To help shed light on this topic, two of Columbia’s own adrenal specialists-Dr. Hyesoo Lowe hosted a conversation, exploring why some people who have hypertension and high blood pressure may have their adrenal glands to blame. In service of Adrenal Awareness Month, 2022, Columbia endocrinologist Dr. Genome-wide approaches including transcriptome, SNP, methylome and miRome analysis have identified new genetic and epigenetic alterations and the further clustering of ACC in subgroups associated with different prognosis, allowing the development of new prognosis markers.ĪRMC5 Cushing’ syndrome PKA adrenal cortex adrenal tumors.Three Doctors Discuss how HyperAldosteronism Causes Hypertension Thus, somatic mutations of cAMP/PKA pathway genes, mainly PRKACA, coding for the catalytic alpha-subunit of PKA, are found in cortisol-secreting adenomas, whereas IGF-II overexpression and alterations of p53 signaling pathway are observed in ACC. Some other signaling pathways are more specific of the tumor dignity. The Wnt/beta-catenin pathway can be activated in both benign and malignant tumors by CTNNB1 mutations and by ZNRF3 inactivation in adrenal cancer (ACC). Unilateral adrenocortical tumors are more frequent, mostly adenomas. However, genome-wide approaches allowed the identification of a new tumor suppressor gene, ARMC5, whose germline alteration could be responsible for at least 25% of PBMAH cases.
PPNAD and Carney complex are mainly due to germline-inactivating mutations of PRKAR1A, coding for a regulatory subunit of PKA, whereas PBMAH genetic seems more complex. The bilateral nature of the tumors suggests the existence of an underlying genetic predisposition. Two main forms of bilateral adrenocortical tumors can be distinguished according to size and aspect of the nodules: primary pigmented nodular adrenal disease (PPNAD), which can be sporadic or part of Carney complex and primary bilateral macro nodular adrenal hyperplasia (PBMAH). This review describes the molecular alterations observed in the various types of tumors of the adrenal cortex, excluding Conn adenomas, especially the alterations identified by genomic approaches these last five years.
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