ACTH Resistance Syndrome: An Experience of Three Cases.
Ontology highlight
ABSTRACT:
SUBMITTER: Goyal A
PROVIDER: S-EPMC6330879 | biostudies-literature | 2018 Nov-Dec
REPOSITORIES: biostudies-literature
Publications
ACTH Resistance Syndrome: An Experience of Three Cases.
Goyal Alpesh A Boro Hiya H Khandelwal Deepak D Khadgawat Rajesh R
Indian journal of endocrinology and metabolism 20181101 6
The term adrenocorticotropin (ACTH) resistance syndrome is used for a group of rare inherited disorders, which present with primary adrenal insufficiency during childhood. The syndrome includes two disorders inherited in an autosomal recessive fashion - familial glucocorticoid deficiency and triple A syndrome. Herein, we report our experience of three cases with ACTH resistance syndrome, highlighting the approach to diagnosis and management in such patients. ...[more]
Similar Datasets
Project description:Ectopic ACTH syndrome (EAS) accounts for 10-20% of endogenous Cushing's syndrome (CS). Hardly any cases of adrenal medullary hyperplasia have been reported to ectopically secrete adrenocorticotropic hormone (ACTH). Here we describe a series of three patients with hypercortisolism secondary to ectopic production of ACTH from adrenal medulla. Cushingoid features were absent in case 1 but evident in the other two cases. Marked hypokalemia was found in all three patients, but hyperglycemia and osteoporosis were present only in case 2. All three patients showed significantly elevated serum cortisol and 24-h urinary cortisol levels. The ACTH levels ranged from 19.8 to 103.0pmol/L, favoring ACTH-dependent Cushing's syndrome. Results of bilateral inferior petrosal sinus sampling (BIPSS) for case 1 and case 3 confirmed ectopic origin of ACTH. The extremely high level of ACTH and failure to suppress cortisol with high dose dexamethasone suppression test (HDDST) suggested EAS for patient 2. However, image studies failed to identify the source of ACTH secretion. Bilateral adrenalectomy was performed for rapid control of hypercortisolism. After surgery, cushingoid features gradually disappeared for case 2 and case 3. Blood pressure, blood glucose and potassium levels returned to normal ranges without medication for case 2. The level of serum potassium also normalized without any supplementation for case 1 and case 3. The ACTH levels of all three patients significantly decreased 3-6 months after surgery. Histopathology revealed bilateral adrenal medullary hyperplasia and immunostaining showed positive ACTH staining located in adrenal medulla cells. In summary, our case series reveals the adrenal medulla to be a site of ectopic ACTH secretion. Adrenal medulla-originated EAS makes the differential diagnosis of ACTH-dependent Cushing's syndrome much more difficult. Control of the hypercortisolism is mandatory for such patients.
| S-EPMC8281927 | biostudies-literature
Project description:Study objectiveAssessment of feasibility of office hysteroscopy in Indian setting.DesignRetrospective study design.SettingTertiary care centre: Galaxy care Hospital, Pune, India.PatientsThree thousand consecutive women undergoing office hysteroscopy between 2012 and May 2018.InterventionsOffice hysteroscopy 2200 cases (2012-2017) with Bettocchi 2.9 scope and Hamou endomat. Eight hundred cases (2017-2018) with Bettocchi 1.9 scope and EASI. Normal saline was used as distension medium. With Hamou endomat, settings have drip rate of 200 ml/min with irrigation pressure of 75 mmHg and suction bar 0.15. With EASI, settings were for Bettocchi 4 (1.9 mm) and Bettocchi 5 (2.9 mm) scope with 45 mmHg. Hysteroscopies were carried out by an experienced operator trained in office hysteroscopy. All hysteroscopies were done in early proliferative phase (4th-11th day).Main outcome measuresSuccess, failure and complication rates.ResultsHysteroscopies were successfully performed in nearly 98.66% of cases with 4 patients requiring a two-step procedure due to > 3 cm pathology. One thousand eight hundred eight (62.2%) were diagnostic hysteroscopies, while operative hysteroscopies were performed in one thousand one hundred twenty (37.8%). One patient (1/3000) had a vasovagal attack.ConclusionsIn outpatient setting, counselling the patient for office hysteroscopy played an important role to overcome pain and anxiety, in addition to low pressure, continuous flow irrigation and vaginoscopic approach. Traditional resectoscopic surgeries should be reserved for challenging cases (i.e. endometrial ablation) or for certain pathologies (myomas > 2.0 cm, broad-base, large-size polyps). Recent advances in technique and instrumentation facilitate this approach and might encourage greater adoption by the gynaecology community. With the right approach, technique and setup, office hysteroscopy is feasible with favourable outcomes.
| S-EPMC7516003 | biostudies-literature
Project description:Previous studies have linked systemic glucocorticoid use with intestinal perforation. However, the association between intestinal perforation and endogenous hypercortisolism has not been well described, with only 14 previously published case reports. In this study, we investigated if intestinal perforation occurred more frequently in patients with ectopic ACTH syndrome and in those with a greater than 10-fold elevation of 24-hour urinary free cortisol level. Of 110 patients with ACTH-dependent Cushing's syndrome followed in two clinics in Canada, six cases with intestinal perforation were identified over 15 years. Age of patients ranged from 52 to 72, five females and one male, four with Cushing's disease and two with ectopic ACTH production, one from a pancreatic neuroendocrine tumor and one from medullary carcinoma of the thyroid. Five had diverticular perforation and one had intestinal perforation from a stercoral ulcer. All cases had their lower intestinal perforation when the cortisol production was high, and one patient had diverticular perforation 15 months prior to the diagnosis of Cushing's disease. As in previously reported cases, most had hypokalemia and abdominal pain with minimal or no peritoneal symptoms and this occurred during the active phase of Cushing's syndrome. Whereas all previously reported cases occurred in patients with 24-hour urinary free cortisol levels greater than 10-fold the upper limit of normal when measured and 11 of 14 patients had ectopic ACTH production, only one of our patients had this degree of hypercortisolism and four of our six patients had Cushing's disease. Similar to exogenous steroid use, patients with endogenous hypercortisolism also have a higher risk of intestinal, in particular diverticular, perforation and should be monitored closely for its occurrence with a low threshold for investigation and surgical intervention. Elective colonoscopy probably should be deferred until Cushing's syndrome is under control.
| S-EPMC6436364 | biostudies-literature
Project description:BACKGROUND:Multicentric carpotarsal osteolysis syndrome (MCTO) is characterized by progressive destruction and disappearance of the carpal and tarsal bones associated with nephropathy. MCTO is caused by loss-of-function mutations in the MAF bZIP transcription factor B (MAFB) gene. CASE PRESENTATION:This report describes three unrelated patients with MAFB mutations, including two male and one female patient. Osteolytic lesions in the carpal and tarsal bones were detected at 2 years, 12 years, and 14 months of age, respectively. Associated proteinuria was noted at 4 years, 12 years, and 3 months of age, respectively. Kidney biopsy was performed in two of them and revealed focal segmental glomerulosclerosis (FSGS). One patient showed progression to end-stage renal disease, that is by 1 year after the detection of proteinuria. The second patient had persistent proteinuria but maintained normal renal function. In the third patient, who did not undergo a kidney biopsy, the proteinuria disappeared spontaneously. The bony lesions worsened progressively in all three patients. Mutational study of MAFB revealed three different mutations, two novel mutations [c.183C?>?A (p.Ser61Arg) and c.211C?>?G (p.Pro71Ala)] and one known mutation [c.212C?>?T (p.Pro71Leu)]. CONCLUSION:We report three cases with MCTO and two novel MAFB mutations. The renal phenotypes were different among the three patients, whereas progressive worsening of the bony lesions was common in all patients. We also confirmed FSGS to be an early renal pathologic finding in two cases. A diagnosis of MCTO should be considered in patients with progressive bone loss concentrated primarily in the carpal and tarsal bones and kidney involvement, such as proteinuria.
| S-EPMC6134760 | biostudies-literature
Project description:BackgroundAssessment of capacity for treatment and discharge decisions is common in the general hospital. Liaison psychiatrists are often asked to support the treating medical or surgical team in difficult capacity assessments. However, empirical research on identification and resolution of difficult capacity cases is limited. Some studies have identified certain patient, decisional, and interpersonal factors which cause difficulty, but no study has explored how these issues are resolved in practice. Our study therefore aimed to describe how experienced liaison psychiatrists identify and resolve difficult capacity cases in a general hospital setting.MethodsWe carried out semi-structured interviews with 26 liaison psychiatrists from England, Scotland, and New Zealand, on their most difficult capacity cases. Thematic analysis was used to examine types of difficulty and how these were resolved in practice. Summaries were prepared and example quotes extracted to illustrate phenomena described.ResultsWe identified four types of difficulty in capacity assessment, spanning both clinical and ethical domains: 1) Difficulty determining whether the decision is the patient's own or driven by illness, 2) Difficulty in applying ethical principles, 3) Difficulty in avoiding personal bias, and 4) Procedural difficulties. The liaison psychiatrists presented as self-reflective and aware of challenges and pitfalls in hard cases. We summarized their creative strategies to resolve difficulty in assessment.ConclusionPractitioners approaching difficult capacity cases require both clinical skills, e.g., to uncover subtle illness impairing decision-making and to consider interpersonal dynamics, and ethical skills, e.g., to negotiate the role of values and risks in capacity assessment. Education and training programmes should incorporate both aspects and could include the resolution strategies identified in our study. Practitioners, supported by health and social care systems, should work to develop self-aware and reflective capacity assessment practice.
| S-EPMC9309683 | biostudies-literature
Project description:Abstract submitted to the Journal of clinical encodcrinology and metabolism: The molecular mechanisms responsible for the ectopic expression of the GIP receptor in the adrenal cortex of patients with GIP-dependent Cushing’s syndrome (CS) are unknown. Chronic adrenal stimulation by ACTH in Cushing’s disease (CD) or by GIP in GIP-dependent AIMAH both lead to induction of a set of genes which stimulate adrenal proliferation and steroidogenesis. The objective of this study was to compare the whole genome expression profile of adrenal glands of five cases of GIP-dependent bilateral macronodular adrenal hyperplasia with CS, one case of GIP-dependent adenoma, compared to five cases of ACTH-dependant hyperplasias (CD) and a pool of adrenals from 62 normal individuals. We used the genome-spanning Affymetrix U133 plus 2.0 microarray oligochips to identify genes differentially expressed specifically in GIP-dependent CS and which would be candidate genes implicated in the ectopic expression of the GIP receptor in the adrenal cortex. After data normalization and filtering, genes with differential expression were identified with a multi-step statistical analysis involving a student’s t-test, a filter on flags and a SAM analysis. A total of 721 probesets were thus isolated with intensity levels robustly related to the presence of a GIP-dependent hyperplasia. We performed a functional classification to further define potentially important biological processes and signaling mechanism for the formation of GIP-dependent AIMAH. Various probesets were related to metabolic processes, cell-surface and intracellular signaling, tumorigenesis, transport and transcription factors. The most relevant genes had their expression profile confirmed by real-time RT-PCR. This study reports an extensive series of potentially novel targets in the identification of the molecular mechanisms of ectopic expression of the GIP-receptor in this pathology. Keywords: Comparative genomic analysis
2006-06-16 | GSE4060 | GEO
Project description:Extra-adrenal pheochromocytomas, or paragangliomas, are rare tumours that derive from extra-adrenal chromaffin cells. Cushing's syndrome (CS) caused by paragangliomas is extremely rare. We report a 53-year-old man with hypertension, diabetes, and symptoms of hypokalemia. Computer tomography (CT) revealed two retroperitoneal masses and bilateral adrenal hyperplasia. Together with the laboratory examinations, ectopic CS caused by multiple paragangliomas was highly suspected. The patient underwent resections of retroperitoneal tumours, left kidney, and left adrenal; postoperative histopathology confirmed two paragangliomas that were both positively stained for adrenocorticotropic hormone (ACTH). He got clinical and biochemical recoveries without any recurrent evidence at the nine-month followup.
| S-EPMC5028219 | biostudies-other
Project description:Chromosome 17q12 microdeletion syndrome is a contiguous gene deletion syndrome caused by an 1-2 Mb loss, characterized by multicystic dysplastic kidneys or other urinary system anomalies starting in utero, including autism or maturity-onset diabetes of the young in its postnatal phenotype. Here, we report on three cases (two prenatal and one postnatal) with distinct and novel clinical presentations as compared with a large number of reviewed patients, thus emphasizing the phenotypic variability of this syndrome and the consequent difficulties in genetic counselling. Prenatal hyperechogenic multicystic kidneys, as well as other urinary tract anomalies, should be considered a marker, therefore indicating the necessity of comprehensive genetic testing, and autism should also be acknowledged as a possible clinical presentation, postnatally.
| S-EPMC9524179 | biostudies-literature
Project description:MECP2 duplication syndrome (MDS) is a rare pediatric disease and mainly manifests as delayed motor development, language loss or delay, recurrent infection, severe intellectual disability, epilepsy, autistic symptoms, and early infantile hypotonia. In this article, the three children with this disease were all boys. Cases 1 and 2 had delayed motor development, and language loss or delay as initial manifestations, and case 3 had recurrent infection as initial manifestation. Physical examination showed hypotonia and negative pathological signs in each case. Case 1 had tonic-clonic seizures and electroencephalography showed focal seizures, for which he was given oxcarbazepine, levetiracetam, and clonazepam as the antiepileptic treatment to control seizures. Case 3 experienced one absence seizure and three head-nodding seizures with normal electroencephalographic findings during these seizures, and therefore, he was not given antiepileptic treatment. In each case, recurrent infection was improved with the increase in age, but there were no significant improvements in language or intelligence. Array-based comparative genomic hybridization (aCGH) showed MECP2 duplication in X chromosome in each case, and so they were diagnosed with MDS. MDS should be considered for children with delayed development complicated by recurrent infection and epileptic seizures, and early aCGH helps with the diagnosis of this disease.
| S-EPMC7389140 | biostudies-literature
Project description:Allgrove syndrome (AS) is an autosomal recessive congenital disease, caused by mutations in the AAAS gene, and is characterized by the triad of Addison's disease, achalasia and alacrima. The present study describes three newly diagnosed cases of AS, in which genetic analysis of the AAAS gene was used to identify AAAS gene mutations, to enhance the understanding of the pathogenesis and clinical manifestations of AS in the Chinese population. Two of the cases exhibited homozygous mutations of c.771delG (p.Arg258GlyfsX33) in exon 8 and one case exhibited a homozygous mutation of c.1366C>T (p.Q456X) in exon 15. A review of the current literature suggests that the AAAS c.771delG mutation has only been reported in the Chinese population. Genetic analysis of the AAAS gene in Chinese AS patients at a young age may facilitate an earlier diagnosis and the timely initiation of the appropriate treatment, ultimately improving the patient outcome.
| S-EPMC4578041 | biostudies-literature