| 1. |
- Dutta, Ravi Kumar, et al.
(författare)
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Genetics of primary hyperaldosteronism
- 2016
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Ingår i: Endocrine-Related Cancer. - : BIOSCIENTIFICA LTD. - 1351-0088 .- 1479-6821. ; 23:10, s. R437-R454
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Forskningsöversikt (refereegranskat)abstract
- Hypertension is a common medical condition and affects approximately 20% of the population in developed countries. Primary aldosteronism is the most common form of secondary hypertension and affects 8-13% of patients with hypertension. The two most common causes of primary aldosteronism are aldosterone-producing adenoma and bilateral adrenal hyperplasia. Familial hyperaldosteronism types I, II and III are the known genetic syndromes, in which both adrenal glands produce excessive amounts of aldosterone. However, only a minority of patients with primary aldosteronism have one of these syndromes. Several novel susceptibility genes have been found to be mutated in aldosterone-producing adenomas: KCNJ5, ATP1A1, ATP2B3, CTNNB1, CACNA1D, CACNA1H and ARMC5. This review describes the genes currently known to be responsible for primary aldosteronism, discusses the origin of aldosterone-producing adenomas and considers the future clinical implications based on these novel insights.
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| 2. |
- Rossitti, Hugo, et al.
(författare)
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Extent of surgery for phaeochromocytomas in the genomic era
- 2018
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Ingår i: British Journal of Surgery. - : John Wiley & Sons. - 0007-1323 .- 1365-2168. ; 105:2, s. E84-E98
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Forskningsöversikt (refereegranskat)abstract
- BackgroundGermline mutations are present in 20–30 per cent of patients with phaeochromocytoma. For patients who develop bilateral disease, complete removal of both adrenal glands (total adrenalectomy) will result in lifelong adrenal insufficiency with an increased risk of death from adrenal crisis. Unilateral/bilateral adrenal‐sparing surgery (subtotal adrenalectomy) offers preservation of cortical function and independence from steroids, but leaves the adrenal medulla in situ and thus at risk of developing new and possibly malignant disease. Here, present knowledge about how tumour genotype relates to clinical behaviour is reviewed, and application of this knowledge when choosing the extent of adrenalectomy is discussed.MethodsA literature review was undertaken of the penetrance of the different genotypes in phaeochromocytomas, the frequency of bilateral disease and malignancy, and the underlying pathophysiological mechanisms, with emphasis on explaining the clinical phenotypes of phaeochromocytomas and their associated syndromes.ResultsPatients with bilateral phaeochromocytomas most often have multiple endocrine neoplasia type 2 (MEN2) or von Hippel–Lindau disease (VHL) with high‐penetrance mutations for benign disease, whereas patients with mutations in the genes encoding SDHB (succinate dehydrogenase subunit B) or MAX (myelocytomatosis viral proto‐oncogene homologue‐associated factor X) are at increased risk of malignancy.ConclusionAdrenal‐sparing surgery should be the standard approach for patients who have already been diagnosed with MEN2 or VHL when operating on the first side, whereas complete removal of the affected adrenal gland(s) is generally recommended for patients with SDHB or MAX germline mutations. Routine assessment of a patient's genotype, even after the first operation, can be crucial for adopting an appropriate strategy for follow‐up and future surgery.
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| 3. |
- Tababi, Mouna, et al.
(författare)
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Hypoxia Signaling and Circadian Disruption in and by Pheochromocytoma
- 2018
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Ingår i: Frontiers in Endocrinology. - : FRONTIERS MEDIA SA. - 1664-2392. ; 9
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Forskningsöversikt (refereegranskat)abstract
- Disruption of the daily (i.e., circadian) rhythms of cell metabolism, proliferation and blood perfusion is a hallmark of many cancer types, perhaps most clearly exemplified by the rare but detrimental pheochromocytomas. These tumors arise from genetic disruption of genes critical for hypoxia signaling, such as von Hippel-Lindau and hypoxia-inducible factor-2 or cellular metabolism, such as succinate dehydrogenase, which in turn impacts on the cellular circadian clock function by interfering with the Bmal1 and/or Clock transcription factors. While pheochromocytomas are often nonmalignant, the resulting changes in cellular physiology are coupled to de-regulated production of catecholamines, which in turn disrupt circadian blood pressure variation and therefore circadian entrainment of other tissues. In this review we thoroughly discuss the molecular and physiological interplay between hypoxia signaling and the circadian clock in pheochromocytoma, and how this underlies endocrine disruption leading to loss of circadian blood pressure variation in the affected patients. We furthermore discuss potential avenues for targeting these tumor-specific pathophysiological mechanisms therapeutically in the future.
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| 4. |
- Tababi, Mouna, et al.
(författare)
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Nuclear and mitochondrial DNA alterations in pheochromocytomas and paragangliomas, and their potential treatment
- 2023
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Ingår i: Endocrine-Related Cancer. - : BIOSCIENTIFICA LTD. - 1351-0088 .- 1479-6821. ; 30:1
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Forskningsöversikt (refereegranskat)abstract
- Mitochondrial DNA (mtDNA) alterations have been reported in different types of cancers and are suggested to play important roles in cancer development and metastasis. However, there is little information about its involvement in pheochromocytomas and paragangliomas (PCCs/PGLs) formation. PCCs and PGLs are rare endocrine tumors of the chromaffin cells in the adrenal medulla and extra-adrenal paraganglia that can synthesize and secrete catecholamines. Over the last 3 decades, the genetic background of about 60% of PCCs/PGLs involving nuclear DNA alterations has been determined. Recently, a study showed that mitochondrial alterations can be found in around 17% of the remaining PCCs/PGLs. In this review, we summarize recent knowledge regarding both nuclear and mitochondrial alterations and their involvement in PCCs/PGLs. We also provide brief insights into the genetics and the molecular pathways associated with PCCs/PGLs and potential therapeutical targets.
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| 5. |
- Welander, Jenny, et al.
(författare)
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Genetics and clinical characteristics of hereditary pheochromocytomas and paragangliomas
- 2011
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Ingår i: Endocrine-Related Cancer. - 1351-0088 .- 1479-6821. ; 18:6, s. 253-276
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Forskningsöversikt (refereegranskat)abstract
- Pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare neuroendocrine tumors of the adrenal glands and the sympathetic and parasympathetic paraganglia. They can occur sporadically or as a part of different hereditary tumor syndromes. About 30% of PCCs and PGLs are currently believed to be caused by germline mutations and several novel susceptibility genes have recently been discovered. The clinical presentation, including localization, malignant potential, and age of onset, varies depending on the genetic background of the tumors. By reviewing more than 1700 reported cases of hereditary PCC and PGL, a thorough summary of the genetics and clinical features of these tumors is given, both as part of the classical syndromes such as multiple endocrine neoplasia type 2 (MEN2), von Hippel-Lindau disease, neurofibromatosis type 1, and succinate dehydrogenase-related PCC-PGL and within syndromes associated with a smaller fraction of PCCs/PGLs, such as Carney triad, Carney-Stratakis syndrome, and MEN1. The review also covers the most recently discovered susceptibility genes including KIF1Bβ, EGLN1/PHD2, SDHAF2, TMEM127, SDHA, and MAX, as well as a comparison with the sporadic form. Further, the latest advances in elucidating the cellular pathways involved in PCC and PGL development are discussed in detail. Finally, an algorithm for genetic testing in patients with PCC and PGL is proposed.
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