title: Familial micronodular adrenocortical disease, Cushing syndrome, and mutations of the gene encoding phosphodiesterase 11A4 (PDE11A).
abstract: We present the pathologic findings in the adrenal glands of 4 patients, aged 10 to 38 years, with Cushing syndrome and germline inactivating mutations of the gene PDE11A4 that encodes phosphodiesterase11A4. The gene is expressed in the adrenal cortex and catalyses the hydrolysis of cyclic adenosine monophosphate and cyclic guanosine monophosphate. Two of the patients were mother and daughter; the third had no affected relative; the fourth patient inherited the mutation from her father. Three of the group, including the mother and daughter, had the same pathology, primary pigmented nodular adrenocortical disease, a disorder known to be caused by inactivating mutations of the PRKAR1A gene. In these cases, the adrenal glands were small and the pathologic change was deep in the cortex in which numerous pigmented micronodules developed. In the remaining patient, the glands were slightly enlarged primarily owing to a diffuse hyperplasia of the superficial cortex that extended into the epi-adrenal fat.
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota 55905, USA. carney.aidan@mayo.edu
authors.forename: J Aidan
authors.initials: JA
authors.lastname: Carney
authors.forename: Rolf C
authors.initials: RC
authors.lastname: Gaillard
authors.forename: Jérôme
authors.initials: J
authors.lastname: Bertherat
authors.forename: Constantine A
authors.initials: CA
authors.lastname: Stratakis
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases; D000302:Adrenal Cortex / Q000378:metabolism / Q000473:pathology; D000303:Adrenal Cortex Diseases / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D000311:Adrenal Glands / Q000473:pathology; D000315:Adrenalectomy; D000328:Adult; D002648:Child; D003480:Cushing Syndrome / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D009929:Organ Size; D010727:Phosphoric Diester Hydrolases / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D010727:Phosphoric Diester Hydrolases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; C406737:PDE11A protein, human