- Low-dose ACTH stimulation testing in dogs suspected of hypoadrenocorticism. [Journal Article]
- JVJ Vet Intern Med 2018 Sep 19
- CONCLUSIONS: A 1 μg/kg dose of cosyntropin is equivalent to a 5 μg/kg dose of cosyntropin for screening dogs suspected of hypoadrenocorticism. The existence of partial ACTH deficiency was not identified in this small group of dogs.
- Recent advances in understanding corticotroph pituitary tumor initiation and progression. [Review]
- FF1000Res 2018; 7
- Cushing's disease is the most frequent form of hypercortisolism and is caused by hypophyseal corticotroph adenomas secreting excessive amounts of adrenocorticotropic hormone. Most of the tumors devel...
Cushing's disease is the most frequent form of hypercortisolism and is caused by hypophyseal corticotroph adenomas secreting excessive amounts of adrenocorticotropic hormone. Most of the tumors develop sporadically and only a limited number of corticotroph adenomas have been found to be associated with different neuroendocrine syndromes or with familial isolated pituitary adenomas. The pathogenic mechanisms of corticotroph adenomas are largely unknown, but the discovered aberrant chaperoning activity of heat shock protein 90 on the one hand and the presence of ubiquitin-specific protease 8 mutations on the other hand partially explained the causes of their development. Corticotroph tumors arise initially as benign microadenomas but with time form invasively growing aggressive macroadenomas which can switch to corticotroph carcinomas in extremely rare cases. The mechanisms through which corticotroph tumors escape from glucocorticoid negative feedback are still poorly understood, as are the processes that trigger the progression of benign corticotroph adenomas toward aggressive and malignant phenotypes. This review summarizes recent findings regarding initiation and progression of corticotroph pituitary tumors.
- The First Report of Small Cell Cancer of the Uvula Presenting With Ectopic Adrenocorticotropic Hormone Syndrome. [Journal Article]
- WJWorld J Oncol 2018; 9(4):115-118
- Small cell carcinoma (SmCC) of the head and neck is a rare occurrence. We herein present a case of a 62-year-old female who was diagnosed with small cell cancer of the uvula. The patient developed in...
Small cell carcinoma (SmCC) of the head and neck is a rare occurrence. We herein present a case of a 62-year-old female who was diagnosed with small cell cancer of the uvula. The patient developed increased body swelling, elevated blood pressure, persistent hypokalemia and new onset diabetes mellitus. Further workup confirmed a diagnosis of Cushing's syndrome secondary to ectopic adrenocorticotropic hormone (ACTH) production. To our knowledge, this is only the second case of SmCC of the uvula described in literature, and the first associated with any paraneoplastic syndrome. By reporting this case, we aim to characterize the tumor clinical course and highlight the aggressive nature of its growth.
- Treatment and outcomes in pheochromocytomas and paragangliomas: a study of 110 cases from a single center. [Journal Article]
- EEndocrine 2018 Sep 15
- CONCLUSIONS: The outcomes seemed slightly better than previous studies. Long-term prognosis was similar between pheochromocytomas and paragangliomas.
- Abiraterone Acetate for Cushing's Syndrome: Study in a Canine Primary Adrenocortical Cell Culture Model. [Journal Article]
- EEndocrinology 2018 Sep 13
- Abiraterone acetate (AA) is a potent inhibitor of steroidogenic enzyme 17α-hydroxylase/17,20-lyase (CYP17A1). AA is approved for the treatment of prostate cancer, but could also be an interesting tre...
Abiraterone acetate (AA) is a potent inhibitor of steroidogenic enzyme 17α-hydroxylase/17,20-lyase (CYP17A1). AA is approved for the treatment of prostate cancer, but could also be an interesting treatment of Cushing's syndrome (CS). Similar to humans, canine glucocorticoid synthesis requires CYP17A1, providing a useful animal model. The objective of this study was to preclinically investigate the effect of AA on adrenocortical hormone production, cell viability, and mRNA expression of steroidogenic enzymes in canine primary adrenocortical cell cultures (n = 9) from the adrenal glands of nine healthy dogs. The cells were incubated with AA (0.125 nM - 10 μM) for 72 hours under basal conditions and with 100 nM ACTH(1-24). Adrenocortical hormone concentrations were measured in culture medium using liquid chromatography-mass spectrometry, RNA was isolated from cells for subsequent real-time quantitative PCR analysis, and cell viability was assessed with an alamarBlue™ assay. AA reduced cortisol (IC50 21.4 ± 4.6 nM) without affecting aldosterone under basal and ACTH-stimulated conditions. AA increased progesterone under basal and ACTH-stimulated conditions but reduced corticosterone under basal conditions, suggesting concurrent inhibition of 21-hydroxylation. AA did not affect the mRNA expression of steroidogenic enzymes and did not inhibit cell viability. In conclusion, primary canine adrenocortical cell culture is a useful model system for drug testing. For the treatment of CS, AA may to be superior to other steroidogenesis inhibitors due to its low toxicity. For future in vivo studies, dogs with endogenous CS may provide a useful animal model.
- Coping with stress, control of emotions and biochemical markers as a common protective element in the inflammatory response to stress. [Journal Article]
- PPPsychiatr Pol 2018 Jun 30; 52(3):511-524
- CONCLUSIONS: In difficult situations, accompanied by an increase in the variables responsible for the biochemical inflammatory response of an organism, the effective model of coping with difficult situations and emotioncontrol increases, while the subjective level of perceived stress drops.
- Developing an optimal follow-up strategy based on the natural history of nonfunctioning pituitary adenomas. [Journal Article]
- JNJ Neurosurg 2018 Sep 14; :1-7
- CONCLUSIONS: The authors have devised a follow-up strategy based on the tumor volume growth rate as well as initial tumor volume. In patients with microadenomas, the next MRI study can be performed at 3 years. In patients with macroadenomas, the second MRI study should be performed between 6 months and 1 year to assess the tumor growth rate. In patients with a tumor growth rate ≥ 0.88 cm3/year, the MRI study should be performed within 2 years. In patients with a tumor growth rate < 0.88 cm3/year, the MRI study can be delayed until 4 years.
- Growth hormone and prolactin-staining tumors causing acromegaly: a retrospective review of clinical presentations and surgical outcomes. [Journal Article]
- JNJ Neurosurg 2018 Sep 14; :1-7
- CONCLUSIONS: Acromegalics with tumors that stain for prolactin and GH, which represented almost a quarter of acromegalics in this cohort, had more aggressive clinical presentations and postoperative outcomes than SSAs. Prolactin staining provides useful information for acromegalics undergoing pituitary surgery.
- Adrenocortical function during prolonged critical illness and beyond: a prospective observational study. [Journal Article]
- ICIntensive Care Med 2018 Sep 13
- CONCLUSIONS: Irrespective of sepsis/septic shock, need for glucocorticoids and survival, low cortisol plasma binding proteins and suppressed cortisol breakdown determine systemic (free)cortisol availability in prolonged critical illness, the latter no longer elevated beyond ICU day 28. The uniform rise in ACTH and cortisol to supra-normal levels 1 week after ICU discharge indicates recovery of a central adrenocortical suppression while in ICU. Low cortisol plasma binding invalidates the cosyntropin test.
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- AZD8055 inhibits ACTH secretion in a case of bilateral ACTH-secreting pheochromocytoma. [Journal Article]
- OLOncol Lett 2018; 16(4):4561-4566
- Ectopic adrenocorticotropic hormone (ACTH) syndrome is usually caused by pulmonary and bronchial tumors and rarely by pheochromocytoma. To date, the majority of ACTH-secreting pheochromocytomas have ...
Ectopic adrenocorticotropic hormone (ACTH) syndrome is usually caused by pulmonary and bronchial tumors and rarely by pheochromocytoma. To date, the majority of ACTH-secreting pheochromocytomas have been unilateral, with the exception of two cases. A 54-year-old male presented with hypertension and bilateral adrenal tumors. The patient did not report having classic cushingoid features or experience of paroxysmal headaches or sweating, but presented with a slight abdominal obesity. The patient was clinically and pathologically diagnosed with bilateral ectopic ACTH-secreting pheochromocytomas. Whole-exome sequencing demonstrated that the 19 pheochromocytoma-related genes were unmutated. The pheochromocytomas on the two sides exhibited negative ACTH staining, but the ACTH concentration was markedly higher in the tumor tissue homogenates than in those tumors of another 3 patients with non-ACTH secretion pheochromocytoma. Electron microscopy identified two types of neuroendocrine cells in the tumor tissues. Primary culture of the pheochromocytoma cells revealed that ACTH secretion was inhibited by a mechanistic target of rapamycin inhibitor, AZD8055.