Adrenocorticotropic Hormone-Secreting Esthesioneuroblastoma with Ectopic Cushing's Syndrome.
Ontology highlight
ABSTRACT:
SUBMITTER: Chung YS
PROVIDER: S-EPMC7044685 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:A 13-year-old Labrador retriever was diagnosed with Cushing's syndrome (CS) caused by primary bilateral nodular adrenocortical hyperplasia with adrenocorticotropic hormone (ACTH) expression. The pituitary origin of CS was ruled out by suppression of plasma ACTH concentration and absence of a proliferative lesion on histological evaluation of the pituitary gland using periodic acid-Schiff (PAS) staining, reticulin staining, and immunostaining for ACTH. A pheochromocytoma also was found at necropsy examination. On histological evaluation of both adrenal glands, at the junction of the fascicular and glomerular zones, multiple cell clusters distributed in both hyperplastic adrenal cortices expressed ACTH, whereas the pheochromocytoma cells did not. These results indicate that a disease similar to primary bilateral macronodular adrenocortical hyperplasia in humans also occurs in dogs, with intra-adrenocortical expression of ACTH, glucocorticoids excess, and clinical signs of CS. Therefore, the term ACTH-independent could be inappropriate in some cases of bilateral adrenocortical hyperplasia and suppressed plasma ACTH concentration in dogs.
| S-EPMC8783325 | biostudies-literature
Project description:Purpose Fluorine-18 (18F)-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and gallium-68 (68Ga)-somatostatin analog (SSA) PET/CT imaging have been increasingly used in ectopic adrenocorticotropic hormone syndrome (EAS); however, the diagnostic efficacies of these two methods in patients with EAS remain unclear. Our study aimed to compare the diagnostic efficacies of 18F-FDG PET/CT and 68Ga-DOTANOC PET/CT in EAS. Methods The clinical and imaging data of 68 patients with EAS who underwent 18F-FDG PET/CT and 68Ga-DOTANOC PET/CT examinations from December 2016 to April 2021 were analyzed retrospectively, and the diagnostic efficacies of these methods were compared. Results In 37 cases, imaging was performed to locate the primary tumor lesion (localization group), and in 31 to evaluate tumor load or metastasis (staging group). Primary tumors were detected in 48.65% (18/37) of the localization group patients. According to scan-based analysis, the tumor lesion detection rates and false positive rates of 18F-FDG PET/CT imaging and 68Ga-DOTANOC PET/CT imaging were 18.92% vs. 45.95% (p < 0.05) and 21.62% vs. 2.70% (p < 0.05) respectively. For lesion-based analysis, the tumor lesion detection rates and false positive rates were 24.13% vs. 58.62% (p >0.05) and 31.04% vs. 3.45% (p < 0.05). In 90.32% (28/31) of the staging group patients, 286 of 292 lesions were confirmed as tumor lesions. Based on scan analysis, the detection rates and false positive rates of 18F-FDG PET/CT imaging and 68Ga-DOTANOC PET/CT imaging were 83.87% vs. 67.74% (p > 0.05) and 12.90% vs. 9.68% (p > 0.05) respectively. Based on lesion analysis, the detection rate and false positive rates were 93.84% vs. 54.80% (p < 0.05) and 1.37% vs. 1.03%(p > 0.05). Conclusion 68Ga-DOTANOC PET/CT imaging may be more suitable than 18F-FDG PET/CT for identifying the primary tumor in patients with EAS, while 18F-FDG PET/CT may be more advantageous than 68Ga-DOTANOC PET/CT for patients with suspected metastasis.
| S-EPMC9538925 | 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: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: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: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:Background Esthesioneuroblastoma is an uncommon malignant neoplasm that arises from the olfactory neuroepithelium. In this article we report a case of esthesioneuroblastoma presenting concomitantly with a growth-hormone (GH)-secreting pituitary macroadenoma. Results A 52 year old woman underwent surgery for suspected nasal polyps. Intralesional debulking of an intranasal tumor disclosed a low-grade esthesioneuroblastoma. Magnetic resonance imaging (MRI) demonstrated a large nasal and intracranial tumor, in addition to a separate sellar and suprasellar tumor. The patient was frankly acromegalic. She underwent a first-stage gross total resection of the esthesioneuroblastoma via a combined extended subfrontal and extended endonasal approach, followed by focused radiation therapy. She then returned for endoscopic removal of the GH-secreting pituitary macroadenoma. Conclusion The combined open and endoscopic management of this patient is described and a review of the literature presented. To our knowledge this is the first case of synchronous esthesioneuroblastoma and macroadenoma, in this case GH secreting, described in the literature.
| S-EPMC4242820 | biostudies-other
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: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