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Basal and Post-ACTH Aldosterone and Its Ratios Are Useful During Adrenal Vein Sampling in Primary Aldosteronism.

Thu, 06/15/2017 - 14:02
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Basal and Post-ACTH Aldosterone and Its Ratios Are Useful During Adrenal Vein Sampling in Primary Aldosteronism.

J Clin Endocrinol Metab. 2016 Apr;101(4):1826-35

Authors: El Ghorayeb N, Mazzuco TL, Bourdeau I, Mailhot JP, Zhu PS, Thérasse E, Lacroix A

Abstract
ACTH improves selectivity, but can modify lateralization. Basal and post-ACTH ratios are important for surgical indication. Basal aldosterone contralateral suppression predicts residual hyperplasia and post-operative outcomes.

PMID: 26918291 [PubMed - indexed for MEDLINE]

adrenal tumor; +23 new citations

Thu, 06/08/2017 - 11:37

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

adrenal tumor

These pubmed results were generated on 2017/06/08

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.

Peripancreatic paraganglioma mimics pancreatic/gastrointestinal neuroendocrine tumor on fine needle aspiration: report of two cases and review of the literature.

Thu, 06/01/2017 - 09:12
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Peripancreatic paraganglioma mimics pancreatic/gastrointestinal neuroendocrine tumor on fine needle aspiration: report of two cases and review of the literature.

Diagn Cytopathol. 2017 May 30;:

Authors: Zeng J, Simsir A, Oweity T, Hajdu C, Cohen S, Shi Y

Abstract
Cytologic diagnosis of extra-adrenal paraganglioma presenting as a peripancreatic mass is challenging with a high error rate due to its rarity. We report two cases of peripancreatic masses identified by radiology. Endoscopic ultrasound-guided fine needle aspiration (FNA) of the masses showed a moderately cellular tumor composed of small to medium sized neoplastic cells with round to oval nuclei, arranged singly and in loose clusters. Focal rosette-like structures were present. The cells were positive for neuroendocrine markers (synaptophysin and chromogranin). A diagnosis of a neoplasm with neuroendocrine differentiation and neuroendocrine tumor was made respectively on FNA for each case. The subsequent surgical resection of the tumors revealed peripancreatic paraganglioma. Although paraganglioma has been reported in the literature, the detailed comparison of perpancreatic paraganglioma versus pancreatic/gastrointestinal neuroendocrine tumor is still lacking. Therefore using these two cases with literature review, we wish to illustrate the differential diagnosis between these two entities based on cytomorphology and immunohistochemical study.

PMID: 28560856 [PubMed - as supplied by publisher]

Complete Responses to Mitotane in Metastatic Adrenocortical Carcinoma-A New Look at an Old Drug.

Thu, 06/01/2017 - 09:12
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Complete Responses to Mitotane in Metastatic Adrenocortical Carcinoma-A New Look at an Old Drug.

Oncologist. 2017 May 30;:

Authors: Reidy-Lagunes DL, Lung B, Untch BR, Raj N, Hrabovsky A, Kelly C, Gerst S, Katz S, Kampel L, Chou J, Gopalan A, Saltz LB

Abstract
PURPOSE: Based largely on reports that predate modern reporting standards, mitotane has been considered a systemic treatment option for both hormone control and antitumor control of metastatic adrenocortical cancer (ACC), although the therapeutic window is narrow.
METHODS: We searched electronic medical records to identify patients with metastatic ACC treated and prescribed single agent mitotane at Memorial Sloan Kettering Cancer Center from March 15, 1989-September 18, 2015. Reference radiologists reviewed all imaging and determined efficacy according to Response Evaluation Criteria in Solid Tumors 1.1. Patient demographics, toxicities, and treatment outcomes were reviewed. Next generation sequencing was performed in selected cases.
RESULTS: Thirty-six patients were identified. The mean age was 54 and 50% had functional tumors. Grade 3 or greater toxicities were documented in 16 out of 36 patients (44%) and 17% had documented long term adrenal insufficiency. Progression of the disease as the best response occurred in 30 out of 36 patients (83%) and one patient (3%) experienced clinical progression. Three patients achieved a complete response (CR) (8%), one patient achieved a partial response (3%), and one patient (3%) had stable disease after slow disease progression prior to initiation of therapy (durable for 6 months). All responders had nonfunctional tumors. Next generation sequencing in two of the three CR patients was performed and failed to identify any novel alterations.
CONCLUSION: In this retrospective series, mitotane had a low response rate and low tumor control rate; however, a disproportionately high complete response rate suggested it should be used in selected individuals. Adrenal insufficiency is common with mitotane use and aggressive treatment with steroid supplementation should be considered when appropriate to avoid excess toxicities. Biomarkers are desperately needed to further define this disease. The Oncologist 2017;22:1-5 IMPLICATIONS FOR PRACTICE: This is the first objective report of single agent mitotane using modern objective criteria. Although the vast majority of patients did not respond (and toxicity was high), we identified a remarkable 8% complete response rate (i.e. cure) in biopsy proven stage IV adrenocortical cancer patients. Biomarkers are desperately needed for this rare disease.

PMID: 28559412 [PubMed - as supplied by publisher]

Systemic N-terminal fragments of adrenocorticotropin reduce inflammation- and stress-induced anhedonia in rats.

Thu, 06/01/2017 - 09:12
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Systemic N-terminal fragments of adrenocorticotropin reduce inflammation- and stress-induced anhedonia in rats.

Psychoneuroendocrinology. 2017 May 07;82:173-186

Authors: Markov DD, Yatsenko KA, Inozemtseva LS, Grivennikov IA, Myasoedov NF, Dolotov OV

Abstract
Emerging evidence implicates impaired self-regulation of the hypothalamic-pituitary-adrenal (HPA) axis and inflammation as important and closely related components of the pathophysiology of major depression. Antidepressants show anti-inflammatory effects and are suggested to enhance glucocorticoid feedback inhibition of the HPA axis. HPA axis activity is also negatively self-regulated by the adrenocorticotropic hormone (ACTH), a potent anti-inflammatory peptide activating five subtypes of melanocortin receptors (MCRs). There are indications that ACTH-mediated feedback can be activated by noncorticotropic N-terminal ACTH fragments such as a potent anti-inflammatory MC1/3/4/5R agonist α-melanocyte-stimulating hormone (α-MSH), corresponding to ACTH(1-13), and a MC3/5R agonist ACTH(4-10). We investigated whether intraperitoneal administration of rats with these peptides affects anhedonia, which is a core symptom of depression. Inflammation-related anhedonia was induced by a single intraperitoneal administration of a low dose (0.025mg/kg) of lipopolysaccharide (LPS). Stress-related anhedonia was induced by the chronic unpredictable stress (CUS) procedure. The sucrose preference test was used to detect anhedonia. We found that ACTH(4-10) pretreatment decreased LPS-induced increase in serum corticosterone and tumor necrosis factor (TNF)-α, and a MC3/4R antagonist SHU9119 blocked this effect. Both α-MSH and ACTH(4-10) alleviated LPS-induced anhedonia. In the CUS model, these peptides reduced anhedonia and normalized body weight gain. The data indicate that systemic α-MSH and ACTH(4-10) produce an antidepressant-like effect on anhedonia induced by stress or inflammation, the stimuli that trigger the release of ACTH and α-MSH into the bloodstream. The results suggest a counterbalancing role of circulating melanocortins in depression and point to a new approach for antidepressant treatment.

PMID: 28551512 [PubMed - as supplied by publisher]

A exceptional collision tumor of primary adrenal angiosarcoma and non-functioning adrenocortical adenoma.

Thu, 06/01/2017 - 09:12
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A exceptional collision tumor of primary adrenal angiosarcoma and non-functioning adrenocortical adenoma.

Pathol Res Pract. 2017 Apr 19;:

Authors: Takizawa K, Kohashi K, Negishi T, Taguchi K, Yamada Y, Nakamura M, Oda Y

Abstract
Primary adrenal angiosarcoma is an extremely rare vascular tumor. We report a case of a 63-year-old man with a collision tumor of epithelioid angiosarcoma and adrenocortical adenoma of the right adrenal gland. The adrenal tumor was incidentally observed by a preoperative computed tomography (CT) scan of penis squamous cell carcinoma. The patient underwent a right laparoscopic adrenalectomy, and the tumor size measured 34×34×15mm. Histological examination revealed two different tumor cell proliferations, namely epithelioid angiosarcoma and adrenocortical adenoma. He had no symptoms or abnormality in his endocrine studies, so the adrenocortical adenoma was considered non-functioning. Three months after the adrenalectomy, bilateral pleural metastasis was observed by CT scan and pleural biopsy. Paclitaxel monotherapy was performed, and the tumor retreated. The patient died one and a half years after the adrenalectomy, but the cause of death was believed to be another disease (metastatic penis squamous cell carcinoma). To the best of our knowledge, this is the fourth report of primary adrenal angiosarcoma combined with adrenocortical adenoma.

PMID: 28551383 [PubMed - as supplied by publisher]

Testicular tumors of adrenogenital syndrome: From physiopathology to therapy.

Thu, 06/01/2017 - 09:12
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Testicular tumors of adrenogenital syndrome: From physiopathology to therapy.

Presse Med. 2017 May 23;:

Authors: Naouar S, Braiek S, El Kamel R

Abstract
Testicular tumor of adrenogenital syndrome is a rare and benign anomaly usually presenting as bilateral testicular masses. It is the most important cause of infertility in adult male congenital adrenal hyperplasia. Distinction between testicular tumors of adrenogenital syndrome and Leydig cell tumors can be problematic; it is based on clinical, histopathologic, immunohistochemical and endocrine features. Biopsy is advised in cases of longstanding tumors in infertile patients and when surgery is indicated. Fertility preservation is a key management goal in testicular tumor of adrenogenital syndrome. In stages 2 and 3, intensified glucocorticoid treatment is recommended as a first step treatment. Sparing surgical approach is preferred for tumors of stage 4 and steroid unresponsive masses. Magnetic resonance imaging is recommended before surgery. The only indication of surgery in stage 5 is testicular pain.

PMID: 28549629 [PubMed - as supplied by publisher]

Birt-Hogg-Dubé Syndrome - report of two cases with two new mutations.

Thu, 06/01/2017 - 09:12
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Birt-Hogg-Dubé Syndrome - report of two cases with two new mutations.

J Dermatol Case Rep. 2017 Mar 31;11(1):12-15

Authors: Rato M, Monteiro AF, Parente J, Aranha J, Tavares E

Abstract
INTRODUCTION: Birt-Hogg-Dubé syndrome (BHDS) is a rare autosomal dominant genodermatosis characterized by cutaneous fibrofolliculomas and/or trichodiscomas, lung cysts, spontaneous pneumothorax and renal tumors. However, its clinical expression is highly variable. This syndrome is caused by germline mutations in the folliculin gene (FLCN) on chromosome 17p11.2.
MAIN OBSERVATIONS: Two men, 60 and 39-year-old, presented with a several year history of asymptomatic whitish papules scattered over the face and neck. Skin biopsies revealed fibrofolliculomas. The clinical diagnosis of BHDS was corroborated by identification of new heterozygotic mutations in FLCN gene, in exon 6 (C.573_574delinsT) and in exon 9 (c.1015C>T), respectively. Computed tomography scan of the thorax and abdomen showed pulmonary cysts with no suspicious kidneys lesions, and, in the case of the second patient, a mass in left adrenal gland. Laparoscopic left adrenalectomy was performed and histopathological examination was compatible with a malignant perivascular epithelioid cell tumor.
CONCLUSIONS: The presence of multiple fibrofolliculomas should raise the suspicion of BHDS. Patients with this syndrome, regardless of the detected mutation, should be carefully monitored to ensure that potentially serious disease-related conditions can be detected early.

PMID: 28539984 [PubMed - in process]

Robotic assisted laparoscopic excision of a retroperitoneal Ganglioneuroma.

Thu, 06/01/2017 - 09:12
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Robotic assisted laparoscopic excision of a retroperitoneal Ganglioneuroma.

Int Braz J Urol. 2017 May 23;43:

Authors: Burttet LM, Abreu FJDS, Varaschin GA, Silva B, Berger M

Abstract
INTRODUCTION: Ganglioneuromas are rare benign neoplasms of the sympathetic nervous system. We describe the case of an incidentally found ganglioneuroma in a woman. To our knowledge this is the first described case of robotic excision of a retroperitoneal ganglioneuroma.
CASE: A 41-year-old female had an incidental retroperitoneal mass found during a routine US. CT scan and MRI showed an 8.3cm homogeneous mass, adjacent to left kidney upper pole, with peripheral contrast enhancement. Metabolic tests were normal. Patient was positioned in a left flank position and five ports were introduced transperitoneally. A 4-arm Da Vinci SI was docked at a 45º angle to the table. Lesion was dissected along with left adrenal gland, beginning at the left renal hilum and proceeding cephalad.
RESULTS: Operating time was 325min and blood loss was 50ml. Patient was discharged after 72hours. There were no post-operative complications. Pathology showed ganglionic cells with neural tissue, and normal adrenal.
DISCUSSION: Ganglioneuromas rare benign tumors originating from neural crest and typically affect young adults. Most frequent locations are posterior mediastinum, retroperitoneum and adrenal gland. As in this case, ganglioneuromas are usually silent, slow growing tumors discovered incidentally or by mass effect. US and CT imaging may suggest the diagnosis while MRI findings can be specific for ganglioneuroma. Percutaneous biopsy is an option. Although benign, usually requires surgical excision for treatment.
CONCLUSIONS: Our case shows that a robotic approach is feasible and allows for meticulous and safe dissection of vascular structures, facilitating adequate hemostasis while maintaining oncological principles.

PMID: 28537695 [PubMed - as supplied by publisher]

Assessment of the potential activity of major dietary compounds as selective estrogen receptor modulators in two distinct cell models for proliferation and differentiation.

Thu, 06/01/2017 - 09:12
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Assessment of the potential activity of major dietary compounds as selective estrogen receptor modulators in two distinct cell models for proliferation and differentiation.

Toxicol Appl Pharmacol. 2017 Jun 15;325:61-70

Authors: Lecomte S, Lelong M, Bourgine G, Efstathiou T, Saligaut C, Pakdel F

Abstract
Estrogen receptors (ERs) α and β are distributed in most tissues of women and men. ERs are bound by estradiol (E2), a natural hormone, and mediate the pleiotropic and tissue-specific effects of E2, such as proliferation of breast epithelial cells or protection and differentiation of neuronal cells. Numerous environmental molecules, called endocrine disrupting compounds, also interact with ERs. Phytoestrogens belong to this large family and are considered potent therapeutic molecules that act through their selective estrogen receptor modulator (SERM) activity. Using breast cancer cell lines as a model of estrogen-dependent proliferation and a stably ER-expressing PC12 cell line as a model of neuronal differentiating cells, we studied the SERM activity of major dietary compounds, such as apigenin, liquiritigenin, daidzein, genistein, coumestrol, resveratrol and zearalenone. The ability of these compounds to induce ER-transactivation and breast cancer cell proliferation and enhance Nerve Growth Factor (NGF) -induced neuritogenesis was assessed. Surprisingly, although all compounds were able to activate the ER through an estrogen responsive element reporter gene, they showed differential activity toward proliferation or differentiation. Apigenin and resveratrol showed a partial or no proliferative effect on breast cancer cells but fully contributed to the neuritogenesis effect of NGF. However, daidzein and zearalenone showed full effects on cellular proliferation but did not induce cellular differentiation. In summary, our results suggest that the therapeutic potential of phytoestrogens can diverge depending on the molecule and the phenotype considered. Hence, apigenin and resveratrol might be used in the development of therapeutics for breast cancer and brain diseases.

PMID: 28396216 [PubMed - indexed for MEDLINE]

Advances in Psoriasis.

Thu, 06/01/2017 - 09:12
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Advances in Psoriasis.

South Med J. 2017 Jan;110(1):65-75

Authors: Smith J, Cline A, Feldman SR

Abstract
Psoriasis treatments range from topical treatments and phototherapy to oral systemic medications and injections. Despite good control of the disease when applying appropriate treatments (according to disease severity, insurance parameters, patient preference, and patients' ability to adhere), continued advancements will allow even better symptomatic control, reduced adverse effects, and patient satisfaction. This review aims to assess traditional and new psoriasis treatments and how to apply them in clinical practice. A literature review on psoriasis treatments and clinical applications was performed using PubMed. Mild-to-moderate psoriasis treatments include topicals, localized phototherapy, and newer therapies combining two types of topicals, phototherapy with topicals, and easy-to-use foam and spray vehicles. Moderate-to-severe psoriasis therapies include monotherapy or various combinations of generalized phototherapy, oral treatments, and biologic agents, with new oral and biologic agents on the horizon. Dermatologists and primary care providers share roles in screening for associated comorbidities (including cardiovascular disorders, chronic kidney disease, Crohn disease, dyslipidemia, diabetes mellitus/insulin resistance, depression, metabolic syndrome, obesity, and psoriatic arthritis), managing patients' treatments, and reevaluating treatment needs as new therapies are approved. Continued advancements in psoriasis treatment and improvement in coordinated care will allow better overall care of patients with psoriasis.

PMID: 28052180 [PubMed - indexed for MEDLINE]

Guidelines for the management of Stevens-Johnson syndrome/toxic epidermal necrolysis: An Indian perspective.

Thu, 06/01/2017 - 09:12
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Guidelines for the management of Stevens-Johnson syndrome/toxic epidermal necrolysis: An Indian perspective.

Indian J Dermatol Venereol Leprol. 2016 Nov-Dec;82(6):603-625

Authors: Gupta LK, Martin AM, Agarwal N, D'Souza P, Das S, Kumar R, Pande S, Das NK, Kumaresan M, Kumar P, Garg A, Singh S

Abstract
BACKGROUND: Stevens-Johnson syndrome and toxic epidermal necrolysis are severe, life-threatening mucocutaneous adverse drug reactions with a high morbidity and mortality that require immediate medical care. The various immunomodulatory treatments include systemic corticosteroids, cyclosporine, intravenous immunoglobulin, cyclophosphamide, plasmapheresis and tumor necrosis factor-α inhibitors.
AIM: The ideal therapy of Stevens-Johnson syndrome/toxic epidermal necrolysis still remains a matter of debate as there are only a limited number of studies of good quality comparing the usefulness of different specific treatments. The aim of this article is to comprehensively review the published medical literature and frame management guidelines suitable in the Indian perspective.
METHODS: The Indian Association of Dermatologists, Venereologists and Leprologists (IADVL) assigned the task of preparing these guidelines to its special interest group on cutaneous adverse drug reactions. The group performed a comprehensive English language literature search for management options in Stevens-Johnson syndrome/toxic epidermal necrolysis across multiple databases (PubMed, EMBASE, MEDLINE and Cochrane) for keywords (alone and in combination) and MeSH items such as "guidelines," "Stevens-Johnson syndrome," "toxic epidermal necrolysis," "corticosteroids," "intravenous immunoglobulin," "cyclosporine" and "management." The available evidence was evaluated using the strength of recommendation taxonomy and graded using a three-point scale. A draft of clinical recommendations was developed on the best available evidence which was also scrutinized and critically evaluated by the IADVL Academy of Dermatology. Based on the inputs received, this final consensus statement was prepared.
RESULTS: A total of 104 articles (meta-analyses, prospective and retrospective studies, reviews [including chapters in books], previous guidelines [including Indian guidelines of 2006] and case series) were critically evaluated and the evidence thus gathered was used in the preparation of these guidelines.
RECOMMENDATIONS: This expert group recommends prompt withdrawal of the culprit drug, meticulous supportive care, and judicious and early (preferably within 72 h) initiation of moderate to high doses of oral or parenteral corticosteroids (prednisolone 1-2 mg/kg/day or equivalent), tapered rapidly within 7-10 days. Cyclosporine (3-5 mg/kg/day) for 10-14 days may also be used either alone, or in combination with corticosteroids. Owing to the systemic nature of the disease, a multidisciplinary approach in the management of these patients is helpful.

PMID: 27716721 [PubMed - indexed for MEDLINE]

Robot assisted "en bloc" radical nephrectomy, splenectomy and distal pancreatectomy for renal cell carcinoma: case report and illustration of technique.

Thu, 06/01/2017 - 09:12
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Robot assisted "en bloc" radical nephrectomy, splenectomy and distal pancreatectomy for renal cell carcinoma: case report and illustration of technique.

J Robot Surg. 2016 Dec;10(4):375-378

Authors: Abdul-Muhsin HM, Stern KL, Katariya NN, Castle EP

Abstract
A 57-year-old female presented with recurrent gross hematuria and a large left renal mass with solitary pancreatic metastasis. After thorough evaluation, an en bloc robot assisted radical nephrectomy, distal pancreatectomy and splenectomy was performed using a team-based approach between urologists and the transplant/hepatobiliary teams. A standard robotic nephrectomy approach was used with intraoperative ultrasound to determine the extent of pancreatic involvement. Left kidney, left adrenal gland, spleen and pancreatic tail were resected en bloc. Total operative time was 194 min. Perioperative Hemoglobin change was 2.3 g/dL. The final pathology demonstrated a 12.5 cm, Fuhrman grade 3, clear cell RCC along with a 2.5 cm pancreatic metastasis consistent with pT3a, N0, M1 with negative surgical margins. The patient was discharged on post-operative day three and experienced no postoperative complications. This case report highlights the feasibility of this procedure and calls for evaluation of surgical outcomes in this disease category.

PMID: 27450465 [PubMed - indexed for MEDLINE]

International Consultation on Urological Diseases and European Association of Urology International Consultation on Minimally Invasive Surgery in Urology: laparoscopic and robotic adrenalectomy.

Thu, 06/01/2017 - 09:12
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International Consultation on Urological Diseases and European Association of Urology International Consultation on Minimally Invasive Surgery in Urology: laparoscopic and robotic adrenalectomy.

BJU Int. 2017 Jan;119(1):13-21

Authors: Ball MW, Hemal AK, Allaf ME

Abstract
The aim of this study was to provide an evidence-based systematic review of the use of laparoscopic and robotic adrenalectomy in the treatment of adrenal disease as part of the International Consultation on Urological Diseases and European Association of Urology consultation on Minimally Invasive Surgery in Urology. A systematic literature search (January 2004 to January 2014) was conducted to identify comparative studies assessing the safety and efficacy of minimally invasive adrenal surgery. Subtopics including the role of minimally invasive surgery for pheochromocytoma, adrenocortical carcinoma (ACC) and large adrenal tumours were examined. Additionally, the role of transperitoneal and retroperitoneal approaches, as well as laparoendoscopic single-site (LESS) and robotic adrenalectomy were reviewed. The major findings are presented in an evidence-based fashion. Large retrospective and prospective data were analysed and a set of recommendations provided by the committee was produced. Laparoscopic surgery should be considered the first-line therapy for benign adrenal masses requiring surgical resection and for patients with pheochromocytoma. While a laparoscopic approach may be feasible for selected cases of ACC without adjacent organ involvement, an open surgical approach remains the 'gold standard'. Large adrenal tumours without preoperative or intra-operative suspicion of ACC may be safely resected via a laparoscopic approach. Both transperitoneal and retroperitoneal approaches to laparoscopic adrenalectomy are safe. The approach should be chosen based on surgeon training and experience. LESS and robotic adrenalectomy should be considered as alternatives to laparoscopic adrenalectomy but require further study.

PMID: 27431446 [PubMed - indexed for MEDLINE]

Robot-assisted laparoscopic excision of organ of Zuckerkandl.

Thu, 06/01/2017 - 09:12
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Robot-assisted laparoscopic excision of organ of Zuckerkandl.

J Robot Surg. 2016 Dec;10(4):373-374

Authors: Ragavan N, Ramesh M, Kandasamy N, Reddy YV

PMID: 27405589 [PubMed - indexed for MEDLINE]

CACNA1H(M1549V) Mutant Calcium Channel Causes Autonomous Aldosterone Production in HAC15 Cells and Is Inhibited by Mibefradil.

Thu, 06/01/2017 - 09:12
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CACNA1H(M1549V) Mutant Calcium Channel Causes Autonomous Aldosterone Production in HAC15 Cells and Is Inhibited by Mibefradil.

Endocrinology. 2016 Aug;157(8):3016-22

Authors: Reimer EN, Walenda G, Seidel E, Scholl UI

Abstract
We recently demonstrated that a recurrent gain-of-function mutation in a T-type calcium channel, CACNA1H(M1549V), causes a novel Mendelian disorder featuring early-onset primary aldosteronism and hypertension. This variant was found independently in five families. CACNA1H(M1549V) leads to impaired channel inactivation and activation at more hyperpolarized potentials, inferred to cause increased calcium entry. We here aimed to study the effect of this variant on aldosterone production. We heterologously expressed empty vector, CACNA1H(WT) and CACNA1H(M1549V) in the aldosterone-producing adrenocortical cancer cell line H295R and its subclone HAC15. Transfection rates, expression levels, and subcellular distribution of the channel were similar between CACNA1H(WT) and CACNA1H(M1549V). We measured aldosterone production by an ELISA and CYP11B2 (aldosterone synthase) expression by real-time PCR. In unstimulated cells, transfection of CACNA1H(WT) led to a 2-fold increase in aldosterone levels compared with vector-transfected cells. Expression of CACNA1H(M1549V) caused a 7-fold increase in aldosterone levels. Treatment with angiotensin II or increased extracellular potassium levels further stimulated aldosterone production in both CACNA1H(WT)- and CACNA1H(M1549V)-transfected cells. Similar results were obtained for CYP11B2 expression. Inhibition of CACNA1H channels with the T-type calcium channel blocker Mibefradil completely abrogated the effects of CACNA1H(WT) and CACNA1H(M1549V) on CYP11B2 expression. These results directly link CACNA1H(M1549V) to increased aldosterone production. They suggest that calcium channel blockers may be beneficial in the treatment of a subset of patients with primary aldosteronism. Such blockers could target CACNA1H or both CACNA1H and the L-type calcium channel CACNA1D that is also expressed in the adrenal gland and mutated in patients with primary aldosteronism.

PMID: 27258646 [PubMed - indexed for MEDLINE]

Synthetic High-Density Lipoprotein (sHDL) Inhibits Steroid Production in HAC15 Adrenal Cells.

Thu, 06/01/2017 - 09:12
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Synthetic High-Density Lipoprotein (sHDL) Inhibits Steroid Production in HAC15 Adrenal Cells.

Endocrinology. 2016 Aug;157(8):3122-9

Authors: Taylor MJ, Sanjanwala AR, Morin EE, Rowland-Fisher E, Anderson K, Schwendeman A, Rainey WE

Abstract
High density lipoprotein (HDL) transported cholesterol represents one of the sources of substrate for adrenal steroid production. Synthetic HDL (sHDL) particles represent a new therapeutic option to reduce atherosclerotic plaque burden by increasing cholesterol efflux from macrophage cells. The effects of the sHDL particles on steroidogenic cells have not been explored. sHDL, specifically ETC-642, was studied in HAC15 adrenocortical cells. Cells were treated with sHDL, forskolin, 22R-hydroxycholesterol, or pregnenolone. Experiments included time and concentration response curves, followed by steroid assay. Quantitative real-time RT-PCR was used to study mRNA of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, lanosterol 14-α-methylase, cholesterol side-chain cleavage enzyme, and steroid acute regulatory protein. Cholesterol assay was performed using cell culture media and cell lipid extracts from a dose response experiment. sHDL significantly inhibited production of cortisol. Inhibition occurred in a concentration- and time-dependent manner and in a concentration range of 3μM-50μM. Forskolin (10μM) stimulated cortisol production was also inhibited. Incubation with 22R-hydroxycholesterol (10μM) and pregnenolone (10μM) increased cortisol production, which was unaffected by sHDL treatment. sHDL increased transcript levels for the rate-limiting cholesterol biosynthetic enzyme, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase. Extracellular cholesterol assayed in culture media showed a positive correlation with increasing concentration of sHDL, whereas intracellular cholesterol decreased after treatment with sHDL. The current study suggests that sHDL inhibits HAC15 adrenal cell steroid production by efflux of cholesterol, leading to an overall decrease in steroid production and an adaptive rise in adrenal cholesterol biosynthesis.

PMID: 27253994 [PubMed - indexed for MEDLINE]

Management of Acute Severe Colitis in Children With Ulcerative Colitis in the Biologics Era.

Thu, 06/01/2017 - 09:12
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Management of Acute Severe Colitis in Children With Ulcerative Colitis in the Biologics Era.

Pediatrics. 2016 May;137(5):

Authors: Romano C, Syed S, Valenti S, Kugathasan S

Abstract
BACKGROUND AND OBJECTIVE: Approximately one-third of children with ulcerative colitis will experience at least 1 attack of acute severe colitis (ASC) before 15 years of age. Severe disease can be defined in children when Pediatric Ulcerative Colitis Activity Index is >65 and/or ≥6 bloody stools per day, and/or 1 of the following: tachycardia, fever, anemia, and elevated erythrocyte sedimentation rate with or without systemic toxicity. Our aim was to provide practical suggestions on the management of ASC in children. The goal of medical therapy is to avoid colectomy while preventing complications of disease, side effects of medications, and mortality.
METHODS: A systematic search was carried out through Medline via PubMed to identify all articles published in English to date, based on the following keywords "ulcerative colitis," "pediatric ulcerative colitis," "biological therapy," and "acute severe colitis." Multidisciplinary clinical evaluation is recommended to identify early nonresponders to conventional treatment with intravenous corticosteroids, and to start, if indicated, second-line therapy or "rescue therapy," such as calcineurin inhibitors (cyclosporine, tacrolimus) and anti-tumor necrosis factor molecules (infliximab).
RESULTS: Pediatric Ulcerative Colitis Activity Index is a valid predictive tool that can guide clinicians in evaluating response to therapy. Surgery should be considered in the case of complications or rapid clinical deterioration during medical treatment.
CONCLUSIONS: Several pitfalls may be present in the management of ASC, and a correct clinical and therapeutic approach is recommended to reduce surgical risk.

PMID: 27244779 [PubMed - indexed for MEDLINE]

Glucocorticoid Sensitivity Is Highly Variable in Critically Ill Patients With Septic Shock and Is Associated With Disease Severity.

Thu, 06/01/2017 - 09:12
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Glucocorticoid Sensitivity Is Highly Variable in Critically Ill Patients With Septic Shock and Is Associated With Disease Severity.

Crit Care Med. 2016 Jun;44(6):1034-41

Authors: Cohen J, Pretorius CJ, Ungerer JP, Cardinal J, Blumenthal A, Presneill J, Gatica-Andrades M, Jarrett P, Lassig-Smith M, Stuart J, Dunlop R, Starr T, Venkatesh B

Abstract
OBJECTIVES: To measure tissue glucocorticoid sensitivity in patients with septic shock and determine its relationship to standard measurements of adrenal function and of outcome.
DESIGN: Prospective observational trial.
SETTING: Teaching hospital ICU.
SUBJECTS: Forty-one patients and 20 controls were studied.
INTERVENTIONS: Glucocorticoid sensitivity was measured by in vitro suppression of cytokine production from lipopolysaccharide-stimulated leukocytes.
MEASUREMENTS AND MAIN RESULTS: There was no significant difference between the groups in the relative suppression of cytokine production, although there was a greater range and variance in the patient data. Patients in the lowest quartile of glucocorticoid sensitivity had higher Acute Physiology and Chronic Health Evaluation II scores (25 [24-28] vs 20 [14-23]; p = 0.02) and a trend toward higher mortality (30% vs 0%; p = 0.2) compared to those in the highest. The mRNA expression of the β variant of the glucocorticoid receptor and the 11-β hydroxysteroid dehydrogenase 2 isozyme were significantly higher in patients compared to controls (8.6-fold, p = 0.002 and 10.1-fold, p = 0.0002, respectively). Changes in mRNA expression of these genes did not correlate with measurements of glucocorticoid sensitivity.
CONCLUSIONS: Patients with septic shock and controls do not differ in their median glucocorticoid sensitivity. However, patients exhibited a greater variability in glucocorticoid responsiveness and had evidence of association between increased sickness sensitivity and reduced glucocorticoid sensitivity. Sensitivity to glucocorticoids did not appear to be mediated by changes in the expression of the β variant of the glucocorticoid receptor or the 11-β hydroxysteroid dehydrogenase 2 isozyme.

PMID: 26963327 [PubMed - indexed for MEDLINE]

adrenal tumor; +21 new citations

Thu, 05/25/2017 - 06:16

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

adrenal tumor

These pubmed results were generated on 2017/05/25

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