title: In vitro studies in primary aldosteronism: baseline steroid production and aldosterone responses to ACTH and angiotensin II.
abstract: The spontaneous glucocorticoid production in control adrenal cells (N = 10) and in the adenoma cells (N = 15) exhibited comparable geometric mean values: 1.896 nmol/ml/4-5 x 10(5) cells per 2 h (confidence limits: 0.428-8.391) and 1.852 nmol/ml (0.326-12.241), respectively. The same results were obtained for the three samples of nodular hyperplasia cells. When cortisol and corticosterone were measured separately, there was no significant difference between the outputs for control cells and those for pathological cells. Baseline aldosterone production in control cells showed a geometric mean of 2.525 pmol/ml (0.236-27.192). In the 15 adenomas, spontaneous production was extremely important: 57.297 pmol/ml (3.357-976.692). The difference was highly significant (P less than 0.0005). Aldosterone levels in the 3 samples of nodular hyperplasia cells were not different from the control values. In 9 out of the 15 adenomas, aldosterone responses to 10(-10) mol/l ACTH, expressed as stimulated/basal production, were above normal: 3.58 +/- 0.86 (SEM) against 1.48 +/- 0.08 (P less than 0.025). In the remaining 6 and in the 3 samples of nodular hyperplasia cells, there was a slight or no response. Angiotensin II (AII) stimulated both adenoma and nodular hyperplasia cells to varying degrees, without any obvious difference between these two categories. A combination of ACTH (10(-12) mol/l) and AII (10(-12) mol/l) had a synergistic action on aldosterone production in cells classed in the adenoma group. These findings demonstrate that despite the abnormal rate of aldosterone formation in adenoma cells, the production rate of corticosterone and cortisol remains normal. They unmask two functional categories with regard to ACTH in the adenoma group. Finally, they underline the relative insensitivity of nodular hyperplasia cells to ACTH.
authors.affiliation: INSERM U 142, Hôpital Trosseau, Paris, France.
authors.forename: M T
authors.initials: MT
authors.lastname: Pham-Huu-Trung
authors.forename: J M
authors.initials: JM
authors.lastname: Duclos
authors.forename: J Y
authors.initials: JY
authors.lastname: Pagny
authors.forename: A
authors.initials: A
authors.lastname: Bogyo
authors.forename: P
authors.initials: P
authors.lastname: Leneuve
authors.forename: F
authors.initials: F
authors.lastname: Girard
mesh_terms: D000236:Adenoma / Q000378:metabolism; D000310:Adrenal Gland Neoplasms / Q000378:metabolism; D000311:Adrenal Glands / Q000473:pathology; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000450:Aldosterone / Q000096:biosynthesis*; D000804:Angiotensin II / Q000494:pharmacology*; D003345:Corticosterone / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000096:biosynthesis*; D006929:Hyperaldosteronism / Q000378:metabolism*; D006965:Hyperplasia; D008297:Male
chemical_list: D000804:Angiotensin II; D000450:Aldosterone; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone; D006854:Hydrocortisone