Ectopic Cushing's syndrome due to retroperitoneal ACTH-producing paragangliomas.
Ontology highlight
ABSTRACT:
SUBMITTER: Chen F
PROVIDER: S-EPMC5028219 | biostudies-other | 2016 Sep-Oct
REPOSITORIES: biostudies-other
Publications
Ectopic Cushing's syndrome due to retroperitoneal ACTH-producing paragangliomas.
Chen Fan F Wang Xiangyu X Wang Yang Y Meng Hui H Hou Xinguo X Zhu Yaofeng Y Gao Wei W Jiang Xuewen X Chen Shouzhen S Zhang Zhaocun Z Zou Zhichuan Z He Tianyi T Yang Yue Y Zhu Kejia K Wang Yong Y Liu Yaxiao Y Cui Jianfeng J Shi Benkang B Yin Gang G
Canadian Urological Association journal = Journal de l'Association des urologues du Canada 20160913 9-10
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 ...[more]
Similar Datasets
Project description:Corticotropinomas and adrenocorticotropic hormone (ACTH)-secreting neuroendocrine tumors exhibit differential levels of some microRNAs (miRs) compared to normal tissue. Because miRs can be released from tissues into circulation, they offer promise as novel disease biomarkers. Objective: To evaluate whether miRs are differentially detected in plasma samples of patients with ACTH-dependent Cushing's syndrome (CS). Design: Case-control study. Methods: Morning fasting plasma samples were collected from 41 consecutive patients with confirmed ACTH-dependent CS and 11 healthy subjects and stored at -80°C. Twenty-one miRs previously reported to be differentially expressed in ACTH-secreting tumors vs. healthy tissue samples were quantified in plasma by qPCR. Results: Among enrolled subjects, 28 were confirmed to have Cushing's disease (CD), 13 had ectopic ACTH secretion (EAS) and 11 were healthy controls. We found statistically significant differences in the circulating levels of miR-16-5p [45.04 (95% CI 28.77-61.31) in CD vs. 5.26 (2.65-7.87) in EAS, P < 0.001; q = 0.001], miR-145-5p [0.097 (0.027-0.167) in CD vs. undetectable levels in EAS, P = 0.008; q = 0.087] and differences in miR-7g-5p [1.842 (1.283-2.400) in CD vs. 0.847 (0.187-1.507) in EAS, P = 0.02; q = 0.14]. The area under the receiver-operator (ROC) curve was 0.879 (95% CI 0.770-0.987), p < 0.001, when using miR-16-5p to distinguish between CD and EAS. Circulating levels of miR-16-5p in the healthy control group differed from that of both the CD and EAS groups. Conclusions: Plasma miR levels differ in patients with CD and EAS. In particular, miR-16-5p, miR-145-5p and miR-7g-5p are promising biomarkers for further research to differentiate ACTH-dependent CS.
| S-EPMC7291947 | biostudies-literature
Project description:ContextBilateral micronodular adrenal hyperplasia and ectopic adrenocortical adenoma are two rare causes of ACTH-independent Cushing's syndrome.ObjectiveThe 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 settingIn vivo and in vitro studies were performed in a University Hospital Department and academic research laboratories.InterventionMutations 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 measureDetection 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.ResultsHistological 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.ConclusionThis 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:A 64-year-old male presented with neurofibromatosis 1 and Cushing's syndrome. Clinically he was over weight, depressed with extensive skin bruising and hypertension. His 24 hours urinary metanephrines, urinary 5HIAA, gut peptides and chromgranin levels were normal. His renal function and renal MRI scan was also normal. His cortisol failed to suppress on overnight dexamethsone suppression test. His low dose dexamethasone suppression with CRH stimulation showed failure of suppression of cortisol to < 50 nmol/L and ACTH was measurable at 10 ng/L on day 3. There was no response of ACTH or cortisol to CRH stimulation. His ACTH precursors were high at 126 pmol/L consistent with defective pro-opiomelanocortin (POMC) processing suggesting an ectopic source of ACTH production. The MRI scan of his pituitary and CT scan of the adrenal glands was normal. His octreotide scan was negative. The source of his ectopic ACTH was most likely a large retroperitoneal plexiform neurofibroma seen on CT abdomen that had undergone malignant peripheral nerve sheath tumour transformation on histology. He was a poor surgical risk for tumour debulking procedure. In view of the available literature and role of c-kit signalling in neurofibromatosis, he was treated with Imitinib. Four months after the treatment his Cushings had resolved on biochemical testing. After a year his plexiform neurofibroma has not increased in size. To our knowledge, this is the first case of NF1 associated with clinical and biochemical features of Cushing's secondary to ectopic ACTH due to MPNST in a plexiform neurofibroma and its resolution on treatment with imatinib.
| S-EPMC3693655 | biostudies-other
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: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: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:BackgroundEctopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is caused by tumours releasing ACTH. Ectopic ACTH-producing tumour regression is rarely induced using steroidogenesis inhibitors. We presented a case of EAS in which ACTH production by a lung tumour was reduced by metyrapone (MTP) and also reviewed previous cases of ectopic ACTH production suppressed via steroidogenesis inhibition.Case presentationA 71-year-old female with general fatigue, central obesity and impaired glucose tolerance was diagnosed with Cushing's syndrome due to elevated ACTH (192.9 pg/mL; normal range, 7.2-63.3 pg/mL), cortisol (73.1 ?g/dL; 6.4-21.0 ?g/dL) and 24-h urinary free cortisol (UFC) (6160 ?g/day; 11.2-80.3 ?g/day) levels. Chest computed tomography identified a solid 26.6?×?22.9?×?30.0 mm tumour with a cavity in the upper lobe of the left lung. There was no adrenal gland enlargement. Tumour markers were not significantly elevated; ACTH levels were not suppressed by 8-mg dexamethasone. A corticotropin-releasing hormone stimulation test revealed blunted ACTH response (basal ACTH, 204.6 pg/mL; highest ACTH level during the 120-min stimulation test, 214.0 pg/mL). She was diagnosed with EAS due to a lung lesion. MTP treatment was started to reduce cortisol production. ACTH levels and cortisol and UFC levels were normalised and the ACTH-producing lung tumour was ablated after MTP treatment. In several reported cases, plasma ACTH levels reduced during steroidogenesis inhibitor treatment for EAS. Among the 10 patients, three cases of pheochromocytoma, one of thymic carcinoid and one of islet cell carcinoma were reported. In four cases, the tumour was not detected. In our case, the pathology of the lung tumour was unknown because of lack of tumour cells in biopsy. The patients were treated with ketoconazole (KTZ) and/or MTP and exhibited ACTH and cortisol/UFC suppression, but tumour regression was observed only in our case.ConclusionMTP and/or KTZ may reduce ACTH and cortisol production. The tumour spontaneously regressed after MTP treatment, indicating that MTP may reduce the tumour size without surgery. The mechanisms of therapeutic effects of steroidogenesis inhibitors and prognosis of spontaneous remission should be elucidated further via molecular biology studies.
| S-EPMC5872391 | biostudies-literature
Project description:Cushing's syndrome is caused by excessive adrenocorticotropic hormone (ACTH) secretion derived from pituitary corticotroph tumors (Cushing disease) or from non-pituitary tumors (ectopic Cushing's syndrome). Hypercortisolemic features of ectopic Cushing's syndrome are severe, and no definitive treatment for paraneoplastic ACTH excess is available. We aimed to identify subcellular therapeutic targets by elucidating transcriptional regulation of the human ACTH precursor POMC (proopiomelanocortin) and ACTH production in non-pituitary tumor cells and in cell lines derived from patients with ectopic Cushing's syndrome. We show that ectopic hPOMC transcription proceeds independently of pituitary-specific Tpit/Pitx1 and demonstrate a novel E2F1-mediated transcriptional mechanism regulating hPOMC We identify an E2F1 cluster binding to the proximal hPOMC promoter region (-42 to +68), with DNA-binding activity determined by the phosphorylation at Ser-337. hPOMC mRNA expression in cancer cells was upregulated (up to 40-fold) by the co-expression of E2F1 and its heterodimer partner DP1. Direct and indirect inhibitors of E2F1 activity suppressed hPOMC gene expression and ACTH by modifying E2F1 DNA-binding activity in ectopic Cushing's cell lines and primary tumor cells, and also suppressed paraneoplastic ACTH and cortisol levels in xenografted mice. E2F1-mediated hPOMC transcription is a potential target for suppressing ACTH production in ectopic Cushing's syndrome.
| S-EPMC5152695 | biostudies-literature
Project description:A 30-year-old Caucasian man presented with severe Cushing's syndrome (CS) resulting from ectopic adrenocorticotropin syndrome (EAS) from a metastatic pancreatic neuroendocrine tumor. The patient remained hypercortisolemic despite treatment with steroidogenesis inhibitors, chemotherapy, and octreotide long-acting release (LAR) and was enrolled in a 24-week, phase 3 clinical trial of mifepristone for inoperable hypercortisolemia. After mifepristone was added to ongoing octreotide LAR treatment, EAS symptoms essentially resolved. Cortisol decreased dramatically, despite mifepristone's competitive glucocorticoid receptor antagonist effects. The clinical and biochemical effects reversed upon mifepristone discontinuation despite the continued use of octreotide LAR therapy. Substantial improvement in octreotide LAR efficacy with mifepristone use was noted in this patient with ectopic CS, consistent with upregulation of somatostatin receptors previously downregulated by hypercortisolemia.
| S-EPMC4773543 | biostudies-literature
Project description:In a small number of cases, the development of ectopic residual adrenal lesions during embryogenesis causing Cushing's syndrome due to the production of excess cortisol has been reported. A 29-year-old woman was admitted to our hospital for fatigue and recent amenorrhea. Her plasma ACTH was <1.5 pg/mL, and her serum cortisol was 21.4 pg/mL after the 8 mg dexamethasone suppression test, revealing the presence of ACTH-independent Cushing's syndrome; however, her bilateral adrenal glands were atrophied. Abdominal CT revealed a 40-mm round tumor on the right renal hilum and remarkably accumulated 131I-labelled adosterol. CT and bone scintigraphy showed that 99mTc-methylene diphosphonate had accumulated in her dissymmetric skull at the right-frontoparietal region. The tumor on the right renal hilum was laparoscopically removed. Her cortisol levels rapidly decreased to below the normal range, and glucocorticoids were administered to rescue adrenal insufficiency. The resected tumor was yellowish in appearance and 4.5×3.0×2.8 cm in size. Immunohistochemical staining for SF-1, P450scc, CYP17A, CYP21A, and CYP11B1 indicated that this tumor produced cortisol. Exome sequencing analysis revealed that the GNAS heterozygous mutation (c.601C>T, p. Arg201Cys; accession number, NM_000516.5) was found in approximately 20% of the adrenal tumor sample. A mutation of GNAS, encoding the Gsα subunit that mediates GPCR signaling, causes the constitutive activation of adenylyl cyclase, resulting in hypersecretion of hormones regulated by the GPCR. GNAS mutation is one of the major genetic causes of cortisol-producing adrenal tumors independent of ACTH secretion. Considering the combination of GNAS mutation with one of the typical clinical triad characteristics, fibrous dysplasia of bone, we diagnosed this patient with McCune-Albright syndrome accompanied by ACTH-independent Cushing's syndrome caused by an ectopic residual adrenal tumor due to GNAS mutation. This case highlights that GNAS involves a previously unknown pathological mechanism in which inhibition of the natural elimination of remnant tissue leads to ectopic endocrine hypersecretion.
| S-EPMC9373900 | biostudies-literature