title: Not all glucocorticoid-induced obesity is the same: differences in adiposity among various diagnostic groups of Cushing syndrome.
abstract: The cAMP signaling pathway is implicated in bilateral adrenocortical hyperplasias (BAHs), which are often associated with ACTH-independent Cushing syndrome (CS). Although CS is invariably associated with obesity and is frequently associated with PKA signaling defects, we recently reported that its different forms appear to also present with variable weight gain and adiposity. The present study was aimed at characterizing further the phenotypic and molecular differences in periadrenal adipose tissue (PAT) among patients with subtypes of CS, by anthropometric/biochemical analyses and quantification of PKA expression and activity in BAHs in comparison to a non-CS group with aldosterone producing adenomas (APAs). Glucocorticoid levels, serum parameters, and BMI were analyzed among a larger patient cohort including those with different forms of CS, APAs, and Cushing disease. Abdominal CT scans were available for a small subset of patients examined for fat distribution. PAT collected during adrenalectomy was assayed for PKA activity, cAMP, and PKA expression. BMI and BMI z-score were lower in adults with PPNAD with PRKAR1A mutations and in pediatric patients with PPNAD with and without PRKAR1A mutations, respectively. Patients with PPNAD had higher cAMP levels in PAT and different fat distribution. Thus, PKA activity in PAT differed between CS diagnostic groups. Increased cAMP and PKA activity may have contributed to phenotypic differences among subtypes of CS. In agreement with the known roles of cAMP signaling in the regulation of adiposity, patients with PPNAD were less obese than other patients with CS.
authors.affiliation: Section on Endocrinology & Genetics, Program on Developmental Endocrinology & Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Bethesda, MD, USA.
authors.forename: E
authors.initials: E
authors.lastname: London
authors.affiliation: Section on Endocrinology & Genetics, Program on Developmental Endocrinology & Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Bethesda, MD, USA.
authors.forename: M
authors.initials: M
authors.lastname: Lodish
authors.affiliation: Section on Endocrinology & Genetics, Program on Developmental Endocrinology & Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Bethesda, MD, USA.
authors.forename: M
authors.initials: M
authors.lastname: Keil
authors.affiliation: Section on Endocrinology & Genetics, Program on Developmental Endocrinology & Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Bethesda, MD, USA.
authors.forename: C
authors.initials: C
authors.lastname: Lyssikatos
authors.affiliation: Section on Endocrinology & Genetics, Program on Developmental Endocrinology & Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Bethesda, MD, USA.
authors.forename: M
authors.initials: M
authors.lastname: de la Luz Sierra
authors.affiliation: Section on Endocrinology & Genetics, Program on Developmental Endocrinology & Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Bethesda, MD, USA.
authors.forename: M
authors.initials: M
authors.lastname: Nesterova
authors.affiliation: Section on Endocrinology & Genetics, Program on Developmental Endocrinology & Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Bethesda, MD, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Stratakis
mesh_terms: D050154:Adiposity; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D015992:Body Mass Index; D002648:Child; D003480:Cushing Syndrome / Q000150:complications / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000473:pathology*; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D005938:Glucocorticoids / Q000009:adverse effects*; D006801:Humans; D050356:Lipid Metabolism; D009765:Obesity / Q000139:chemically induced* / Q000150:complications* / Q000000981:diagnostic imaging; D021122:Protein Subunits / Q000378:metabolism; D050151:Subcutaneous Fat / Q000473:pathology; D014057:Tomography, X-Ray Computed
chemical_list: D015415:Biomarkers; D005938:Glucocorticoids; D021122:Protein Subunits; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases