title: Urinary protease inhibitor Serpin B3 is higher in women and is further increased in female patients affected by aldosterone producing adenoma.
abstract: A correct diagnosis of primary aldosteronism (PA) requires adrenal venous sampling (AVS) for the classification of subtypes (bilateral hyperplasia, BAH, or adenoma, APA). Since such testing is not easily practicable, appropriate markers for the definition of subtypes are desirable. We hypothesized that an aldosterone excess was associated with abnormalities in urinary proteome, specific for PA subtypes. The project work was divided into 3 phases: (1) screening/identification by proteomic analysis and further characterization by RT-PCR and immunohistochemistry of the candidate protein; (2) clinical validation by quantitative ELISA assay of 57 (33 M, 24 F) PA patients and 50 normotensive controls (21 M, 29 F); (3) analysis of adrenal tissue of 8 individuals who had undergone adrenalectomy for APA or other adrenal tumors. The proteomic analysis showed a different expression of Serpin B3 Inhibitor-SCCA1 (SB3) in APA and BAH patients. Urine SB3 concentrations in normotensive controls, quantified by ELISA assay and normalized by urinary creatinine, resulted much lower in males (6.72 ng SB3 per mg creatinine, C.I. 4.43-10.19) than in females (20.56 ng SB3 per mg creatinine, C.I. 12.43-33.99, p < 0.00001). SB3 concentrations were not significantly different in males affected by different PA subtypes (BAH, n = 19 and APA, n = 14) compared with normotensive subjects (n = 21). In contrast, in PA females, SB3 was significantly higher in APA (n = 13) than in BAH patients (n = 11) or in normotensive controls (n = 29) (P < 0.01 and <0.05, respectively). Neither messenger RNA nor SB3 protein were identified in tissue obtained from adrenal tumors and from the surrounding normal gland. In conclusion urine SB3 concentrations are physiologically much lower in males than in females. Hypertensive women, affected by APA, present urinary SB3 concentrations significantly higher than women affected by BAH.
authors: Department of Medicine, Unit of Internal Medicine, University of Verona, P.le L.A. Scuro10, Verona, Italy. oliviero.olivieri@univr.it.
authors: Oliviero
authors: O
authors: Olivieri
authors: Daniela
authors: D
authors: Cecconi
authors: Annalisa
authors: A
authors: Castagna
authors: Laura
authors: L
authors: Chiecchi
authors: Patrizia
authors: P
authors: Guarini
authors: Muthukumar
authors: M
authors: Gunasekaran
authors: Francesca
authors: F
authors: Morandini
authors: Paolo
authors: P
authors: Brazzarola
authors: Lello
authors: L
authors: Zolla
authors: Angelo
authors: A
authors: D'Alessandro
authors: Franco
authors: F
authors: Veglio
authors: Paolo
authors: P
authors: Mulatero
authors: Francesca
authors: F
authors: Pizzolo
mesh_terms: D000236:Adenoma / Q000378:metabolism* / Q000473:pathology / Q000652:urine; D000311:Adrenal Glands / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000096:biosynthesis / Q000652:urine; D000951:Antigens, Neoplasm / Q000378:metabolism* / Q000652:urine; D015415:Biomarkers / Q000378:metabolism / Q000652:urine; D016022:Case-Control Studies; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D006929:Hyperaldosteronism / Q000145:classification* / Q000378:metabolism / Q000652:urine; D006965:Hyperplasia / Q000378:metabolism* / Q000652:urine; D006973:Hypertension / Q000150:complications* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D040901:Proteomics; D015843:Serpins / Q000378:metabolism* / Q000652:urine; D012727:Sex Characteristics
chemical_list: D000951:Antigens, Neoplasm; D015415:Biomarkers; D015843:Serpins; C051072:squamous cell carcinoma-related antigen; D000450:Aldosterone