LEVELS OF THE CORTISOL, CORTISONE AND THEIR METABOLITES AS A MARKERS OF APPARENT MINERALOCORTICOID EXCESS (AME) – CASE PRESENTATION: PP.18.200

Abstract

Among the causes of secondary hypertension are a group of disorders with a Mendelian inheritance pattern. Apparent mineralocorticoid excess (AME) is an autosomal recessive disease caused by deficiency of the enzyme 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2). 11beta-HSD2 is responsible for conversion of cortisol (F) to inactive cortisone (E). In AME deficiency of 11beta-HSD2 allows the unmetabolized cortisol to bind to the mineralocorticoid receptor inducing sodium retention, hypokalemia, suppression of plasma renin activity (PRA) and hypertension. F and E are metabolized in the liver - the reaction is catalyzed by alfa-reductase obtaining allo-tetrahydrocortisol (allo-THF) and allo-tetrahydrocortisone (allo-THE). For beta-reductase followed the products are: tetrahydrocortisol (THF) and tetrahydrocortisone (THE). The balance between 11beta-HSD1 and 11beta-HSD2 activity can be demonstrated by measuring the ratio of reduced metabolites of F and E in urine as well as by determining of urinary free cortisol (UFF) and cortisone (UFE). Plasma F/E ratio is another valuable parameter in estimation of the coordinated activity of two isoforms of 11beta-hydroxysteroid dehydrogenase. Case presentation: 67 years old white men with the five years history of hypertension was admitted to the hospital with the suspicion of primary aldosteronism. Lab tests: unprovoked low plasma potassium (3.3 mmol/l), decreased serum aldosterone level (11.64 pg/ml) and normal PRA (1.30 ng/ml/h). Left ventricular hypertrophy was found in echocardiography, but in ultrasound suprarenal glands were normal. F, E and their metabolites, after extraction from human plasma and urine and after pre-column derivatization, were determined using high performance liquid chromatography methods. The following results were obtain: serum F/E - 13.12; UFF/UFE in urine – 1.48; (THF+allo-THF)/(THE+allo-THE) in urine - 1,70. Patient's hormone levels were significantly different in compare with levels obtain in control group (healthy volunteers, n = 14) – 3.97 ± 1.43; 0.42 ± 0.16 and 0.79 ± 0.19 respectively. The presented data show the screening tool in the assessment of abnormalities of 11beta-hydroxysteroid dehydrogenase activity, but the final diagnosis should be confirm by molecular analysis of the gene.