Abnormal Adrenocorticotropic Hormone Research Articles

Comparison of two strategies of glucocorticoid withdrawal in patients with rheumatoid arthritis in low disease activity (STAR): a randomised, placebo- controlled, double-blind trial.

To compare two strategies-a hydrocortisone replacement strategy and a prednisone tapering strategy-for their success in glucocorticoid discontinuation in patients with rheumatoid arthritis (RA) with low disease activity (LDA). The Strategies for glucocorticoid TApering in Rheumatoid arthritis (STAR) study was a double- blind, double-placebo randomised controlled trial including patients with RA receiving a stable dose of glucocorticoid 5 mg/day for ≥3 months and were in LDA for ≥3 months. Patients were randomly assigned in a 1:1 ratio to either replace prednisone with 20 mg/day of hydrocortisone for 3 months, then reduce to 10 mg/day for 3 months before discontinuation or to taper prednisone by 1 mg/day every month until complete discontinuation, contingent on maintaining LDA. The primary outcome was the percentage of patients achieving glucocorticoid discontinuation at 12 months. Other secondary outcomes were proportion of flares, need for additional glucocorticoid use, disease activity, patient-reported outcomes and the results of adrenocorticotropic hormone (ACTH) stimulation tests. Of the 102 patients randomised in the trial (mean age 62.4 years, 70.6% females), 53 had hydrocortisone replacement and 49 tapered prednisone. At 12 months, 29 patients (55%) in the hydrocortisone replacement group and 23 patients (47%) in the prednisone tapering group achieved glucocorticoid discontinuation (p=0.4). No difference was observed between groups in the secondary outcomes. No cases of acute adrenal insufficiency were observed; however, 17 patients still had an abnormal ACTH stimulation test at 12 months, with no differences between arms. A hydrocortisone replacement strategy was not superior to a prednisone tapering strategy for achieving glucocorticoid discontinuation success in patients with RA in LDA. NCT02997605.

The antianxiety effects of koumine and gelsemine, two main active components in the traditional Chinese herbal medicine Gelsemium: A comprehensive review

AbstractThe genus Gelsemium belongs to the family Loganiaceae, one of the traditional Chinese herbs. Gelsemium is traditionally used to treat rheumatoid and neuropathic pain. Its root extracts were found to protect against anxiety, especially the alkaloids koumine and gelsemine. Indeed, koumine and gelsemine can act as positive agonists of the glycine receptor (GlyR), which reduces neuronal excitability through chloride influx and can also increase neuroactive steroid content by enhancing 3alpha‐hydroxysteroid oxidoreductase (3α‐HSOR) expression. The latter can activate the excitation‐inhibitory response via the γ‐aminobutyric acid type A receptor (GABAAR), reduce the abnormal corticotropin‐releasing hormone (CRH) increase in the hypothalamus, inhibit adrenocorticotropic hormone (ACTH) secretion, and effectively inhibit the abnormal ACTH and corticosterone increases in the circulation. In addition, koumine and gelsemine inhibited the expression of the NLR family pyrin domain containing 3 (NLRP3) inflammasome, inhibiting the release of inflammatory factors and regulating anxiety‐related neural circuits. Gelsemine also inhibited the overexpression of brain‐derived neurotrophic factor (BDNF) and cAMP response element‐binding protein (CREB) in the hypothalamus to maintain the plasticity of brain neurons and protect neurogenesis to achieve anxiety regulation. In general, this article reviews the recent studies on Gelsemium in the anxiety field, discusses its possible antianxiety mechanism, and confirms the potential of Gelsemium as a therapeutic drug for anxiety‐related diseases.

Endocrine characteristics and risk factors of type 2 diabetes complicated with gastrointestinal autonomic neuropathy: A single-center retrospective study.

To analyze endocrine characteristics and risk factors of type 2 diabetes mellitus (T2DM) gastrointestinal autonomic neuropathy. A total of 202 patients with T2DM with obesity who were hospitalized at our institute between January 2019 and June 2021 were selected. Based on adrenocorticotropic hormone (ACTH) levels, 102 patients were placed in the ACTH abnormal group and 100 patients were placed in the non-ACTH abnormal group. Ninety-five healthy adults without diabetes, hyperlipidemia, osteoporosis, or endocrine system abnormalities who were examined at our hospital during the same period were selected as the control group. Fasting plasma glucose (FPG), fasting insulin (FINS), triglycerides (TG), total cholesterol (TC), homeostasis model assessment of insulin resistance (HOMA-IR), ACTH level, body mass index (BMI), and bone mineral density (BMD) were measured to evaluate endocrine characteristics and risk factors. BMI, FPG, FINS, HOMA-IR, TG, TC, and ACTH levels in the abnormal ACTH group were significantly higher than those in the other 2 groups, while BMD was significantly lower than that in the other 2 groups (all P < .05). BMI, FPG, FINS, HOMA-IR, TG, TC, and ACTH in the non-ACTH abnormal group were significantly higher than those in the control group, whereas BMD was significantly lower than that in the control group (all P < .05). The plasma ACTH level in patients with abnormal ACTH levels was significantly positively correlated with BMI, FPG, FINS, HOMA-IR, TG, and TC and negatively correlated with BMD (all P < .05). Multivariate regression analysis showed that BMI, advanced age, FINS, TG, and FPG were risk factors for ACTH abnormalities in patients with diabetes (odds ratio > 1, all P < .05). BMI, advanced age, FINS, TG and FPG are the risk factors of abnormal ACTH in T2DM patients with gastrointestinal autonomic neuropathy.

Anterior pituitary hormones in first-episode psychosis: a systematic review and meta-analysis

IntroductionAlthough the role of pituitary gland in schizophrenia and psychotic disorders has been studied for decades, evidence on anterior pituitary hormones in the early phases of psychoses – without the influence of chronicity, comorbidities, and pharmacological treatment – is mostly unclear and inconsistent.ObjectivesOur systematic review and meta-analysis was aimed at comparing the blood concentrations of adrenocorticotropic hormone (ACTH), follicle stimulating and luteinizing hormones (FSH and LH), growth hormone (GH), prolactin (PRL), and thyroid-stimulating hormone (TSH) between people with drug-naïve first-episode psychosis (FEP) and healthy controls.MethodsWe searched main electronic databases for articles indexed up to September 2022. We appraised the quality of data. We carried out random-effects meta-analyses, generating pooled standardized mean differences (SMDs) and estimating between-study heterogeneity. Moreover, we performed sensitivity and meta-regression analyses.ResultsTwenty-six studies were included. People with drug-naïve FEP had higher ACTH (p&lt;0.001; moderate-to-high heterogeneity) and PRL (p&lt;0.001; high heterogeneity) concentrations, as well as lower TSH concentrations (p=0.001; low heterogeneity), than healthy subjects. Sensitivity analyses confirmed these findings. Data were not sufficient to perform meta-analyses on other hormones (FSH, LH, and GH).ConclusionsPeople with drug-naïve FEP have abnormal ACTH, PRL, and TSH blood concentrations, supporting the hypothesis that anterior pituitary hormone secretion is altered in the first stages of schizophrenia and psychoses. Additional research is needed to clarify the complex interconnections between vulnerability, environmental factors, and pituitary hormones in FEP.Disclosure of InterestNone Declared

S382 Long-Term Safety of Budesonide Oral Suspension for Eosinophilic Esophagitis: An Integrated Safety Analysis of Phase 1–3 Clinical Trial Data

Introduction: Budesonide oral suspension (BOS) is an immediate-release swallowed topical corticosteroid developed for eosinophilic esophagitis (EoE). We present an integrated safety analysis of all clinical trials of BOS to provide the largest set of safety data on a topical corticosteroid for EoE to date. Methods: Data were pooled from 6 trials (phase 1, SHP621-101; phase 2, MPI 101-01, MPI 101-06; phase 3, SHP621-301, SHP621-302 and SHP621-303) for all participants who received ≥1 dose of BOS (any trial) or induction placebo (MPI 101-01/MPI 101-06/SHP621-301). For the ongoing open-label study SHP621-303, data were collected until August 14, 2020 (interim data cut-off). Treatment groups were BOS 2.0 mg b.i.d., BOS any dose (including BOS 2.0 mg b.i.d.) and placebo. Adverse events (AEs), clinical laboratory testing, vital-sign monitoring and physical examinations were assessed (all trials). Dual-energy X-ray absorptiometry (DXA) (participants 11–17 years old) and adrenocorticotropic hormone (ACTH) stimulation tests (all participants) were performed in the phase 3 studies. Exposure-adjusted incidence rates were calculated for AEs and AEs of special interest (AESIs); AESIs were categorized as infections, systemic effects of corticosteroids, or gastrointestinal effects. Results: Overall, 514 unique participants were included (BOS 2.0 mg b.i.d., n=292; BOS any dose, n=448; placebo, n=168). The BOS 2.0 mg b.i.d., BOS any dose and placebo groups totaled 87.2, 116.0 and 25.0 patient-years of exposure, respectively. BOS was well tolerated; most treatment-emergent AEs (TEAEs) were mild/moderate in severity (Table 1). The most common exposure-TEAEs (≥5% participants) and AESIs were upper respiratory tract infection, nasopharyngitis and sinusitis; TEAEs, AESIs and AEs leading to study or study drug discontinuation were more common in BOS- than placebo-treated participants (Table 1). AESIs of abnormal ACTH stimulation test and decreased blood cortisol were more frequent in the BOS 2.0 mg b.i.d. and BOS any dose groups (Table 1); most were mild/moderate and without other signs of adrenal insufficiency. DXA scans demonstrated no effect on growth (n=26); the intra-age distribution of TEAEs was similar for the BOS 2.0 mg b.i.d. and BOS any dose groups for participants 11–17 and ≥18 years old (data not shown). One death occurred (unrelated to BOS 2.0 mg b.i.d.). Conclusion: BOS was well tolerated, including at the highest dose (2.0 mg b.i.d.) and for maintenance therapy. Most TEAEs were mild/moderate in severity.Table 1.: Summary Of TEAEs, Exposure-Adjusted TEAEs Per 100 Patient-Years Experienced By ≥5% Of Participants In Any Treatment Group And Exposure-Adjusted AESIs Per 100-Patient Years,* By Preferred Term†.

Efficacy and Safety of Novel Formulation of Clobetasol Propionate 0.025% Cream in Indian Moderate-to-Severe Psoriasis Patients: Phase-2a, Randomized 3-Arm Study.

IntroductionClobetasol propionate (0.05% standard dose formulation), a topical corticosteroid, leads to systemic side-effects like hypothalamic–pituitary–adrenal (HPA) axis suppression at doses as low as 2 g/day. The aim of this study was to evaluate HPA axis suppression, efficacy, and safety of clobetasol propionate (0.025%, formulation 5 and 13) versus currently marketed 0.05% cream in Indian patients with moderate-to-severe psoriasis.MethodsIn this phase 2a investigator-blinded study, patients aged ≥ 18 years with moderate-to-severe psoriasis were randomized 1:1:1 to receive clobetasol propionate 0.025% formulation 5, or 13, or 0.05% cream; twice daily for 28 days. Safety endpoints included adrenocorticotropic hormone (ACTH) test results at day 28 (primary), and local tolerability at each visit (burning/stinging/pruritus, secondary). Efficacy endpoints included Psoriasis Global Assessment (PGA) score.ResultsOverall, 88 patients received clobetasol propionate 0.025% formulation 5 and 13 (n = 29 for both) and 0.05% cream (n = 30). At day 28, the proportion of patients with an abnormal ACTH stimulation test (cortisol levels ≤ 18 µg/dl) was numerically lower in 0.025% formulations: 5 (20.7%) and 13 (17.2%) compared with 0.05% cream (30.0%), (p = 0.320). Decrease in burning/stinging /pruritus scores were comparable in all treatment groups and PGA success rates were higher with 0.025% formulations: 5 (38.9%) and 13 (36.8%) compared with 0.05% cream (30.8%).ConclusionClobetasol propionate 0.025% could be an effective treatment for moderate-to-severe psoriasis compared with 0.05% cream, demonstrating comparable efficacy with a better systemic safety profile.Trial Registration NumberREF/2018/01/016779.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13555-021-00591-z.

Budesonide for the Induction and Maintenance of Remission in Crohn's Disease: Systematic Review and Meta-Analysis for the Cochrane Collaboration.

BackgroundBudesonide is an oral glucocorticoid designed for the treatment of inflammatory bowel disease (IBD) that may reduce systemic adverse events (AEs). This review examined the efficacy and safety of budesonide for the induction and maintenance of clinical remission in Crohn’s disease (CD).MethodsMEDLINE, EMBASE, other electronic databases, reference lists and conference proceedings were searched to November 2017 to identify randomized controlled trials of budesonide. Outcomes were the induction and maintenance of remission at eight weeks and one year, respectively, as well as corticosteroid-related AEs and abnormal adrenocorticotropic hormone (ACTH) tests. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were estimated using random effects models.ResultsThirteen induction and 10 maintenance trials were included. Budesonide 9 mg/day was more effective than placebo (RR 1.93; 95% CI, 1.37–2.73; GRADE: moderate) but less effective than conventional steroids (RR 0.85; 95% CI, 0.75–0.97; GRADE: moderate) to induce remission. Corticosteroid-related AEs occurred less often with induction doses of budesonide than steroids (RR 0.64; 95% CI, 0.54–0.76; GRADE: moderate); budesonide did not increase AEs relative to placebo (RR 0.97; 95% CI, 0.76–1.23; GRADE: moderate). Budesonide 6 mg/day was not different from placebo for maintaining remission (RR 1.13; 95% CI, 0.94–1.35; GRADE: moderate). Both induction (GRADE: low for 3 mg/day, moderate for 9 mg/day) and maintenance budesonide treatment (GRADE: very low for 3 mg/day, low for 6 mg/day) increased the risk of an abnormal ACTH test compared with placebo, but less than conventional steroids (GRADE: very low for both induction and maintenance).ConclusionFor induction of clinical remission, budesonide was more effective than placebo, but less effective than conventional steroids. Budesonide was not effective for the maintenance of remission. Budesonide was safer than conventional steroids, but the long-term effects on the adrenal axis and bone health remain unknown.

A Novel Aerosol Foam Formulation of Calcipotriol and Betamethasone Has No Impact on HPA Axis and Calcium Homeostasis in Patients With Extensive Psoriasis Vulgaris.

Background:Fixed combination calcipotriol 50 µg/g (Cal; as hydrate) plus betamethasone 0.5 mg/g (as dipropionate; BD) has been formulated in an innovative aerosol foam.Objective:To assess systemic safety of Cal/BD aerosol foam.Methods:In a multicentre, single-arm, open-label, maximal-use systemic-exposure trial, adult patients with moderate to severe, extensive psoriasis (15%-30% of body surface area, including ≥30% of scalp) applied Cal/BD foam once daily. Endpoints were week 4 abnormal adrenocorticotropic hormone (ACTH) challenge test and change in albumin-corrected serum calcium, 24-hour urinary calcium excretion, and urinary calcium-creatinine ratio.Results:35 patients reaching week 4 exhibited normal ACTH responses. At week 4, changes in calcium homeostasis were minor and not clinically relevant; no patients experienced elevations above normal. Disease severity generally improved, and 49% of patients achieved treatment success according to the Physician’s Global Assessment of Disease Severity.Conclusion:No clinically relevant HPA axis or calcium homeostasis impact was observed with 4 weeks of once-daily Cal/BD foam in patients with extensive psoriasis vulgaris.

Type II muscle fibers atrophy associated with silent corticotroph adenoma in a dog.

The Silent Corticotroph Adenoma (SCA) is a pituitary adenoma variant characterized by the immunoreactivity for adrenocorticotropic hormone (ACTH) and related peptides, without the clinical signs of Cushing's disease. SCA has been postulated to either secrete structurally abnormal ACTH that is inactive but detectable by immunohistochemistry or radioimmunoassay, or to secrete ACTH intermittently or at low levels continuously. Excess of ACTH has been associated to type II muscle atrophy. We describe a case of type II muscle fibers atrophy associated with silent corticotroph adenoma in a dog. The dog showed moderate to severe proximal muscle wasting and weakness with normal levels of muscle-associated enzymes. In the limb muscle biopsies, type II fibers were uniformly smaller than type I fibers. In temporalis muscles, there were few atrophic fibers, and several irregular areas of loss of enzymatic activity observed in NADH, SDH and COX stains. The tumour showed a trabecular growth pattern and immunohistochemical analysis demonstrated the presence of cytoplasmic immunoreactivity for ACTH. The muscle atrophy was considered to be related to an excess of inactive ACTH. Studying spontaneous occurring rare diseases in animals could help to understand the mechanism of similar diseases in human has well.

Adrenal Antibodies Detect Asymptomatic Autoimmune Adrenal Insufficiency in Young Women With Spontaneous Premature Ovarian Failure

Obstetrical & Gynecological Survey: March 2003 - Volume 58 - Issue 3 - p 180-181 doi: 10.1097/01.OGX.0000055758.75837.AE

Pancreatic Exocrine Carcinoma Producing Adrenocorticotropic Hormone

A rare case of pancreatic exocrine carcinoma with an endocrine component secreting adrenocorticotropic hormone (ACTH) is reported and discussed in relation to other cases previously published. The patient initially presented with a severe form of diabetes, which was treated accordingly. Persistence of hyperglycemia, along with other metabolic alterations and marked hypokalemia, led to the suggestion of abnormal ACTH secretion. In this patient, however, a florid Cushing's syndrome was not observed. The patient also developed hematological alterations, mainly leukopenia and thrombocytopenia, whose origins were unclear. At autopsy, a poorly-defined mass was discovered between the body and tail of the pancreas. Standard histology showed a moderately-differentiated adenocarcinoma. Immunohistochemical analysis of the tumor specimen demonstrated the presence of some neoplastic cells immunoreactive for chromogranin A, neuron-specific enolase and ACTH. These findings are consistent with the existence of an endocrine component within the exocrine carcinoma with ACTH differentiation.

Rapid Adrenocorticotropic Hormone Test in Practice. Retrospective Review

Retrospective analysis of the rapid adrenocorticotropic hormone (ACTH) test in a large adult population shows a marked interdependence of the basal cortisol concentration, peak cortisol concentration, and increase in cortisol concentration. Repetition of the rapid ACTH test in the same patient does not improve diagnostic accuracy. A significant number of falsely abnormal rapid ACTH test results were observed (in comparison to continuous ACTH infusion as a reference test). This supports the use of the rapid ACTH test as a screening test, but not as a diagnostic test for adrenocortical failure. It is proposed that a peak cortisol level greater than or equal to 20 micrograms/dl (550 nmol/liter) is a sufficient single criterion for normal adrenal function as assessed by the rapid ACTH test.

Rapid adrenocorticotropic hormone test in practice. Retrospective review

Retrospective analysis of the rapid adrenocorticotropic hormone (ACTH) test in a large adult population shows a marked interdependence of the basal cortisol concentration, peak cortisol concentration, and increase in cortisol concentration. Repetition of the rapid ACTH test in the same patient does not improve diagnostic accuracy. A significant number of falsely abnormal rapid ACTH test results were observed (in comparison to continuous ACTH infusion as a reference test). This supports the use of the rapid ACTH test as a screening test, but not as a diagnostic test for adrenocortical failure. It is proposed that a peak cortisol level greater than or equal to 20 μg/dl (550 nmol/liter) is a sufficient single criterion for normal adrenal function as assessed by the rapid ACTH test.

Pituitary and adrenal function in epileptic patients.

ACTH and cortisol were measured simultaneously in plasma samples obtained every 5 min from subjects at two different diurnal times. In the first study adrenocorticotropic hormone (ACTH) mean concentration and secretory rate were elevated in anticonvulsant drug-treated temporal lobe epileptic patients in comparison to anticonvulsant drug-treated patients with pseudoseizures. Cortisol mean concentrations and secretory rate were similar in these groups of subjects. In the second study, mean ACTH concentration and secretory rate were higher in temporal lobe epileptic patients than in normal controls. Both measures of ACTH secretion were similar in post-temporal lobectomy patients and normal controls. Mean cortisol concentration and secretory rates were highest in the temporal lobe epileptic patients, lowest in normal controls, and intermediate in post-temporal lobectomy patients. We conclude that ACTH and cortisol secretion is abnormal in temporal lobe epileptic patients. Temporal lobectomy restores abnormal ACTH secretion to normal whether or not seizures are controlled. The absence of ACTH changes in the pseudoseizure patients suggests that these changes are not drug induced. Cortisol secretion is similar in temporal lobe epileptic patients and pseudoseizure patients, suggesting a direct effect of the drugs upon the adrenal cortex.

Preoperative Assessment of Adrenal Insufficiency in Glucocorticoid Therapy

To the Editor .—Despite the recent findings of Cunningham et al, 1 the synthetic adrenocorticotropic hormone (ACTH) test remains the best technique for establishing whether a patient with possible adrenal insufficiency secondary to exogenous glucocorticoid therapy can undergo the stress of surgery without supplemental steroid coverage. Jasani et al 2 found in 1968 that the metyrapone and insulin-induced hypoglycemia tests were more sensitive than the ACTH stimulation test in detecting mild degrees of secondary adrenal insufficiency. They studied 21 patients with steroid-treated rheumatoid arthritis undergoing anterior synovectomy of the knee without steroid coverage. Preoperatively, 16 patients had abnormal responses to the metyrapone or insulin-induced hypoglycemia tests, and nine of these 16 patients also had abnormal ACTH stimulation test results. Only one patient, from the group with abnormal responses to the ACTH test, developed intraoperative hypotension associated with a low serum cortisol. These results are further supported by the work of

Effect of adrenocorticotropic hormone and human chorionic gonadotropin before and after bilateral oophorectomy in a patient with acquired adult-onset adrenal hyperplasia: A case report

A 29-year-old woman presented with hirsutism, obesity, oligomenorrhea, and infertility caused by oligoovulation and tubal occlusion. Partial 21-hydroxylase deficiency of the adrenal was suggested by an abnormal adrenocorticotropic hormone (ACTH) stimulation test. The patient subsequently developed bilateral tuboovarian abscesses and underwent abdominal hysterectomy and bilateral salpingo-oophorectomy. Thus, an opportunity was presented to study the adrenal endocrine disorder in the absence of ovaries and to investigate the effect of human chorionic gonadotropin (hCG) on the adrenals. There was no change in the adrenal response to ACTH stimulation after oophorectomy. hCG stimulation resulted in an increase in dehydroepiandrosterone sulfate and 17β-estradiol levels, suggesting that hCG had a stimulatory effect on the adrenal. The ovarian-adrenal relationship and effects of adrenal stimulation in the absence of ovaries are discussed.