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NCBI: db=pubmed; Term=adrenal tumor
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Effects of metformin on endometrial cancer: Systematic review and meta-analysis.

Fri, 08/04/2017 - 01:15
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Effects of metformin on endometrial cancer: Systematic review and meta-analysis.

Gynecol Oncol. 2017 Jul 28;:

Authors: Meireles CG, Pereira SA, Valadares LP, Rêgo DF, Simeoni LA, Guerra ENS, Lofrano-Porto A

Abstract
BACKGROUND: Endometrial cancer is one of the most common gynecological cancers, which is frequently preceded by atypical endometrial hyperplasia, a premalignant lesion. Metformin, an antidiabetic drug, has emerged as a new adjunctive strategy for different cancer types, including endometrial cancer. This systematic review and meta-analysis aimed to evaluate the effects of metformin in atypical endometrial hyperplasia and endometrial cancer patients.
METHODS: The search was conducted on January 2017 and the articles were collected in Cochrane, LILACS, PubMed, Scopus and Web of Science. A grey literature search was undertaken using Google SCHOLAR, ProQuest and Open Grey. Nineteen studies were included, which contained information about the following outcomes: reversal of atypical endometrial hyperplasia, cellular proliferation biomarkers expression and overall survival in metformin-users compared to non-users.
RESULTS: Metformin was associated with reversion of atypical endometrial hyperplasia to a normal endometrial, and with decreased cell proliferation biomarkers staining, from 51.94% (CI=36.23% to 67.46%) to 34.47% (CI=18.55% to 52.43%). However, there is a high heterogeneity among studies. Metformin-users endometrial cancer patients had a higher overall survival compared to non-metformin users and non-diabetic patients (HR=0.82; CI: 0.70-0.95; p=0.09, I(2)=40%).
CONCLUSION: Regardless the high heterogeneity of the analyzed studies, the present review suggests that adjunct metformin treatment may assist in the reversal of atypical endometrial hyperplasia to normal endometrial histology, in the reduction of cell proliferation biomarkers implicated in tumor progression, and in the improvement of overall survival in endometrial cancer. Further work on prospective controlled trials designed to address the effects of adjunct metformin on clinical outcomes is necessary for definite conclusions.

PMID: 28760367 [PubMed - as supplied by publisher]

[Carney triad: Report of one case].

Fri, 08/04/2017 - 01:15
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[Carney triad: Report of one case].

Rev Med Chil. 2017 Apr;145(4):533-537

Authors: Vega J, Navarro Subiabre J, Lovera Riquelme C, Opazo H, Santamarina M

Abstract
Carney described a disorder characterized by the presence of several uncommon tumors which were pulmonary chondromas, gastric sarcomas and extra-adrenal paragangliomas. We report a 14 year-old girl in whom multiple gastric tumors were discovered during a study of an iron deficiency anemia and was subjected to a partial gastrectomy. At 25 years of age, she developed several pulmonary chondromas and at 33 years, a mediastinal tumor with features of an extra-adrenal paraganglioma was found. At 35 years of age, a total gastrectomy was performed to remove a gastrointestinal stromal tumor with excision of peritoneal and lymph node metastasis. One year later, the patient died due to liver failure secondary to liver metastases.

PMID: 28749001 [PubMed - in process]

Fluorodeoxyglucose-positron emission tomography/computed tomography imaging features of colloid adenocarcinoma of the lung: a case report.

Fri, 08/04/2017 - 01:15
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Fluorodeoxyglucose-positron emission tomography/computed tomography imaging features of colloid adenocarcinoma of the lung: a case report.

J Med Case Rep. 2017 Jul 27;11(1):202

Authors: Wang Z, Yu M, Chen Y, Kong Y

Abstract
BACKGROUND: Colloid adenocarcinoma of the lung is a rare subtype of variants of invasive adenocarcinomas. We report the appearance of this unusual entity on (18)F-fluorodeoxyglucose positron emission tomography/computed tomography.
CASE PRESENTATION: A 60-year-old man of Chinese Han nationality coughed with a little white sputum for 1 month. Chest computed tomography showed multiple bilateral subpleural nodules and plaques accompanied by air bronchograms, which were most concentrated in the lower lobe of his right lung. Positron emission tomography indicated increased radioactivity uptake with a maximum standardized uptake value of 3.5. Positron emission tomography/computed tomography showed a soft tissue density lesion in his left adrenal gland with a maximum standardized uptake value of 4.1. The positron emission tomography/computed tomography appearance suggested a primary colloid adenocarcinoma in the lower lobe of his right lung accompanied by intrapulmonary and left adrenal gland metastases. The diagnostic rate of colloid adenocarcinoma can be increased by combining the anatomic and metabolic information of lesions.
CONCLUSIONS: The advantage of positron emission tomography/computed tomography in the diagnosis of colloid adenocarcinoma, as with other cancers, is the ability to locate extrapulmonary disease, facilitating clinical staging.

PMID: 28747211 [PubMed - in process]

Can Imaging Predict Subclinical Cortisol Secretion in Patients With Adrenal Adenomas? A CT Predictive Score.

Fri, 08/04/2017 - 01:15
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Can Imaging Predict Subclinical Cortisol Secretion in Patients With Adrenal Adenomas? A CT Predictive Score.

AJR Am J Roentgenol. 2017 Jul;209(1):122-129

Authors: Mosconi C, Vicennati V, Papadopoulos D, Dalmazi GD, Morselli-Labate AM, Golfieri R, Pasquali R

Abstract
OBJECTIVE: The aim of this study is to determine whether any correlation between CT findings and functional parameters exists to predict subclinical glucocorticoid secretion.
MATERIALS AND METHODS: This is a retrospective database study of 55 patients with incidentally discovered adenomas, investigated through CT with an adrenal protocol, assessing diameters and attenuation values on the unenhanced and contrast-enhanced phases. Patients underwent blood cortisol and corticotropin evaluation and overnight dexamethasone suppression test (DST), in accordance with clinical recommendations. Cortisol levels higher than 50 nmol/L after DST identified subclinical cortisol secretion. We identified 28 subjects with lipid-rich nonsecreting adenomas, nine with lipid-rich secreting adenomas, 11 with lipid-poor nonsecreting adenomas, and seven with lipid-poor secreting adenoma.
RESULTS: Cortisol levels after DST were significantly and positively related to mass diameters. At univariate analysis, maximum and minimum diameters and attenuation in the delayed phase were significantly related to the presence of secreting or nonsecreting adenoma; at multivariate analysis, only the minimum diameter and the attenuation in the venous phase entered the stepwise logistic regression. Similarly, minimum diameter and attenuation in the venous phase emerged also at the multivariate stepwise regression between radiologic parameters and cortisol levels after DST. The formula of the radiologic score computed by using the coefficients of the multivariate regression was as follows: (0.1914 × minimum diameter) + (0.0308 × enhanced attenuation). The diagnostic accuracy of this discriminatory score in differentiating secreting from nonsecreting adenomas was 84.9%, the sensitivity was 81.3%, and the specificity was 87.2%. Adenomas with scores greater than 7.59 were considered as secreting adenomas, and adenomas with scores less than 7.36 were considered as nonsecreting adenomas.
CONCLUSION: This study shows that imaging parameters can predict subclinical cortisol hypersecretion in patients with adrenal adenomas.

PMID: 28402131 [PubMed - indexed for MEDLINE]

Work up of incidental adrenal mass: state of the art.

Fri, 08/04/2017 - 01:15
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Work up of incidental adrenal mass: state of the art.

Urologia. 2016 Nov 18;83(4):179-185

Authors: Bada M, Castellan P, Tamburro FR, Berardinelli F, Neri F, Cindolo L, Schips L

Abstract
Due to the increasing use of radiological investigations, the detection of incidental adrenal masses has become even more frequent. Therefore, it is crucial to identify the nature of the adrenal mass in order to decide the type of treatment that should be undertaken. Toward this goal, biochemical tests are useful in order to assess catecholamines levels for the presence of a pheochromocytoma or cortisol excess in case of Cushing's syndrome. Furthermore, the dexamethasone suppression test and late-night salivary cortisol may be useful in measuring plasma cortisol, respectively, in the blood and urine. Hyperaldosteronism could be suspected in the presence of arterial hypertension. With regard to imaging modalities, the contrast washout and Hounsfield units estimation might play a role as indicators on computed tomography. In terms of treatment, a surgical approach is most suitable for a hyperfunctioning adrenal mass irrespective of size, and for nonfunctioning masses >4 cm. For indeterminate smaller lesions, with washout >50%, <10 Hounsfield Unit, nonfunctioning, benign-appearing, undergoing a follow-up in regular intervals is more appropriate in order to estimate mass growth. This paper summarizes recent findings on the management of incidental adrenal masses, with a special focus on the use of imaging, surgical management and follow-up modalities in improving patient outcomes.

PMID: 27338981 [PubMed - indexed for MEDLINE]

Frequency of Cushing's syndrome due to ACTH-secreting adrenal medullary lesions: a retrospective study over 10 years from a single center.

Fri, 08/04/2017 - 01:15
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Frequency of Cushing's syndrome due to ACTH-secreting adrenal medullary lesions: a retrospective study over 10 years from a single center.

Endocrine. 2017 Jan;55(1):296-302

Authors: Falhammar H, Calissendorff J, Höybye C

Abstract
Cushing's syndrome due to ectopic adrenocorticotropic hormone production from adrenal medullary lesions has occasionally been described. We retrospectively reviewed all 164 cases of Cushing's syndrome and 77 cases of pheochromocytomas during 10 years. Of all cases with Cushing's syndrome, only two cases (1.2 %) were due to ectopic adrenocorticotropic hormone production from adrenal medullary lesions (one case of pheochromocytoma and one case of adrenal medullary hyperplasia). Of all pheochromocytomas only the above-mentioned case (1.3 %) also gave rise to an ectopic adrenocorticotropic hormone syndrome. The clinical presentation of adrenocorticotropic hormone-secreting pheochromocytoma and adrenal medullary hyperplasia can be anything from mild to dramatic. These are rare conditions important to bear in mind in the workup of a patient with Cushing's syndrome or with pheochromocytoma. The identification of ectopic adrenocorticotropic hormone secretion from adrenal medullary lesions can be life-saving.

PMID: 27699708 [PubMed - indexed for MEDLINE]

Techniques to perform robotic left adrenalectomy in the obese patient.

Fri, 08/04/2017 - 01:15
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Techniques to perform robotic left adrenalectomy in the obese patient.

Surg Endosc. 2017 Feb;31(2):950

Authors: Maker AV, Maker VK

Abstract
INTRODUCTION: Minimally invasive adrenalectomy may be associated with reduction in postoperative pain, morbidity, and length of stay and, as a result, has become a preferred approach for many adrenal tumors. Left-sided adrenal tumors, however, are particularly challenging to address in the morbidly obese patient due to difficulties in maintaining exposure and dissection. The robotic platform offers instruments with greater degrees of freedom that aid in retraction and dissection, especially of the adrenal vein, but fixed patient positioning and the large distance needed between patient ports to avoid arm collisions can be restrictive in patients with a large amount of retroperitoneal fat and small working space.
METHODS/RESULTS: We demonstrate robotic left adrenalectomy (RLA) in a consecutive series of patients with a mean weight of 99 kg and mean BMI of 36. Techniques to safely and efficiently perform RLA in obese patients are stepwise demonstrated, including (1) Patient positioning, (2) Management of the pannus, (3) Customized port placement, (4) Medial retraction of the pancreas, (5) Finding the left adrenal vein, and (6) Management of bleeding. Intraoperative videos from multiple patients also show surgical pitfalls, examples of poor port placement, arm collisions, alternative approaches to the vein, and techniques to control unexpected bleeding. All patients in the series underwent successful RLA with negative margins, no major intra- or postoperative complications, and discharge on POD 1-2.
CONCLUSION: Though poor exposure due to patient body habitus is a relative contraindication, even large left-sided adrenal tumors can be safely approached robotically while adhering to oncologic principles, as is demonstrated in this video.

PMID: 27387175 [PubMed - indexed for MEDLINE]

Utility of FDG-PET imaging in screening for succinate dehydrogenase B and D mutation-related lesions.

Fri, 08/04/2017 - 01:15
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Utility of FDG-PET imaging in screening for succinate dehydrogenase B and D mutation-related lesions.

Clin Endocrinol (Oxf). 2016 Aug;85(2):172-9

Authors: Kornaczewski ER, Pointon OP, Burgess JR

Abstract
OBJECTIVE: Mutations of the genes encoding succinate dehydrogenase B and D (SDHB, SDHD) are associated with highly penetrant phenotypes, including paragangliomas and phaeochromocytomas. Patients with these mutations require lifelong surveillance; however, there is currently ambiguity regarding the optimal screening regimen. We sought to determine the utility of fluorodeoxyglucose (18F) positron emission tomography (18F-FDG PET) imaging, compared to other modalities for detecting SDHB and SDHD mutation-related lesions.
DESIGN: A retrospective audit of patients with SDHB or SDHD mutation.
PATIENTS: All adult patients with confirmed SDHB and SDHD mutations who underwent 18F-FDG PET/CT at our institution between 1 July 2011 and 30 May 2015.
MEASUREMENTS: 18F-FDG PET/computed tomography (CT) performed during surveillance of patients with SDHB and SDHD mutations. Lesion numbers and locations detected by 18F-FDG PET were compared to those identified on the CT component, as well as other imaging modalities and histology when available.
RESULTS: Thirty-one 18F-FDG PET/CT studies were completed on 22 patients. For SDHB (20 patients), there were five positive and 21 negative studies. There were no false-negative 18F-FDG PET studies. Positive 18F-FDG PET findings correlated with magnetic resonance imaging (MRI), CT and [68 Ga]-DOTA(0)-Tyr(3)-octreotate (68 Ga DOTATATE PET/CT) imaging with no missed lesions; the only potential false-positive result relating to nonspecific postoperative changes (sensitivity 100·0%, specificity 95·5%). For SDHD (two patients), lesions were detected on 18F-FDG PET and correlated with other imaging in three of five studies. Metastatic lesions were incompletely visualized on 18F-FDG PET but were detected on the noncontrast fusion CT.
CONCLUSIONS: 18F-FDG PET/CT is suitable for detecting SDHB and SDHD mutation-related lesions and may be considered effective for periodic surveillance of patients with these mutations.

PMID: 26776272 [PubMed - indexed for MEDLINE]

Laparoscopic radical 'no-touch' left pancreatosplenectomy for pancreatic ductal adenocarcinoma: technique and results.

Fri, 08/04/2017 - 01:15
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Laparoscopic radical 'no-touch' left pancreatosplenectomy for pancreatic ductal adenocarcinoma: technique and results.

Surg Endosc. 2016 Sep;30(9):3830-8

Authors: Abu Hilal M, Richardson JR, de Rooij T, Dimovska E, Al-Saati H, Besselink MG

Abstract
BACKGROUND: Laparoscopic left pancreatectomy has been well described for benign pancreatic lesions, but its role in pancreatic adenocarcinoma remains open to debate. We report our results adopting a laparoscopic technique that obeys established oncologic principles of open distal pancreatosplenectomy.
METHODS: This is a post hoc analysis of a prospectively kept database of 135 consecutive patients undergoing laparoscopic left pancreatectomy, performed across two sites in the UK and the Netherlands (07/2007-07/2015 Southampton and 10/2013-07/2015 Amsterdam). Primary outcomes were resection margin and lymph node retrieval. Secondary endpoints were other perioperative outcomes, including post-operative pancreatic fistula. Definition of radical resection was distance tumour to resection margin >1 mm. All patients underwent 'laparoscopic radical left pancreatosplenectomy' (LRLP) which involves 'hanging' the pancreas including Gerota's fascia, followed by clockwise dissection, including formal lymphadenectomy.
RESULTS: LRLP for pancreatic adenocarcinoma was performed in 25 patients. Seven of the 25 patients (28 %) had extended resections, including the adrenal gland (n = 3), duodenojejunal flexure (n = 2) or transverse mesocolon (n = 3). Mean age was 68 years (54-81). Conversion rate was 0 %, mean operative time 240 min and mean blood loss 340 ml. Median intensive/high care and hospital stay were 1 and 5 days, respectively. Clavien-Dindo score 3+ complication rate was 12 % and ISGPF grade B/C pancreatic fistula rate 28 %; 90-day (or in-hospital) mortality was 0 %. The pancreatic resection margin was clear in all patients, and the posterior margin was involved (<1 mm) in 6 patients, meaning an overall R0 resection rate of 76 %. No resection margin was microscopically involved. Median nodal sample was 15 nodes (3-26). With an average follow-up of 17.2 months, 1-year survival was 88 %.
CONCLUSIONS: A standardised laparoscopic approach to pancreatic adenocarcinoma in the left pancreas can be adopted safely. Our study shows that these results can be reproduced across multiple sites using the same technique.

PMID: 26675941 [PubMed - indexed for MEDLINE]

Sialadenitis after radioiodine therapy. Analysis of factors that influence the response to medical treatment.

Fri, 08/04/2017 - 01:15
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Sialadenitis after radioiodine therapy. Analysis of factors that influence the response to medical treatment.

Endocrinol Nutr. 2015 Dec;62(10):493-8

Authors: Geres AE, Mereshian PS, Fernández S, Rey Caro DG, Castro R, Podio R, Ojeda S

Abstract
OBJECTIVES: To assess the incidence of 131I-induced sialadenitis (SD) in patients with differentiated thyroid cancer (DTC), to analyze clinical and other factors related to metabolic radiotherapy that may predict the lack of response to conventional medical therapy (CMT), and to determine the effectiveness of intraductal steroid instillation in patients failing CMT.
MATERIAL AND METHODS: Fifty-two patients with DTC, 45 females (86.5%) and 7 males (13.5%) with a mean age of 44.21±13.3 years (r=17-74) who received ablation therapy with 131I after total thyroidectomy. Patients with diseases and/or medication causing xerostomia were excluded. Patients underwent salivary gland scintigraphy with 99Tc (10mCi).
RESULTS: Eighteen patients (34.62%) had SD and received antibiotics, antispasmodics, and oral steroids for 15 days. They were divided into two groups: responders to medical therapy (n=12, age 44.3±14.4 years, 2 men [17%], 10 women [83%], cumulative dose 225±167.1 mCi) and non-responders to medical treatment, who underwent steroid instillation into the Stensen's duct (n=6 [33%], 2 men [33%], 4 women [67%], age 50±13.8 years, cumulative dose 138.3±61.7 mCi). Scintigraphy showed damage to the parotid and submaxillary glands.
CONCLUSION: Incidence of 131I-induced sialadenitis was similar to that reported by other authors. Age, mean cumulative dose of 131I, and involvement of parotid and submaxillary glands did not condition response to CMT; however, male sex was a conditioning factor. Symptom persistence for more than 15 days makes instillation into the Stensen's duct advisable. This is an effective and safe method to avoid surgical excision of salivary glands.

PMID: 26459118 [PubMed - indexed for MEDLINE]

Primary adrenal leiomyosarcoma treated by laparoscopic adrenalectomy.

Fri, 08/04/2017 - 01:15
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Primary adrenal leiomyosarcoma treated by laparoscopic adrenalectomy.

Endocrinol Nutr. 2015 Nov;62(9):472-3

Authors: Quildrian S, Califano I, Carrizo F, Daffinoti A, Calónico N

PMID: 26215892 [PubMed - indexed for MEDLINE]

Black adrenal adenoma causing Cushing's syndrome: 40 years ago and today.

Fri, 08/04/2017 - 01:15
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Black adrenal adenoma causing Cushing's syndrome: 40 years ago and today.

Endocrinol Nutr. 2015 Nov;62(9):466-9

Authors: Yu R, Wei M, Fan X, Ellis RR, Braunstein GD

PMID: 26088906 [PubMed - indexed for MEDLINE]

A Case Report of Cystic Pheochromocytoma.

Fri, 07/28/2017 - 00:54
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A Case Report of Cystic Pheochromocytoma.

Am J Case Rep. 2017 Jul 25;18:826-829

Authors: Junejo SZ, Tuli S, Heimann DM, Sachmechi I, Reich D

Abstract
BACKGROUND Pheochromocytoma is a rare catecholamine-producing tumor with an estimated incidence of less than 0.1% in the global population. We present a case of cystic pheochromocytoma that was diagnosed as an incidental finding. The patient presented with abdominal pain and had a history of hypertension. CASE REPORT A 64-year-old man with hypertension presented with a clinical history of intermittent abdominal pain for one year. He denied sweating, palpitations, headache or back pain. He was found to have an elevated blood pressure of 170/90 and no palpable abdominal mass. Contrast-enhanced computed tomography (CT) imaging of the abdomen and pelvis were performed that showed cystic mass measuring 9 cm in diameter arising from the left adrenal gland with contrast-enhancing mural nodules. Magnetic resonance imaging (MRI) confirmed the cystic nature of the mass. Laboratory analysis showed an elevated plasma normetanephrine (NMN) of 1,087 pg/ml and metanephrine (MN) of 372 pg/ml; 24-hour urine showed elevated levels of NMN and MN, 3,002 mg/24 h and 1,596 mg/24 h, respectively. Given the laboratory and radiologic findings, a diagnosis of cystic pheochromocytoma was made. After controlling blood pressure with the alpha-blocker, doxazosin, the patient was hydrated and scheduled for an elective adrenalectomy. The histopathology of the excised adrenal gland was consistent with a cystic pheochromocytoma. CONCLUSIONS Cystic pheochromocytoma is a very rare tumor that may present without symptoms. The clinical course of cystic pheochromocytoma is similar to that of solid pheochromocytoma. Early surgical intervention is recommended, following blood pressure control with an alpha-blocker, and adequate hydration.

PMID: 28740068 [PubMed - in process]

Late onset asymptomatic pancreatic neuroendocrine tumor - A case report on the phenotypic expansion for MEN1.

Fri, 07/28/2017 - 00:54
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Late onset asymptomatic pancreatic neuroendocrine tumor - A case report on the phenotypic expansion for MEN1.

Hered Cancer Clin Pract. 2017;15:10

Authors: Kaiwar C, Macklin SK, Gass JM, Jackson J, Klee EW, Hines SL, Stauffer JA, Atwal PS

Abstract
BACKGROUND: Multiple endocrine neoplasia type 1 (MEN1) is a hereditary cancer syndrome associated with several endocrine as well as non-endocrine tumors and is caused by mutations in the MEN1 gene. Primary hyperparathyroidism affects the majority of MEN1 individuals by age 50 years. Additionally, MEN1 mutations trigger familial isolated hyperparathyroidism. We describe a seemingly unaffected 76-year-old female who presented to our Genetics Clinic with a family history of primary hyperparathyroidism and the identification of a pathogenic MEN1 variant.
CASE PRESENTATION: The patient was a 76 year-old woman who appeared to be unaffected. She had a family history of a known MEN1 pathogenic variant. Molecular testing for the known MEN1 mutation c.1A > G, as well as, biochemical testing, MRI of the brain and abdomen were all performed using standard methods. Molecular testing revealed our patient possessed the MEN1 pathogenic variant previously identified in her two offspring. Physical exam revealed red facial papules with onset in her seventies, involving her cheeks, nose and upper lip. Formerly, she was diagnosed with rosacea by a dermatologist and noted no improvement with treatment. Clinically, these lesions appeared to be facial angiofibromas. Brain MRI was normal. However, an MRI of her abdomen revealed a 1.5 cm lesion at the tail of the pancreas with normal adrenal glands. Glucagon was mildly elevated and pancreatic polypeptide was nearly seven times the upper limit of the normal range. The patient underwent spleen sparing distal pancreatectomy and subsequent pathology was consistent with a well-differentiated pancreatic neuroendocrine tumor (pNET).
CONCLUSIONS: Age-related penetrance and variable expressivity are well documented in families with MEN1. It is thought that nearly all individuals with MEN1 manifest disease by age 40. We present a case of late-onset MEN1 in the absence of the most common feature, primary hyperparathyroidism, but with the presence of a pNET and cutaneous findings. This family expands the phenotype associated with the c.1A > G pathogenic variant and highlights the importance of providing comprehensive assessment of MEN1 mutation carriers in families that at first blush may appear to have isolated hyperparathyroidism.

PMID: 28736585 [PubMed]

New insights in the clinical and translational relevance of miR483-5p in adrenocortical cancer.

Fri, 07/28/2017 - 00:54
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New insights in the clinical and translational relevance of miR483-5p in adrenocortical cancer.

Oncotarget. 2017 Jul 10;:

Authors: Salvianti F, Canu L, Poli G, Armignacco R, Scatena C, Cantini G, Di Franco A, Gelmini S, Ercolino T, Pazzagli M, Nesi G, Mannelli M, Pinzani P, Luconi M

Abstract
Adrenocortical cancer (ACC) is a rare aggressive malignancy. Recent ACC integrated genomics analysis contributed to redefine the risk groups on molecular basis, including tumor microRNAs (miRs), detectable also in the bloodstream. We developed a quantitative real-time (RT) assay for the measurement of miR483 and miR483-5p absolute levels in plasma samples. miR483/miR483-5p levels were evaluated in plasma samples of 27 patients with ACC before surgery and at follow-up.Statistically significant differences in miR483-5p and miR483 levels were found between stage 1/2 and stage 3/4 ACCs in pre-surgery and post-surgery samples. ROC curve analysis of miR483-5p levels gave a prediction of the clinical stage (accuracy 0.917±0.084), with the best cut-off value of 0.221 ng/ml, prognosticating overall and recurrence-free survival. In a multivariate Cox analysis (HR 16.2, 95%CI[1.39-188.6, P<0.026]), miR483-5p was the only variable that significantly predicted recurrence, but not overall survival. In addition, miR483 and miR483-5p levels correlated with the number of circulating tumor cells (CTCs) detected in the same blood samples, independently of the timing of sampling. In conclusion, we demonstrated that miR483-5p absolute plasma levels in ACC patients are powerful molecular markers that may help in the follow-up of patients after surgery and chemotherapy, and contribute to more accurately classify and predict tumor progression.

PMID: 28733552 [PubMed - as supplied by publisher]

Total and free cortisol levels during 1 μg, 25 μg, and 250 μg cosyntropin stimulation tests compared to insulin tolerance test: results of a randomized, prospective, pilot study.

Fri, 07/28/2017 - 00:54
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Total and free cortisol levels during 1 μg, 25 μg, and 250 μg cosyntropin stimulation tests compared to insulin tolerance test: results of a randomized, prospective, pilot study.

Endocrine. 2017 Jul 20;:

Authors: Peechakara S, Bena J, Clarke NJ, McPhaul MJ, Reitz RE, Weil RJ, Recinos P, Kennedy L, Hamrahian AH

Abstract
PURPOSE: The appropriate cosyntropin dose during cosyntropin stimulation tests remains uncertain. We conducted a prospective, randomized pilot study to compare 1 μg IV low dose cosyntropin test, 25 μg IM medium dose cosyntropin test, and 250 μg IM standard dose cosyntropin test to evaluate secondary adrenal insufficiency. Insulin tolerance test was used as the gold standard.
METHOD: The study included patients with hypothalamic/pituitary disease (n  = 10) with at least one pituitary axis deficiency other than ACTH deficiency and controls (n  = 12). All tests were done in random order. Sensitivity and specificity were calculated for total cortisol and serum free cortisol cut-off levels during cosyntropin stimulation tests.
RESULTS: The median (range) age and F/M sex ratios for patients and controls were 54 years (23-62), 2/8, and 33 years (21-51), 6/6, respectively. The best total cortisol cut-off during low dose cosyntropin test, medium dose cosyntropin test, 30 min and 60 min standard dose cosyntropin test were 14.6 μg/dL (100% sensitivity & specificity), 18.7 μg/dL (100% sensitivity, 88% specificity), 16.1 (100% sensitivity & specificity), and 19.5 μg/dL (100% sensitivity & specificity), respectively. There was no difference in the ROC curve for cortisol values between the cosyntropin stimulation tests (p  > 0.41). Using a cortisol cut-off of 18 μg/dL during cosyntropin stimulation tests, only cortisol level at 30 min during standard dose cosyntropin test provided discrimination similar to insulin tolerance test. The best peak free cortisol cut-off levels were 1 μg/dL for insulin tolerance test, 0.9 μg/dL for low dose cosyntropin test, 0.9 μg/dL for medium dose cosyntropin test, and 0.9 μg/dL and 1.3 μg/dL for 30 min and 60 min standard dose cosyntropin test, respectively.
CONCLUSION: All cosyntropin stimulation tests had excellent correlations with insulin tolerance test, when appropriate cut-offs were used. This pilot study does not suggest an advantage in using 25 μg cosyntropin dose during the cosyntropin stimulation test. A serum free cortisol cut-off of 0.9 μg/dL may be used as pass criterion during low dose cosyntropin test, standard dose cosyntropin test cosyntropin test, and 30 min standard dose cosyntropin test.

PMID: 28730418 [PubMed - as supplied by publisher]

Long-term Results after CT-Guided Percutaneous Ethanol Ablation for the Treatment of Hyperfunctioning Adrenal Disorders.

Fri, 07/28/2017 - 00:54
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Long-term Results after CT-Guided Percutaneous Ethanol Ablation for the Treatment of Hyperfunctioning Adrenal Disorders.

Clinics (Sao Paulo). 2016 Oct 01;71(10):600-605

Authors: Frenk NE, Sebastianes F, Lerario AM, Fragoso MC, Mendonca BB, Menezes MR

Abstract
OBJECTIVES:: To evaluate the safety and long-term efficacy of computed tomography-guided percutaneous ethanol ablation for benign primary and secondary hyperfunctioning adrenal disorders.
METHOD:: We retrospectively evaluated the long-term results of nine patients treated with computed tomography-guided percutaneous ethanol ablation: eight subjects who presented with primary adrenal disorders, such as pheochromocytoma, primary macronodular adrenal hyperplasia and aldosterone-producing adenoma, and one subject with Cushing disease refractory to conventional treatment. Eleven sessions were performed for the nine patients. The patient data were reviewed for the clinical outcome and procedure-related complications over ten years.
RESULTS:: Patients with aldosterone-producing adenoma had clinical improvement: symptoms recurred in one case 96 months after ethanol ablation, and the other patient was still in remission 110 months later. All patients with pheochromocytoma had clinical improvement but were eventually submitted to surgery for complete remission. No significant clinical improvement was seen in patients with hypercortisolism due to primary macronodular adrenal hyperplasia or Cushing disease. Major complications were seen in five of the eleven procedures and included cardiovascular instability and myocardial infarction. Minor complications attributed to sedation were seen in two patients.
CONCLUSION:: Computed tomography-guided ethanol ablation does not appear to be suitable for the long-term treatment of hyperfunctioning adrenal disorders and is not without risks.

PMID: 27759849 [PubMed - indexed for MEDLINE]

Cushing's syndrome and pregnancy outcomes: a systematic review of published cases.

Fri, 07/28/2017 - 00:54
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Cushing's syndrome and pregnancy outcomes: a systematic review of published cases.

Endocrine. 2017 Feb;55(2):555-563

Authors: Caimari F, Valassi E, Garbayo P, Steffensen C, Santos A, Corcoy R, Webb SM

Abstract
Pregnancy in Cushing's syndrome (CS) is extremely rare due to the influence of hypercortisolism on the reproductive axis. Purpose of this study is to investigate whether the etiology of CS in pregnancy determines a different impact on the fetal/newborn and maternal outcomes. We performed a systematic review of cases published in the literature from January 1952 to April 2015 including the words "Cushing AND pregnancy". We included 168 manuscripts containing 220 patients and 263 pregnancies with active CS during pregnancy and with a history of CS but treated and cured hypercortisolism at the time of gestation. Adrenal adenoma was the main cause of active CS during pregnancy (44.1 %). Women with active CS had more gestational diabetes mellitus (36.9 vs. 2.3 %, p = 0.003), gestational hypertension (40.5 vs. 2.3 %, p < 0.001) and preeclampsia (26.3 vs. 2.3 %, p = 0.001) than those with cured disease. The proportion of fetal loss in active CS was higher than in cured CS (23.6 vs. 8.5 %, p = 0.021), as well as global fetal morbidity (33.3 vs. 4.9 %, p < 0.001). The predictors of fetal loss in active CS were etiology of hypercortisolism [Odds Ratio -OR-for pregnancy-induced CS 4.7 (95 % Confidence Interval-CI 1.16-18.96), p = 0.03], publication period [OR for "1975-1994" 0.10 (95 % CI 0.03-0.40), p = 0.001] and treatment during gestation (p = 0.037, [OR medical treatment 0.25 (95 % CI 0.06-1.02), p = 0.052], [OR surgical treatment 0.34 (95 % CI 0.11-1.06), p = 0.063]). The period of diagnosis of CS (before, during or after pregnancy) was the only predictor of overall fetal morbimortality [OR for diagnosis during pregnancy 4.66 (95 % CI 1.37-15.83), p = 0.014]. Patients with active CS, especially in pregnancy-induced CS, experienced more problems in pregnancy and had the worst fetal prognosis in comparison to other causes. Diagnosis of CS during pregnancy was also associated with worse overall fetal morbimortality. Both medical treatment and surgery during pregnancy appeared to be protective in avoiding fetal loss.

PMID: 27704478 [PubMed - indexed for MEDLINE]

11-Ketotestosterone and 11-Ketodihydrotestosterone in Castration Resistant Prostate Cancer: Potent Androgens Which Can No Longer Be Ignored.

Fri, 07/28/2017 - 00:54
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11-Ketotestosterone and 11-Ketodihydrotestosterone in Castration Resistant Prostate Cancer: Potent Androgens Which Can No Longer Be Ignored.

PLoS One. 2016;11(7):e0159867

Authors: Pretorius E, Africander DJ, Vlok M, Perkins MS, Quanson J, Storbeck KH

Abstract
Dihydrotestosterone (DHT) is regarded as the most potent natural androgen and is implicated in the development and progression of castration resistant prostate cancer (CRPC). Under castrate conditions, DHT is produced from the metabolism of the adrenal androgen precursors, DHEA and androstenedione. Recent studies have shown that the adrenal steroid 11β-hydroxyandrostenedione (11OHA4) serves as the precursor to the androgens 11-ketotestosterone (11KT) and 11-ketodihydrotestosterone (11KDHT). In this study we comprehensively assess the androgenic activity of 11KT and 11KDHT. This is the first study, to our knowledge, to show that 11KT and 11KDHT, like T and DHT, are potent and efficacious agonists of the human androgen receptor (AR) and induced both the expression of representative AR-regulated genes as well as cellular proliferation in the androgen dependent prostate cancer cell lines, LNCaP and VCaP. Proteomic analysis revealed that 11KDHT regulated the expression of more AR-regulated proteins than DHT in VCaP cells, while in vitro conversion assays showed that 11KT and 11KDHT are metabolized at a significantly lower rate in both LNCaP and VCaP cells when compared to T and DHT, respectively. Our findings show that 11KT and 11KDHT are bona fide androgens capable of inducing androgen-dependant gene expression and cell growth, and that these steroids have the potential to remain active longer than T and DHT due to the decreased rate at which they are metabolised. Collectively, our data demonstrates that 11KT and 11KDHT likely play a vital, but overlooked, role in the development and progression of CRPC.

PMID: 27442248 [PubMed - indexed for MEDLINE]

Uveitis in children.

Fri, 07/28/2017 - 00:54
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Uveitis in children.

Curr Opin Rheumatol. 2016 Sep;28(5):544-9

Authors: Angeles-Han ST, Rabinovich CE

Abstract
PURPOSE OF REVIEW: The review provides updates on novel risk markers for the development of pediatric inflammatory uveitis and a severe disease course, on treatment of refractory disease, and on the measurement of visual outcomes.
RECENT FINDINGS: There are several new genetic markers, biomarkers, and clinical factors that may influence a child's uveitis disease course. It is important to identify children at risk for poor visual outcomes and who are refractory to traditional therapy. Racial disparities have recently been reported. We describe agents of potential benefit. In addition, we discuss the importance of patient reported outcomes in this population.
SUMMARY: Uveitis can lead to vision-threatening complications. Timely and aggressive treatment of children identified to be at risk for a severe uveitis course may lead to improved outcomes.

PMID: 27328333 [PubMed - indexed for MEDLINE]

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