title: Intraadrenal adrenocorticotropin production in a case of bilateral macronodular adrenal hyperplasia causing Cushing's syndrome.
abstract: Adrenochromaffin cells have been shown to physiologically synthesize and secrete ACTH. We have thus hypothesized that excessive intraadrenal ACTH production may be involved in the pathogenesis of primary adrenal Cushing's syndrome. In this report we describe a case of Cushing's syndrome due to bilateral adrenocortical macronodular hyperplasia associated with suppression of plasma ACTH levels. HPLC analysis of adrenal tissue extracts revealed the presence of a peptide coeluting with bioactive ACTH. Immunohistochemical studies showed that ACTH immunoreactivity was detectable in a subpopulation of steroidogenic cells, but not in chromaffin cells. ACTH-positive cells were also labeled by antibodies against relaxin-like factor, a marker of Leydig cells. The presence of ACTH in the hyperplastic tissue resulted from local expression of the gene encoding the ACTH precursor proopiomelanocortin. Finally, hyperplasia fragments, contrary to normal adrenal cortex explants, appeared to release in vitro measurable amounts of ACTH. In conclusion, this observation shows that Cushing's syndromes associated with suppressed plasma ACTH levels may be dependent upon ACTH produced within adrenocortical tissue. The term ACTH-independent used to designate primary adrenal Cushing's syndrome may therefore be inappropriate in some cases of bilateral macronodular adrenal hyperplasia with hypercortisolism and undetectable plasma ACTH levels.
authors.affiliation: European Institute for Peptide Research, Department of Endocrinology and Metabolic Diseases, INSERM, U-413, 76031 Rouen, France. lefebvre@chu-roun.fr
authors.forename: Herve
authors.initials: H
authors.lastname: Lefebvre
authors.forename: Celine
authors.initials: C
authors.lastname: Duparc
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chartrel
authors.forename: Sylvie
authors.initials: S
authors.lastname: Jegou
authors.forename: Anne
authors.initials: A
authors.lastname: Pellerin
authors.forename: Annie
authors.initials: A
authors.lastname: Laquerriere
authors.forename: Richard
authors.initials: R
authors.lastname: Ivell
authors.forename: Hubert
authors.initials: H
authors.lastname: Vaudry
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Kuhn
mesh_terms: D000302:Adrenal Cortex / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D000324:Adrenocorticotropic Hormone / Q000032:analysis / Q000096:biosynthesis*; D003480:Cushing Syndrome / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D015870:Gene Expression; D006801:Humans; D006965:Hyperplasia; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D010477:Perfusion; D011333:Pro-Opiomelanocortin / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone