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ACTH-Independent Cushing’s Syndrome: Primary Pigmented Nodular Adrenal Disease in the Context of Carney’s Complex

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Cushing's Syndrome

Part of the book series: Contemporary Endocrinology ((COE))

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Summary

In this chapter, we discuss clinical and molecular findings of micronodular adrenal hyperplasias (MAHs) that lead to ACTH-independent Cushing syndrome. We focus on the role of genetic defects in cyclic AMP (cAMP) signaling-related molecules, namely PRKAR1A, GNAS, PDE11A, and PDE8B; molecular defects in the phosphodiesterases (PDE) family are the most recently discovered genetic defects predisposing to adrenocortical tumor formation. The prototype of these disorders was Carney complex (CNC) in the context of which the first MAH was described: primary pigmented nodular adrenocortical disease or PPNAD. PPNAD is due to defects in PRKAR1A, the gene that functions as a receptor for the cAMP. In contrast to GNAS and PRKAR1A, defects in PDE genes are associated more frequently with incomplete penetrance. Identifying low-penetrance mutations in more than one PDE in patients with MAHs is suggestive for a complementary role of the different PDEs in the adrenal gland, and possible involvement of other members of this gene family in adrenocortical tumors and ACTH-independent Cushing syndrome.

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Acknowledgments

This work was supported by the Intramural Program of the Eunice Kennedy Shriver National Institutes of Child Health & Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD; funds for this project are provided by the NICHD, NIH intramural project Z01-HD-000642-04 to Dr. C. A. Stratakis.

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  1. Section on Endocrinology, Genetics (SEGEN), Program on Developmental Endocrinology & Genetics (PDEGEN), National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, MD, USA

    Constantine Stratakis MD/D(MED)SCI

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  1. Constantine Stratakis MD/D(MED)SCI
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  1. , Division of Endocrinology and Metabolism, Hospital das Clínicas, University of Sao, Sao Paulo, 05403-000, Brazil

    Marcello D. Bronstein

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Stratakis, C. (2010). ACTH-Independent Cushing’s Syndrome: Primary Pigmented Nodular Adrenal Disease in the Context of Carney’s Complex. In: Bronstein, M. (eds) Cushing's Syndrome. Contemporary Endocrinology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60327-449-4_18

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  • DOI: https://doi.org/10.1007/978-1-60327-449-4_18

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