Cushing's syndrome caused by intra-adrenocortical adrenocorticotropic hormone in a dog.
Ontology highlight
ABSTRACT:
SUBMITTER: Soler Arias EA
PROVIDER: S-EPMC8783325 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Esthesioneuroblastoma as a source of ectopic Cushing's syndrome is rare, and to the best of our knowledge, only 20 cases have been reported worldwide. A 46-year-old healthy man visited a local clinic for general weakness and hyposmia, and underwent examination with serial endocrinological workup and brain imaging. 68Gallium-DOTA-TOC positron emission tomography scan was helpful where diagnosis of sellar MRI and inferior petrosal sinus sampling were discordant. Combined transcranial and endoscopic endonasal approach surgery was performed, and a diagnosis of esthesioneuroblastoma was given.
| S-EPMC7044685 | biostudies-literature
Project description:BACKGROUND AND OBJECTIVES:There is renewed interest in adrenocorticotropic hormone (ACTH) for the treatment of nephrotic syndrome. We evaluated the efficacy and safety of ACTH in children with frequently relapsing or steroid-dependent nephrotic syndrome in a randomized trial. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:Participants aged 2-20 years old with frequently relapsing or steroid-dependent nephrotic syndrome were enrolled from 16 sites in the United States and randomized 1:1 to ACTH (repository corticotropin injection) or no relapse-preventing treatment. ACTH treatment regimen was 80 U/1.73 m2 administered twice weekly for 6 months, followed by 40 U/1.73 m2 administered twice weekly for 6 months. The primary outcome was disease relapse during the first 6 months. Participants in the control group were offered crossover to ACTH treatment if they relapsed within 6 months. Secondary outcomes were relapse after ACTH dose reduction and treatment side effects. RESULTS:The trial was stopped at a preplanned interim analysis after enrollment of 31 participants because of a lack of discernible treatment efficacy. Fourteen out of 15 (93%) participants in the ACTH arm experienced disease relapse in the first 6 months, with a median time to first relapse of 23 days (interquartile range, 9-32), compared with 15 out of 16 (94%) participants and at a median of 21 days (interquartile range, 14-51) in the control group. There was no difference in the proportion of relapsed patients (odds ratio, 0.93; 95% confidence interval, 0.05 to 16.40; P>0.99) or time to first relapse (hazard ratio, 1.03; 95% confidence interval, 0.50 to 2.15; P=0.93). Thirteen out of 16 participants in the control group crossed over to ACTH treatment. Three out of 28 participants completed 12 months of ACTH treatment; the others exited the trial because of frequent relapses or side effects. There were no disease relapses after ACTH dose reduction among the three participants. Most side effects were mild and similar to side effects of corticosteroids. CONCLUSIONS:ACTH at 80 U/1.73 m2 administered twice weekly was ineffective at preventing disease relapses in pediatric nephrotic syndrome.
| S-EPMC6302334 | biostudies-literature
Project description:CONTEXT: Bilateral micronodular adrenal hyperplasia and ectopic adrenocortical adenoma are two rare causes of ACTH-independent Cushing's syndrome. OBJECTIVE: The aim of the study was to evaluate a 35-yr-old woman with ACTH-independent hypercortisolism associated with both micronodular adrenal hyperplasia and ectopic pararenal adrenocortical adenoma. DESIGN AND SETTING: In vivo and in vitro studies were performed in a University Hospital Department and academic research laboratories. INTERVENTION: Mutations of the PRKAR1A, PDE8B, and PDE11A genes were searched for in leukocytes and adrenocortical tissues. The ability of adrenal and adenoma tissues to synthesize cortisol was investigated by immunohistochemistry, quantitative PCR, and/or cell culture studies. MAIN OUTCOME MEASURE: Detection of 17alpha-hydroxylase and 21-hydroxylase immunoreactivities, quantification of CYP11B1 mRNA in adrenal and adenoma tissues, and measurement of cortisol levels in supernatants by radioimmunological assays were the main outcomes. RESULTS: Histological examination of the adrenals revealed nonpigmented micronodular cortical hyperplasia associated with relative atrophy of internodular cortex. No genomic and/or somatic adrenal mutations of the PRKAR1A, PDE8B, and PDE11A genes were detected. 17alpha-Hydroxylase and 21-hydroxylase immunoreactivities as well as CYP11B1 mRNA were detected in adrenal and adenoma tissues. ACTH and dexamethasone activated cortisol secretion from adenoma cells. The stimulatory action of dexamethasone was mediated by a nongenomic effect involving the protein kinase A pathway. CONCLUSION: This case suggests that unknown molecular defects can favor both micronodular adrenal hyperplasia and ectopic adrenocortical adenoma associated with Cushing's syndrome.
| S-EPMC2805485 | biostudies-literature
Project description:BackgroundPlasma adrenocorticotropic hormone (ACTH) and serum cortisol concentrations increase with illness-associated stress. Dynamics of plasma ACTH and serum cortisol concentrations in adult horses with systemic illness are undocumented.Hypothesis/objectiveTo determine whether ACTH and cortisol concentrations and the ACTH/cortisol ratio vary with survival, the presence of systemic inflammatory response syndrome (SIRS), or ischemic gastrointestinal lesions at admission, or throughout hospitalization.AnimalsOne hundred fifty-one adult horses.MethodsProspective study measuring serum cortisol and plasma ACTH at admission and on days 2, 4, and 6 of hospitalization. Horses were grouped by outcome (survival, SIRS status, number of SIRS criteria [SIRS score], SIRS severity group, and the presence of an ischemic lesion). Differences between groups and over time for ACTH, cortisol, and ACTH/cortisol ratio were investigated with a mixed effect model. Receiving operator characteristic curves and odds ratios were calculated for survival and ischemia.ResultsIn all groups, ACTH, cortisol, and ACTH/cortisol ratio significantly decreased over time (P < .0001). ACTH, cortisol, and ACTH/cortisol ratio were higher at admission in nonsurvivors, and ACTH and cortisol were higher in horses with ischemic lesions (P < .01). Horses with ACTH above reference interval at admission were 6.10 (2.73-13.68 [95% confidence interval]) times less likely to survive (P < .0001). No significant difference in ACTH, cortisol, and ACTH/cortisol ratio between horses with different SIRS status, scores, or groups were detected, although nonsurvivors had a higher SIRS score (P < .0001).Conclusions and clinical importancePituitary and adrenal responses are altered in nonsurviving horses and those with an ischemic gastrointestinal lesion.
| S-EPMC6766528 | biostudies-literature
Project description:A study of bovine adrenocortical cell shape on adrenocorticotropic hormone (ACTH) challenge showed that the cells round up and develop arborized processes. This effect was found to be (1) specific for ACTH because angiotensin II and basic fibroblast growth factor have no effect; (2) mediated by a cAMP-dependent pathway because forskolin reproduces the effect of the hormone; (3) inhibited by sodium orthovanadate, a phosphotyrosine phosphatase inhibitor, but unchanged by okadaic acid, a serine/threonine phosphatase inhibitor; and (4) correlated with a complete loss of focal adhesions. Biochemical studies of the focal-adhesion-associated proteins showed that pp125fak, vinculin (110 kDa) and paxillin (70 kDa) were detected in the Triton X-100-insoluble fraction from adrenocortical cells. During cell adhesion on fibronectin as substratum, two major phosphotyrosine-containing proteins of molecular masses 125 and 68 kDa were immunodetected in the same fraction. A dramatic decrease in the extent of tyrosine phosphorylation of these proteins was observed within 60 min after treatment with ACTH. No change in pp125fak tyrosine phosphorylation nor in Src activity was detected. In contrast, paxillin was found to be tyrosine-dephosphorylated in a time-dependent manner in ACTH-treated cells. Sodium orthovanadate completely prevented the effect of ACTH. These observations suggest a possible role for phosphotyrosine phosphatases in hormone-dependent cellular regulatory processes.
| S-EPMC1219510 | biostudies-other
Project description:ObjectiveTo compare androgen responses during ACTH infusion among women with polycystic ovary syndrome (PCOS) and healthy women.DesignCross-sectional study.SettingAcademic medical center.Patient(s)Women with PCOS (n = 13) and healthy controls (n = 15).Intervention(s)Blood samples were obtained frequently during a 6-hour dose-response ACTH infusion.Main outcome measure(s)Comparison of basal and stimulated levels of 17α-hydroxyprogesterone (17-OHP), androgens, and cortisol (F) during ACTH infusion with those after hCG injection within individual subjects.Result(s)In women with PCOS increased 17-OHP, androstenedione (A), and DHEA responses during ACTH infusion were comparable to those observed in healthy controls. The magnitude of responses was highly variable among women with PCOS. Within individual women with PCOS adrenal responses to ACTH and ovarian responses to hCG were significantly correlated. Cortisol responses to ACTH were similar in women with PCOS and healthy controls.Conclusion(s)Within individual women with PCOS, enhanced androgen responses to ACTH are accompanied by comparable androgen responsiveness to hCG. These findings suggest that dysregulated steroidogenesis leading to hyperandrogenemia in this disorder is likely present in both adrenal and ovarian tissues.Clinical trial registration numberNCT00747617.
| S-EPMC5048513 | biostudies-literature
Project description:Congenital isolated adrenocorticotropic hormone (ACTH) deficiency (CIAD) is a rare disorder which can result in 20% mortality in the neonatal period if misdiagnosed. A 2 years and 7 months old boy was hospitalized many times because of recurrent hypoglycemia. On initial physical examination, the patient showed special appearance and indications of fast growth (?P97). Laboratory investigations revealed low levels of ACTH and cortisol in his plasma. Except thyroid-stimulating hormone, the anterior pituitary hormone concentrations were normal. Molecular data showed compound heterozygosity for two novel mutations in the TBX19 gene (encoding the transcription factor T-Box 19). Mutation c.205C>T was inherited from mother and the fragment deletion (from g.168,247,374 to g.168,278,264) was from father. Hydrocortisone replacement therapy was effective. We reported two novel TBX19 mutations, expanding the mutation spectrum of this disorder, in a CIAD patient who presented with special appearance, signs of fast growth, and thyroid-stimulating hormone derangement. In addition, for avoiding misdiagnosis, criterion for ACTH and cortisol detection of CIAD should be established.
| S-EPMC6482258 | biostudies-literature
Project description:ObjectivesLong-term adrenocorticotropic therapy (LT-ACTH), which consisted of 2-4 weeks of daily injections of adrenocorticotropic hormone (ACTH) and subsequent months of weekly injections, was tried for relapsed West syndrome (WS) or other intractable epilepsies in small case reports. Our aim was to explore the efficacy of LT-ACTH for preventing WS relapse, as well as the prevalence of its adverse events.MethodsThis is a retrospective, nationwide, multicenter case series of patients with WS who underwent LT-ACTH. Clinical information of the patients and protocol of LT-ACTH were collected from participating institutes in this study. We defined clinical response to ACTH as achievement of hypsarrhythmia and epileptic spasms resolution. Patients who responded to daily ACTH injections were identified and assessed whether they experienced WS relapse during/after the weekly ACTH injection period. The outcome was measured by the nonrelapse rate at 24 months after daily ACTH injections using the Kaplan-Meier method.ResultsClinical information of 16 children with WS was analyzed. The median age at LT-ACTH initiation was 14.5 months (range: 7-68 months). Thirteen (81%) patients had previously undergone conventional ACTH treatment. The LT-ACTH regimens comprised a median of 16 days of daily injections (range: 11-28 days) and 10 months of weekly injections (range: 3-22 months). Seven patients experienced WS relapse during/after subsequent weekly ACTH period, and the nonrelapse rate at 24 months after daily injections was estimated at 60.6% (95% confidence interval: 32.3%-80.0%). Height stagnation, hypertension, and irritability were observed; lethal adverse events were not reported.SignificanceOur study firstly explored the efficacy of LT-ACTH for preventing WS relapse. LT-ACTH might be a treatment option for patients with relapsed or intractable WS; however, we note that our study is limited by its small sample size and the lack of an appropriate control group.
| S-EPMC8166796 | biostudies-literature
Project description: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.
| S-EPMC3848392 | biostudies-literature
Project description:Glucocorticoid use is the most common cause of secondary osteoporosis. Poor skeletal health related to glucocorticoid use is thought to involve inhibition of the Wnt/β-catenin signaling pathway, a key pathway in osteoblastogenesis. Sclerostin, a peptide produced primarily by osteocytes, is an antagonist of the Wnt/β-catenin signaling pathway, raising the possibility that sclerostin is involved in glucocorticoids' adverse effects on bone. The aim of this study was to determine whether an acute infusion of cosyntropin (i.e. ACTH(1-24)), which increases endogenous cortisol, increases serum sclerostin levels as compared to a placebo infusion. This study was performed using blood samples obtained from a previously published, double-blind, placebo-controlled, randomized, cross-over study among healthy men and women who received infusions of placebo or cosyntropin after being supine and fasted overnight (ClinicalTrials.gov NCT02339506). A total of 17 participants were analyzed. There was a strong correlation (R2 = 0.65, P < 0.0001) between the two baseline sclerostin measurements measured at the start of each visit, and men had a significantly higher average baseline sclerostin compared to women. As anticipated, cosyntropin significantly increased serum cortisol levels, whereas cortisol levels fell during placebo infusion, consistent with the diurnal variation in cortisol. There was no significant effect of cosyntropin as compared to placebo infusions on serum sclerostin over 6-24 h (P = 0.10). In conclusion, this randomized, placebo-controlled study was unable to detect a significant effect of a cosyntropin infusion on serum sclerostin levels in healthy men and women.
| S-EPMC8679878 | biostudies-literature