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NCBI: db=pubmed; Term=adrenal tumor
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Effects of mitotane on the hypothalamic-pituitary-adrenal axis in patients with adrenocortical carcinoma.

Fri, 10/06/2017 - 15:05
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Effects of mitotane on the hypothalamic-pituitary-adrenal axis in patients with adrenocortical carcinoma.

Eur J Endocrinol. 2017 Oct;177(4):361-367

Authors: Reimondo G, Puglisi S, Zaggia B, Basile V, Saba L, Perotti P, De Francia S, Volante M, Zatelli MC, Cannavò S, Terzolo M

Abstract
OBJECTIVE: Mitotane, a drug used to treat adrenocortical cancer (ACC), inhibits multiple enzymatic steps of adrenocortical steroid biosynthesis, potentially causing adrenal insufficiency. Recent studies in vitro have also documented a direct inhibitory effect of mitotane at the pituitary level. The present study was aimed to assess the hypothalamic-pituitary-adrenal axis in patients with ACC receiving mitotane.
DESIGN AND METHODS: We prospectively enrolled 16 patients on adjuvant treatment with mitotane after radical surgical resection of ACC, who underwent standard hormone evaluation and h-CRH stimulation. A group of 10 patients with primary adrenal insufficiency (PAI) served as controls for the CRH test.
RESULTS: We demonstrated a close correlation between cortisol-binding globulin (CBG) and plasma mitotane levels, and a non-significant trend between mitotane dose and either serum or salivary cortisol in ACC patients. We did not find any correlation between the dose of cortisone acetate and either ACTH or cortisol levels. ACTH levels were significantly higher in patients with PAI than that in patients with ACC, both in baseline conditions (88.99 (11.04-275.00) vs 24.53 (6.16-121.88) pmol/L, P = 0.031) and following CRH (158.40 (34.32-275.00) vs 67.43 (8.8-179.52) pmol/L P = 0.016).
CONCLUSIONS: The observation of lower ACTH levels in patients with ACC than that in patients with PAI, both in basal conditions and after CRH stimulation, suggests that mitotane may play an inhibitory effect on ACTH secretion at the pituitary levels. In conclusion, the present study shows that mitotane affects the HPA axis at multiple levels and no single biomarker may be used for the assessment of adrenal insufficiency.

PMID: 28780517 [PubMed - indexed for MEDLINE]

ACSL3 promotes intratumoral steroidogenesis in prostate cancer cells.

Fri, 10/06/2017 - 15:05
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ACSL3 promotes intratumoral steroidogenesis in prostate cancer cells.

Cancer Sci. 2017 Oct;108(10):2011-2021

Authors: Migita T, Takayama KI, Urano T, Obinata D, Ikeda K, Soga T, Takahashi S, Inoue S

Abstract
Long-chain acyl-coenzyme A (CoA) synthetase 3 (ACSL3) is an androgen-responsive gene involved in the generation of fatty acyl-CoA esters. ACSL3 is expressed in both androgen-sensitive and castration-resistant prostate cancer (CRPC). However, its role in prostate cancer remains elusive. We overexpressed ACSL3 in androgen-dependent LNCaP cells and examined the downstream effectors of ACSL3. Furthermore, we examined the role of ACSL3 in the androgen metabolism of prostate cancer. ACSL3 overexpression led to upregulation of several genes such as aldo-keto reductase 1C3 (AKR1C3) involved in steroidogenesis, which utilizes adrenal androgen dehydroepiandrosterone sulfate (DHEAS) as substrate, and downregulated androgen-inactivating enzyme UDP-glucuronosyltransferase 2 (UGT2B). Exposure to DHEAS significantly increased testosterone levels and cell proliferative response in ACSL3-overexpressing cells when compared to that in control cells. A public database showed that ACSL3 level was higher in CRPC than in hormone-sensitive prostate cancer. CRPC cells showed an increased expression of ACSL3 and an expression pattern of AKR1C3 and UGT2B similar to ACSL3-overexpressing cells. DHEAS stimulation significantly promoted the proliferation of CRPC cells when compared to that of LNCaP cells. These findings suggest that ACSL3 contributes to the growth of CRPC through intratumoral steroidogenesis (i.e. promoting androgen synthesis from DHEAS and preventing the catabolism of active androgens).

PMID: 28771887 [PubMed - indexed for MEDLINE]

Nationwide review of hormonally active adrenal tumors highlights high morbidity in pheochromocytoma.

Fri, 10/06/2017 - 15:05
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Nationwide review of hormonally active adrenal tumors highlights high morbidity in pheochromocytoma.

J Surg Res. 2017 Jul;215:204-210

Authors: Parikh PP, Rubio GA, Farra JC, Lew JI

Abstract
BACKGROUND: Adrenal adenomas are benign tumors often discovered incidentally, and >70% are hormonally inactive. The remaining subset may produce excess aldosterone, cortisol, or catecholamine. Perioperative outcomes after adrenalectomy for such "hormonally active" tumors remain unclear. This study examines in-hospital outcomes after unilateral adrenalectomy for hormonally active tumors.
METHODS: A retrospective review was performed using the Nationwide Inpatient Sample (2006-2011) to identify patients undergoing unilateral adrenalectomy for hormonally active or inactive tumors. Malignant adrenal tumors were excluded. Demographics, comorbidities, and postoperative complications were evaluated by univariate analysis, using two-tailed Chi-square and t-tests and multivariate logistic regression.
RESULTS: Of 27,312 patients who underwent adrenalectomy, 78% (n = 21,279) had hormonally inactive and 22% (n = 6033) had hormonally active adrenal tumors. Among the latter, 65% (n = 4000) had primary hyperaldosteronism (Conn's syndrome), 33% (n = 1996) had hypercortisolism (Cushing's syndrome), and 1.4% (n = 85) had pheochromocytoma. Patients with pheochromocytoma had higher rate of comorbidities including congestive heart failure, chronic lung disease, and malignant hypertension compared with remaining hormonally active tumors (12% versus 4%, 18% versus 11%, 6% versus 2%; P < 0.01). For patients with pheochromocytoma versus other hormonally active tumors, mean length of stay was 5 versus 3 d and total in-hospital cost was $50,000 versus $41,000 (P < 0.01). On multivariate analysis, pheochromocytoma had an independently higher risk for intraoperative blood transfusion (4.2, 95% confidence interval [CI] 2.4-7.2), postoperative cardiac (7.6, 95% CI 2.8-20.2), and respiratory (1.9, 95% CI 1.0-3.3) complications.
CONCLUSIONS: Patients with pheochromocytoma have high rates of preoperative comorbidities, postoperative cardiopulmonary complications, and longer and more costly hospitalizations. Such high-risk patients should undergo appropriate preoperative medical optimization in preparation for adrenalectomy.

PMID: 28688648 [PubMed - indexed for MEDLINE]

Efficacy of Peptide Receptor Radionuclide Therapy for Functional Metastatic Paraganglioma and Pheochromocytoma.

Fri, 10/06/2017 - 15:05
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Efficacy of Peptide Receptor Radionuclide Therapy for Functional Metastatic Paraganglioma and Pheochromocytoma.

J Clin Endocrinol Metab. 2017 Sep 01;102(9):3278-3287

Authors: Kong G, Grozinsky-Glasberg S, Hofman MS, Callahan J, Meirovitz A, Maimon O, Pattison DA, Gross DJ, Hicks RJ

Abstract
Purpose: Treatment options for unresectable paraganglioma (PGL)/pheochromocytoma (PCC), especially with uncontrolled secondary hypertension (HTN), are limited. Preliminary studies with peptide receptor radionuclide therapy (PRRT) suggest efficacy, but data on HTN control and survival are lacking. We assessed PRRT outcomes in such patients from two referral centers.
Methods: Twenty consecutive patients (13 men; age range, 21 to 77 years) with high somatostatin receptor (SSTR) expression treated with 177Lu-DOTA-octreotate, nine with radiosensitizing chemotherapy, were retrospectively reviewed. Median cumulative activity was 22 GBq (median 4 cycles). Fourteen patients were treated for uncontrolled HTN and six for progressive or symptomatic metastatic disease or local recurrence.
Results: Three months after PRRT, 8 of 14 patients treated for HTN required reduced medication doses, 5 had no change in anti-HTN doses, and 1 was lost to follow-up. Eighty-six percent had serum chromogranin-A reduction. Of the entire cohort, 36% had disease regression (29% partial and 7% minor response) on computed tomography, with stable findings in 50%. Three other patients had bony disease evaluable only on SSTR imaging (2 partial response and 1 stable). Median progression-free survival was 39 months; median overall survival was not reached (5 deaths; median follow-up, 28 months). Four patients had grade 3 lymphopenia; 2 had grade 3 thrombocytopenia. Renal impairment in 2 patients was attributed to underlying disease processes.
Conclusions: PRRT achieves worthwhile clinical and biochemical responses with low toxicity and encouraging survival in PGL/PCC. Because PRRT has logistic and radiation-safety advantages compared to 131I-MIBG therapy, further prospective evaluation is warranted.

PMID: 28605448 [PubMed - indexed for MEDLINE]

SDHB-related pheochromocytoma and paraganglioma penetrance and genotype-phenotype correlations.

Fri, 10/06/2017 - 15:05
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SDHB-related pheochromocytoma and paraganglioma penetrance and genotype-phenotype correlations.

J Cancer Res Clin Oncol. 2017 Aug;143(8):1421-1435

Authors: Jochmanova I, Wolf KI, King KS, Nambuba J, Wesley R, Martucci V, Raygada M, Adams KT, Prodanov T, Fojo AT, Lazurova I, Pacak K

Abstract
PURPOSE: Succinate dehydrogenase subunit B (SDHB) gene mutations are associated with an aggressive clinical disease course of pheochromocytoma/paraganglioma (PHEO/PGL). Limited information is available concerning PHEO/PGL penetrance among SDHB mutation carriers with regards to primary tumor location, specific mutation type, and gender. We assessed PHEO/PGL penetrance in SDHB mutation carriers and described the clinical presentation and disease course.
METHODS: Asymptomatic relatives (N = 611) of 103 index patients were tested for SDHB mutations. Mutation carriers (N = 328) were offered PHEO/PGL screening, of which 241 participated and were included in penetrance analysis. For additional disease outcome analysis, the 103 index patients and 40 screened individuals who developed PHEO/PGL were included. Clinical data were collected between October 2004 and June 2016.
RESULTS: Forty (16.60%) of the 241 screened individuals developed PHEO/PGL during the study. The penetrance estimate in this population was 49.80% (95% CI 29-74.9) at 85 years. A significantly higher age-related penetrance of disease was observed in males compared to females, with 50% penetrance achieved at age 74 vs. not reached. Age-related penetrance analysis demonstrated 4 mutations (Ile127Ser, IVS1+1G>T, Exon 1 deletion, Arg90X) presenting with a slower rate of disease development (50% penetrance ages, respectively: not achieved, 70, 63, 61 years) compared to Arg46X and Val140Phe mutations (50% penetrance at 38 years).
CONCLUSIONS: Here, we found a higher estimated penetrance compared to several other studies, and a striking difference in age-related penetrance between male and female SDHB mutation carriers with no association between mutation and gender or tumor location.

PMID: 28374168 [PubMed - indexed for MEDLINE]

Role of Ad4-binding protein/steroidogenic factor 1 in regulating NADPH production in adrenocortical Y-1 cells.

Fri, 10/06/2017 - 15:05
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Role of Ad4-binding protein/steroidogenic factor 1 in regulating NADPH production in adrenocortical Y-1 cells.

Endocr J. 2017 Mar 31;64(3):315-324

Authors: Li B, Baba T, Miyabayashi K, Sato T, Shima Y, Ichinose T, Miura D, Ohkawa Y, Suyama M, Morohashi KI

Abstract
Ad4-binding protein/steroidogenic factor 1 (Ad4BP/SF-1), a member of the nuclear receptor superfamily, is expressed in steroidogenic cells and regulates all steroidogenic gene expression. We recently employed mRNA and chromatin immunoprecipitation sequence (ChIP-seq) to demonstrate that Ad4BP/SF-1 directly regulates the expression of nearly all glycolytic genes. The pentose phosphate pathway (PPP) contributes to the production of nicotinamide adenine dinucleotide phosphate (NADPH). Although the expression of PPP genes and intracellular NADPH were decreased by Ad4BP/SF-1 knockdown, these genes were not the direct targets of Ad4BP/SF-1. This study therefore investigates whether Ad4BP/SF-1 directly regulates genes implicated in NADPH production. Examination of previously published data sets of mRNA sequence (mRNA-seq) and ChIP-seq strongly suggested a possibility that other NADPH-producing genes, such as malic enzyme 1 (Me1) and methylenetetrahydrofolate dehydrogenase 2 (Mthfd2), are the direct targets of Ad4BP/SF-1. Reporter gene assays and determination of intracellular NADPH concentration supported the notion that Ad4BP/SF-1 regulates NADPH production by regulating these genes. NADPH is required for macromolecule synthesis of compounds such as steroids, and for detoxification of reactive oxygen species. When synthesizing steroid hormones, steroidogenic cells consume NADPH through enzymatic reactions mediated by steroidogenic P450s. NADPH is also consumed through elimination of reactive oxygen species produced as the byproducts of the P450 reactions. Overall, Ad4BP/SF-1 potentially maintains the intracellular NADPH level through cooperative regulation of genes involved in the biological processes for consumption and supply.

PMID: 28202838 [PubMed - indexed for MEDLINE]

Safety of treatments for inflammatory bowel disease: Clinical practice guidelines of the Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD).

Fri, 10/06/2017 - 15:05
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Safety of treatments for inflammatory bowel disease: Clinical practice guidelines of the Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD).

Dig Liver Dis. 2017 04;49(4):338-358

Authors: Biancone L, Annese V, Ardizzone S, Armuzzi A, Calabrese E, Caprioli F, Castiglione F, Comberlato M, Cottone M, Danese S, Daperno M, D'Incà R, Frieri G, Fries W, Gionchetti P, Kohn A, Latella G, Milla M, Orlando A, Papi C, Petruzziello C, Riegler G, Rizzello F, Saibeni S, Scribano ML, Vecchi M, Vernia P, Meucci G, Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD)

Abstract
Inflammatory bowel diseases are chronic conditions of unknown etiology, showing a growing incidence and prevalence in several countries, including Italy. Although the etiology of Crohn's disease and ulcerative colitis is unknown, due to the current knowledge regarding their pathogenesis, effective treatment strategies have been developed. Several guidelines are available regarding the efficacy and safety of available drug treatments for inflammatory bowel diseases. Nevertheless, national guidelines provide additional information adapted to local feasibility, costs and legal issues related to the use of the same drugs. These observations prompted the Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD) to establish Italian guidelines on the safety of currently available treatments for Crohn's disease and ulcerative colitis. These guidelines discuss the use of aminosalicylates, systemic and low bioavailability corticosteroids, antibiotics (metronidazole, ciprofloxacin, rifaximin), thiopurines, methotrexate, cyclosporine A, TNFα antagonists, vedolizumab, and combination therapies. These guidelines are based on current knowledge derived from evidence-based medicine coupled with clinical experience of a national working group.

PMID: 28161290 [PubMed - indexed for MEDLINE]

Optimization of left adrenal vein sampling in primary aldosteronism: Coping with asymmetrical cortisol secretion.

Fri, 10/06/2017 - 15:05
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Optimization of left adrenal vein sampling in primary aldosteronism: Coping with asymmetrical cortisol secretion.

Endocr J. 2017 Mar 31;64(3):347-355

Authors: Kishino M, Yoshimoto T, Nakadate M, Katada Y, Kanda E, Nakaminato S, Saida Y, Ogawa Y, Tateishi U

Abstract
We evaluated the influence of catheter sampling position and size on left adrenal venous sampling (AVS) in patients with primary aldosteronism (PA) and analyzed their relationship to cortisol secretion. This retrospective study included 111 patients with a diagnosis of primary aldosteronism who underwent tetracosactide-stimulated AVS. Left AVS was obtained from two catheter positions - the central adrenal vein (CAV) and the common trunk. For common trunk sampling, 5-French catheters were used in 51 patients, and microcatheters were used in 60 patients. Autonomous cortisol secretion was evaluated with a low-dose dexamethasone suppression test in 87 patients. The adrenal/inferior vena cava cortisol concentration ratio [selectivity index (SI)] was significantly lower in samples from the left common trunk than those of the left CAV and right adrenal veins, but this difference was reduced when a microcatheter was used for common trunk sampling. Sample dilution in the common trunk of the left adrenal vein can be decreased by limiting sampling speed with the use of a microcatheter. Meanwhile, there was no significant difference in SI between the left CAV and right adrenal veins. Laterality, determined according to aldosterone/cortisol ratio (A/C ratio) based criteria, showed good reproducibility regardless of sampling position, unlike the absolute aldosterone value based criteria. However, in 11 cases with autonomous cortisol co-secretion, the cortisol hypersecreting side tended to be underestimated when using A/C ratio based criteria. Left CAV sampling enables symmetrical sampling, and may be essential when using absolute aldosterone value based criteria in cases where symmetrical cortisol secretion is uncertain.

PMID: 28132968 [PubMed - indexed for MEDLINE]

Aldosterone excess may inhibit insulin secretion: A comparative study on glucose metabolism pre- and post-adrenalectomy in patients with primary aldosteronism.

Fri, 10/06/2017 - 15:05
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Aldosterone excess may inhibit insulin secretion: A comparative study on glucose metabolism pre- and post-adrenalectomy in patients with primary aldosteronism.

Endocr J. 2017 Mar 31;64(3):339-346

Authors: Tsurutani Y, Sugisawa C, Ishida A, Inoue K, Saito J, Omura M, Nagasaka S, Nishikawa T

Abstract
Conflicting data have been published on the effects of aldosterone excess on glucose metabolism. Specifically, there are limited data on whether adrenalectomy in patients with aldosterone-producing adenomas (APA) can improve glucose metabolism. In this study we evaluated changes in glucose metabolism, before and after surgery for APA. The subjects were 61 patients treated with unilateral adrenalectomy, localized by adrenal venous sampling. A 75g-oral glucose tolerance test (OGTT) was performed before and 1 year after adrenalectomy. Patients with diabetes mellitus or a serum cortisol level >3 μg/dL after a 1 mg dexamethasone suppression test, were excluded. Using the 75g-OGTT data, insulin secretion and insulin resistance (or sensitivity) indices were calculated. The results showed that immunoreactive insulin levels during the OGTT increased significantly after adrenalectomy, whereas plasma glucose levels, before and after surgery, were comparable. The insulinogenic index significantly increased after surgery (0.5 [0.4-0.8] to 0.8 [0.4-1.1], p < 0.001). The disposition index remained largely unchanged (806.2 [489.4-1,138.9] to 686.6 [479.4-922.1], p = 0.25). The homeostatic model assessment of insulin resistance increased significantly (1.0 [0.6-1.5] to 1.5 [1.0-2.2], p < 0.001) and the ISImatsuda decreased significantly (6.9 [4.5-10.4] to 5.2 [3.4-7.9], p < 0.001). Changes in these indices were not correlated with changes in potassium and aldosterone levels before and after surgery. In conclusion, insulin secretion increased after adrenalectomy for APA, indicating that aldosterone excess inhibits insulin secretion. However, because of a parallel increase in insulin resistance, plasma glucose levels remained unchanged.

PMID: 28111382 [PubMed - indexed for MEDLINE]

Carney complex: A familial lentiginosis predisposing to a variety of tumors.

Fri, 10/06/2017 - 15:05
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Carney complex: A familial lentiginosis predisposing to a variety of tumors.

Rev Endocr Metab Disord. 2016 Sep;17(3):367-371

Authors: Stratakis CA

Abstract
Carney complex is a familial lentiginosis syndrome; these disorders cover a wide phenotypic spectrum ranging from a benign inherited predisposition to develop cutaneous spots not associated with systemic disease to associations with several syndromes. Carney complex is caused by PRKAR1A mutations and perturbations of the cyclic AMP-dependent protein kinase (PKA) signaling pathway. In addition to the cutaneous findings, the main tumors associated with Carney complex are endocrine: 1) primary pigmented nodular adrenocortical disease, a bilateral adrenal hyperplasia leading to Cushing syndrome; 2) growth-hormone secreting pituitary adenoma or pituitary somatotropic hyperplasia leading to acromegaly; 3) thyroid and gonadal tumors, including a predisposition to thyroid cancer. Other tumors associated with Carney complex include: 1) myxomas of the heart, breast and other sites; 2) psamommatous melanotic schwannomas which can become malignant; 4) a predisposition to a variety of cancers.

PMID: 27943004 [PubMed - indexed for MEDLINE]

[Corticosteroids in the management of advanced prostate cancer].

Fri, 10/06/2017 - 15:05
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[Corticosteroids in the management of advanced prostate cancer].

Urologe A. 2017 Feb;56(2):217-223

Authors: Kübler H

Abstract
Corticosteroids have been widely used for decades in cancer therapy, predominantly due to their anti-inflammatory activity. In the treatment of metastatic castration-resistant prostate cancer (mCRPC), corticosteroids play an important role both in the management of tumor-related symptoms, especially bone metastasis-related pain, and as concomitant treatment to counteract side effects associated with approved active prostatic anticancer agents such as docetaxel, cabazitaxel, and abiraterone acetate. In association with abiraterone acetate, low-dose corticosteroids (prednisone or prednisolone) reduce the mineralocorticoid side effects of abiraterone. In addition, corticosteroids may exert direct antitumoral activities, resulting in PSA decline.

PMID: 27878318 [PubMed - indexed for MEDLINE]

Phaeochromocytoma and transient left ventricular apical ballooning syndrome.

Fri, 10/06/2017 - 15:05
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Phaeochromocytoma and transient left ventricular apical ballooning syndrome.

Int J Cardiol. 2016 Nov 01;222:479-80

Authors: Petersen MH, Christophersen TB, Hansen PS, Hangaard J

PMID: 27505337 [PubMed - indexed for MEDLINE]

Applications of dual energy computed tomography in abdominal imaging.

Fri, 10/06/2017 - 15:05
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Applications of dual energy computed tomography in abdominal imaging.

Diagn Interv Imaging. 2016 Jun;97(6):593-603

Authors: Lestra T, Mulé S, Millet I, Carsin-Vu A, Taourel P, Hoeffel C

Abstract
Dual energy computed tomography (CT) is an imaging technique based on data acquisition at two different energy settings. Recent advances in CT have allowed data acquisition and almost simultaneously analysis of two spectra of X-rays at different energy levels resulting in novel developments in the field of abdominal imaging. This technique is widely used in cardiovascular imaging, especially for pulmonary embolism work-up but is now also increasingly developed in the field of abdominal imaging. With dual-energy CT it is possible to obtain virtual unenhanced images from monochromatic reconstructions as well as attenuation maps of different elements, thereby improving detection and characterization of a variety of renal, adrenal, hepatic and pancreatic abnormalities. Also, dual-energy CT can provide information regarding urinary calculi composition. This article reviews and illustrates the different applications of dual-energy CT in routine abdominal imaging.

PMID: 26993967 [PubMed - indexed for MEDLINE]

adrenal tumor; +27 new citations

Fri, 09/29/2017 - 12:56

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adrenal tumor; +27 new citations

Fri, 09/22/2017 - 11:10

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adrenal tumor; +27 new citations

Fri, 09/15/2017 - 09:12

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adrenal tumor; +29 new citations

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adrenal tumor; +29 new citations

Fri, 09/01/2017 - 06:47

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adrenal tumor; +29 new citations

Fri, 08/25/2017 - 04:02

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adrenal tumor; +22 new citations

Fri, 08/18/2017 - 04:01

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