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NCBI: db=pubmed; Term=adrenal tumor
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Adrenal Vein Sampling Is the Preferred Method to Select Patients With Primary Aldosteronism for Adrenalectomy: Pro Side of the Argument.

Sun, 01/28/2018 - 00:10
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Adrenal Vein Sampling Is the Preferred Method to Select Patients With Primary Aldosteronism for Adrenalectomy: Pro Side of the Argument.

Hypertension. 2018 01;71(1):5-9

Authors: Rossi GP, Funder JW

PMID: 29229742 [PubMed - indexed for MEDLINE]

Isorhapontigenin, a bioavailable dietary polyphenol, suppresses airway epithelial cell inflammation through a corticosteroid-independent mechanism.

Sun, 01/28/2018 - 00:10
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Isorhapontigenin, a bioavailable dietary polyphenol, suppresses airway epithelial cell inflammation through a corticosteroid-independent mechanism.

Br J Pharmacol. 2017 Jul;174(13):2043-2059

Authors: Yeo SCM, Fenwick PS, Barnes PJ, Lin HS, Donnelly LE

Abstract
BACKGROUND AND PURPOSE: Chronic obstructive pulmonary disease (COPD) is a corticosteroid-resistant airway inflammatory condition. Resveratrol exhibits anti-inflammatory activities in COPD but has weak potency and poor pharmacokinetics. This study aimed to evaluate the potential of isorhapontigenin, another dietary polyphenol, as a novel anti-inflammatory agent for COPD by examining its effects in vitro and pharmacokinetics in vivo.
EXPERIMENTAL APPROACH: Primary human airway epithelial cells derived from healthy and COPD subjects, and A549 epithelial cells were incubated with isorhapontigenin or resveratrol and stimulated with IL-1β in the presence or absence of cigarette smoke extract. Effects of isorhapontigenin and resveratrol on the release of IL-6 and chemokine (C-X-C motif) ligand 8 (CXCL8), and the activation of NF-κB, activator protein-1 (AP-1), MAPKs and PI3K/Akt/FoxO3A pathways were determined and compared with those of dexamethasone. The pharmacokinetic profiles of isorhapontigenin, after i.v. or oral administration, were assessed in Sprague-Dawley rats.
KEY RESULTS: Isorhapontigenin concentration-dependently inhibited IL-6 and CXCL8 release, with IC50 values at least twofold lower than those of resveratrol. These were associated with reduced activation of NF-κB and AP-1 and, notably, the PI3K/Akt/FoxO3A pathway, that was relatively insensitive to dexamethasone. In vivo, isorhapontigenin was rapidly absorbed with abundant plasma levels after oral dosing. Its oral bioavailability was approximately 50% higher than resveratrol.
CONCLUSIONS AND IMPLICATIONS: Isorhapontigenin, an orally bioavailable dietary polyphenol, displayed superior anti-inflammatory effects compared with resveratrol. Furthermore, it suppressed the PI3K/Akt pathway that is insensitive to corticosteroids. These favourable efficacy and pharmacokinetic properties support its further development as a novel anti-inflammatory agent for COPD.

PMID: 28369685 [PubMed - indexed for MEDLINE]

Individual and interactive sex-specific effects of acute restraint and systemic IFN-γ treatment on neurochemistry.

Sun, 01/28/2018 - 00:10
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Individual and interactive sex-specific effects of acute restraint and systemic IFN-γ treatment on neurochemistry.

Neurochem Int. 2017 Jan;102:95-104

Authors: Litteljohn D, Rudyk C, Razmjou S, Dwyer Z, Syed S, Hayley S

Abstract
Compelling evidence supports the involvement of the pro-inflammatory cytokines, IL-6, IFN-α and TNF-α in depression and related stress-associated pathologies. A role has also been suggested for the Th1-type cytokine, IFN-γ, with most mechanistic accounts focusing on the cytokine's capacity to induce indoleamine 2,3-dioxygenase (IDO), leading to diminished tryptophan and the generation of kynurenine metabolites. Beyond these IDO-dependent routes, there is surprisingly little evidence directly linking IFN-γ to alterations of brain regional monoamine activity and HPA axis functioning. Our specific aims in the present study were twofold: 1) assess the behavioural, plasma corticosterone and brain regional monoamine effects of acute systemic IFN-γ, with or without short duration restraint stress (15 min), and 2) determine the sex-specific nature of these effects. As predicted, IFN-γ stimulated monoaminergic activity within a number of stressor-sensitive limbic brain regions, most notably the paraventricular nucleus of the hypothalamus, central amygdala and prefrontal cortex. While several of these effects were sex-specific, there was little in the way of synergism between the cytokine and stressor treatments. Nonetheless, IFN-γ did synergistically interact with acute restraint stress to increase plasma corticosterone concentrations, and this effect was most pronounced in the male mice. These data are among the first to show that systemically administered IFN-γ can alone or in conjunction with psychologically relevant stressor, modify brain regional monoamine activity and the plasma corticosterone response.

PMID: 27876634 [PubMed - indexed for MEDLINE]

Frequency of varicella zoster virus DNA in human adrenal glands.

Sun, 01/28/2018 - 00:10
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Frequency of varicella zoster virus DNA in human adrenal glands.

J Neurovirol. 2016 Jun;22(3):400-2

Authors: Badani H, White T, Schulick N, Raeburn CD, Topkaya I, Gilden D, Nagel MA

Abstract
Varicella zoster virus (VZV) becomes latent in ganglionic neurons derived from neural crest cells. Because the adrenal gland also contains medullary chromaffin cells of neural crest origin, we examined human adrenal glands and medullary chromaffin cell tumors (pheochromocytomas) for VZV and herpes simplex virus type 1 (HSV-1). We found VZV, but not HSV-1, DNA in 4/63 (6 %) normal adrenal glands. No VZV transcripts or antigens were detected in the 4 VZV DNA-positive samples. No VZV or HSV-1 DNA was found in 21 pheochromocytomas.

PMID: 26843382 [PubMed - indexed for MEDLINE]

A case of bilateral aldosterone-producing adenomas differentiated by segmental adrenal venous sampling for bilateral adrenal sparing surgery.

Sun, 01/28/2018 - 00:10
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A case of bilateral aldosterone-producing adenomas differentiated by segmental adrenal venous sampling for bilateral adrenal sparing surgery.

J Hum Hypertens. 2016 Jun;30(6):379-85

Authors: Morimoto R, Satani N, Iwakura Y, Ono Y, Kudo M, Nezu M, Omata K, Tezuka Y, Seiji K, Ota H, Kawasaki Y, Ishidoya S, Nakamura Y, Arai Y, Takase K, Sasano H, Ito S, Satoh F

Abstract
Primary aldosteronism due to unilateral aldosterone-producing adenoma (APA) is a surgically curable form of hypertension. Bilateral APA can also be surgically curable in theory but few successful cases can be found in the literature. It has been reported that even using successful adrenal venous sampling (AVS) via bilateral adrenal central veins, it is extremely difficult to differentiate bilateral APA from bilateral idiopathic hyperaldosteronism (IHA) harbouring computed tomography (CT)-detectable bilateral adrenocortical nodules. We report a case of bilateral APA diagnosed by segmental AVS (S-AVS) and blood sampling via intra-adrenal first-degree tributary veins to localize the sites of intra-adrenal hormone production. A 36-year-old man with marked long-standing hypertension was referred to us with a clinical diagnosis of bilateral APA. He had typical clinical and laboratory profiles of marked hypertension, hypokalaemia, elevated plasma aldosterone concentration (PAC) of 45.1 ng dl(-1) and aldosterone renin activity ratio of 90.2 (ng dl(-1) per ng ml(-1 )h(-1)), which was still high after 50 mg-captopril loading. CT revealed bilateral adrenocortical tumours of 10 and 12 mm in diameter on the right and left sides, respectively. S-AVS confirmed excess aldosterone secretion from a tumour segment vein and suppressed secretion from a non-tumour segment vein bilaterally, leading to the diagnosis of bilateral APA. The patient underwent simultaneous bilateral sparing adrenalectomy. Histopathological analysis of the resected adrenals together with decreased blood pressure and PAC of 5.2 ng dl(-1) confirmed the removal of bilateral APA. S-AVS was reliable to differentiate bilateral APA from IHA by direct evaluation of intra-adrenal hormone production.

PMID: 26538381 [PubMed - indexed for MEDLINE]

ARMC5 mutation analysis in patients with primary aldosteronism and bilateral adrenal lesions.

Sun, 01/28/2018 - 00:10
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ARMC5 mutation analysis in patients with primary aldosteronism and bilateral adrenal lesions.

J Hum Hypertens. 2016 Jun;30(6):374-8

Authors: Mulatero P, Schiavi F, Williams TA, Monticone S, Barbon G, Opocher G, Fallo F

Abstract
Idiopathic hyperaldosteronism (IHA) due to bilateral adrenal hyperplasia is the most common subtype of primary aldosteronism (PA). The pathogenesis of IHA is still unknown, but the bilateral disease suggests a potential predisposing genetic alteration. Heterozygous germline mutations of armadillo repeat containing 5 (ARMC5) have been shown to be associated with hypercortisolism due to sporadic primary bilateral macronodular adrenal hyperplasia and are also observed in African-American PA patients. We investigated the presence of germline ARMC5 mutations in a group of PA patients who had bilateral computed tomography-detectable adrenal alterations. We sequenced the entire coding region of ARMC5 and all intron/exon boundaries in 39 patients (37 Caucasians and 2 black Africans) with confirmed PA (8 unilateral, 27 bilateral and 4 undetermined subtype) and bilateral adrenal lesions. We identified 11 common variants, 5 rare variants with a minor allele frequency <1% and 2 new variants not previously reported in public databases. We did not detect by in silico analysis any ARMC5 sequence variations that were predicted to alter protein function. In conclusion, ARMC5 mutations are not present in a fairly large series of Caucasian patients with PA associated to bilateral adrenal disease. Further studies are required to definitively clarify the role of ARMC5 in the pathogenesis of adrenal nodules and aldosterone excess in patients with PA.

PMID: 26446392 [PubMed - indexed for MEDLINE]

Effectiveness and Safety of CT-guided Percutaneous Radiofrequency Ablation of Adrenal Metastases.

Sun, 01/21/2018 - 00:08
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Effectiveness and Safety of CT-guided Percutaneous Radiofrequency Ablation of Adrenal Metastases.

Br J Radiol. 2018 Jan 19;:20170607

Authors: Zhou K, Pan J, Yang N, Shi HF, Cao J, Li YM, Zhang HZ, Wang KF, Chen SH

Abstract
OBJECTIVE: The imaging-guided percutaneous radiofrequency (RF) ablation of adrenal metastases is a relatively new treatment procedure, compared to the more widespread application of the technique for the treatment of liver and renal cancers, the present study aims to evaluate the safety and efficacy of the computed tomography (CT)-guided percutaneous radiofrequency ablation of adrenal metastases in a cohort of patients.
METHODS: Thirty-three patients with 38 adrenal metastases who received percutaneous CT-guided radiofrequency ablation between 2012 to 2015 were retrospectively reviewed. The average diameter of the treated adrenal metastases was 3.0±1.6 cm. The treatment outcomes, including presence of residual tumors, technical success rate, recurrence rate, and complications, were evaluated. Patients were followed up for every 3 months to monitor the progression of the disease.
RESULTS: Postoperative CT images showed the lack of tumor enhancement in 30 tumors (30/38 tumors, technical success rate = 78.9%), and residual disease was found in 7 tumors (7/37 tumors, 18.9%). The rate of residual disease was significantly lower in the group with tumor size < 3cm than the group with tumor size ≥ 3 cm (p = 0.025). The severe complication rate was 4.3%, and the mild complication rate was 48%, with intraoperative hypertensive crisis as the most frequently observed complication (27.3%). The follow-up data showed that 76.3% of patients had recurrence-free survival in 27.4 months.
CONCLUSION: The current study demonstrated that radiofrequency ablation is a relatively safe and effective treatment for controlling adrenal metastases, especially for patients with tumor size < 3cm. Advances in knowledge: Surgical resection of the adrenal metastases was advocated as one of the treatment options for patients. The present study showed that radiofrequency ablation is a relatively safe and effective treatment for controlling adrenal metastases.

PMID: 29350539 [PubMed - as supplied by publisher]

Effects of surgery and anesthetic choice on immunosuppression and cancer recurrence.

Sun, 01/21/2018 - 00:08
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Effects of surgery and anesthetic choice on immunosuppression and cancer recurrence.

J Transl Med. 2018 Jan 18;16(1):8

Authors: Kim R

Abstract
BACKGROUND: The relationship between surgery and anesthetic-induced immunosuppression and cancer recurrence remains unresolved. Surgery and anesthesia stimulate the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system (SNS) to cause immunosuppression through several tumor-derived soluble factors. The potential impact of surgery and anesthesia on cancer recurrence was reviewed to provide guidance for cancer surgical treatment.
METHODS: PubMed was searched up to December 31, 2016 using search terms such as, "anesthetic technique and cancer recurrence," "regional anesthesia and cancer recurrence," "local anesthesia and cancer recurrence," "anesthetic technique and immunosuppression," and "anesthetic technique and oncologic surgery."
RESULTS: Surgery-induced stress responses and surgical manipulation enhance tumor metastasis via release of angiogenic factors and suppression of natural killer (NK) cells and cell-mediated immunity. Intravenous agents such as ketamine and thiopental suppress NK cell activity, whereas propofol does not. Ketamine induces T-lymphocyte apoptosis but midazolam does not affect cytotoxic T-lymphocytes. Volatile anesthetics suppress NK cell activity, induce T-lymphocyte apoptosis, and enhance angiogenesis through hypoxia inducible factor-1α (HIF-1α) activity. Opioids suppress NK cell activity and increase regulatory T cells.
CONCLUSION: Local anesthetics such as lidocaine increase NK cell activity. Anesthetics such as propofol and locoregional anesthesia, which decrease surgery-induced neuroendocrine responses through HPA-axis and SNS suppression, may cause less immunosuppression and recurrence of certain types of cancer compared to volatile anesthetics and opioids.

PMID: 29347949 [PubMed - in process]

A Case of Psychosis in a Patient with Secondary Adrenal Insufficiency: A Possible Etiological Role of a Hypocortisolemic-induced Increase in Proinflammatory Cytokines.

Sun, 01/21/2018 - 00:08
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A Case of Psychosis in a Patient with Secondary Adrenal Insufficiency: A Possible Etiological Role of a Hypocortisolemic-induced Increase in Proinflammatory Cytokines.

Innov Clin Neurosci. 2017 Sep-Oct;14(9-10):4-10

Authors: Spiegel DR, Nelson AB, Lieb DC, Pattison AM, Smith J, Zigrossi P, Godbout E

Abstract
Adrenal insufficiency is divided into three types based on the etiology of its development. In primary adrenal insufficiency, pathology resides in end-organ failure at the level of the adrenal cortex, while in secondary and tertiary adrenal insufficiency, impairment rests in the pituitary gland and hypothalamus, respectively. Regardless of etiology, adrenal insufficiency results in a hypocortisolemic condition. While the relationship between neuropsychiatric symptoms, especially psychosis, and hypercortisolemia has been extensively documented, the development of hypocortisolemia-induced psychosis is less common. We present a case of secondary adrenal insufficiency caused by a pituitary tumor. During the course of evaluation and treatment, the patient developed a psychotic episode. We will briefly review the condition of adrenal insufficiency and propose how hypocortisolemia can result in psychosis.

PMID: 29344425 [PubMed]

Extensive ARMC5 genetic variance in primary bilateral macronodular adrenal hyperplasia that started with exophthalmos: a case report.

Sun, 01/21/2018 - 00:08
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Extensive ARMC5 genetic variance in primary bilateral macronodular adrenal hyperplasia that started with exophthalmos: a case report.

J Med Case Rep. 2018 Jan 18;12(1):13

Authors: Jin P, Janjua MU, Zhang Q, Dong CS, Yang Y, Mo ZH

Abstract
BACKGROUND: Primary bilateral macronodular adrenal hyperplasia is a rare cause of Cushing's syndrome characterized by the presence of bilateral secretory adrenal nodules. Recent studies have shown that primary bilateral macronodular adrenal hyperplasia is caused by combined germline and somatic mutations of the ARMC5 gene. Exophthalmos is an underappreciated sign of Cushing's syndrome.
CASE PRESENTATION: A 52-year-old Chinese woman with progressively worsening bilateral proptosis presented to our hospital. Subsequently she was diagnosed as having primary bilateral macronodular adrenal hyperplasia and underwent bilateral laparoscopic adrenalectomy. Genomic deoxyribonucleic acid was isolated from lymphocytes as well as seven different adrenal nodules and the ARMC5 sequence was determined by Sanger sequencing. We identified one heterozygous ARMC5 germline mutation c.682C>T (p. Gln228*) and five heterozygous somatic mutations (c.310delG, c.347_357del11, c.267delC, c.283_289del7, and c.205-322del118) in five different adrenal nodules. All mutations are novel and were not found in any of the available online databases. To test whether the ARMC5 mutation induced messenger ribonucleic acid decay, real-time reverse transcriptase polymerase chain reaction was performed on patient and control adrenal tissue. We found that the adrenal cortex of our patient showed a low ARMC5 messenger ribonucleic acid expression compared with normal adrenal cortex, possibly as a result of nonsense-mediated messenger ribonucleic acid decay CONCLUSIONS: We demonstrated extensive genetic diversity of ARMC5 in a patient with primary bilateral macronodular adrenal hyperplasia that started with exophthalmos, which contributes to further understanding of the pathogenesis of this disease. Early recognition of atypical symptoms and screening for ARMC5 mutation in patients with primary bilateral macronodular adrenal hyperplasia has important clinical implications for the diagnosis and genetic counseling.

PMID: 29343284 [PubMed - in process]

Immunohistochemical Biomarkers of Mesenchymal Neoplasms in Endocrine Organs: Diagnostic Pitfalls and Recent Discoveries.

Sun, 01/21/2018 - 00:08
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Immunohistochemical Biomarkers of Mesenchymal Neoplasms in Endocrine Organs: Diagnostic Pitfalls and Recent Discoveries.

Endocr Pathol. 2018 Jan 16;:

Authors: Hung YP, Hornick JL

Abstract
Mesenchymal neoplasms rarely present in or adjacent to endocrine organs. In this context, the recognition of these rare tumor types can be challenging, with significant potential for misdiagnosis as sarcomatoid carcinomas (i.e., anaplastic thyroid carcinoma and sarcomatoid adrenal cortical carcinoma) or neuroendocrine carcinomas, depending upon the dominant histologic patterns. In this review, we address potential pitfalls in diagnosing selected mesenchymal neoplasms arising within or near endocrine organs, including dedifferentiated liposarcoma, synovial sarcoma, angiosarcoma, PEComa, proximal-type epithelioid sarcoma, Ewing sarcoma, and neuroblastoma. For each of these tumor types, we review clinical and pathologic features, histologic clues to distinguish them from endocrine neoplasms, and recently developed immunohistochemical markers that can be particularly useful for establishing the correct diagnosis.

PMID: 29340997 [PubMed - as supplied by publisher]

Gonadal Function in Adult Male Patients with Congenital Adrenal Hyperplasia.

Sun, 01/21/2018 - 00:08
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Gonadal Function in Adult Male Patients with Congenital Adrenal Hyperplasia.

Eur J Endocrinol. 2018 Jan 16;:

Authors: Engels M, Gehrmann K, Falhammar H, Webb EA, Nordenstrom A, Sweep F, Span PN, van Herwaarden AE, Rohayem J, Richter-Unruh A, Bouvattier C, Koehler B, Kortmann BB, Arlt W, Roeleveld N, Reisch N, Stikkelbroeck N, Claahsen-van der Grinten HL

Abstract
CONTEXT: Current knowledge on gonadal function in Congenital Adrenal Hyperplasia (CAH) is mostly limited to single center/country studies enrolling small patient numbers. Overall data indicate that gonadal function can be compromised in men with CAH.
OBJECTIVE: To determine gonadal function in men with CAH within the European "dsd-LIFE" cohort.
DESIGN: Cross-sectional clinical outcome study, including retrospective data from medical records.
METHODS: Fourteen academic hospitals included 121 men with CAH aged 16-68 years. Main outcome measures were serum hormone concentrations, semen parameters, and imaging data of the testes.
RESULTS: At the time of assessment, 14/69 patients had a serum testosterone concentration below the reference range; 7 of those were hypogonadotropic, 6 normogonadotropic, and 1 hypergonadotropic. In contrast, among the patients with normal serum testosterone (55/69), 4 were hypogonadotropic, 44 normogonadotropic, and 7hypergonadotropic. The association of decreased testosterone with reduced gonadotropin concentrations (Odds Ratio (OR)=12.8 [2.9-57.3]) was weaker than the association between serum androstenedione/testosterone ratio≥1 and reduced gonadotropin concentrations (OR=39.3 [2.1-732.4]). Evaluation of sperm quality revealed decreased sperm concentrations (15/39), motility (13/37), and abnormal morphology (4/28). Testicular adrenal rest tumor (TART)s were present in 39/80 patients, with a higher prevalence in patients with the most severe genotype (14/18), and in patients with increased current 17-hydroxyprogesterone (20/35) or androstenedione (12/18) serum concentrations. Forty-three children were fathered by 26/113 patients.
CONCLUSIONS: Men with CAH have a high risk of developing hypothalamic-pituitary-gonadal disturbances and spermatogenic abnormalities. Regular assessment of endocrine gonadal function and imaging for TART development are recommended, in addition to measures for fertility protection.

PMID: 29339528 [PubMed - as supplied by publisher]

LINC00673 rs11655237 C>T confers neuroblastoma susceptibility in Chinese population.

Sun, 01/21/2018 - 00:08
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LINC00673 rs11655237 C>T confers neuroblastoma susceptibility in Chinese population.

Biosci Rep. 2018 Jan 16;:

Authors: Zhang Z, Chang Y, Jia W, Zhang J, Zhang R, Zhu J, Yang T, Xia H, Zou Y, He J

Abstract
Neuroblastoma, which accounts for approximately 10% of all pediatric cancer-related deaths, has become a therapeutic challenge and global burden attributed to poor outcomes and mortality rates of its high-risk form. Previous genome-wide association studies identified the LINC00673 rs11655237 C>T polymorphism to be associated with the susceptibility of several malignant tumors. However, the association between this polymorphism and neuroblastoma susceptibility is not clear. We genotyped LINC00673 rs11655237 C>T in 393 neuroblastoma patients in comparison with 812 age-, gender- and ethnic-matched healthy controls. We found a significant association between the LINC00673 rs11655237 C>T polymorphism and neuroblastoma risk (TT vs. CC: adjusted odds ratio [OR]=1.80, 95% confidence interval [CI]=1.06-3.06, P =0.029; TT/CT vs. CC: adjusted OR=1.31, 95% CI=1.02-1.67, P =0.033; and T vs. C: adjusted OR=1.29, 95% CI=1.06-1.58, P =0.013). Furthermore, stratified analysis indicated that the rs11655237 T allele carriers were associated with increased neuroblastoma risk for patients with tumor originating from the adrenal gland (adjusted OR=1.51, 95% CI=1.06-2.14, P =0.021) and International Neuroblastoma Staging System stage IV disease (adjusted OR=1.60, 95% CI=1.12-2.30, P =0.011). In conclusion, we verified that the LINC00673 rs11655237 C>T polymorphism might be associated with neuroblastoma susceptibility. Prospective studies with a large sample size and different ethnicities are needed to validate our findings.

PMID: 29339420 [PubMed - as supplied by publisher]

[Endocrinopathies induced by immune checkpoint inhibitors].

Sun, 01/21/2018 - 00:08
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[Endocrinopathies induced by immune checkpoint inhibitors].

Rev Med Suisse. 2018 Jan 10;14(588-589):34-38

Authors: Jaafar J, Mavromati M, Philippe J

Abstract
Immune checkpoint Inhibitors are new immunomodulatory treatments that have proven their anti-tumor efficacy in several advanced cancers. Nevertheless, their use has paved the way for multiple immunological adverse effects that affect many systems and organs including endocrine glands such as the pituitary, thyroid, adrenal and pancreas. Hypophysitis is the most common complication of anti-CTLA-4 monoclonal antibodies, while anti-PD-1 and anti-PD-L1 antibodies cause more thyroid complications. Adrenal insufficiency and type 1 diabetes are relatively less common. Endocrinologists and primary care physicians as well as oncologists are likely to deal with these complications and as such, knowledge of these drugs and their side effects is essential for good practice.

PMID: 29337446 [PubMed - in process]

Effects of Macrolide and Corticosteroid in Neutrophilic Asthma Mouse Model.

Sun, 01/21/2018 - 00:08
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Effects of Macrolide and Corticosteroid in Neutrophilic Asthma Mouse Model.

Tuberc Respir Dis (Seoul). 2018 Jan;81(1):80-87

Authors: An TJ, Rhee CK, Kim JH, Lee YR, Chon JY, Park CK, Yoon HK

Abstract
BACKGROUND: Asthma is a disease of chronic airway inflammation with heterogeneous features. Neutrophilic asthma is corticosteroid-insensitive asthma related to absence or suppression of TH2 process and increased TH1 and/or TH17 process. Macrolides are immunomodulatory drug that reduce airway inflammation, but their role in asthma is not fully known. The purpose of this study was to evaluate the role of macrolides in neutrophilic asthma and compare their effects with those of corticosteroids.
METHODS: C57BL/6 female mice were sensitized with ovalbumin (OVA) and lipopolysaccharides (LPS). Clarithromycin (CAM) and/or dexamethasone (DXM) were administered at days 14, 15, 21, 22, and 23. At day 24, the mice were sacrificed.
RESULTS: Airway resistance in the OVA+LPS exposed mice was elevated but was more attenuated after treatment with CAM+DXM compared with the monotherapy group (p<0.05 and p<0.01). In bronchoalveolar lavage fluid study, total cells and neutrophil counts in OVA+LPS mice were elevated but decreased after CAM+DXM treatment. In hematoxylin and eosin stain, the CAM+DXM-treated group showed less inflammation additively than the monotherapy group. There was less total protein, interleukin 17 (IL-17), interferon γ, and tumor necrosis factor α in the CAM+DXM group than in the monotherapy group (p<0.001, p<0.05, and p<0.001). More histone deacetylase 2 (HDAC2) activity was recovered in the DXM and CAM+DXM challenged groups than in the control group (p<0.05).
CONCLUSION: Decreased IL-17 and recovered relative HDAC2 activity correlated with airway resistance and inflammation in a neutrophilic asthma mouse model. This result suggests macrolides as a potential corticosteroid-sparing agent in neutrophilic asthma.

PMID: 29332324 [PubMed]

Posterior Retroperitoneoscopic Resection of Extra-adrenal Paraganglioma Located in the Aorto-caval Space.

Sun, 01/21/2018 - 00:08
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Posterior Retroperitoneoscopic Resection of Extra-adrenal Paraganglioma Located in the Aorto-caval Space.

Ann Surg Oncol. 2018 Jan 12;:

Authors: Kang SW, Kandil E, Kim MJ, Kim KS, Lee CR, Jeong JJ, Nam KH, Chung WY, Park CS

Abstract
BACKGROUND: The posterior retroperitoneoscopic adrenalec tomy has several advantages compared with the transperitoneal approach such as a shorter and more direct route to the target organ, no breach of the intraperitoneal space, and no required retraction of the adjacent organs. It also is a safe procedure with a short learning curve.1-5 This report presents a challenging case of an extra-adrenal paraganglioma located in the aorto-caval space and managed using the retroperitoneal approach.
METHODS: A 39-year-old man was placed in the prone jackknife position, and three incisions were made in the right posterior abdominal wall for placement of the laparoscopic ports. The retroperitoneal space was entered with diathermy and blunt finger dissection, and retropneumoperitoneum was achieved with carbon dioxide insufflation pressure up to 18 mmHg. After identification of the right kidney and vessels, the tumor was meticulously dissected and excised with an energy device. The specimen was removed using a laparoscopic specimen retrieval bag, and the port sites were closed in layers.
RESULTS: The operative time was 130 min, and the total blood loss was 30 ml. The tumor was diagnosed as a moderately differentiated extra-adrenal paraganglioma. The Von Hippel-Lindau gene mutation was detected using next-generation sequencing.
CONCLUSIONS: The posterior retroperitoneoscopic approach is a safe, feasible, and effective method for excising an extra-adrenal paraganglioma even in the aorto-caval space. The authors suggest that this procedure is a useful surgical option for treatment of an aorto-caval paraganglioma for selected patients and by experienced surgeons.

PMID: 29330717 [PubMed - as supplied by publisher]

Testicular adrenal rest tumor screening and fertility counseling among males with congenital adrenal hyperplasia.

Sun, 01/21/2018 - 00:08
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Testicular adrenal rest tumor screening and fertility counseling among males with congenital adrenal hyperplasia.

J Pediatr Urol. 2017 Dec 21;:

Authors: Chaudhari M, Johnson EK, DaJusta D, Nahata L

Abstract
BACKGROUND: Reduced fertility is a common potential problem among males with congenital adrenal hyperplasia (CAH), with nearly half experiencing impaired sperm production. The major cause of oligo/azoospermia in CAH is testicular adrenal rest tumors (TARTs). Studies indicate that ultrasound screening for TARTs should begin during childhood, yet it remains unclear whether boys with CAH are routinely screened for TARTs and/or counseled about infertility risk and potential interventions such as fertility testing and/or preservation.
OBJECTIVE: The purpose of this study was to examine TART screening and fertility counseling practices among boys with CAH.
STUDY DESIGN: An IRB-approved retrospective chart review was conducted of all males with ICD-9/10 codes for CAH (2007-2016) at a large pediatric academic center to examine: age and indication for diagnosis; age at first and last documented pediatric endocrinology and urology visit; history of ultrasound examinations; and documentation of fertility counseling.
RESULTS: Forty-six patients were included, of whom 38 had 21-hydroxylase deficiency. Median age at diagnosis was 2 weeks (range 7 days-10 years). Median age at the most recent pediatric endocrinology clinic visit was 14 years (range 2-42 years). Twenty-nine patients were >11 years old (63% of the sample) at the time of the study and 14 of these were >18 years old (30% of the sample). Seven patients (15%) had a screening ultrasound at some point in their care, of whom three had TARTs. Fertility was mentioned in the records of six subjects (13% of the sample). Six of the subjects (13%) had any mention of fertility in their records. None of the patients had biochemical testing or semen analysis to assess gonadal function, and none were offered fertility preservation. Only one patient was seen by a pediatric urologist.
DISCUSSION: Despite the limitations of a single-center retrospective design, our findings highlight that TART screening and fertility counseling remain underutilized in boys with CAH. There is a need for increased awareness and development of practice guidelines within pediatric urology and endocrinology to address this common and understudied problem.
CONCLUSION: In addition to a screening ultrasound in puberty and consideration of semen analysis after puberty, these boys may benefit from seeing a pediatric urologist independently or in an interdisciplinary program. Boys with CAH and their families should be educated about infertility risk and potential interventions, with the goal of improving reproductive outcomes in this population.

PMID: 29330018 [PubMed - as supplied by publisher]

Aldosterone-Producing Adenomas: Genotypes and Phenotypes.

Sun, 01/21/2018 - 00:08
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Aldosterone-Producing Adenomas: Genotypes and Phenotypes.

Hypertension. 2017 07;70(1):38-41

Authors: Satoh F, Sasano H, Yamazaki Y, Ito S

PMID: 28584015 [PubMed - indexed for MEDLINE]

Hypoxia potentiates the cytotoxic effect of piperlongumine in pheochromocytoma models.

Sun, 01/21/2018 - 00:08
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Hypoxia potentiates the cytotoxic effect of piperlongumine in pheochromocytoma models.

Oncotarget. 2016 Jun 28;7(26):40531-40545

Authors: Bullova P, Cougnoux A, Abunimer L, Kopacek J, Pastorekova S, Pacak K

Abstract
Hypoxia is a common feature of solid tumors that activates a plethora of pathways, resulting in proliferation and resistance of cancer cells to radio- and chemotherapy. Pheochromocytomas/paragangliomas (PHEOs/PGLs) with mutations in the gene coding for the subunit B of succinate dehydrogenase (SDHB) are the most aggressive forms of the disease, which is partially due to their pseudohypoxic character, metabolic abnormalities, and elevated reactive oxygen species (ROS) levels. We investigated the effect of piperlongumine (PL), a natural product with cytotoxic properties restricted to cancer cells by significantly increasing intracellular ROS levels, on PHEO cells. Here we report for the first time that PL mediates PHEO cell death by activating both apoptosis and necroptosis in vitro and in vivo. This effect is magnified in hypoxic conditions, making PL a promising potential candidate for use as a therapeutic option for patients with PHEO/PGL, including those with SDHB mutations.

PMID: 27244895 [PubMed - indexed for MEDLINE]

Risk factors for hypertensive attack during pheochromocytoma resection.

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Risk factors for hypertensive attack during pheochromocytoma resection.

Investig Clin Urol. 2016 05;57(3):184-90

Authors: Kwon SY, Lee KS, Lee JN, Ha YS, Choi SH, Kim HT, Kim TH, Yoo ES, Kwon TG

Abstract
PURPOSE: We aimed to retrospectively evaluate the risk factors for hypertensive attack during adrenalectomy in patients with pheochromocytoma. Despite the development of newer surgical and anesthetic techniques for the management of pheochromocytoma, intraoperative hypertensive attack continues to present a challenge.
MATERIALS AND METHODS: Data from 53 patients diagnosed with pheochromocytoma at Kyungpook National Uriversity Medical Center between January 2000 and June 2012 were retrospectively analyzed. The subjects were divided into 2 groups depending on the presence or absence of hypertensive attack at the time of surgery. Patient demographic characteristics and preoperative evaluations were assessed for their prognostic relevance with respect to hypertensive attack. A univariate analysis was conducted, and a multivariate logistic regression analysis was also performed.
RESULTS: In the univariate analysis, systolic blood pressure at presentation, preoperative hormonal status (including epinephrine, norepinephrine, vanillylmandelic acid, and metanephrine levels in a 24-hour urine sample), tumor size, and postoperative systolic blood pressure were significantly associated with the development of hypertensive attack. In the multivariate analysis, preoperative epinephrine level and tumor size were independent factors that predicted hypertensive attack. The highest odds ratio for tumor size (2.169) was obtained at a cutoff value of 4.25 cm and the highest odds ratio for preoperative epinephrine (1.020) was obtained at a cutoff value of 166.3 µg/d.
CONCLUSIONS: In this study, a large tumor size and an elevated preoperative urinary epinephrine level were risk factors for intraoperative hypertensive attack in patients with pheochromocytoma.

PMID: 27194549 [PubMed - indexed for MEDLINE]

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