Adrenocorticotropic hormone-independent Cushing's syndrome.
OBJECTIVE
Endogenous Cushing's syndrome is adrenocorticotropic hormone (or corticotropin)-independent in 15-20% of cases. Primary Cushing's syndrome is most often secondary to adrenocortical adenomas or carcinomas, and more rarely to bilateral adrenal hyperplasias. Corticotropin-independent cortisol-producing hyperplasia is caused by micronodular diseases, including primary pigmented nodular adrenocortical disease and nonpigmented micronodular hyperplasia and adrenocorticotropic hormone-independent macronodular adrenal hyperplasia. Primary pigmented nodular adrenocortical disease can be found either alone or in the context of Carney complex, a multiple endocrine neoplasia syndrome.


RESULTS
In recent years, the pathophysiology of adrenocortical tumors and hyperplasias became better understood following the identification of genes responsible for syndromes associated with corticotropin-independent Cushing's syndrome and the demonstration of aberrant expression and function of various hormone receptors in adrenocortical adenomas and adrenocorticotropic hormone-independent macronodular adrenal hyperplasia. This article reviews findings on the molecular and genetic aspects of corticotropin-independent Cushing's syndrome including recent gene expression profiling studies of adrenocortical tumors and hyperplasias and animal models that provided clues on the pathogenesis of primary Cushing's syndrome.


CONCLUSIONS
A better understanding of molecular mechanisms involved in adrenocortical tumors and hyperplasias may lead to improved diagnostic and prognostic markers and treatment strategies to assist clinicians in the management of corticotropin-independent Cushing's syndrome.
Bourdeau
Isabelle
I
Division of Endocrinology, Department of Medicine and Research Center, Centre Hospitalier de l'Université de Montréal (CHUM), Montréal, Québec, Canada. isabelle.bourdeau@umontreal.ca
Lampron
Antoine
A
Costa
Marcia Helena Soares
MH
Tadjine
Mimi
M
Lacroix
André
A
D000303:Adrenal Cortex Diseases / Q000150:complications* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000306:Adrenal Cortex Neoplasms / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D003480:Cushing Syndrome / Q000209:etiology*; D020869:Gene Expression Profiling; D006801:Humans; D006965:Hyperplasia
D000324:Adrenocorticotropic Hormone