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Australian Journal of General Practice 2021Diseases of the adrenal gland occur rather more frequently than is appreciated and provide a series of challenges for the treating practitioner.
BACKGROUND
Diseases of the adrenal gland occur rather more frequently than is appreciated and provide a series of challenges for the treating practitioner.
OBJECTIVE
The aim of this article is to provide a practical approach to common adrenal disorders encountered in general practice, including adrenal incidentalomas, primary aldosteronism and adrenal insufficiency.
DISCUSSION
Adrenal incidentalomas are adrenal mass lesions >1 cm in diameter serendipitously discovered by radiological examination. They require structural assessment to distinguish common benign pathologies from the rare malignant ones, and biochemistry to exclude hypersecretion syndromes resulting from excess cortisol, aldosterone or catecholamines. Primary aldosteronism represents >5% of hypertension and may be cured or specifically treated, yet is rarely screened for in primary care. Low cortisol levels may reflect adrenal insufficiency due to either adrenal failure, where adrenocorticotropic hormone levels will be elevated, or secondary to hypothalamic-pituitary dysfunction resulting from structural lesions or, increasingly, prescribed exogenous synthetic glucocorticoids and nonconventional therapies.
Topics: Adrenal Gland Neoplasms; Adrenal Glands; Aldosterone; Humans; Hydrocortisone; Hyperaldosteronism
PubMed: 33543156
DOI: 10.31128/AJGP-09-20-5619 -
Frontiers in Endocrinology 2022Endocrine tumors derive from endocrine cells with high heterogeneity in function, structure and embryology, and are characteristic of a marked diversity and tissue... (Review)
Review
Endocrine tumors derive from endocrine cells with high heterogeneity in function, structure and embryology, and are characteristic of a marked diversity and tissue heterogeneity. There are still challenges in analyzing the molecular alternations within the heterogeneous microenvironment for endocrine tumors. Recently, several proteomic, lipidomic and metabolomic platforms have been applied to the analysis of endocrine tumors to explore the cellular and molecular mechanisms of tumor genesis, progression and metastasis. In this review, we provide a comprehensive overview of spatially resolved proteomics, lipidomics and metabolomics guided by mass spectrometry imaging and spatially resolved microproteomics directed by microextraction and tandem mass spectrometry. In this regard, we will discuss different mass spectrometry imaging techniques, including secondary ion mass spectrometry, matrix-assisted laser desorption/ionization and desorption electrospray ionization. Additionally, we will highlight microextraction approaches such as laser capture microdissection and liquid microjunction extraction. With these methods, proteins can be extracted precisely from specific regions of the endocrine tumor. Finally, we compare applications of proteomic, lipidomic and metabolomic platforms in the field of endocrine tumors and outline their potentials in elucidating cellular and molecular processes involved in endocrine tumors.
Topics: Humans; Proteomics; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Tandem Mass Spectrometry; Metabolomics; Endocrine Gland Neoplasms; Neoplasms; Tumor Microenvironment
PubMed: 36704039
DOI: 10.3389/fendo.2022.993081 -
Neuroendocrinology 2016Pituitary adenomas are a common feature of a subset of endocrine neoplasia syndromes, which have otherwise highly variable disease manifestations. We provide here a... (Review)
Review
Pituitary adenomas are a common feature of a subset of endocrine neoplasia syndromes, which have otherwise highly variable disease manifestations. We provide here a review of the clinical features and human molecular genetics of multiple endocrine neoplasia (MEN) type 1 and 4 (MEN1 and MEN4, respectively) and Carney complex (CNC). MEN1, MEN4, and CNC are hereditary autosomal dominant syndromes that can present with pituitary adenomas. MEN1 is caused by inactivating mutations in the MEN1 gene, whose product menin is involved in multiple intracellular pathways contributing to transcriptional control and cell proliferation. MEN1 clinical features include primary hyperparathyroidism, pancreatic neuroendocrine tumours and prolactinomas as well as other pituitary adenomas. A subset of patients with pituitary adenomas and other MEN1 features have mutations in the CDKN1B gene; their disease has been called MEN4. Inactivating mutations in the type 1α regulatory subunit of protein kinase A (PKA; the PRKAR1A gene), that lead to dysregulation and activation of the PKA pathway, are the main genetic cause of CNC, which is clinically characterised by primary pigmented nodular adrenocortical disease, spotty skin pigmentation (lentigines), cardiac and other myxomas and acromegaly due to somatotropinomas or somatotrope hyperplasia.
Topics: Acromegaly; Animals; Carney Complex; Endocrine Gland Neoplasms; Humans; Multiple Endocrine Neoplasia; Pituitary Neoplasms; Prolactinoma
PubMed: 25592387
DOI: 10.1159/000371819 -
Endocrinology and Metabolism (Seoul,... Feb 2021This review discusses articles published in 2020 that presented noteworthy achievements in translational and basic thyroidology. Previously unresolved questions about... (Review)
Review
This review discusses articles published in 2020 that presented noteworthy achievements in translational and basic thyroidology. Previously unresolved questions about thyroid hormone receptor actions and signaling mechanisms were answered using various novel in vitro and in vivo models. Using high resolution cryo-electron microscopy, the fine functional structure of thyroglobulin was demonstrated, and new insights into the pathogenesis of thyroid disease were achieved, with a focus on research into thyroid-disrupting chemicals and the gut microbiome. Novel therapeutic approaches were tried in the field of advanced thyroid cancer treatments.
Topics: Cryoelectron Microscopy; Humans; Signal Transduction; Thyroid Diseases; Thyroid Gland; Thyroid Neoplasms
PubMed: 33677924
DOI: 10.3803/EnM.2021.104 -
Bulletin Du Cancer Feb 1999Endocrine tumors are characteristically hypervascularized. This property recalls that of normal endocrine tissues, which possess a dense and specialized capillary... (Review)
Review
Endocrine tumors are characteristically hypervascularized. This property recalls that of normal endocrine tissues, which possess a dense and specialized capillary network. The cellular and molecular mechanisms of the angiogenesis process associated with endocrine tumorigenesis are poorly known. Most normal endocrine cells constituvely express high levels of angiogenic factors, such as VEGF, which likely play an important role in the development of the characteristic vascular architecture of normal endocrine tissues. Clinical and experimental data suggest that a surexpression of such angiogenic factors is unlikely to be involved in the induction of the angiogenic process associated with endocrine tumorigenesis. In contrast, according to some experimental observations, the loss of endocrine-specific anti-angiogenic factors may be required for the initiation of the angiogenic process and the transition from endocrine hyperplasia to endocrine neoplasia. Such inhibitory factors remain to be identified and characterized. A better understanding of the mechanisms of angiogenesis in endocrine tumors is important for the delineation of novel therapeutic strategies.
Topics: Animals; Capillaries; Cell Division; Endocrine Gland Neoplasms; Endocrine System; Endothelial Growth Factors; Endothelium, Vascular; Humans; Lymphokines; Mice; Mice, Transgenic; Neovascularization, Pathologic; Pancreatic Neoplasms; Transforming Growth Factor alpha; Transforming Growth Factor beta; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors
PubMed: 10066945
DOI: No ID Found -
Discovery Medicine Oct 2010The enzyme, telomerase, is a reverse transcriptase that synthesizes the telomeric ends of linear chromosomes and compensate for the shortened telomere, thereby... (Review)
Review
The enzyme, telomerase, is a reverse transcriptase that synthesizes the telomeric ends of linear chromosomes and compensate for the shortened telomere, thereby immortalizing the cell. It is present at the blastocyst stage of embryological development, low or undetectable in most somatic cells, and activated in cancer. Because of its strong association with cancer cell immortalization and proliferation, numerous attempts have been made to capitalize on its diagnostic, prognostic, and therapeutic potential. Herein we discuss the role of telomerase in normal, benign, and cancerous endocrine tissues.
Topics: Adenoma; Animals; Carcinoma; Endocrine Gland Neoplasms; Humans; Telomerase; Telomere
PubMed: 21034675
DOI: No ID Found -
Current Hypertension Reports Dec 2010Pheochromocytomas (PHEOs) and paragangliomas (PGLs) are rare, catecholamine-producing tumors that are usually sporadic. However, about 30% of these tumors have been... (Review)
Review
Pheochromocytomas (PHEOs) and paragangliomas (PGLs) are rare, catecholamine-producing tumors that are usually sporadic. However, about 30% of these tumors have been identified as being of inherited origin. To date, nine genes have been confirmed as participating in PHEO or PGL tumorigenesis. Germline mutations were found in 100% of syndromic cases and in about 90% of patients with positive familial history. In nonsyndromic patients with apparently sporadic tumors, genetic mutations have been found in up to 27%, and genetic testing is now recommended for all patients with PHEOs and PGLs. Patients with syndromic lesions, a positive family history, or both should be tested for the appertaining gene. Recent discoveries have shown that the order of tested genes in nonsyndromic, nonfamilial cases can be based on histologic evaluation, location, and the biochemical phenotype of PHEOs and PGLs--the "rule of three." Identification of a gene mutation may lead to early diagnosis and treatment, regular surveillance, and a better prognosis for patients and their relatives.
Topics: Adrenal Gland Neoplasms; Adult; Asymptomatic Diseases; Catecholamines; Early Detection of Cancer; Genetic Testing; Germ-Line Mutation; Humans; Middle Aged; Multiple Endocrine Neoplasia Type 2a; Pheochromocytoma; Succinate Dehydrogenase; Survival Rate; Treatment Outcome
PubMed: 20938758
DOI: 10.1007/s11906-010-0151-1 -
World Journal of Surgical Oncology Mar 2013We report a case of concomitant pancreatic endocrine neoplasm (PEN) and intraductal papillary mucinous neoplasm (IPMN). A 74-year-old man had been followed-up for... (Review)
Review
We report a case of concomitant pancreatic endocrine neoplasm (PEN) and intraductal papillary mucinous neoplasm (IPMN). A 74-year-old man had been followed-up for mixed-type IPMN for 10 years. Recent magnetic resonance images revealed an increase in size of the branch duct IPMN in the pancreas head, while the dilation of the main pancreatic duct showed minimal change. Although contrast-enhanced computed tomography and magnetic resonance imaging did not reveal any nodules in the branch duct IPMN, endoscopic ultrasound indicated a suspected nodule in the IPMN. A malignancy in the branch duct IPMN was suspected and we performed pylorus-preserving pancreatoduodenectomy with lymphadenectomy. The resected specimen contained a cystic lesion, 10 x 10 mm in diameter, in the head of the pancreas. Histological examination revealed that the dilated main pancreatic duct and the branch ducts were composed of intraductal papillary mucinous adenoma with mild atypia. No evidence of carcinoma was detected in the specimen. Incidentally, a 3-mm nodule consisting of small neuroendocrine cells was found in the main pancreatic duct. The cells demonstrated positive staining for chromogranin A, synaptophysin, and glucagon but negative staining for insulin and somatostatin. Therefore, the 3-mm nodule was diagnosed as a PEN. Since the mitotic count per 10 high-power fields was less than 2 and the Ki-67 index was less than 2%, the PEN was pathologically classified as low-grade (G1) according to the 2010 World Health Organization (WHO) criteria. Herein, we review the case and relevant studies in the literature and discuss issues related to the synchronous occurrence of the relatively rare tumors, PEN and IPMN.
Topics: Adenocarcinoma, Mucinous; Aged; Carcinoma, Pancreatic Ductal; Carcinoma, Papillary; Endocrine Gland Neoplasms; Endosonography; Humans; Magnetic Resonance Imaging; Male; Neoplasms, Multiple Primary; Pancreatic Neoplasms; Pancreaticoduodenectomy; Prognosis; Review Literature as Topic; Tomography, X-Ray Computed
PubMed: 23517520
DOI: 10.1186/1477-7819-11-75 -
Current Opinion in Pharmacology Dec 2011Phosphodiesterases (PDEs) are enzymes that regulate the intracellular levels of cyclic adenosine monophosphate and cyclic guanosine monophosphate, and, consequently,... (Review)
Review
Phosphodiesterases (PDEs) are enzymes that regulate the intracellular levels of cyclic adenosine monophosphate and cyclic guanosine monophosphate, and, consequently, exhibit a central role in multiple cellular functions. The pharmacological exploitation of the ability of PDEs to regulate specific pathways has led to the discovery of drugs with selective action against specific PDE isoforms. Considerable attention has been given to the development of selective PDE inhibitors, especially after the therapeutic success of PDE5 inhibitors in the treatment of erectile dysfunction. Several associations between PDE genes and genetic diseases have been described, and more recently PDE11A and PDE8B have been implicated in predisposition to tumor formation. This review focuses on the possible function of PDEs in a variety of tumors, primarily in endocrine glands, both in tumor predisposition and as potential therapeutic targets.
Topics: 3',5'-Cyclic-AMP Phosphodiesterases; 3',5'-Cyclic-GMP Phosphodiesterases; Animals; Antineoplastic Agents; Cell Differentiation; Cell Proliferation; Cyclic AMP; Cyclic GMP; Endocrine Cells; Endocrine Gland Neoplasms; Humans; Isoenzymes; Molecular Targeted Therapy; Neoplasm Proteins; Phosphodiesterase Inhibitors
PubMed: 22047791
DOI: 10.1016/j.coph.2011.10.003 -
Scientific Reports Feb 2022G Protein-Coupled Receptors (GPCRs) represent the largest superfamily of cell-surface proteins. However, the expression and function of majority of GPCRs remain...
G Protein-Coupled Receptors (GPCRs) represent the largest superfamily of cell-surface proteins. However, the expression and function of majority of GPCRs remain unexplored in breast cancer (BC). We interrogated the expression and phosphorylation status of 398 non-sensory GPCRs using the landmark BC proteogenomics and phosphoproteomic dataset from The Cancer Genome Atlas. Neuropeptide Y Receptor Y1 (NPY1R) gene and protein expression were significantly higher in Luminal A tumors versus other BC subtypes. The trend of NPY1R gene, protein, and phosphosite (NPY1R-S368s) expression was decreasing in the order of Luminal A, Luminal B, Basal, and human epidermal growth factor receptor 2 (HER2) subtypes. NPY1R gene expression increased in response to estrogen and reduced with endocrine therapy in estrogen receptor-positive (ER+) BC cells and xenograft models. Conversely, NPY1R expression decreased in ER+ BC cells resistant to endocrine therapies (estrogen deprivation, tamoxifen, and fulvestrant) in vitro and in vivo. NPY treatment reduced estradiol-stimulated cell growth, which was reversed by NPY1R antagonist (BIBP-3226) in ER+ BC cells. Higher NPY1R gene expression predicted better relapse-free survival and overall survival in ER+ BC. Our study demonstrates that NPY1R mediates the inhibitory action of NPY on estradiol-stimulated growth of ER+ BC cells, and its expression serves as a biomarker to predict endocrine sensitivity and survival in ER+ BC patients.
Topics: Animals; Antineoplastic Agents, Hormonal; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Drug Resistance, Neoplasm; Endocrine Gland Neoplasms; Estradiol; Estrogen Receptor alpha; Estrogens; Female; Fulvestrant; Gene Expression Regulation, Neoplastic; Heterografts; Humans; Mice; Neoplasm Recurrence, Local; Receptor, ErbB-2; Receptors, G-Protein-Coupled; Receptors, Neuropeptide Y; Tamoxifen
PubMed: 35121782
DOI: 10.1038/s41598-022-05949-7