Doses Of Adrenocorticotropic Hormone Research Articles

Adrenocorticotropic hormone elicits gonadotropin secretion in premenopausal women.

Does adrenocorticotropic hormone (ACTH) induce gonadotropin release in premenopausal women? Administration of ACTH stimulates gonadotropin release, most likely by stimulation of the production of cortisol, in premenopausal women. In animal models, acute activation of the hypothalamic-pituitary-adrenal (HPA) axis has been shown to induce gonadotropin release in the presence of sufficiently high estrogen levels. However, it is unknown whether the HPA axis has a similar influence on gonadotropin release in humans. This study had a mixed factorial design. A total of 60 healthy female participants participated in the experimental study. The study sample comprised three distinct hormonal-based populations according to their levels of progesterone (PROG) and estradiol (E2): (i) low-PROG-low-E2, (ii) low-PROG-high-E2 and (iii) high-PROG-high-E2 women. A low dose (1 µg) of ACTH was administered to all study participants. Serum steroid and gonadotropin concentrations were measured prior to, and at 30 and 90 minutes after, intravenous ACTH administration. Mean serum cortisol levels increased significantly following ACTH administration in all groups (P<0.001). Similarly, the serum levels of 17-OH-PROG, androstenedione, dehydroepiandrosterone and testosterone increased significantly in all groups (P<0.01). The low-PROG-high-E2 and high-PROG-high-E2 groups exhibited a significant increase in LH and FSH levels (P<0.001), whereas the low-PROG-low-E2 group demonstrated blunted LH and FSH responses to ACTH administration (P<0.05). Testing was performed during the luteal phase of the natural menstrual cycle. Testing during the follicular phase might have elicited premature, or more pronounced, LH surges in response to ACTH administration. Our findings suggest a novel mechanism by which the adrenal cortex functions as a mediator of gonadotropin release. These findings contribute to a greater understanding of the influence of acute stress on reproductive endocrinology. Funding was received from the Erasmus University Medical Center. The authors have no conflicts of interest. EudraCT Number 2012-005640-14.

Dysregulation of Hypothalamo-Pituitary-Adrenocortical Axis in Overweight Female Diabetic Subjects is Associated with Downregulation of Corticosteroid Receptors and 11β-HSD1 in the Brain.

The objective of this work was to assess hypothalamo-pituitary-adrenocortical (HPA) axis dysregulation in overweight diabetic women and investigate the possible mechanism using overweight diabetic rats. Twenty-two overweight diabetic women were recruited alongside 34 lean and 23 overweight healthy women serving as controls. Dexamethasone suppression test (0.25 mg DST) and low dose adrenocorticotropic hormone (ACTH) stimulation assay were used to evaluate the HPA axis activity. Then, high fat diet (HF) and STZ-induced diabetic rats were utilized to investigate the possible mechanism. After measurement of corticosterone circadian patterns and dexamethasone suppression levels, mRNA amounts of mineralocorticoid receptors (MR), glucocorticoid receptors (GR), and 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) were determined by real time PCR at hippocampus, hypothalamus, and pituitary levels. Overweight diabetic women showed impaired HPA axis with negative feedback efficacy (suppression ratio F-DEX%: 0.52±0.06% vs. 0.49±0.06% vs. 0.14±0.08%), as well as increased adrenal cortisol secretion response to low dose ACTH stimulation. Interestingly, F-DEX% was negatively correlated with BMI (r=- 0.323, p=0.003), waist circumference (r=- 0.319, p=0.004), and HbA1c (r=- 0.334, p=0.002). Stepwise linear regression analysis showed F-DEX% was significantly related to HbA1c level (β=- 0.328, p=0.007) after adjusting for other covariates (age, BMI, waist circumference, SBP, TC, TG, and HOMA-IR). Furthermore, 11β-HSD1, MR, and GR mRNA expression levels were reduced at pituitary level while GR expression was downregulated at hippocampus level in HF and HF+STZ rats. In conclusion, hyperactive HPA axis in overweight diabetic subjects may be associated with downregulation of 11β-HSD1, MR, and GR in the brain.

The utility of the corticotropin test to diagnose adrenal insufficiency in critical illness: an update.

One of the most common dynamic testing procedures for assessment of adrenocortical function is the standard corticotropin or the cosyntropin test. The aim of this review was to examine the evidence base underlying the corticotropin test in the management of the critically ill patient. The principle behind the corticotropin test is the demonstration of an inappropriately low cortisol production in response to exogenous ACTH, a situation analogous to physiological stress. The corticotropin test was originally described in nonstressed subjects, and its applicability and interpretation in the setting of critical illness continues to generate controversy. Attempting to determine the prevalence of an abnormal corticotropin test in critical illness is complicated by the use of different end-points and different populations. Moreover, the test result is also influenced by the assay used for measurement of plasma cortisol. Trials assessing the relationship between corticotropin response and severity of stress and organ dysfunction have produced divergent results, which may reflect differences in the methodology and the association being measured. Moreover, controversy exists with respect to the methodology and the interpretation with respect to the following variables: dose of corticotropin, end-points for assessment of total or free cortisol, effect of plasma cortisol variability, adrenal blood flow and its equivalence with other tests of adrenocortical function. The corticotropin test is used widely in the evaluation of adrenocortical function in the endocrine clinics. Its role in the critically ill patient is less well established. Several confounding variables exist and to have a 'one-size-fits-all' approach with a single end-point in the face of several methodological and pathophysiological confounders may be flawed and may result in the institution of inappropriate therapy. The current evidence does not support the use of the corticotrophin test in critical illness to assess adrenocortical function and guiding steroid therapy in critical illness.

Efficacy assessment and follow-up study with different small doses of adrenocorticotropic hormone in treating infantile spasms

Objective To investigate the efficacy and optimal dose of adrenocorticotropic hormone(ACTH) in treatment of infantile spasms(IS). Methods Sixty patients with IS were randomly divided into group A (ACTH 20 IU/d, n=20), group B (ACTH 40 IU/d, n=20) and group C (Depakine syrup, n=20) in a prospective randomized study.Patients in group A and group B were given ACTH in the dose of 20 IU/d and 40 IU/d for 2 weeks, respectively.After 2 weeks of treatment, ACTH administration was replaced by oral prednisone if the seizure frequency decreased by 50.0% or less.Patients showing incomplete control of epilepsy(seizure frequency reduction less than 50.0%) or fai-ling to respond to treatment were continuously treated with the original amount of ACTH for another 2 weeks, then ACTH was replaced by oral prednisone.Patients in group C were treated with the combination regimen of oral clonazepam and Depakine syrup routinely.All participants were followed up by 0.5-3.0 years.The differences in clinical efficacy, changes in electroen cephalogram(EEG) and adverse reactions in 3 groups were compared and analyzed. Results After 4 weeks of treatment, the total effective rates(TER) and EEG remission rate (ERR) in group A [TER: 75.0%(15/20 cases), ERR: 40.0%(8/20 cases)] and group B [TER: 70.0%(14/20 cases), ARE: 45.0%(9/20 cases)] were significantly higher than those in group C[TER: 30.0%(6/20 cases), ERR: 10.0%(2/20 cases)](χ2=10.011, 6.624, all P 0.05). During follow-up study, the TER and ERR in group A [TER: 30.0%(16/20 cases), ERR: 35.3%(6/17 cases)] and group B [TER: 30.0%(6/20 cases), ARE: 37.5%(6/16 cases)] were also significantly higher than those in group C [TER: 5.0%(1/20 cases), ARE: 5.9%(1/17 cases)] (χ2=4.329, 6.455, all P<0.05), respectively.The incidence of adverse reactions in group A was lower than that in group B (χ2=3.956, P<0.05). Conclusions ACTH proves to be an effective drug for the treatment of IS.Administration of ACTH in the dose of 20 IU/d for 2 weeks seems to be an optimal treatment recipe with remarkable efficacy with fewer adverse effects and may be worthy of clinical trials in a larger cohort. Key words: Adrenocorticotropic hormone; Infantile spasms; Follow-up study

Adrenocorticotropic Insufficiency: Important Differential Diagnosis in Neuropsychiatric Diseases

The adrenal stress response is a neuroendocrine regulation system of essential importance. Current clinical symptoms of its impaired function are exercise intolerance, vertigo, syncope, confused consciousness, fatigue, mood depression, and hence neuropediatric presentations. Because of this unspecific presentation, patients are often suspected to have a psychiatric or dissociative disease. Patients: We report approximately 15 patients aged 5 to 17 years presenting with earlier mentioned symptoms, some of them with years of prehistory before approaching neuropediatric diagnostic work-up. Besides this, all of them received a stepwise testing of the adrenocorticotropic axis using a low dose adrenocorticotropic hormone—stimulation test und further stimulation tests if necessary. Results: Pf the 15 patients, 5 patients suffered from adrenal insufficiency, 3 with increased adrenal antibodies, 1 with X-ALD, and 1 unclear. The other 10 patients showed pituitary or hypothalamic malfunction, 7 unclear, 1 craniopharyngeoma, 1 prolactinoma, and 1 hypothalamic lipoma. One girl with autoimmune adrenal insufficiency also suffered from temporal lobe epilepsy. Of the 15 patients, 2 patients demonstrated with depressive symptoms. The two pituitary tumor patients also had additive hormonal impairments. Therapeutic substitution with hydrocortisone or dexamethasone led to clinical improvement in all patients. Discussion: Disturbed stress regulation often leads to unspecific symptoms overlapping the field of neuropediatric and psychogenic differential diagnosis. Basal diagnostic work-up using low dose ACTH testing regularly identifies patients with endocrine disease and should be part of the diagnostic protocol.

A Korean boy with atypical X-linked adrenoleukodystrophy confirmed by an unpublished mutation of ABCD1.

X-linked adrenoleukodystrophy (X-ALD) is a rare peroxisomal disorder, that is rapidly progressive, neurodegenerative, and recessive, and characteristically primary affects the central nervous system white matter and the adrenal cortex. X-ALD is diagnosed basaed on clinical, radiological, and serological parameters, including elevated plasma levels of very long chain fatty acids (VLCFA), such as C24:0 and C26:0, and high C24:0/C22:0 and C26:0/C22:0 ratios. These tests are complemented with genetic analyses. A 7.5-year-old boy was admitted to Department of Pediatrics, Chungnam National University Hospital with progressive weakness of the bilateral lower extremities. Brain magnetic resonance imaging confirmed clinically suspected ALD. A low dose adrenocorticotropic hormone stimulation test revealed parital adrenal insufficiency. His fasting plasma levels of VLCFA showed that his C24:0/C22:0 and C26:0/C22:0 ratios were significantly elevated to 1.609 (normal, 0-1.390) and 0.075 (normal, 0-0.023), respectively. Genomic DNA was extracted from peripheral whole blood samples collected from the patient and his family. All exons of ABCD1 gene were amplified by polymerase chain reaction (PCR) using specific primers. Amplified PCR products were sequenced using the same primer pairs according to the manufacturer's instructions. We identified a missense mutation (p.Arg163Leu) in the ABCD1 gene of the proband caused by the nucleotide change 488G>T in exon 1. His asymptomatic mother carried the same mutation. We have reported an unpublished mutation in the ABCD1 gene in a patient with X-ALD, who showed increased ratio of C24:0/C22:0 and C26:0/C22:0, despite a normal VLCFA concentrations.

Treatment of infantile spasms with very high dose prednisolone before high dose adrenocorticotropic hormone

This study investigated the short-term response to a standardized hormonal therapy protocol for treatment of infantile spasms. Twenty-seven children with video electroencephalography (EEG)-confirmed infantile spasms received very high dose (8 mg/kg/day, max 60 mg/day) oral prednisolone for 2 weeks. Response (absence of both hypsarrhythmia and spasms) to prednisolone was ascertained by repeat overnight video-EEG. Responders were tapered over 2 weeks and nonresponders were immediately transitioned to high dose (150 IU/m(2)/day) intramuscular adrenocorticotropic hormone (ACTH) for two additional weeks. Response was again determined by overnight video-EEG after ACTH therapy. Sixty-three percent (17/27) of patients responded completely to prednisolone. Subsequently, 40% (4/10) of prednisolone nonresponders exhibited a complete response after an additional 2-week course with ACTH. Among 27 subjects with median follow-up of 13.5 months (interquartile range [IQR] 4.8-25.9), 12% (2/17) of prednisolone responders and 50% (2/4) of ACTH responders experienced a relapse between 2 and 9 months after initial response. Very high dose prednisolone demonstrated significantly higher efficacy than previously reported for lower doses in prior studies. High dose ACTH may be superior to very high dose prednisolone, and in lieu of a definitive clinical trial, the choice between prednisolone and ACTH for initial treatment of infantile spasms remains controversial.

Prevalence of hypopituitarism after intracranial operations not directly associated with the pituitary gland

BackgroundOver the last few years, awareness and detection rates of hypopituitarism following traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH) has steadily increased. Moreover, recent studies have found that a clinically relevant number of patients develop pituitary insufficiency after intracranial operations and radiation treatment for non-pituitary tumors. But, in a substantial portion of more than 40%, the hypopituitarism already exists before surgery. We sought to determine the frequency, pattern, and severity of endocrine disturbances using basal and advanced dynamic pituitary testing following non-pituitary intracranial procedures.Methods51 patients (29 women, 22 men) with a mean age of 55 years (range of 20 to 75 years) underwent prospective evaluation of basal parameters and pituitary function testing (combined growth hormone releasing hormone (GHRH)/arginine test, insulin tolerance test (ITT), low dose adrenocorticotropic hormone (ACTH) test), performed 5 to 168 months (median 47.2 months) after intracranial operation (4 patients had additional radiation and 2 patients received additional radiation combined with chemotherapy).ResultsWe discovered an overall rate of hypopituitarism with distinct magnitude in 64.7% (solitary in 45.1%, multiple in 19.6%, complete in 0%). Adrenocorticotropic hormone insufficiency was found in 51.0% (partial in 41.2%, complete in 9.8%) and growth hormone deficiency (GHD) occurred in 31.4% (partial in 25.5%, severe in 5.9%). Thyrotropic hormone deficiency was not identified. The frequency of hypogonadism was 9.1% in men. Pituitary deficits were associated with operations both in close proximity to the sella turcica and more distant regions (p = 0.91). Age (p = 0.76) and gender (p = 0.24) did not significantly differ across patients with versus those without hormonal deficiencies. Groups did not significantly differ across pathology and operation type (p = 0.07).ConclusionHypopituitarism occurs more frequently than expected in patients who have undergone neurosurgical intracranial procedures for conditions other then pituitary tumors or may already exists in a neurosurgical population before surgery. Pituitary function testing and adequate substitution may be warranted for neurosurgical patients with intracranial pathologies at least if unexplained symptoms like fatigue, weakness, altered mental activity, and decreased exercise tolerance are present.

Treatment of Idiopathic FSGS with Adrenocorticotropic Hormone Gel

Adrenocorticotropic hormone (ACTH) has shown efficacy as primary and secondary therapy for nephrotic syndrome due to membranous nephropathy. The data on using ACTH to treat idiopathic FSGS are limited. This report describes our experience using ACTH for nephrotic syndrome due to idiopathic FSGS in the United States. Twenty-four patients with nephrotic syndrome from idiopathic FSGS were treated with ACTH gel at two academic medical centers between 2009 and 2012, either as part of investigator-initiated pilot studies (n=16) or by prescription for treatment-resistant FSGS (n=8). The primary outcome was remission of proteinuria. The median dose of ACTH was 80 units injected subcutaneously twice weekly. Treatment durations were not uniform. Twenty-two patients had received immunosuppression (mean, 2.2 medications) before ACTH therapy. Six patients had steroid-dependent and 15 had steroid-resistant FSGS. At the time of ACTH initiation, the median serum creatinine (interquartile range) was 2.0 (1.1-2.7) mg/dl, estimated GFR was 36 (28-78) ml/min per 1.73 m(2), and urine protein-to-creatinine ratio was 4595 (2200-8020) mg/g. At the end of ACTH therapy, 7 of 24 patients (29%) experienced remission (n=2 complete remissions, n=5 partial remissions). All remitters had steroid-resistant (n=5) or steroid-dependent (n=2) FSGS. Two responders relapsed during the follow-up period (mean ± SD, 70±31 weeks). Adverse events occurred in 21 of 24 patients, including one episode of new-onset diabetes that resolved after stopping ACTH and two episodes of AKI. Response to ACTH treatment among steroid-resistant or steroid-dependent patients with FSGS is low, but ACTH gel may be a viable treatment option for some patients with resistant nephrotic syndrome due to idiopathic FSGS. Further research is necessary to determine which patients will respond to therapy.

Plasma cortisol activity in rats under conditions of chronic stress supplemented with resveratrol

Objective: Determine the activity of cortisol in rats treated with exogenous adrenocorticotropic hormone (ACTH) and a resveratrol supplement.Methods: Forty-eight adult male rats and 16 adult female rats (Rattus norvegicus) three months old with a body weight of 200 to 250 g and 300 to 350 g for both male and female were used and kept in controlled environmental conditions, temperature of 20±2° C and light-dark cycles of 14 and 10 hours. They were fed with balanced food and had free access to water. The rats were randomly divided into four groups: group 1, was treated with 5 μg/kg of ACTH i.p. every twelve hours; group 2, received the same treatment with ACTH plus a grape extract supplementation of 40 mg/kg; group 3, only received grape extract and group 4,served as control and only received saline solution (0.9%) i.p. The experimental was designed as a 2×2 factorial with two ACTH levels and two extract grape levels.Results: Significant differences were not found in cortisol concentrations for day, gender or treatment effects (0.75 μg/dL ± 0.11; p &lt;0.001).Conclusion: Results suggest that chronic stress and consume of resveratrol did not produce any effect in the activity of plasmatic cortisol, in stressed and unstressed rats stressed. In the same way, possibly, dose of ACTH did not produce stimulation of the suprarenal gland for these animals.

Effects of adrenal dysfunction and high-dose adrenocorticotropic hormone on NMDA-induced spasm seizures in young Wistar rats

Infantile spasms (IS) is a devastating epilepsy syndrome treated with adrenocorticotropic hormone (ACTH). To demonstrate the effects of adrenal dysfunction, adrenalectomy (ADX) and N-methyl-d-aspartate (NMDA)-induced rat model studies of IS were performed. The latency of the seizure in the ADX group decreased and the severity of seizures increased significantly. Hippocampal corticotropin-releasing hormone (CRH) mRNA was overexpressed in ADX rats. After ACTH administration, the latency increased and the severity of seizures decreased significantly. ADX increased seizure susceptibility of the rats to NMDA. Pretreatment with a single high dose of ACTH caused an obvious reduction in susceptibility to NMDA-induced seizures and suppressed CRH mRNA expression. These findings are especially useful for IS patients with adrenal diseases and worthy of further clinical study.

Low dose adrenocorticotropic hormone test and adrenal insufficiency in critically ill acquired immunodeficiency syndrome patients

Context:Prevalence of adrenal insufficiency (AI) is not uncommon in HIV infected population. However, AI is rarely diagnosed in clinical practice because many patients have non-specific symptoms and signs. Critical illness in such patients further complicates the evaluation of adrenal function. A 1μgm ACTH test can be used for diagnosis, since it results in more physiological levels of ACTH. A serum cortisol of <18 μg/dL, 30 or 60-minutes after ACTH test has been accepted as indicative of AI, but many experts advocate the normal cortisol response should exceed 25 μg/dL, in critically ill patients.Aim:To determine the prevalence of AI in critically ill AIDS patients, by using 1 μg ACTH test and also, to compare the diagnostic criteria for adrenal insufficiency between cortisol response of <18 μg/dL and <25 μg/dL.Settings and Design:This prospective study was done in the Department of Medicine.Materials and Methods:After taking blood for basal plasma cortisol from AIDS affected fifty adult men and women aged over 18 yrs, 1 μg ACTH was given intravenously, and blood samples were again collected at 30 and 60 minutes for plasma cortisol estimation.Statistical analysis:It was done by Mann-Whitney test.Results:Prevalence of AI was 74% (37 patients) and 92% (46 patients), when the peak stimulated cortisol level of <18 μg/dL and <25 μg/dL, respectively, was used.Conclusion:AI is more prevalent in critically ill AIDS patients. Hence, this test can be performed for early intervention and better management.

Glucocorticosteroid concentrations in feces and hair of captive caribou and reindeer following adrenocorticotropic hormone challenge

Climate change and industrial development are contributing to synchronous declines in Rangifer populations across the Arctic. Chronic stress has been implicated as a proximate factor associated with decline in free-ranging populations, but its role in Rangifer is unspecified. Analysis of glucocorticosteroid (GC) concentration in feces, and more recently in hair, is a non-invasive method for monitoring stress in wildlife. Adrenocorticotropic hormone (ACTH) released from the pituitary gland stimulates GC release from the adrenals and can be administered to reflect adrenal activation. In this study, we assessed concentrations of GC metabolites in feces and cortisol in hair of Alaskan caribou (Rangifer tarandus granti) and reindeer (R. t. tarandus) following ACTH treatment. We predicted that ACTH challenge would increase concentrations of fecal GCs, but not hair cortisol because steroid deposited into the hair shaft occurs over an extended period of time (months) and is likely insensitive to acute adrenal stimulation. Adult caribou (n=10; mean age, 6.5 years old) exhibited a peak increase in fecal GCs 8h following a 2IU/kg dose of ACTH compared to pre-injection concentrations. In contrast, sub-adult reindeer (n=10, 0.8 years old) elicited a diminished response to the same dose. Quadrupling the dose (8IU/kg) prolonged the fecal GC response in female reindeer, but male reindeer were unresponsive. Hair cortisol was unaffected by a single ACTH challenge. Further investigation is required to ascertain whether subspecific differences in adrenal sensitivity are attributed to age or sex differences, or historical selective pressures from semi-domestication and/or sedentary life cycle in reindeer.

Recent approach of adrenal dysfunction in critical illness

There is high incidence of relative adrenal insufficiency (RAI) in critical children. The causes of adrenal insufficiency in patients with severe sepsis and septic shock are the mechanical injury of the hypothalamic-pituitary-adrenal axis, cytokines and other mediators of inflammatory or hormone resistance. There are many symptoms associated with adrenal insufficiency. Diagnosis is often suspected when these patients have hypotension refractory to fluid therapy and to vasoactive drugs. The corticotropin stimulation test is widely used as a method to identify adrenocortical hyporesponsiveness, but controversy exists as to the corticotropin dose to be used. The 250 μg dose is the standard dose. Low doses of corticotropin (1 μg) have recenfly been proposed,suggesting that they may have higher sensitivity and the characteristics of safe and effective. Key words: Adrenal insufficiency; ACTH stimulation test; Critical illness; Children

Effects of stimulated adrenocortical activity on the concentration of thyroxine and triiodothyronine in blood serum of piglets.

The effects of elevated adrenocortical activity, induced by cold exposure, weaning or starvation, or exogenous adrenocorticotrophin (ACTH) on the concentrations of thyroxine (T4) and triiodothyronine (T3) in blood serum were investigated in 99 sucking piglets and weaners, divided into five experiments. No changes in concentrations of circulating iodothyronines were recorded during a 3-hour exposure of 3- to 4-day-old piglets to ambient temperature of 8-12 degrees C. Two days after weaning of 4-week-old piglets the concentration of T4 increased. At the same time a decrease of the concentration of T3 was observed in their starving littermates. Two hours after the administration of ACTH, the concentration of both iodothyronines decreased, that of T4 nonsignificantly. 17 hours after the administration of the second of two doses of ACTH, i.e. at the time when the concentration of corticosteroids approached initial values, the blood concentration of iodothyronines both in sucking piglets and in weaners was elevated, that of T4 nonsignificantly. We suggest that for the changes of T4 and T3 concentrations in blood sera of stressed animals both specific stressor effects and circulating corticosteroids are responsible. The suppressive action of corticosteroids seems to be limited to the period of adrenocortical stimulation only.

Androgen Suppresses Corticotropin-Induced Increase in Plasma Cortisol Level but Enhances The Increase in Plasma Aldosterone Level in Goats

Previously we reported that androgen treatment reduced the extent of the increase in plasma cortisol (Cor) levels induced by adrenocorticotropic hormone (ACTH) administration in goats. In this study, we investigated the effect of androgen on the plasma levels of androstenedione and aldosterone. Four castrated male goats, which were treated with either 5alpha-dihydrotestosterone (DHT) or cholesterol (cho), were injected intravenously with 0.005, 0.02 or 0.1 mg of ACTH(1-24). Plasma Cor levels were increased significantly by all doses of ACTH injection, and these extents were lower in DHT-treated goats. Plasma androstenedione levels were also increased by ACTH injection, but DHT treatment seemed to little affect. Plasma aldosterone levels were also increased by ACTH injection, and there were no differences between cho- and DHT treated goats at 15 and 30 min after the ACTH injection. However, when goats were given the lower doses of ACTH (0.02 and 0.005 mg), plasma aldosterone levels were restored rapidly only in cho-treated goats, whereas those in DHT-treated goats were maintained throughout the 60 min experimental period. Consequently, plasma aldosterone levels in DHT-treated goats were higher than those in cho-treated goats at 45 and 60 min. One possible mechanism of the effect of DHT on the ACTH-induced increase in aldosterone synthesis may be the reduction of the activity of P450-17alpha, that is the enzyme to convert pregnenolone to 17alpha-OH-pregnenolone, and this mechanism may also be responsible to the suppressive effect of DHT on the ACTH-induced Cor synthesis.

Effects of continuous elevated cortisol concentrations during oestrus on concentrations and patterns of progesterone, oestradiol and LH in the sow

This study investigated the effect of continuous elevated cortisol concentrations during standing oestrus on time of ovulation and patterns of progesterone, oestradiol and luteinising hormone (LH) in sows. The elevation of cortisol concentrations was achieved through repeated intravenous injections of synthetic adrenocorticotropic hormone (ACTH) every 2 h for approximately 48 h, from the onset of the second standing oestrus after weaning. Treatment was terminated when ovulation was detected (monitored by transrectal ultrasonography every 4 h) or when the sow had received a maximum of 24 injections. The dose of ACTH (2.5 μg/kg) was chosen to mimic the cortisol concentrations seen during mixing of unfamiliar sows. The sows ( n = 14) were surgically fitted with jugular vein catheters and randomly divided into a control (C group where only NaCl solution were injected) or an ACTH group. Blood samples were collected every 2 h. In parallel with the blood sampling, saliva samples for cortisol analyses were taken from eight sows before onset of treatment and from four of the sows during treatment. There was no difference in time from onset of standing oestrus to ovulation between the two groups. The interval between the peaks of oestradiol and LH to ovulation was prolonged in the ACTH group compared to the C group ( p < 0.05), with a tendency towards an earlier decline of oestradiol in the ACTH group. Cortisol and progesterone concentrations were significantly elevated during treatment in the ACTH group ( p < 0.001), with cortisol peak concentrations occurring between 40 and 80 min after each ACTH injection. Cortisol concentrations in saliva and plasma were highly correlated ( p < 0.001). In conclusion, elevated cortisol concentrations from the onset of standing oestrus increase progesterone concentrations and prolong the interval between oestradiol and LH peaks to ovulation, the latter possible due to an early decline in oestradiol concentrations and a change of the LH peak outline. The effect these hormonal changes have on reproductive performance need to be further investigated. Saliva samples might be a useful and non-invasive method to assess cortisol concentrations in sows.

Função adrenal na sepse e choque séptico

OBJECTIVE:To review diagnostic criteria and treatment of adrenal insufficiency in pediatric patients with severe sepsis and septic shock. SOURCES: Articles were selected using MEDLINE (1966-June 2007), Embase (1994-2007) and Cochrane Library (2000-2007) databases. following key words were utilized: septic shock, sepsis, corticosteroids, adrenal insufficiency and children. SUMMARY OF THE FINDINGS: There are no well established and accepted criteria to define adrenal insufficiency in critically ill patients. Incidence of adrenal insufficiency varies according to different criteria, and it may range between low values of 15% and high values of 61%. The rapid corticotropin stimulation test is widely used as a method to identify adrenocortical hyporesponsiveness, but controversy exists as to the corticotropin dose to be used. The 250 µg dose is the standard dose. Low doses of corticotropin (1 µg) have recently been proposed, suggesting that they may have higher sensitivity. There are still doubts as to the efficacy of low doses of corticosteroids in children with catecholamine-refractory shock. Further studies are needed to determine whether the treatment of these patients would change morbidity and/or mortality. CONCLUSION: Adrenal insufficiency is common in children with severe sepsis and septic shock and may contribute to the development of catecholamine-refractory shock. However, doubts still persist regarding the efficacy of replacement therapy with low-doses steroids.

Adrenal function in sepsis and septic shock

To review diagnostic criteria and treatment of adrenal insufficiency in pediatric patients with severe sepsis and septic shock. Articles were selected using MEDLINE (1966-June 2007), Embase (1994-2007) and Cochrane Library (2000-2007) databases. following key words were utilized: septic shock, sepsis, corticosteroids, adrenal insufficiency and children. There are no well established and accepted criteria to define adrenal insufficiency in critically ill patients. Incidence of adrenal insufficiency varies according to different criteria, and it may range between low values of 15% and high values of 61%. The rapid corticotropin stimulation test is widely used as a method to identify adrenocortical hyporesponsiveness, but controversy exists as to the corticotropin dose to be used. The 250 microg dose is the standard dose. Low doses of corticotropin (1microg) have recently been proposed, suggesting that they may have higher sensitivity. There are still doubts as to the efficacy of low doses of corticosteroids in children with catecholamine-refractory shock. Further studies are needed to determine whether the treatment of these patients would change morbidity and/or mortality. Adrenal insufficiency is common in children with severe sepsis and septic shock and may contribute to the development of catecholamine-refractory shock. However, doubts still persist regarding the efficacy of replacement therapy with low-doses steroids.

A Low Dose Adrenocorticotropin Test (1 μg ACTH) for the Evaluation of Adrenal Function in Children with ß-Thalassemia Receiving Hypertransfusion with Suboptimal Iron-chelating Therapy

A cross-sectional study of adrenal function was carried out in 48 patients with beta-thalassemia who were receiving hypertransfusion with suboptimal desferoxamine. A low dose adrenocorticotropic hormone (1 microg ACTH) stimulation test was performed using the cut-off criteria of peak cortisol for adrenal sufficiency >18 microg/dl. Adrenal impairment was diagnosed in 22 patients, giving a prevalence of 45.8%. The peak cortisol concentrations in normal and impaired adrenal function groups were 26.22 +/- 2.84 and 14.03 +/- 3.12 microg/dl, respectively, and the mean basal morning cortisol was 8.93 +/- 2.97 and 6.52 +/- 2.45 microg/dl, respectively. There was no significant difference in any clinical characteristic between the patients with impaired adrenal function and those with normal adrenal function.