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NCBI: db=pubmed; Term=adrenal tumor
Updated: 6 days 16 hours ago

Thyroid gland metastasis of rectal cancer.

Fri, 05/15/2015 - 02:43
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Thyroid gland metastasis of rectal cancer.

J Surg Case Rep. 2015;2015(5)

Authors: Ozawa T, Saito S, Matsuura S, Kishi H, Maeda M, Watanabe T

Abstract
A 72-year-old woman with a history of rectal cancer was admitted to our hospital to undergo thyroidectomy and left adrenalectomy. She had undergone low anterior resection and regional lymph node dissection for rectal cancer 52 months pre-admission (T3 N1 M0, stage IIIb according to International Union Against Cancer tumor-node-metastasis), and she had also undergone metastasectomy for lung metastases and right adrenal gland metastasis after the rectal surgery. Follow-up computed tomography scans detected nodules in the bilateral lobes of the thyroid gland and in the left adrenal gland. Subtotal thyroidectomy and left adrenalectomy were performed, and pathological examination revealed metastases of rectal cancer to the thyroid gland and left adrenal gland.

PMID: 25952954 [PubMed]

The effects of tumour necrosis factor inhibitors, methotrexate, non-steroidal anti-inflammatory drugs and corticosteroids on cardiovascular events in rheumatoid arthritis, psoriasis and psoriatic arthritis: a systematic review and meta-analysis.

Fri, 05/15/2015 - 02:43
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The effects of tumour necrosis factor inhibitors, methotrexate, non-steroidal anti-inflammatory drugs and corticosteroids on cardiovascular events in rheumatoid arthritis, psoriasis and psoriatic arthritis: a systematic review and meta-analysis.

Ann Rheum Dis. 2015 Mar;74(3):480-9

Authors: Roubille C, Richer V, Starnino T, McCourt C, McFarlane A, Fleming P, Siu S, Kraft J, Lynde C, Pope J, Gulliver W, Keeling S, Dutz J, Bessette L, Bissonnette R, Haraoui B

Abstract
The objective of this systematic literature review was to determine the association between cardiovascular events (CVEs) and antirheumatic drugs in rheumatoid arthritis (RA) and psoriatic arthritis (PsA)/psoriasis (Pso). Systematic searches were performed of MEDLINE, EMBASE and Cochrane databases (1960 to December 2012) and proceedings from major relevant congresses (2010-2012) for controlled studies and randomised trials reporting confirmed CVEs in patients with RA or PsA/Pso treated with antirheumatic drugs. Random-effects meta-analyses were performed on extracted data. Out of 2630 references screened, 34 studies were included: 28 in RA and 6 in PsA/Pso. In RA, a reduced risk of all CVEs was reported with tumour necrosis factor inhibitors (relative risk (RR), 0.70; 95% CI 0.54 to 0.90; p=0.005) and methotrexate (RR, 0.72; 95% CI 0.57 to 0.91; p=0.007). Non-steroidal anti-inflammatory drugs (NSAIDs) increased the risk of all CVEs (RR, 1.18; 95% CI 1.01 to 1.38; p=0.04), which may have been specifically related to the effects of rofecoxib. Corticosteroids increased the risk of all CVEs (RR, 1.47; 95% CI 1.34 to 1.60; p<0.001). In PsA/Pso, systemic therapy decreased the risk of all CVEs (RR, 0.75; 95% CI 0.63 to 0.91; p=0.003). In RA, tumour necrosis factor inhibitors and methotrexate are associated with a decreased risk of all CVEs while corticosteroids and NSAIDs are associated with an increased risk. Targeting inflammation with tumour necrosis factor inhibitors or methotrexate may have positive cardiovascular effects in RA. In PsA/Pso, limited evidence suggests that systemic therapies are associated with a decrease in all CVE risk.

PMID: 25561362 [PubMed - indexed for MEDLINE]

Heterogeneous genetic background of the association of pheochromocytoma/paraganglioma and pituitary adenoma: results from a large patient cohort.

Fri, 05/15/2015 - 02:43
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Heterogeneous genetic background of the association of pheochromocytoma/paraganglioma and pituitary adenoma: results from a large patient cohort.

J Clin Endocrinol Metab. 2015 Mar;100(3):E531-41

Authors: Dénes J, Swords F, Rattenberry E, Stals K, Owens M, Cranston T, Xekouki P, Moran L, Kumar A, Wassif C, Fersht N, Baldeweg SE, Morris D, Lightman S, Agha A, Rees A, Grieve J, Powell M, Boguszewski CL, Dutta P, Thakker RV, Srirangalingam U, Thompson CJ, Druce M, Higham C, Davis J, Eeles R, Stevenson M, O'Sullivan B, Taniere P, Skordilis K, Gabrovska P, Barlier A, Webb SM, Aulinas A, Drake WM, Bevan JS, Preda C, Dalantaeva N, Ribeiro-Oliveira A, Garcia IT, Yordanova G, Iotova V, Evanson J, Grossman AB, Trouillas J, Ellard S, Stratakis CA, Maher ER, Roncaroli F, Korbonits M

Abstract
CONTEXT: Pituitary adenomas and pheochromocytomas/paragangliomas (pheo/PGL) can occur in the same patient or in the same family. Coexistence of the two diseases could be due to either a common pathogenic mechanism or a coincidence.
OBJECTIVE: The objective of the investigation was to study the possible coexistence of pituitary adenoma and pheo/PGL.
DESIGN: Thirty-nine cases of sporadic or familial pheo/PGL and pituitary adenomas were investigated. Known pheo/PGL genes (SDHA-D, SDHAF2, RET, VHL, TMEM127, MAX, FH) and pituitary adenoma genes (MEN1, AIP, CDKN1B) were sequenced using next generation or Sanger sequencing. Loss of heterozygosity study and pathological studies were performed on the available tumor samples.
SETTING: The study was conducted at university hospitals.
PATIENTS: Thirty-nine patients with sporadic of familial pituitary adenoma and pheo/PGL participated in the study.
OUTCOME: Outcomes included genetic screening and clinical characteristics.
RESULTS: Eleven germline mutations (five SDHB, one SDHC, one SDHD, two VHL, and two MEN1) and four variants of unknown significance (two SDHA, one SDHB, and one SDHAF2) were identified in the studied genes in our patient cohort. Tumor tissue analysis identified LOH at the SDHB locus in three pituitary adenomas and loss of heterozygosity at the MEN1 locus in two pheochromocytomas. All the pituitary adenomas of patients affected by SDHX alterations have a unique histological feature not previously described in this context.
CONCLUSIONS: Mutations in the genes known to cause pheo/PGL can rarely be associated with pituitary adenomas, whereas mutation in a gene predisposing to pituitary adenomas (MEN1) can be associated with pheo/PGL. Our findings suggest that genetic testing should be considered in all patients or families with the constellation of pheo/PGL and a pituitary adenoma.

PMID: 25494863 [PubMed - indexed for MEDLINE]

Whole-exome sequencing characterizes the landscape of somatic mutations and copy number alterations in adrenocortical carcinoma.

Fri, 05/15/2015 - 02:43
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Whole-exome sequencing characterizes the landscape of somatic mutations and copy number alterations in adrenocortical carcinoma.

J Clin Endocrinol Metab. 2015 Mar;100(3):E493-502

Authors: Juhlin CC, Goh G, Healy JM, Fonseca AL, Scholl UI, Stenman A, Kunstman JW, Brown TC, Overton JD, Mane SM, Nelson-Williams C, Bäckdahl M, Suttorp AC, Haase M, Choi M, Schlessinger J, Rimm DL, Höög A, Prasad ML, Korah R, Larsson C, Lifton RP, Carling T

Abstract
CONTEXT: Adrenocortical carcinoma (ACC) is a rare and lethal malignancy with a poorly defined etiology, and the molecular genetics of ACC are incompletely understood.
OBJECTIVE: To utilize whole-exome sequencing for genetic characterization of the underlying somatic mutations and copy number alterations present in ACC.
DESIGN: Screening for somatic mutation events and copy number alterations (CNAs) was performed by comparative analysis of tumors and matched normal samples from 41 patients with ACC.
RESULTS: In total, 966 nonsynonymous somatic mutations were detected, including 40 tumors with a mean of 16 mutations per sample and one tumor with 314 mutations. Somatic mutations in ACC-associated genes included TP53 (8/41 tumors, 19.5%) and CTNNB1 (4/41, 9.8%). Genes with potential disease-causing mutations included GNAS, NF2, and RB1, and recurrently mutated genes with unknown roles in tumorigenesis comprised CDC27, SCN7A, and SDK1. Recurrent CNAs included amplification at 5p15.33 including TERT (6/41, 14.6%) and homozygous deletion at 22q12.1 including the Wnt repressors ZNRF3 and KREMEN1 (4/41 9.8% and 3/41, 7.3%, respectively). Somatic mutations in ACC-established genes and recurrent ZNRF3 and TERT loci CNAs were mutually exclusive in the majority of cases. Moreover, gene ontology identified Wnt signaling as the most frequently mutated pathway in ACCs.
CONCLUSIONS: These findings highlight the importance of Wnt pathway dysregulation in ACC and corroborate the finding of homozygous deletion of Wnt repressors ZNRF3 and KREMEN1. Overall, mutations in either TP53 or CTNNB1 as well as focal CNAs at the ZNRF3 or TERT loci denote mutually exclusive events, suggesting separate mechanisms underlying the development of these tumors.

PMID: 25490274 [PubMed - indexed for MEDLINE]

Molecular characterization of testicular adrenal rest tumors in congenital adrenal hyperplasia: lesions with both adrenocortical and Leydig cell features.

Fri, 05/15/2015 - 02:43
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Molecular characterization of testicular adrenal rest tumors in congenital adrenal hyperplasia: lesions with both adrenocortical and Leydig cell features.

J Clin Endocrinol Metab. 2015 Mar;100(3):E524-30

Authors: Smeets EE, Span PN, van Herwaarden AE, Wevers RA, Hermus AR, Sweep FC, Claahsen-van der Grinten HL

Abstract
CONTEXT: Testicular adrenal rest tumors (TART) are one of the major long term complications in patients with congenital adrenal hyperplasia. Although several adrenal-like properties have been assigned to these benign lesions, the etiology has not been confirmed yet.
OBJECTIVE: The aim of this study was to describe TART in more detail by analyzing several (steroidogenic) characteristics that may be classified as adrenal cortex or Leydig cell specific.
METHODS: Gene expression analysis by qPCR was performed for 14 genes in TART tissue (n = 12) and compared with the expression in healthy control fibroblasts (nonsteroidogenic control). In addition, a comparison was made with the expression levels in testis tissue (n = 9) and adrenal tissue (n = 13).
RESULTS: Nearly all genes were highly expressed in TART tissue, including all genes that encode the key steroidogenic enzymes. TART expression levels are in the majority almost identical to those found in adrenal tissue. The expression of adrenal cortex specific genes (CYP11B1, CYP11B2, and MC2R) in both TART and adrenal tissue is approximately 1000-10 000 times higher compared to that in testes samples. In addition, the Leydig cell markers INSL3 and HSD17B3 were not only found in testes, but also in TART, both at significantly higher levels than in the adrenal (p < 0.01).
CONCLUSION: Our study shows for the first time that TART have multiple steroidogenic properties, which include not only the expression of adrenal cortex but also of Leydig cell markers. Therefore, the origin of these tumors might be a more totipotent embryonic cell type.

PMID: 25485724 [PubMed - indexed for MEDLINE]

Coexisting pancreatic mucinous cyst adenoma and adrenal lymphangioma.

Fri, 05/15/2015 - 02:43
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Coexisting pancreatic mucinous cyst adenoma and adrenal lymphangioma.

Intern Med. 2014;53(18):2171-2

Authors: Aoyama H, Kikuyama M, Suzuki N

PMID: 25224209 [PubMed - indexed for MEDLINE]

Adrenocortical tumors in Italian children: analysis of clinical characteristics and P53 status. Data from the national registries.

Fri, 05/15/2015 - 02:43
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Adrenocortical tumors in Italian children: analysis of clinical characteristics and P53 status. Data from the national registries.

J Pediatr Surg. 2014 Sep;49(9):1367-71

Authors: Dall'Igna P, Virgone C, De Salvo GL, Bertorelle R, Indolfi P, De Paoli A, Buffa P, Conte M, Esposito G, Inserra A, Candiotto C, D'Onofrio V, Boldrini R, Ferrari A, Bisogno G, Alaggio R, Cecchetto G

Abstract
AIM: Adrenocortical tumors are very rare in children. The distinction between adenoma and carcinoma is complex because of their clinical/histological characteristics. The analysis of the cases registered in two consecutive Italian Studies is described, in order to provide additional insight into their nature and possibly identify benign and malignant lesions.
MATERIALS AND METHODS: The analysis includes patients registered from?? 1.1982 to 6.2011 into two consecutive Italian protocols.
RESULTS: Fifty-eight children (age 2-210months) were evaluated. Endocrine manifestations were the most frequent symptoms. Stage distribution at diagnosis was: ST I 35, ST II 17, ST III 1, ST IV 5. Treatment consisted in mitotane for ST II, mitotane+chemotherapy for ST III/IV. Forty-four patients are alive without evidence of disease, 1 is alive with disease, 12 died of disease and 1 because of cardiomyopathy. The Wienecke score system was applied in 24 patients with good significance. A p53 mutation was found in 7 cases, and it was diagnostic for Li-Fraumeni syndrome in 2 benign tumors.
CONCLUSIONS: The results highlight the importance of a complete excision to obtain the cure of patients. The efficacy of chemotherapy is controversial, however it was able to control the disease in 4 patients in ST II. The value of the Wienecke score system in predicting patients' outcome was confirmed. p53 mutation was more frequent in malignant tumors and represented the sentinel of the Li-Fraumeni syndrome.

PMID: 25148739 [PubMed - indexed for MEDLINE]

Adrenal cortical scintigraphy for lateralization of bilateral adrenal nodules in primary aldosteronism.

Fri, 05/15/2015 - 02:43
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Adrenal cortical scintigraphy for lateralization of bilateral adrenal nodules in primary aldosteronism.

Korean J Urol. 2014 Aug;55(8):551-3

Authors: Hwang I, Chong A, Kim JB, Kim KH, Kwon D

PMID: 25132951 [PubMed - indexed for MEDLINE]

Autocrine positive regulatory feedback of glucocorticoid secretion: glucocorticoid receptor directly impacts H295R human adrenocortical cell function.

Fri, 05/15/2015 - 02:43
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Autocrine positive regulatory feedback of glucocorticoid secretion: glucocorticoid receptor directly impacts H295R human adrenocortical cell function.

Mol Cell Endocrinol. 2014 Sep;395(1-2):1-9

Authors: Asser L, Hescot S, Viengchareun S, Delemer B, Trabado S, Lombès M

Abstract
Glucocorticoid receptor (GR), a ubiquitous transcriptional factor, regulates target gene expression upon activation by glucocorticoids, notably cortisol, a corticosteroid hormone synthesized in the adrenal cortex. We thus hypothesized that both GR and cortisol might be involved in the regulation of adrenal physiology and steroidogenesis in an autocrine manner. In a cortisol-secreting human adrenocortical cell line (H295R), the GR-dependent signaling pathway was pharmacologically modulated either by dexamethasone (DEX), a GR agonist or by RU486, a GR antagonist, or was knocked-down by small interfering RNA strategy (SiRNA). We showed that GR activation, elicited by 48 h exposure to DEX, exerts a global positive regulatory effect on adrenal steroidogenesis as revealed by a 1.5- to 2-fold increase in cortisol, 11-deoxycortisol and 17-hydroxyprogesterone secretion associated with a significant enhanced expression of steroidogenesis factors such as StAR, CYP11A1, CYP21A2 and CYP11B1. In sharp contrast, RU486 treatment exerted opposite effects by decreasing both steroid production and expression of these steroidogenic factors. Likewise, GR repression by SiRNA also significantly reduced StAR, CYP11A1, and CYP11B1 mRNA levels. Interestingly, RU486 resulted in a significant CYP21A2 enzymatic blockade as demonstrated by a massive increase in 17-hydroxyprogesterone concentrations in RU486-treated H295R cell supernatants, while cortisol and 11-deoxycortisol secretions were reduced by more than 60%. Consistently, we also demonstrated that metabolic conversion of 17-hydroxyprogesterone into 11-deoxycortisol onto H295R cells was drastically blunted in the presence of RU 486. Finally, steady state levels of MC2R transcripts encoding for the ACTH receptor were significantly induced by DEX, unlikely through a direct GR-mediated transcriptional activation as opposed to CYP11A1 and FKBP5 target genes. These results could account for a higher glucocorticoid-elicited ACTH sensitivity of adrenocortical cells. Our study identifies a positive ultra-short regulatory loop exerted by GR on steroidogenesis in H295R cells, thus supporting a complex intra-adrenal GR-mediated feedback, likely relevant for human adrenocortical pathologies.

PMID: 25058354 [PubMed - indexed for MEDLINE]

Giant adrenal myelolipoma.

Fri, 05/15/2015 - 02:43
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Giant adrenal myelolipoma.

J Gastrointest Surg. 2014 Sep;18(9):1716-8

Authors: Alvarez JF, Goldstein L, Samreen N, Beegle R, Carter C, Shaw A, Ben-David K

PMID: 24889790 [PubMed - indexed for MEDLINE]

Pheochromocytoma associated with pregnancy: unexpected favourable outcome in patients diagnosed after delivery.

Fri, 05/15/2015 - 02:43
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Pheochromocytoma associated with pregnancy: unexpected favourable outcome in patients diagnosed after delivery.

J Hypertens. 2014 Jul;32(7):1458-63; discussion 1463

Authors: Salazar-Vega JL, Levin G, Sansó G, Vieites A, Gómez R, Barontini M

Abstract
OBJECTIVE: The objective of this study is to present the clinical findings and outcome of a large cohort of pregnant women with pheochromocytoma (PHEO) with the aim to contribute to the better recognition, detection and management of pregnancy-related PHEO in the population of pregnant patients with hypertension.
METHODS: This is a longitudinal follow-up of a single cohort of 15 patients aged 19-40 years with PHEO associated with pregnancy. Urinary catecholamines and vanillylmandelic acid (VMA) were analysed. Ret proto-oncogene, SDHB and VHL mutations were determined in germline DNA from seven women using PCR followed by direct sequencing.
RESULTS: During pregnancy, all women presented typical features of catecholamines excess. Nevertheless, biochemical diagnosis was performed only in four out of 15 cases during pregnancy and postpartum in the remaining 11. Paroxysmal hypertension was the predominant pattern. Urinary catecholamines and/or VMA were increased in all patients. Tumours were adrenal in 13 patients and extraadrenal in two. Mutations in the Ret proto-oncogene were found in four patients, in the VHL gene in one and in the SDHB gene in one. Antihypertensive treatment resulted in effective control of blood pressure and all women survived. In the group of women diagnosed postpartum, one foetus demised. Newborns from mothers receiving adequate treatment survived. One woman left the hospital after caesarean section but before PHEO surgery became pregnant again and this gestation ended with maternal-foetal dead.
CONCLUSION: A high index of suspicion in all pregnant women presenting hypertension mainly paroxystic during any gestational phase and/or a history of familial PHEO are the keys to disclose this important diagnosis.

PMID: 24805952 [PubMed - indexed for MEDLINE]

Two rare cases of familial (mother and daughter) adrenocorticotropic hormone-independent Cushing's syndrome due to adrenal adenoma, as well as the asynchronous development of another contralateral adrenal adenoma in the mother.

Fri, 05/15/2015 - 02:43
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Two rare cases of familial (mother and daughter) adrenocorticotropic hormone-independent Cushing's syndrome due to adrenal adenoma, as well as the asynchronous development of another contralateral adrenal adenoma in the mother.

Intern Med. 2014;53(9):987-95

Authors: Ogo A, Sakaki Y, Hasuzawa N, Saitou R, Matoba Y, Usui T, Naruse M

Abstract
We herein report two cases involving a mother and daughter who presented with clinical features of Cushing's syndrome (CS) at 50 and 29 years of age, respectively, and were both found to have adrenocorticotropic hormone-independent adrenal adenoma. Furthermore, a new adenoma was detected in the contralateral adrenal gland in the mother 10 years after surgical treatment, when she presented with subclinical CS. The pathogenesis of this disorder, including the presence of unknown genetic abnormalities causing hereditary CS, is currently poorly understood. In this report, we describe our experience with and consider the pathophysiological implications of two rare and very interesting cases of familial CS.

PMID: 24785891 [PubMed - indexed for MEDLINE]

KCNJ5 gene somatic mutations affect cardiac remodelling but do not preclude cure of high blood pressure and regression of left ventricular hypertrophy in primary aldosteronism.

Fri, 05/15/2015 - 02:43
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KCNJ5 gene somatic mutations affect cardiac remodelling but do not preclude cure of high blood pressure and regression of left ventricular hypertrophy in primary aldosteronism.

J Hypertens. 2014 Jul;32(7):1514-21; discussion 1522

Authors: Rossi GP, Cesari M, Letizia C, Seccia TM, Cicala MV, Zinnamosca L, Kuppusamy M, Mareso S, Sciomer S, Iacobone M, Mantero F, Pessina AC

Abstract
OBJECTIVE: Aldosterone exerts detrimental cardiovascular effects, and patients with an aldosterone-producing adenoma (APA) carrying somatic mutations in the KCNJ5 K(+) channel (mutAPA) have higher plasma aldosterone concentration than wild-type APA (wtAPA) patients. We therefore investigated whether mutAPA patients develop a more prominent cardiovascular damage than wtAPA patients.
METHODS AND FINDINGS: From 257 consecutive primary aldosteronism patients, we identified 176 who had both a diagnosis of APA by the 'four corners' criteria and high-quality echocardiographic data. Of them, 129 with KCNJ5 sequencing information and long-term follow-up data were compared for echocardiographic changes according to presence (mutAPA, 26%) or absence (wtAPA, 74%) of the KCNJ5 mutations. At baseline, the mutAPA were similar to the wtAPA for blood pressure (BP) and need for antihypertensive medications. However, they had higher left ventricular mass index (59 ± 19 vs. 51 ± 13 g/h(2.7); P < 0.05) and plasma aldosterone concentration [49 (32-68) vs. 36 (25-52) ng/dl); P = 0.048] than the wtAPA patients. In spite of their more prominent cardiac involvement, the mutAPA patients exhibited a fall of BP and plasma aldosterone similar to wtAPA, and a regression of left ventricular mass index.
CONCLUSIONS: Compared to the wild-type APA patients those with KCNJ5 mutations showed more prominent cardiovascular damage. Notwithstanding this, their chances of being cured from the hyperaldosteronism and the high BP, and of regression of left ventricular hypertrophy after adrenalectomy, were not compromised by the presence of these mutations.

PMID: 24759126 [PubMed - indexed for MEDLINE]

Complete surgical removal of a very enlarged pituitary corticotroph adenoma in a dog.

Fri, 05/15/2015 - 02:43
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Complete surgical removal of a very enlarged pituitary corticotroph adenoma in a dog.

J Am Anim Hosp Assoc. 2014 May-Jun;50(3):192-7

Authors: Fracassi F, Mandrioli L, Shehdula D, Diana A, Grinwis GC, Meij BP

Abstract
A 13 yr old castrated male vizsla was referred to the authors' institute because of polyuria, polydipsia, polyphagia, and weight loss. Pituitary-dependent hypercortisolism (PDH) was diagnosed by hormone testing and adrenal and pituitary imaging. Computed tomography (CT) revealed a pituitary mass measuring 21 mm in width. Medical therapy was initiated with trilostane. Despite adequate control of the hypercortisolemia, the polyuria and polydipsia persisted and the dog developed neurologic signs due to the pituitary mass effect. Pituitary transsphenoidal debulking surgery was performed and immunocytochemistry confirmed a corticotroph adenoma. The dog survived for 13 mo after surgery. Postmortem examination revealed an empty fossa without pituitary remnants and the presence of a malignant pheochromocytoma in the right adrenal gland. This case report demonstrates, for the first time, that a large pituitary adenoma in the dog may be treated successfully by pituitary surgery.

PMID: 24659728 [PubMed - indexed for MEDLINE]

Comparison of plasma free metanephrines between healthy dogs and 3 dogs with pheochromocytoma.

Fri, 05/15/2015 - 02:43
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Comparison of plasma free metanephrines between healthy dogs and 3 dogs with pheochromocytoma.

Vet Clin Pathol. 2013 Dec;42(4):499-503

Authors: Green BA, Frank EL

Abstract
BACKGROUND: Adrenomegaly and hypertension are common clinical entities in canine medicine for which testing for pheochromocytoma is recommended. Yet, a validated biochemical test for the diagnosis of pheochromocytoma in dogs does not exist. In human medicine, plasma free metanephrine testing is the diagnostic standard for the biochemical diagnosis of pheochromocytoma.
OBJECTIVES: The purpose of this study was to investigate the utility of measurement of plasma free metanephrines in dogs for the diagnosis of pheochromocytoma.
METHODS: Plasma free metanephrines were measured in 11 healthy dogs and in 3 dogs confirmed to have a pheochromocytoma. The metanephrine assays were performed at a reference laboratory using high-performance liquid chromatography with electrochemical detection.
RESULTS: The plasma free metanephrine and normetanephrine concentrations in 11 healthy dogs were normally distributed and were used to create tentative reference intervals. All 3 dogs with histologically confirmed pheochromocytoma clearly had higher concentrations of plasma free metanephrines.
CONCLUSIONS: This pilot study demonstrates the potential utility of plasma free metanephrines levels for the biochemical diagnosis of pheochromocytoma in dogs.

PMID: 24320781 [PubMed - indexed for MEDLINE]

Myxoid variant of adrenocortical carcinoma: a report of two illustrative cases and a brief review of the literature.

Fri, 05/15/2015 - 02:43
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Myxoid variant of adrenocortical carcinoma: a report of two illustrative cases and a brief review of the literature.

Pathology. 2014 Jan;46(1):83-5

Authors: Gurzu S, Szentirmay Z, Bara T, Bara T, Jung I

PMID: 24300732 [PubMed - indexed for MEDLINE]

MAX mutations status in Swedish patients with pheochromocytoma and paraganglioma tumours.

Fri, 05/15/2015 - 02:43
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MAX mutations status in Swedish patients with pheochromocytoma and paraganglioma tumours.

Fam Cancer. 2014 Mar;13(1):121-5

Authors: Crona J, Maharjan R, Delgado Verdugo A, Stålberg P, Granberg D, Hellman P, Björklund P

Abstract
Pheochromocytoma (PCC) and Paraganglioma are rare tumours originating from neuroendocrine cells. Up to 60% of cases have either germline or somatic mutation in one of eleven described susceptibility loci, SDHA, SDHB, SDHC, SDHD, SDHAF2, VHL, EPAS1, RET, NF1, TMEM127 and MYC associated factor-X (MAX). Recently, germline mutations in MAX were found to confer susceptibility to PCC and paraganglioma (PGL). A subsequent multicentre study found about 1% of PCCs and PGLs to have germline or somatic mutations in MAX. However, there has been no study investigating the frequency of MAX mutations in a Scandinavian cohort. We analysed tumour specimens from 63 patients with PCC and PGL treated at Uppsala University hospital, Sweden, for re-sequencing of MAX using automated Sanger sequencing. Our results show that 0% (0/63) of tumours had mutations in MAX. Allele frequencies of known single nucleotide polymorphisms rs4902359, rs45440292, rs1957948 and rs1957949 corresponded to those available in the Single Nucleotide Polymorphism Database. We conclude that MAX mutations remain unusual events and targeted genetic screening should be considered after more common genetic events have been excluded.

PMID: 23743562 [PubMed - indexed for MEDLINE]

Catecholamine Metabolism in Paraganglioma and Pheochromocytoma: Similar Tumors in Different Sites?

Fri, 05/08/2015 - 00:46
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Catecholamine Metabolism in Paraganglioma and Pheochromocytoma: Similar Tumors in Different Sites?

PLoS One. 2015;10(5):e0125426

Authors: Grouzmann E, Tschopp O, Triponez F, Matter M, Bilz S, Brändle M, Drechser T, Sigrist S, Zulewski H, Henzen C, Fischli S, Abid K

Abstract
Pheochromocytoma (PHEO) and paraganglioma (PGL) are catecholamine-producing neuroendocrine tumors that arise respectively inside or outside the adrenal medulla. Several reports have shown that adrenal glucocorticoids (GC) play an important regulatory role on the genes encoding the main enzymes involved in catecholamine (CAT) synthesis i.e. tyrosine hydroxylase (TH), dopamine β-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT). To assess the influence of tumor location on CAT metabolism, 66 tissue samples (53 PHEO, 13 PGL) and 73 plasma samples (50 PHEO, 23 PGL) were studied. Western blot and qPCR were performed for TH, DBH and PNMT expression. We found a significantly lower intra-tumoral concentration of CAT and metanephrines (MNs) in PGL along with a downregulation of TH and PNMT at both mRNA and protein level compared with PHEO. However, when PHEO were partitioned into noradrenergic (NorAd) and mixed tumors based on an intra-tumoral CAT ratio (NE/E >90%), PGL and NorAd PHEO sustained similar TH, DBH and PNMT gene and protein expression. CAT concentration and composition were also similar between NorAd PHEO and PGL, excluding the use of CAT or MNs to discriminate between PGL and PHEO on the basis of biochemical tests. We observed an increase of TH mRNA concentration without correlation with TH protein expression in primary cell culture of PHEO and PGL incubated with dexamethasone during 24 hours; no changes were monitored for PNMT and DBH at both mRNA and protein level in PHEO and PGL. Altogether, these results indicate that long term CAT synthesis is not driven by the close environment where the tumor develops and suggest that GC alone is not sufficient to regulate CAT synthesis pathway in PHEO/PGL.

PMID: 25946206 [PubMed - as supplied by publisher]

Downregulation of miR-375 in aldosterone-producing adenomas promotes tumor cell growth via MTDH.

Fri, 05/08/2015 - 00:46
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Downregulation of miR-375 in aldosterone-producing adenomas promotes tumor cell growth via MTDH.

Clin Endocrinol (Oxf). 2015 May 6;

Authors: He J, Cao Y, Su T, Jiang Y, Jiang L, Zhou W, Zhang C, Wang W, Ning G

Abstract
OBJECTIVE: Previous studies have investigated the genetic and molecular basis of primary aldosteronism (PA), a common cause of human hypertension, but the effects of microRNAs (miRNAs) on the adrenocortical cell proliferation and aldosterone production are largely obscure. Here, we characterized miRNA expression patterns in the subtypes of PA to gain a better understanding of its pathogenesis.
METHODS: miRNA expression was assessed by microarray profiling analysis in aldosterone-producing adenoma (APA), unilateral adrenal hyperplasia (UAH) and normal adrenal cortex tissues. Selected differentially expressed miRNAs were further validated in a validation cohort by qRT-PCR. A gain-of-function approach was used to explore the functional role of the specific miRNA in vitro.
RESULTS: 31 miRNAs including miR-375, miR-7, miR-29b were found to be significantly differentially expressed among these three groups. miR-375 was the most downregulated one in adrenal cortex tissues from PA patients and its expression level was inversely correlated with the tumor size in APA. Overexpression of miR-375 in a human adrenocortical cell line (H295R) reduced cell proliferation and suppressed the expression of MTDH (metadherin, also known as Astrocyte Elevated Gene-1). Moreover, MTDH was verified as a direct target of miR-375 through luciferase reporter assays. Knockdown of MTDH in H295R cells attenuated Akt-Ser473 phosphorylation and inhibited cell viability.
CONCLUSION: Our findings suggest that miR-375 exerts its tumor-suppressive function via targeting MTDH/Akt pathway and implicate a potential therapeutic target in PA. This article is protected by copyright. All rights reserved.

PMID: 25944465 [PubMed - as supplied by publisher]

False Positive Radioiodinated Metaiodobenzylguanidine ((123)I-MIBG) Uptake in Undifferentiated Adrenal Malignant Tumor.

Thu, 04/30/2015 - 22:43

False Positive Radioiodinated Metaiodobenzylguanidine ((123)I-MIBG) Uptake in Undifferentiated Adrenal Malignant Tumor.

Case Rep Oncol Med. 2015;2015:164280

Authors: Jung HS, Moon SJ, Kim YM, Kang HR, Lee SM, Jung SJ, Choi SJ, Kim TK, Kwon MJ, Park JH, Lee SH

Abstract
(123)I-Metaiodobenzylguanidine ((123)I-MIBG) scintigraphy is a widely used functional imaging tool with a high degree of sensitivity and specificity in diagnosis of pheochromocytoma. However, rare cases of false positive reactions have been reported. A 67-year-old male patient was admitted with epigastric pain. Abdominal computed tomography (CT) revealed a heterogeneous left adrenal mass 6 cm in diameter; following hormone testing, (123)I-MIBG scintigraphy was performed to determine the presence of pheochromocytoma, which confirmed eccentric uptake by a large left adrenal gland mass. Chest CT and PET-CT confirmed metastatic lymphadenopathy; therefore, endobronchial ultrasound transbronchial needle aspiration was performed. Metastatic carcinoma of unknown origin was suspected from a lymph node biopsy, and surgical resection was performed for definitive diagnosis and correction of excess hormonal secretion. A final diagnosis of undifferentiated adrenal malignant tumor was rendered, instead of histologically malignant pheochromocytoma, despite the uptake of (123)I-MIBG demonstrated by scintigraphy.

PMID: 25918656 [PubMed]

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