ACTH Study

[Guest Camille]

Some have recently asked about ambiguous ACTH levels.  This study may hold some clues.  According to these guys, it is possible to have adrenal Cushing's that is, in fact, ACTH dependent.

 

Camille

 

Intraadrenal adrenocorticotropin production in a case of bilateral macronodular adrenal hyperplasia causing Cushing's syndrome.

 

Lefebvre H, Duparc C, Chartrel N, Jegou S, Pellerin A, Laquerriere A, Ivell R, Vaudry H, Kuhn JM.

 

European Institute for Peptide Research, Department of Endocrinology and Metabolic Diseases, INSERM, U-413, 76031 Rouen, France. lefebvre@chu-roun.fr

 

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.