Showing papers on "Adrenocortical hyperfunction published in 2017"
1 Jan 2017
TL;DR: This chapter presents a logically structured approach to the medical and biochemical features of all such diseases along with practical approaches to laboratory-supported clinical diagnosis.
Abstract: Adrenal diseases may arise from either the steroidogenic adrenal cortex or catecholamine-producing adrenal medulla. Knowledge of steroidogenic and catecholamine biosynthetic pathways of formation and metabolism are critical for the understanding and diagnosis of many different potential functional disorders. The measurement and accurate differentiation between many steroid products of very similar structure is a critical task of the medical laboratory. Specific steroid immunoassays have significant limitations and the field of steroid measurement is rapidly evolving toward use of liquid chromatography/mass spectrometry methodology for higher precision than ever before. Diseases of adrenocortical hyperfunction such as primary cortisol or aldosterone excess represent common forms of resistant hypertension, whereas adrenocortical hypofunction from either pituitary injury or autoimmune adrenal destruction may be life threatening. Benign and malignant tumors of the adrenal may produce excessive amounts of either cortical or medullary hormones, each with a distinct phenotype. Congenital disorders of steroidogenesis may include abnormal production of reproductive steroids, resulting in a combination of adrenal dysfunction with disordered sexual development. This chapter presents a logically structured approach to the medical and biochemical features of all such diseases along with practical approaches to laboratory-supported clinical diagnosis.
4 citations
TL;DR: Data confirm that Armc5 plays an important role in early mouse embryonic development and leads to Cushing syndrome in mice, but only later in life, and this involves PKA, its catalytic subunit Cα, and the Wnt/β-catenin pathway.
Abstract: Inactivating mutations in the Armadillo repeat-containing 5 (ARMC5) gene have recently been discovered in primary macronodular adrenal hyperplasia (PMAH), a cause of Cushing syndrome. Biallelic ARMC5 inactivation in PMAH suggested that ARMC5 may have tumor suppressor functions in the adrenal cortex. We generated and characterized a new mouse model of Armc5 deficiency. Almost all Armc5 knockout mice died during early embryonic development, around 6.5 and 8.5 days. Knockout embryos did not undergo gastrulation, as demonstrated by the absence of mesoderm development at E7.5. Armc5 heterozygote mice (Armc5+/-) developed normally but at the age of 1 year, their corticosterone levels decreased; this was associated with a decrease of protein kinase A (PKA) catalytic subunit α (Cα) expression both at the RNA and protein levels that were also seen in human patients with PMAH and ARMC5 defects. However, this was transient, as corticosterone levels normalized later, followed by the development of hypercorticosteronemia in one-third of the mice at 18 months of age, which was associated with increases in PKA and Cα expression. Adrenocortical tissue analysis from Armc5+/- mice at 18 months showed an abnormal activation of the Wnt/β-catenin signaling pathway in a subset of zona fasciculata cells. These data confirm that Armc5 plays an important role in early mouse embryonic development. Our new mouse line can be used to study tissue-specific effects of Armc5. Finally, Armc5 haploinsufficiency leads to Cushing syndrome in mice, but only later in life, and this involves PKA, its catalytic subunit Cα, and the Wnt/β-catenin pathway.