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Adrenocortical Hyperfunction
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RATIONALE: Typical pulmonary carcinoid is a kind of low-grade malignancy neuroendocrine tumor. Cushing's syndrome is a very rare clinical feature of typical pulmonary carcinoid caused by hypercorticism. Complete tumor resection is the standard curative treatment for primary typical pulmonary carcinoid. However, our knowledge on the gene level of typical pulmonary carcinoid is limited. PATIENT CONCERNS: A 42-year-old man was admitted to our hospital for progressive weight gain within one year. No other obvious symptoms were obsessed in this patient. He was clinical diagnosed with ectopic adrenocorticotropic hormone syndrome through hormonal tests and imaging exams. Positron emission tomography-computed tomography detected a pulmonary nodule localized in the middle lobe of the lung and it is thought to be the ectopic source. INTERVENTION: This patient received a pulmonary wedge resection. After the surgery, a genetic sequencing was performed and it reported a mutation (S1240Cfs*21) in the BCOR gene. DIAGNOSIS: Postoperative pathology confirmed the diagnosis of ACTH-producing typical pulmonary carcinoid. OUTCOMES: The patient had a smooth postoperative course and no recurrence of the tumor was found for 3 years. LESSONS: Mutation in BCOR gene is quite common in pulmonary neuroendocrine tumor and it has been proven to play a role in the development of some tumor. We herein first report BCOR gene mutation in Cushing's syndrome secondary to TPC and it may become a promising therapeutic target in the future.
Carcinoid Tumor (7), Cushing Syndrome (4), Neoplasms (3), more mentions
Hypertension (Dallas, Tex. : 1979)
Measurement of plasma aldosterone and renin concentration, or activity, is useful for selecting antihypertensive agents and detecting hyperaldosteronism in hypertensive patients. However, it takes several days to get results when measured by radioimmunoassay and development of more rapid assays has been long expected. We have developed chemiluminescent enzyme immunoassays enabling the simultaneous measurement of both aldosterone and renin concentrations in 10 minutes by a fully automated assay using antibody-immobilized magnetic particles with quick aggregation and dispersion. We performed clinical validation of diagnostic ability of this newly developed assay-based screening of 125 patients with primary aldosteronism from 97 patients with essential hypertension. Results of this novel assay significantly correlated with the results of radioimmunoassay (aldosterone, active renin concentration, and renin activity) and liquid chromatography-tandem mass spectrometry (aldosterone). The analytic sensitivity of this particularly novel active renin assay was 0.1 pg/mL, which was better than that of radioimmunoassay (2.0 pg/mL). The ratio of aldosterone-to-renin concentrations of 6.0 (ng/dL per pg/mL) provided 92.0% sensitivity and 76.3% specificity as a cutoff for differentiating primary aldosteronism from essential hypertension. This novel measurement is expected to be a clinically reliable alternative for conventional radioimmunoassay and to provide better throughput and cost effectiveness in diagnosis of hyperaldosteronism from larger numbers of hypertensive patients in clinical settings.
Cardiovascular Diseases (3)
Hyperaldosteronism (6), Hypertension (3), more mentions
The American journal of medicine
No Abstract Available
PURPOSE: To compare long-term outcomes in patients with adrenal incidentalomas (AIs) with the response to a 1 mg overnight dexamethasone suppression test (DST). METHODS: Consecutive patients with "non-functional" AIs (n = 365) were examined. Patients with overt hormone excess, adrenocortical cancer and known malignancy had been excluded. Patients were classified to normal cortisol secretion group (n = 204, DST ≤ 50 nmol/l), possible autonomous cortisol secretion group (n = 128, DST 51-138 nmol/l) and autonomous cortisol secretion group (n = 33, DST ≥ 138 nmol/l). RESULTS: Thirty-seven patients (10.1%) deceased during the follow-up period (5.2 ± 2.3 years): 16(7.8%) in the non-secreting group (time from diagnosis to death: 3.9 ± 2.9 years), 15 in the possible autonomous cortisol secretion group (11.7%, 3.2 ± 1.8 years) and 6 in the autonomous cortisol secretion group (18.2%, 2.3 ± 1.5 years), respectively (P = 0.019). Multivariate analysis only found significant association with age and the tumour size but if cortisol levels post-DST were analysed as a continuous variable it was significant as well. All deaths in autonomous cortisol secretion group were due to cancer not related to adrenal glands. Hypertension, cardiovascular disease and medications were more common in the possible and autonomous cortisol secretion group, especially in the former. More bilateral AIs and larger AI size were found in the two latter groups. CONCLUSIONS: Patients with autonomous cortisol secretion had higher mortality than those with non-functioning AIs though cortisol levels post-DST as a continuous variable, age and tumour size were better predictor of mortality. Cardiovascular disease and osteoporosis medication seemed more prevalent in the possible and autonomous cortisol secretion groups, especially in the former.
Cardiovascular Diseases (3), Oncology (3), Muscular and Skeletal Diseases (1)
Cardiovascular Diseases (2), Neoplasms (2), Osteoporosis (1), more mentions
5. Genetics of Cushing's disease.  
Date: 08/29/2017
Clinical endocrinology
Cushing's disease (CD) is a rare disabling condition caused by ACTH-secreting adenomas of the pituitary. The majority of corticotropic adenomas are monoclonal and occur sporadically. Only rarely does CD arise in the context of genetic familial syndromes. Targeted sequencing of oncogenes and tumour-suppressor genes commonly mutated in other tumours did not identify recurrent mutations. In contrast, next generation sequencing allowed us recently to clarify the genetic basis of CD: We identified somatic driver mutations in the ubiquitin-specific protease 8 (USP8) gene in a significant portion of corticotropinomas. These mutations represent a novel and unique mechanism leading to ACTH excess. Inhibition of USP8 or its downstream signalling pathways could represent a new therapeutic approach for the management of CD. In this review we will focus on this new evidence and its implication for clinical care of affected patients. This article is protected by copyright. All rights reserved.
Adenoma (2), Cushing Syndrome (1), Pituitary Adenoma (1), more mentions
Sleep medicine
OBJECTIVE: Previous studies have demonstrated the association between Cushing's syndrome (CS), obstructive sleep apnea (OSA), and the risk factors for OSA, but rarely provided the evidence within a large population. Using the Taiwan National Health Insurance Research Database, we attempted to investigate the association between CS and OSA, and to provide persuading evidences. METHODS: In our study, 1612 patients with CS and 1612 age-, sex-, and comorbidities-matched controls were included, and followed up to the end of 2011. Cases of OSA were identified during the follow-up. RESULTS: Among patients with CS, 53 developed OSA (incidence: 4.11 per thousand person-year) compared with 22 in the control group (incidence: 1.70 per thousand person-year) during the follow-up (p < 0.001). CS patients had a 2.82-fold higher risk of developing OSA (HR = 2.82; 95% CI: 1.67-4.77) in later life. DISCUSSION: Our study was the first longitudinal study to support the temporal association between CS and risk of OSA. Patients with CS were associated with an increased likelihood of OSA. Further studies would be required to investigate the exact underlying mechanisms between CS and OSA, and elucidate whether the prompt intervention for CS may reduce the risk of subsequent OSA.
Cushing Syndrome (3), Obstructive Sleep Apnea (3), more mentions
PURPOSE: Obesity and its metabolic impairments are discussed as major risk factors for sarcopenia leading to sarcopenic obesity. Cushing's syndrome is known to be associated with obesity and muscle atrophy. We compared Cushing's syndrome with matched obese controls regarding body composition, physical performance, and biochemical markers to test the hypothesis that Cushing's syndrome could be a model for sarcopenic obesity. METHODS: By propensity score matching, 47 controls were selected by body mass index and gender as obese controls. Fat mass and muscle mass were measured by bioelectrical impedance analysis. Muscle function was assessed by chair rising test and hand grip strength. Biochemical markers of glucose and lipid metabolism and inflammation (hsCRP) were measured in peripheral blood. RESULTS: Muscle mass did not differ between Cushing's syndrome and obese controls. However, Cushing's syndrome patients showed significantly greater chair rising time (9.5 s vs. 7.3 s, p = 0.008) and significantly lower hand grip strength (32.1 kg vs. 36.8 kg, p = 0.003). Cushing's syndrome patients with impaired fasting glucose have shown the highest limitations in hand grip strength and chair rising time. CONCLUSIONS: Similar to published data in ageing medicine, Cushing's syndrome patients show loss of muscle function that cannot be explained by loss of muscle mass. Impaired muscle quality due to fat infiltration may be the reason. This is supported by the observation that Cushing's syndrome patients with impaired glucose metabolism show strongest deterioration of muscle function. Research in sarcopenic obesity in elderly is hampered by confounding comorbidities and polypharmacy. As Cushing's syndrome patients are frequently free of comorbidities and as Cushing's syndrome is potentially curable we suggest Cushing's syndrome as a clinical model for further research in sarcopenic obesity.
Anti-Obesity and Weight Loss (13)
Cushing Syndrome (12), Obesity (9), Sarcopenia (2), more mentions
Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists
OBJECTIVE: To determine cut-off values of late-night salivary cortisol (LNSC) using an electrochemiluminescent immunoassay (ECLIA) and to investigate whether the diagnostic performance of the assay was influenced by the presence of obesity or polycystic ovary syndrome (PCOS). METHODS: A total of 124 subjects comprising 25 patients with Cushing's syndrome (CS), 44 with PCOS (22 nonobese and 22 obese), 21 with constitutional obesity (CO), and 34 healthy subjects (HS) were included in the study. Two consecutive LNSC samples were collected from all participants. RESULTS: The median LNSC levels of patients with CS were significantly higher than LNSC levels of HS, patients with CO, and obese and non-obese patients with PCOS, respectively (p<0.01 for all). Healthy subjects, patients with CO, and obese and non-obese patients with PCOS did not differ in terms of median LNSC levels (p>0.05 for all). The cut-off values and corresponding sensitivity and specificity were similar between the groups. The comparison of the area under curve (AUC) of the first (LNSC1) [0.963 (95% CI: 0.910-0.989)], second (LNSC2) [0.954 (95% CI: 0.898-0.984)], and the mean of two consecutive LNSC (mLNSC) [0.962 (95% CI: 0.909-0.989)] did not differ significantly from each other (p>0.05 for all). A cut-off value for mLNSC of 7.45 nmol/L yielded a sensitivity of 100% and specificity of 87.5% in HS. CONCLUSIONS: In conclusion, LNSC is a reliable test with high diagnostic accuracy in both HS and patients with PCOS and obesity.
Anti-Obesity and Weight Loss (8), Women's Health (1)
Obesity (4), Polycystic Ovary Syndrome (3), Cushing Syndrome (2), more mentions
European radiology
OBJECTIVES: To compare the performance of on-site quick cortisol assay (QCA) and C-arm computed tomography (CT) assistance on adrenal venous sampling (AVS) without adrenocorticotropic hormone stimulation. METHODS: The institutional review board at our hospital approved this retrospective study, which included 178 consecutive patients with primary aldosteronism. During AVS, we used C-arm CT to confirm right adrenal cannulation between May 2012 and June 2015 (n = 100) and QCA for bilateral adrenal cannulation between July 2015 and September 2016 (n = 78). Successful AVS required a selectivity index (cortisoladrenal vein/cortisolperipheral) of ≥ 2.0 bilaterally. RESULTS: The overall success rate of C-arm CT-assisted AVS was 87%, which increased to 97.4% under QCA (P = .013). The procedure time (C-arm CT, 49.5 ± 21.3 min; QCA, 37.5 ± 15.6 min; P < .001) and radiation dose (C-arm CT, 673.9 ± 613.8 mGy; QCA, 346.4 ± 387.8 mGy; P < .001) were also improved. The resampling rate was 16% and 21.8% for C-arm CT and QCA, respectively. The initial success rate of the performing radiologist remained stable during the study period (C-arm CT 75%; QCA, 82.1%, P = .259). CONCLUSIONS: QCA might be superior to C-arm CT for improving the performance of AVS. KEY POINTS: • Adrenal venous sampling (AVS) is a technically challenging procedure. • C-arm CT and quick cortisol assay (QCA) are efficient for assisting AVS. • QCA might outperform C-arm CT in enhancing AVS performance.
Hyperaldosteronism (2), more mentions
Clinical endocrinology
CONTEXT: Steroidogenesis inhibitors, such as ketoconazole (KTZ) and metyrapone (MTP), are used to lower hypercortisolism in patients with Cushing's syndrome (CS). Cortisol normalization is not reached in all patients taking these medications. OBJECTIVE: To test the hypothesis that variants in genes affecting steroidogenesis contribute to different responses to KTZ and/or MTP in patients with CS. PATIENTS AND METHODS: Fifty-four CS patients (46 women; mean [±SD] age, 39.7±12.7; 83% with Cushing's disease [CD] and 17% with an adrenal adenoma) preoperatively treated with KTZ (20%), MTP (37%) or a combination of both (43%). Thirty-nine of these (72%) were described in a previous study investigating the outcome of preoperative treatment with KTZ or MTP in CS patients. Following single-nucleotide polymorphisms (SNPs) were analysed: rs6410 (CYP11B1 gene), rs1799998 and rs4546 (CYP11B2 gene), and rs6163 (CYP17A1 gene). The associations between SNPs and cortisol levels at the end of medical treatment were evaluated. RESULTS: Normalization of urinary free cortisol (UFC) was achieved in 50% of patients after 5 months of treatment. Patients carrying the CC genotype of SNP rs6163 were more likely to be controlled than AC/AA (OR 0.25 [95%CI, 0.075-0.88]; P=.031). When only patients reaching eucortisolism after medical treatment were analysed, median interquartile range (IQR) duration of treatment was shorter in patients carrying the CC genotype of SNP rs6163 as compared to AA/AC carriers (4 [4.57] months vs 5.2 [6.1] months; P=.026). CONCLUSIONS: A polymorphism in the CYP17A1 gene was associated with the response to steroidogenesis inhibitors in CS. Genetic differences in the steroidogenic enzymes might account for inter-individual variations in the responsiveness to adrenal-blocking agents.
Cushing Syndrome (4), Adenoma (1), more mentions
Clinical endocrinology
Cushing's Syndrome (CS) is critical to identify because of the numerous and sometimes irreversible sequelae. Surreptitious glucocorticoid use is usually a straightforward consideration in the Cushingoid patient having suppressed ACTH levels, in the absence of adrenal mass or hyperplasia, and in whom screening tests for CS have unexpectedly low or high results depending on the specific steroid used and vulnerability of the assay employed to analytical cross-reactivity. We present a case of a patient with factitious hypercortisolism without suppressed ACTH. This article is protected by copyright. All rights reserved.
Cushing Syndrome (3), Hyperplasia (1), more mentions