ACTH-independent Cushing's syndrome with bilateral micronodular adrenal hyperplasia and ectopic adrenocortical adenoma.
BACKGROUND
Bilateral micronodular adrenal hyperplasia and ectopic adrenocortical adenoma are two rare causes of ACTH-independent Cushing's syndrome.


OBJECTIVE
The aim of the study was to evaluate a 35-yr-old woman with ACTH-independent hypercortisolism associated with both micronodular adrenal hyperplasia and ectopic pararenal adrenocortical adenoma.


METHODS
In vivo and in vitro studies were performed in a University Hospital Department and academic research laboratories.


METHODS
Mutations of the PRKAR1A, PDE8B, and PDE11A genes were searched for in leukocytes and adrenocortical tissues. The ability of adrenal and adenoma tissues to synthesize cortisol was investigated by immunohistochemistry, quantitative PCR, and/or cell culture studies.


METHODS
Detection of 17alpha-hydroxylase and 21-hydroxylase immunoreactivities, quantification of CYP11B1 mRNA in adrenal and adenoma tissues, and measurement of cortisol levels in supernatants by radioimmunological assays were the main outcomes.


RESULTS
Histological examination of the adrenals revealed nonpigmented micronodular cortical hyperplasia associated with relative atrophy of internodular cortex. No genomic and/or somatic adrenal mutations of the PRKAR1A, PDE8B, and PDE11A genes were detected. 17alpha-Hydroxylase and 21-hydroxylase immunoreactivities as well as CYP11B1 mRNA were detected in adrenal and adenoma tissues. ACTH and dexamethasone activated cortisol secretion from adenoma cells. The stimulatory action of dexamethasone was mediated by a nongenomic effect involving the protein kinase A pathway.


CONCLUSIONS
This case suggests that unknown molecular defects can favor both micronodular adrenal hyperplasia and ectopic adrenocortical adenoma associated with Cushing's syndrome.
Louiset
Estelle
E
Institut National de la Santé et de la Recherche Médicale, Unité 982/Equipe Associée 4310, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institut Fédératif de Recherches Multidisciplinaires sur les Peptides 23, University of Rouen, 76821 Mont-Saint-Aignan, France.
Gobet
Françoise
F
Libé
Rossella
R
Horvath
Anelia
A
Renouf
Sylvie
S
Cariou
Juliette
J
Rothenbuhler
Anya
A
Bertherat
Jérôme
J
Clauser
Eric
E
Grise
Philippe
P
Stratakis
Constantine A
CA
Kuhn
Jean-Marc
JM
Lefebvre
Hervé
H
D000306:Adrenal Cortex Neoplasms / Q000150:complications* / Q000000981:diagnostic imaging / Q000235:genetics; D000311:Adrenal Glands / Q000000981:diagnostic imaging / Q000473:pathology*; D018246:Adrenocortical Adenoma / Q000150:complications* / Q000000981:diagnostic imaging / Q000235:genetics; D000324:Adrenocorticotropic Hormone / Q000378:metabolism / Q000494:pharmacology; D000328:Adult; D002828:Choristoma / Q000150:complications* / Q000000981:diagnostic imaging / Q000235:genetics; D003480:Cushing Syndrome / Q000150:complications* / Q000000981:diagnostic imaging / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics / Q000502:physiology; D005260:Female; D006801:Humans; D006965:Hyperplasia / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics; D007674:Kidney Diseases / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics; D011859:Radiography
D000324:Adrenocorticotropic Hormone