ACTH, while they decreased (P less than 0.01) in males at periods of active testicular secretion (early infancy, puberty, and adulthood). In prepubertal boys, in the absence of significant Leydig cell activity, T levels increased after ACTH, as they did in girls. The post-ACTH values of T, expressed as percent-ages of the control levels, were significantly lower (P less than 0.01) in infants (3.17 +/- 16.7%) than in pubertal boys (59.5 +/- 14.6%) or adult men (57.9 +/- 7.7%). F levels were significantly higher after ACTH stimulation at 1-4 months of age (253 +/- 129 micrograms/dl) than at any later age studied (64 +/- 17 micrograms/dl). It would seem, therefore, that the suppressive effect of ACTh on testicular secretion might be glucocorticoid mediated and its magnitude might be related to circulating levels of F.

Topics: Adolescent; Adrenocorticotropic Hormone; Adult; Aging; Androstenedione; Child; Child, Preschool; Cosyntropin; Female; Humans; Hydrocortisone; Infant; Infant, Newborn; Male; Sex Factors; Testosterone

Topics: 17-Hydroxycorticosteroids; 17-Ketosteroids; Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Cosyntropin; Humans; Zinc

Topics: 17-Hydroxycorticosteroids; 17-Ketosteroids; Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Anorexia Nervosa; Cosyntropin; Endocrinology; Mineralocorticoid Receptor Antagonists; Pigmentation Disorders; Zinc

Topics: Adrenal Cortex Function Tests; Adrenocorticotropic Hormone; Cosyntropin; Physical Therapy Modalities; Zinc

Topics: Adrenal Cortex; Adrenocorticotropic Hormone; Cosyntropin; Humans; Zinc

The response of plasma 17-hydroxycorticoids to corticotrophin has been determined using a simplified technique. Steroid levels appeared to be maximal four hours after the injection of 40 units of corticotrophin zinc. No response was obtained in cases of Addison's disease and a sluggish increase occurred in hypopituitarism. The effect of steroid therapy is discussed.

Topics: Adrenal Cortex; Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Cosyntropin; Humans; Plasma; Zinc

Topics: 17-Hydroxycorticosteroids; Adrenal Cortex; Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Cosyntropin; Humans; Injections, Intramuscular

Topics: Adrenal Cortex Hormones; Adrenalectomy; Adrenocorticotropic Hormone; Animals; Animals, Laboratory; Cosyntropin; Injections; Steroids; Zinc

Topics: 17-Hydroxycorticosteroids; 17-Ketosteroids; Adrenocorticotropic Hormone; Cosyntropin; Humans; Injections, Intramuscular; Zinc

Topics: Adrenal Cortex; Adrenal Cortex Function Tests; Adrenocorticotropic Hormone; Cosyntropin; Zinc

Topics: Adrenocorticotropic Hormone; Adsorption; Cosyntropin; Delayed-Action Preparations; Humans; Zinc

Topics: Adrenocorticotropic Hormone; Cosyntropin; Zinc

Topics: Adrenocorticotropic Hormone; Cosyntropin; Humans; Hydroxides; Phosphates; Zinc; Zinc Compounds

Topics: Adrenocorticotropic Hormone; Cosyntropin; Humans; Phosphates; Zinc Compounds

Topics: Adrenocorticotropic Hormone; Cosyntropin; Humans; Phosphates; Zinc; Zinc Compounds

Topics: Adrenocorticotropic Hormone; Cosyntropin; Humans; Phosphates; Zinc; Zinc Compounds

Topics: Adrenocorticotropic Hormone; Cosyntropin; Humans; Zinc

Topics: Adrenocorticotropic Hormone; Cosyntropin; Humans; Zinc