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A growing body of evidence now suggests that paracrine mechanisms may also play an important role in the physiopathology of adrenocortical hyperplasias and tumors responsible for primary adrenal steroid excess. These intra-adrenal regulatory systems, although globally involving the same actors as those observed in the normal gland, display alterations at different levels, which reinforce the capacity of paracrine factors to stimulate the activity of adrenocortical cells. The main modifications in the adrenal local control systems reported by now include hyperplasia of cells producing the paracrine factors and abnormal expression of the latter and their receptors. Because steroid-secreting adrenal neoplasms are independent of the classical endocrine regulatory factors angiotensin II and ACTH, which are respectively suppressed by hyperaldosteronism and hypercortisolism, these lesions have long been considered as autonomous tissues. However, the presence of stimulatory substances within the neoplastic tissues suggests that steroid hypersecretion is driven by autocrine\/paracrine loops that should be regarded as promising targets for pharmacological treatments of primary adrenal disorders. This new potential therapeutic approach may constitute an alternative to surgical removal of the lesions that is classically recommended in order to cure steroid excess.<\/jats:p>","DOI":"10.1530\/eje-13-0308","type":"journal-article","created":{"date-parts":[[2013,8,17]],"date-time":"2013-08-17T04:25:13Z","timestamp":1376713513000},"page":"R115-R138","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":56,"title":["MECHANISMS IN ENDOCRINOLOGY: Autocrine\/paracrine regulatory mechanisms in adrenocortical neoplasms responsible for primary adrenal hypercorticism"],"prefix":"10.1093","volume":"169","author":[{"given":"H","family":"Lefebvre","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Pr\u00e9vost","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Louiset","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","reference":[{"issue":"8","key":"1_18443843","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1016\/j.tem.2004.08.007","volume":"15","author":"Lacroix","year":"2004","journal-title":"Trends in endocrinology and metabolism: TEM","ISSN":"https:\/\/id.crossref.org\/issn\/1043-2760","issn-type":"print"},{"issue":"1","key":"2_14667890","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1210\/jc.78.1.225","volume":"78","author":"Bornstein","year":"1994","journal-title":"Journal of Clinical Endocrinology &amp; Metabolism","ISSN":"https:\/\/id.crossref.org\/issn\/0021-972X","issn-type":"print"},{"issue":"1-2","key":"3_9488155","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1007\/BF01249111","volume":"84","author":"Dorovini-Zis","year":"1991","journal-title":"Journal of neural transmission","ISSN":"https:\/\/id.crossref.org\/issn\/0300-9564","issn-type":"print"},{"issue":"6-7","key":"4_6105820","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1055\/s-2007-978890","volume":"30","author":"Engeland","year":"1998","journal-title":"Hormone and metabolic research. 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