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Updated: 6 hours 57 min ago

Cutaneous lupus erythematosus: updates on pathogenesis and associations with systemic lupus.

Fri, 07/28/2017 - 00:54
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Cutaneous lupus erythematosus: updates on pathogenesis and associations with systemic lupus.

Curr Opin Rheumatol. 2016 Sep;28(5):453-9

Authors: Stannard JN, Kahlenberg JM

Abstract
PURPOSE OF REVIEW: Cutaneous lupus erythematosus (CLE) is a common manifestation among systemic lupus patients. There are no U.S. Food and Drug Administration approved therapies for CLE, and these lesions are frequently disfiguring and refractory to treatment. The present review will cover the recent inroads made into understanding the mechanisms behind CLE lesions and discuss promising therapeutic developments.
RECENT FINDINGS: The definition of cutaneous lupus is being refined to facilitate diagnostic and research protocols. Research into the pathogenesis of CLE is accelerating, and discoveries are now identifying genetic and epigenetic changes which may predispose to particular disease manifestations. Furthermore, unique features of disease subtypes are being defined. Murine work supports a connection between cutaneous inflammation and systemic lupus disease activity. Importantly, human trials of type I interferon blockade hold promise for improving our treatment armamentarium for refractory CLE lesions.
SUMMARY: Continued research to understand the mechanisms driving CLE will provide new methods for prevention and treatment of cutaneous lesions. These improvements may also have important effects on systemic disease activity, and thus, efforts to understand this link should be supported.

PMID: 27270345 [PubMed - indexed for MEDLINE]

The Metabolism, Analysis, and Targeting of Steroid Hormones in Breast and Prostate Cancer.

Fri, 07/28/2017 - 00:54
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The Metabolism, Analysis, and Targeting of Steroid Hormones in Breast and Prostate Cancer.

Horm Cancer. 2016 Jun;7(3):149-64

Authors: Capper CP, Rae JM, Auchus RJ

Abstract
Breast and prostate cancers are malignancies in which steroid hormones drive cellular proliferation. Over the past century, this understanding has led to successful treatment strategies aimed to inhibit hormone-mediated tumor growth. Nonetheless, disease relapse and progression still pose significant clinical problems, with recurrent and metastatic tumors often exhibiting resistance to current drug therapies. The central role of androgens and estrogens in prostate and breast cancer etiology explains not only why endocrine therapies are often initially successful but also why many tumors ultimately become resistant. It is hypothesized that reducing the concentration of active hormones in the systemic circulation may be insufficient to block cancer progression, as this action selects for tumor cells that can generate active steroids from circulating precursors. This review aims to highlight the currently known differences of steroid biosynthesis in normal physiology versus hormone-dependent cancers, modern approaches to the assessment and targeting of these pathways, and priorities for future research.

PMID: 26969590 [PubMed - indexed for MEDLINE]

Diagnosis of pheochromocytoma in a hemodialysis patient through measurement of plasma catecholamines.

Fri, 07/28/2017 - 00:54
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Diagnosis of pheochromocytoma in a hemodialysis patient through measurement of plasma catecholamines.

Hemodial Int. 2016 Jul;20(3):E6-9

Authors: Vantomme B, Donck J, van Hooland S, Wauters A, De Clippele M, Neirynck V, Huysman F

Abstract
We report the case of a patient on chronic hemodialysis treatment with paroxysms of severe arterial hypertension accompanied by tachycardia, pallor, sweating and tremor. Measurement of plasma catecholamines revealed norepinephrine level of 4625 pg/mL (reference range 191-225 pg/mL), epinephrine level of 1035 pg/mL (58-76 pg/mL) and dopamine level of 148 pg/mL (50-100 pg/mL). MRI showed a left adrenal mass of 2 cm. After the patient was started on an alpha-1 adrenergic receptor blocker, she underwent a left adrenalectomy. Anatomopathological examination confirmed the diagnosis of pheochromocytoma. Although urinary testing is not possible in anuric hemodialysis patients, diagnosis of pheochromocytoma can be made through measurement of plasma free metanephrines and/or plasma catecholamines.

PMID: 26749316 [PubMed - indexed for MEDLINE]

adrenal tumor; +27 new citations

Fri, 07/21/2017 - 00:41

27 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

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These pubmed results were generated on 2017/07/21

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Functional Ulnar Nerve Paraganglioma: First Documented Occurrence in the Extremity With Hitherto Undescribed Associated Extensive Glomus Cell Hyperplasia and Tumorlet Formation.

Fri, 07/14/2017 - 00:19
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Functional Ulnar Nerve Paraganglioma: First Documented Occurrence in the Extremity With Hitherto Undescribed Associated Extensive Glomus Cell Hyperplasia and Tumorlet Formation.

Int J Surg Pathol. 2017 Jul 01;:1066896917720750

Authors: Chow LTC, Chan MHM, Wong SKC

Abstract
Extra-adrenal paraganglioma has never been described in the extremities. A 34-year-old woman complained of an enlarging mass in the right forearm for 18 months. Imaging showed a circumscribed vascular tumor attached to the ulnar nerve; biopsy revealed features of paraganglioma. The resected tumor consisted of zellballen pattern of chief cells staining positively for chromogranin with surrounding S100-positive sustentacular cells. The chief cells contained many neurosecretory granules and mitochondria, whereas the sustentacular cells contained a large amount of rough endoplasmic reticulum and some microfilaments. There was adjacent extensive glomus cell hyperplasia and tumorlet formation. The intraoperative blood pressure dropped abruptly on tumor removal. The serum normetanephrine level decreased from a preoperative level of 1987 pg/mL (normal < 149 pg/mL) to normal after operation. The patient admitted on questioning to a history of paroxysmal attacks of transient palpitation, hand tremors, and sweating; imaging showed no evidence of tumor in other parts of the body, and there was no family history of similar tumor; she remained well 33 months after the operation. This occurrence of functional ulnar nerve paraganglioma with the hitherto undescribed associated glomus cell hyperplasia and tumorlet formation attests to the probable existence of normal sympathetic paraganglia in the extremity and their intimate functional relationship with glomus bodies.

PMID: 28697655 [PubMed - as supplied by publisher]

Fluorine-18-FDG PET/CT in a patient with angiomyolipoma: Response to mammalian target of rapamycin inhibitor therapy.

Fri, 07/14/2017 - 00:19
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Fluorine-18-FDG PET/CT in a patient with angiomyolipoma: Response to mammalian target of rapamycin inhibitor therapy.

Hell J Nucl Med. 2017 Jul 12;:

Authors: Anwar H, Sachpekidis C, Schwarzbach M, Dimitrakopoulou-Strauss A

Abstract
We report on a 27 years old female patient who was referred to our department for whole-body as well as dynamic positron emission tomography/computed tomography (dPET/CT) scan of the upper and middle abdomen with fluorine-18-fluorodeoxy glucose ((18)F-FDG), for further evaluation of a mass in the left adrenal gland region. Positron emission tomography showed a suspicious, enlarged, hypermetabolic mass with an average standardized uptake value (SUV) of 4.5 and a maximum SUV of 5.9. The patient was referred for biopsy, which revealed an angiomyolipoma, a perivascular epithelioid cell tumor (PEComa) of the adrenal gland. Perivascular epithelioid cell tumors are mesenchymal tumors consisting of blood vessels, smooth muscles and fat cells. The patient received anti-proliferative treatment with Afinitor, a mammalian target of rapamycin (mTOR) inhibitor, and was referred again one month after onset of therapy for early response assessment. The follow-up (18)F-FDG PET/CT scan showed a nearly complete resolution of the previously detected adrenal mass, with very low tracer uptake and a decrease in its functional volume. Fluorine- 18-FDG PET/CT can be used for treatment response evaluation of angiomyolipoma treated with mTOR-inhibitors.

PMID: 28697195 [PubMed - as supplied by publisher]

Angiogenesis and Lymphangiogenesis in the Adrenocortical Tumors.

Fri, 07/14/2017 - 00:19
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Angiogenesis and Lymphangiogenesis in the Adrenocortical Tumors.

Pathol Oncol Res. 2017 Jul 10;:

Authors: Pereira SS, Costa MM, Guerreiro SG, Monteiro MP, Pignatelli D

Abstract
Adrenocortical tumors (ACT) are common adrenal tumors. The majority of ACTs are non-functioning and benign, while adrenocortical carcinomas (ACC) are rare, usually very aggressive and often metastasized when first diagnosed. Our aim was to assess whether blood and lymph vessel density within ACTs correlate with the malignancy character or tumor functionality. For that, the microvascular distribution was evaluated by immunohistochemistry staining with D2-40 antibody, for lymph vessels and CD-31 antibody, for blood vessels, in ACCs (n = 15), adenomas with Cushing syndrome (n = 9) and non-functioning adenomas (n = 10). The percentage of stained area was quantified by computerized morphometric analysis. D2-40 expression was significantly lower in ACC as compared to adenomas with Cushing syndrome (p < 0.01) and correlated positively with the expression of the steroidogenic acute regulatory protein (StAR) (R(2) = 0.553, p < 0.001). CD31 expression was found to be significantly higher in ACC as compared to adenomas with Cushing syndrome (p < 0.05). Our results show that angiogenesis is increased in ACC, suggesting that this phenomenon may have an important role in ACT biological behavior, while lymph vascular density seems to be more closely related to the tumor functional status than malignancy.

PMID: 28695321 [PubMed - as supplied by publisher]

Antidepressant effect of taurine in chronic unpredictable mild stress-induced depressive rats.

Fri, 07/14/2017 - 00:19
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Antidepressant effect of taurine in chronic unpredictable mild stress-induced depressive rats.

Sci Rep. 2017 Jul 10;7(1):4989

Authors: Wu GF, Ren S, Tang RY, Xu C, Zhou JQ, Lin SM, Feng Y, Yang QH, Hu JM, Yang JC

Abstract
Depression, a psychiatric and dysthymic disorder, severely affects the learning, work and life quality. The main pathogenesis of depression is associated with central nervous system (CNS) dysfunction. Taurine has been demonstrated to exert protective effects on the brain development and can improve learning ability and memory. Our study investigated the antidepressant-like effects of taurine pre-treatment by examining the changes in depression-like behavior, hormones, neurotransmitters, inflammatory factors and neurotrophic factors in the hippocampus of a chronic unpredictable mild stress (CUMS)-induced depressive rat model. Taurine was found to inhibit the decrease of sucrose consumption and prevent the deficiency of spatial memory and anxiety in rats exposed to CUMS, suggesting a preventive effect of taurine on depression-like behavior. Furthermore, the decreased levels of 5-hydroxytryptamine, dopamine, noradrenaline; the increased levels of glutamate, corticosterone; and the decreased expressions of fibroblast growth factor-2, vascular endothelial growth factor and brain derived neurotrophic factor in depressive rats were hindered by taurine pre-administration. However, tumor necrosis factor-α and interleukin-1β levels were not significantly changed by taurine. The results demonstrated that the anti-depressive effect of taurine may be involved in the regulation of hypothalamic-pituitary-adrenal (HPA) axis and the promotion of neurogenesis, neuronal survival and growth in the hippocampus.

PMID: 28694433 [PubMed - in process]

β-human chorionic gonadotropin-secreting intracranial germ-cell tumor associated with high testosterone in an adult man: A case report.

Fri, 07/14/2017 - 00:19
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β-human chorionic gonadotropin-secreting intracranial germ-cell tumor associated with high testosterone in an adult man: A case report.

Oncol Lett. 2017 Jul;14(1):1129-1132

Authors: Yang WP, Chien HY, Lin YC

Abstract
A 38-year-old male patient presented with general weakness, polydipsia and a body weight loss of 10 kg in two years. Hypopituitarism with central hypothyroidism and central adrenal insufficiency were noted at Taipei City Hospital (Taipei, Taiwan). However, hypogonadotropic hypergonadism was also observed. The patient was diagnosed with an intracranial β-human chorionic gonadotropin (β-hCG) secreting germ-cell tumor, and brain magnetic resonance imaging revealed that the tumor involved the pineal gland, stalk, posterior pituitary gland, right basal ganglion, hypothalamus, corpus callosum and posterior hippocampus. The cerebrospinal fluid (CSF) β-hCG level was 1936 IU/l, while the α-fetoprotein (AFP) level was <0.24 ng/ml. The serum AFP level of the patient was 3.28 ng/ml, and the β-hCG level was 178 IU/l with a CSF:serum β-hCG ratio >2:1. The patient was successfully treated with chemotherapy and radiotherapy, as demonstrated by a marked decrease in size of the tumor and in the serum β-hCG levels. Intracranial β-hCG secreting germ-cell tumors are rare in adults and manifest differently compared with patients of early pubertal age. In contrast with the precocious puberty frequently observed in young patients, the diagnosis of adult patients is often delayed and the symptoms are associated with tumor size and location. The present case report described an adult male with an intracranial β-hCG secreting GCT, demonstrating hypopituitarism and asymptomatic hyperandrogenemia, and reviews and discusses the literature relevant to the case.

PMID: 28693284 [PubMed - in process]

[Subclinical Cushing's syndrome in patients with incidental adrenal tumor].

Fri, 07/14/2017 - 00:19
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[Subclinical Cushing's syndrome in patients with incidental adrenal tumor].

Zhonghua Nei Ke Za Zhi. 2017 Jul 01;56(7):526-528

Authors:

PMID: 28693064 [PubMed - in process]

Diagnostic importance of 18F-FDG PET/CT parameters and total lesion glycolysis in differentiating between benign and malignant adrenal lesions.

Fri, 07/14/2017 - 00:19
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Diagnostic importance of 18F-FDG PET/CT parameters and total lesion glycolysis in differentiating between benign and malignant adrenal lesions.

Nucl Med Commun. 2017 Jul 07;:

Authors: Ciftci E, Turgut B, Cakmakcilar A, Erturk SA

Abstract
PURPOSE: Benign adrenal lesions are prevalent in oncologic imaging and make metastatic disease diagnoses difficult. This study evaluates the diagnostic importance of metabolic, volumetric, and metabolovolumetric parameters measured by fluorine-18-fluorodeoxyglucose (F-FDG) PET/CT in differentiating between benign and malignant adrenal lesions in cancer patients.
PATIENTS AND METHODS: In this retrospective study, we evaluated F-FDG PET/CT parameters of adrenal lesions of follow-up cancer patients referred to our clinic between January 2012 and November 2016. The diagnosis of adrenal malignant lesions was made on the basis of interval growth or reduction after chemotherapy. Patient demographics, analysis of metabolic parameters such as maximum standard uptake value (SUVmax), tumor SUVmax/liver SUVmean ratio (T/LR), morphologic parameters such as size, Hounsfield Units, and computed tomography (CT) volume, and metabolovolumetric parameters such as metabolic tumor volume and total lesion glycolysis (TLG) of adrenal lesions were calculated. PET/CT parameters were assessed using the Mann-Whitney U-test and receiving operating characteristic analysis.
RESULTS: In total, 186 adrenal lesions in 163 cancer patients (108 men/54 women; mean±SD age: 64±10.9 years) were subjected to F-FDG PET/CT for tumor evaluation. SUVmax values (mean±SD) were 2.8±0.8 and 10.6±6; TLG were 10.8±9.2 and 124.4±347.9; and T/LR were 1±0.3 and 4.1±2.6 in benign and malignant adrenal lesions, respectively. On the basis of the area under the curve, adrenal lesion SUVmax and T/LR had similar highest diagnostic performance for predicting malignant lesions (area under the curve: 0.993 and 0.991, respectively, P<0.001). Multivariate logistic regression analysis showed that T/LR, adrenal lesion SUVmax, and Hounsfield Units were independent predictive factors for malignancy rather than TLG.
CONCLUSION: Irrespective of whether TLG was statistically highly significant for differentiating benign from malignant adrenal lesions, it did not reach the expected performance with a low negative predictive value. This may be because of the malignant but small and benign but large lesions on metabolovolumetric calculation.

PMID: 28692494 [PubMed - as supplied by publisher]

Endocrine-related adverse events associated with immune checkpoint blockade and expert insights on their management.

Fri, 07/14/2017 - 00:19
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Endocrine-related adverse events associated with immune checkpoint blockade and expert insights on their management.

Cancer Treat Rev. 2017 Jun 22;58:70-76

Authors: Sznol M, Postow MA, Davies MJ, Pavlick AC, Plimack ER, Shaheen M, Veloski C, Robert C

Abstract
Agents that modulate immune checkpoint proteins, such as cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed death receptor-1 (PD-1), have become a mainstay in cancer treatment. The clinical benefit afforded by immune checkpoint inhibitors can be accompanied by immune-related adverse events (irAE) that affect the skin, gastrointestinal tract, liver, and endocrine system. The types of irAEs associated with immune checkpoint inhibitors are generally consistent across tumor types. Immune-related endocrine events can affect the pituitary, thyroid, and adrenal glands, as well as other downstream target organs. These events are unique when compared with other irAEs because the manifestations are often irreversible. Immune-related endocrine events are typically grade 1/2 in severity and often present with non-specific symptoms, making them difficult to diagnose. The mechanisms underlying immune-related target organ damage in select individuals remain mostly undefined. Management includes close patient monitoring, appropriate laboratory testing for endocrine function, replacement of hormones, and consultation with an endocrinologist when appropriate. An awareness of the symptoms and management of immune-related endocrine events may aid in the safe and appropriate use of immune checkpoint inhibitors in clinical practice.

PMID: 28689073 [PubMed - as supplied by publisher]

Update on Modern Management of Pheochromocytoma and Paraganglioma.

Fri, 07/14/2017 - 00:19
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Update on Modern Management of Pheochromocytoma and Paraganglioma.

Endocrinol Metab (Seoul). 2017 Jun;32(2):152-161

Authors: Lenders JWM, Eisenhofer G

Abstract
Despite all technical progress in modern diagnostic methods and treatment modalities of pheochromocytoma/paraganglioma, early consideration of the presence of these tumors remains the pivotal link towards the best possible outcome for patients. A timely diagnosis and proper treatment can prevent the wide variety of potentially catastrophic cardiovascular complications. Modern biochemical testing should include tests that offer the best available diagnostic performance, measurements of metanephrines and 3-methoxytyramine in plasma or urine. To minimize false-positive test results particular attention should be paid to pre-analytical sampling conditions. In addition to anatomical imaging by computed tomography (CT) or magnetic resonance imaging, new promising functional imaging modalities of photon emission tomography/CT using with somatostatin analogues such as ⁶⁸Ga-DOTATATE (⁶⁸Ga-labeled DOTA(0)-Tyr(3)-octreotide) will probably replace ¹²³I-MIBG (iodine-123-metaiodobenzylguanidine) in the near future. As nearly half of all pheochromocytoma patients harbor a mutation in one of the 14 tumor susceptibility genes, genetic testing and counseling should at least be considered in all patients with a proven tumor. Post-surgical annual follow-up of patients by measurements of plasma or urinary metanephrines should last for at least 10 years for timely detection of recurrent or metastatic disease. Patients with a high risk for recurrence or metastatic disease (paraganglioma, young age, multiple or large tumors, genetic background) should be followed up lifelong.

PMID: 28685506 [PubMed - in process]

Bilateral primary adrenal diffuse large B cell lymphoma without adrenal insufficiency: A case report and review of the literature.

Fri, 07/14/2017 - 00:19
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Bilateral primary adrenal diffuse large B cell lymphoma without adrenal insufficiency: A case report and review of the literature.

Mol Clin Oncol. 2017 Jul;7(1):145-147

Authors: Chen P, Jin L, Yang Y, Ni L, Yang S, Lai Y

Abstract
Primary adrenal lymphoma (PAL) is an infrequent malignant tumor, occurring in the bilateral adrenal glands as a mass in the majority of cases. The current study presents a case of bilateral primary adrenal diffuse large B cell lymphoma in a 52-year-old female patient, who presented with abdominal pain in the left lumbar region for ~2 weeks. Abdominal ultrasound examination and computed tomography scanning revealed a mass of 132×119×101 mm on the left adrenal gland and a mass of 53×27 mm on the right adrenal gland. A percutaneous biopsy was performed and histopathological examination further confirmed this lesion as diffuse large B cell lymphoma. The present study highlights the importance of early diagnosis of PAL, and performs a literature review of the subject.

PMID: 28685093 [PubMed - in process]

Nonfunctional pancreatic neuroendocrine tumor masked as anemia: A case report.

Fri, 07/14/2017 - 00:19
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Nonfunctional pancreatic neuroendocrine tumor masked as anemia: A case report.

Medicine (Baltimore). 2017 Jul;96(27):e7441

Authors: Xu B, Wang Y, Li X, Lin J

Abstract
After a series of clinical relevant examinations. The patient was dignosed as pancreatic tomor in the pancreatic tail accompanied with the symptom of anenmia and dizziness.Until now surgery is the best treatment strategy for pancreatic tumors.So we take a joint multiple organ removal surgery.Before surgery, the main concerns of patient is whether the operation can relieve the anemia-related symptoms and improve the quality of life.The patient was dignosed as nonfunctional pancreatic neuroendocrine tumor.A joint multiple organ removal surgery including pancreaticbody and tail, spleen, part of the stomach wall, left adrenal gland,and portal splenic vein thrombosis and lymphadenectomy were performed on this patient.After surgery, the concentration of hemoglobin gradually increased and remained stable (88 g/L) on the postoperative day7. Furthermore, complete resolution of the symptom of anemia was achieved on postoperative day 30. There was no recurrence of the tumor or the symptom of anemia during the 3-month follow-up.We conclude that NF-PNETs can manifest as anemia at the time of diagnosis, and if the tumor is resectable, surgical resection is a safe and curative form of therapy not only for the anemia but also for the original tumor.

PMID: 28682910 [PubMed - in process]

Effects of Cellular 11β-hydroxysteroid Dehydrogenase 1 on LPS-induced Inflammatory Responses in Synovial Cell Line, SW982.

Fri, 07/14/2017 - 00:19
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Effects of Cellular 11β-hydroxysteroid Dehydrogenase 1 on LPS-induced Inflammatory Responses in Synovial Cell Line, SW982.

Immune Netw. 2017 Jun;17(3):171-178

Authors: Cho YS, Kim KN, Shim JH

Abstract
11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) catalyzes the conversion of inactive cortisone into active cortisol, which has pleiotropic roles in various biological conditions, such as immunological and metabolic homeostasis. Cortisol is mainly produced in the adrenal gland, but can be locally regenerated in the liver, fat, and muscle. Its diverse actions are primarily mediated by binding to the glucocorticoid receptor. SW982, a human synovial cell line, expresses 11β-HSD type 1, but not type 2, that catalyzes the conversion of cortisone to cortisol. In this study, therefore, we investigated the control of lipopolysaccharide (LPS)-induced inflammatory responses by prereceptor regulation-mediated maintenance of cortisol levels. Preliminarily, cell seeding density and incubation period were optimized for analyzing the catalytic activity of SW982. Additionally, cellular 11β-HSD1 still remained active irrespective of monolayer or spheroid culture conditions. Inflammatory stimulants, such as interleukin (IL)-1β, tumor necrosis factor (TNF)α, and LPS, did not affect the catalytic activity of 11β-HSD1, although a high dose of LPS significantly decreased its activity. Additionally, autocrine effects of cortisol on inflammatory responses were investigated in LPS-stimulated SW982 cells. LPS upregulated pro-inflammatory cytokines, including IL-6 and IL-1β, in SW982 cells, while cortisol production, catalyzed by cellular 11β-HSD1, downregulated LPS-stimulated cytokines. Furthermore, suppression of NFκB activation-mediated pro-inflammatory responses by cortisol was revealed. In conclusion, the activity of cellular 11β-HSD1 was closely correlated with suppression of LPS-induced inflammation. Therefore, these results partly support the notion that prereceptor regulation of locally regenerated cortisol could be taken into consideration for treatment of inflammation-associated diseases, including arthritis.

PMID: 28680378 [PubMed - in process]

Glomus Tumor of the Larynx: A Rare Synchronous Paraganglioma in a Patient with Bilateral Carotid Body Tumor Detected on (68)Ga-DOTANOC PET/CT.

Fri, 07/14/2017 - 00:19
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Glomus Tumor of the Larynx: A Rare Synchronous Paraganglioma in a Patient with Bilateral Carotid Body Tumor Detected on (68)Ga-DOTANOC PET/CT.

Indian J Nucl Med. 2017 Jul-Sep;32(3):241-242

Authors: Tripathy S, Mukherjee A, Singh CA, Jat B, Bal C, Shamim SA

Abstract
Paragangliomas are neoplasms arising from extra-adrenal chromaffin tissue. They frequently cause symptoms by overproduction of catecholamines with known predilection to multicentricity. We describe the case of a patient with bilateral carotid body tumor who underwent a baseline 68 Gallium labeled [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-NaI3-Octreotide.

PMID: 28680217 [PubMed - in process]

Feedback inhibition of CREB signaling by p38 MAPK contributes to the negative regulation of steroidogenesis.

Fri, 07/14/2017 - 00:19
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Feedback inhibition of CREB signaling by p38 MAPK contributes to the negative regulation of steroidogenesis.

Reprod Biol Endocrinol. 2017 Mar 16;15(1):19

Authors: Li J, Zhou Q, Ma Z, Wang M, Shen WJ, Azhar S, Guo Z, Hu Z

Abstract
BACKGROUND: Steroidogenesis is a complex, multi-steps biological process in which, cholesterol precursor is converted to steroids in a tissue specific and tropic hormone dependent manner. Given that steroidogenesis is achieved by coordinated functioning of multiple tissue specific enzymes, many steroids intermediates/metabolites are generated during this process. Both the steroid products as well as major lipoprotein cholesterol donor, high-density lipoprotein 3 (hHDL3) have the potential to negatively regulate steroidogenesis via increased oxidative stress/reactive oxygen species (ROS) generation.
METHODS: In the current study, we examined the effects of treatment of a mouse model of steroidogenesis, Y1-BS1 adrenocortical tumor cells with pregnenolone, 22(R)-Hydroxycholesterol [22(R)-diol] or hHDL3 on ROS production, phosphorylation status of p38 MAPK and cAMP response element-binding protein (CREB), CREB transcriptional activity and mRNA expression of StAR, CPY11A1/P450scc and antioxidant enzymes, superoxide dismutases [Cu,ZnSOD (SOD1), MnSOD (SOD2)], catalase (CAT) and glutathione peroxidase 1 (GPX1). We also detected the steroid product in p38 MAPK inhibitor treated Y1 cells by HPLC-MS / MS.
RESULTS: Treatment of Y1 cells with H2O2 greatly enhanced the phosphorylation of both p38 MAPK and CREB protein. Likewise, treatment of cells with pregnenolone, 22(R) diol or hHDL3 increased ROS production measured with the oxidation-sensitive fluorescent probe 2',7'-Dichlorofluorescin diacetate (DCFH-DA). Under identical experimental conditions, treatment of cells with these agents also increased the phosphorylation of p38 MAPK and CREB. This increased CREB phosphorylation however, was associated with its decreased transcriptional activity. The stimulatory effects of pregnenolone, 22(R)-diol and hHDL3 on CREB phosphorylation was abolished by a specific p38 MAPK inhibitor, SB203580. Pregnenolone, and 22(R) diol but not hHDL3 upregulated the mRNA expression of SOD1, SOD2 and GPX1, while down-regulated the mRNA levels of StAR and CYP11A1. The p38 inhibitor SB203580 could increase the steroid production in HDL3, 22(R)-diol or pregnenolone treated cells.
CONCLUSION: Our data demonstrate induction of a ROS/p38 MAPK -mediated feedback inhibitory pathway by oxy-cholesterol and steroid intermediates and products attenuates steroidogenesis via inhibition of CREB transcriptional activity.

PMID: 28302174 [PubMed - indexed for MEDLINE]

Symptom-dependent cut-offs of urine metanephrines improve diagnostic accuracy for detecting pheochromocytomas in two separate cohorts, compared to symptom-independent cut-offs.

Fri, 07/14/2017 - 00:19
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Symptom-dependent cut-offs of urine metanephrines improve diagnostic accuracy for detecting pheochromocytomas in two separate cohorts, compared to symptom-independent cut-offs.

Endocrine. 2016 Oct;54(1):206-216

Authors: Cho YY, Song KH, Kim YN, Ahn SH, Kim H, Park S, Suh S, Kim BJ, Lee SY, Chun S, Koh JM, Lee SH, Kim JH

Abstract
The development of advanced imaging techniques has increased the detection of subclinical pheochromocytomas. Because of the substantial proportions of subclinical pheochromocytomas, measurement of urine metanephrine concentrations is crucial due to detect or exclude pheochromocytoma. Although urine metanephrines are elevated in symptomatic subjects, diagnostic cut-offs according to the presence of adrenergic symptoms have not been studied. Pheochromocytomas patients who underwent adrenalectomy at Samsung Medical Center and a control group were compared to determine cut-off concentrations of urine metanephrines. An independent population was analyzed for urine metanephrines with different kits to validate the improvement in diagnostic accuracy using adjusted cut-offs. Symptom-dependent cut-offs of urine metanephrines were higher for symptomatic patients (307 μg/day in males, 235 μg/day in females for urine metanephrine, and 1,045 μg/day in males and 457 μg/day in females for urine normetanephrine) than for asymptomatic patients (206 μg/day in males, 199 μg/day in females for urine metanephrine, and 489 μg/day in males and 442 μg/day in females for urine normetanephrine). Symptom-dependent cut-offs of urine metanephrines improved a specificity from 92.7 % to 96.3 % and a high sensitivity of 97.8 % was maintained. Using the Symptom-dependent cut-offs raised diagnostic accuracy by 5.5 % (p <0.001). Similar trend was also observed in an independent population using different hormone kits. Using symptom-dependent cut-offs of urine metanephrines in symptomatic patients for pheochromocytomas resulted in a significant improvement in diagnostic accuracy in two separate cohorts.

PMID: 27481364 [PubMed - indexed for MEDLINE]

Worsening of lipid metabolism after successful treatment of primary aldosteronism.

Fri, 07/14/2017 - 00:19
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Worsening of lipid metabolism after successful treatment of primary aldosteronism.

Endocrine. 2016 Oct;54(1):198-205

Authors: Adolf C, Asbach E, Dietz AS, Lang K, Hahner S, Quinkler M, Rump LC, Bidlingmaier M, Treitl M, Ladurner R, Beuschlein F, Reincke M

Abstract
Primary aldosteronism (PA) describes the most frequent cause of secondary arterial hypertension. Recently, deterioration of lipid metabolism after adrenalectomy (ADX) for aldosterone-producing adenoma (APA) has been described. We analysed longitudinal changes in lipid profiles in a large prospective cohort of PA patients. Data of 215 consecutive PA patients with APA (n = 144) or bilateral idiopathic adrenal hyperplasia (IHA, n = 71) were extracted from the database of the German Conn's Registry. Patients were investigated before and 1 year after successful treatment by ADX or by mineralocorticoid receptor antagonists (MRA). Glomerular filtration rate (GFR), fasting plasma glucose and components of lipid metabolism including triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were determined at 8.00 after a 12-h fasting period. One year after initiation of treatment mean serum potassium levels and blood pressure normalized in the patients. HDL-C and TG developed inversely with decreasing HDL-C levels in patients with APA (p = .046) and IHA (p = .004) and increasing TG levels (APA p = .000; IHA p = .020). BMI remained unchanged and fasting plasma glucose improved in patients with APA (p = .004). Furthermore, there was a significant decrease of GFR in both subgroups at follow-up (p = .000). Changes in HDL-C and TG correlated with decrease in GFR in multivariate analysis (p = .024). Treatment of PA is associated with a deterioration of lipid parameters despite stable BMI and improved fasting plasma glucose and blood pressure. This effect can be explained by renal dysfunction following ADX or MRA therapy.

PMID: 27179655 [PubMed - indexed for MEDLINE]

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