Bartter's syndrome [5] Gitelman's Bartter's Liddle's Gitelman's syndrome Glucocorticoid remediable aldosteronism ( [2] ) Apparent mineralocorticoid excess (AME) (congenital adrenal hyperplasia CYP11B1 CYP17 ) [6] [7] 50 80% Bartter's syndrome Gitelman's syndrome (Chloride channel) thiazide-sensitive Na-Cl cotransporter Bartter's syndrome Bartter's syndrome [8] (hyperreninemia) (hyperaldosteronism) (prostaglandin) Bartter's Juxtaglomerular apparatus syndrome [1] [1,2] [9] Gitelman's syndrome (medullary thick ascending limb of the loop of Henle) [2] loop diuretics thiazide diuretic Bart- [10] renin-angiotensin-aldosterone system [3] ter's Gitelman's Na-K-2Cl cotransporter Loop diuretic (Potassium channel) 20 meq/l [4] 94 17 2 111
Liddle's syndrome Liddle's syndrome Bartter's syndrome Gitelman's GRA (hemorrhagic Liddle's syndrome stroke) 18% 70% (mineralocorticoid) 61% 32 GRA (MRA) Na channel Na [15] ( z o n a Liddle's syndrome triad glomerulosa) 17-hydroxylase cortisol (zona fasciculate) corticosterone 18-carbon syndrome Apparent mineralocorticoid excess (AME lico- 40 meq/l rice ingestion) DOC (deoxycorticoid)-producing Bartter's syndrome Gitelman's syndrome spironolactone [12] (NSAID) (spironolactone amiloride) 300 40 mg/day spironolactone amiloride GRA ( ) Na channel (ACE) angiotensin II aldosterone [11] (familial hyperaldosteronism type 1) (primary Bartter's syndrome hyperaldosteronism) (adrenal adenoma) (medullary thick ascending limb of the loop of Henle) Na-K-2Cl cotransporter (aldosterone) GRA amiloride ACEI ACTH ACTH Liddle's syndrome (Congenital Adrenal Hyperplasia) Amiloride triamterene Na channels Glucocorticorid-remediable aldosteronism (GRA) [13,14] thiazide [14] 112 94 17 2
11-beta-hydroxylase (isoenzymes) 11β -HSD spironolactone cortisol dexamethasone CYP11B2 (aldosterone synthase) ACTH cortisol deoxycortocosterone corticosterone 18-hydroxycorticosterone (nephrocalcinosis) thiazide isozyme CYP11B1 11-deoxy- cortisol cortisol GRA CYP11B1 promotor region CYP11B2 coding sequences (ACTH) corticosterone cortisol precursors 18-oxocortisol 18- hydroxycortisol [13,15] [21] [14] cortisol Dexamethasone suppression test cortisol 18-carbon oxida- (androgenic hormone) deoxy- tion 18-hydroxylcortisol 18-oxocortisol corticosterone [13] CYP11B1 (11-betahydroxylase) CYP17 (17-alpha-hydroxylase) (chimeric gene) [16] [17] CYP11B1 dexamethasone 5 8% [22] prednisolone [23] [18] (renin-angiotensin system) 8 chromosone 8q21-q22 Apparent mineralocorticoid excess (AME) Apparent mineralocorticoid excess (AME) deoxycorticos- [19] terone 11β -hydroxysteroid dehydrogenase (11β - AME (congenital adrenal hyperplasia) cortisol (late onset) HSD) 11β -HSD cortisol cortisone cortisol CYP11B1 CYP21A2 (21-hydroxylase deficiency) 94 17 2 113
CYP17 deoxycortisol deoxycorticosterone (DOC) (androgens) hydroxylase progesterone cortisol deoxycortisol deoxycorticosterone 17 20-lyase 11-deoxycortisol ACTH 11-deoxysteroids 17-ketoster- estrogenic C18 oids steroids 17-hydroxylase cortisol tetra-hydro-11-11-deoxycorticosterone 18-hydroxy- deoxycortisol 11-deoxdeoxycorticosterone ycortisol 17 20- (glucocorticoid) (aeromatized) CYP17 11-deoxycorticosterone Hydrocortisone 10 25 mg dexamethasone 0.5 17-hydroxylase mg cortisol 11-deoxycortisol 17-alpha- hydrocortisone hydroxyprogesterone 17 20-lyase dehydroepiandrosterone (DHEA) dehydroe- piandrosterone (DHEA sulfate) androstenedione 11-deoxycortisol DOC testosterone and estradiol 11-deoxycorticosterone corticoster- one spironolactone amiloride [22] 11-deoxycorticosterone renin-angiotensin-aldos- CYP17 120 terone axis [24] 35 cortisol pregnanetriol corticosterone deoxycorticosterone 17-hydroxylase 17 20-lyase lyase CYP17 (DOC) (male pseudohermaphroditism) CYP17 ( 1) 114 94 17 2
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diable aldosteronism is associated with severe hypertension in early childhood. J Pediatr 2001; 138: 715-20. 18. Stowasser M, Bachmann AW, Huggard PR, et al: Treatment of familial hyperaldosteronism type I: only partial suppression of adrenocorticotropin required to correct hypertension. J Clin Endocrinol Metab 2000; 85: 3313-8. 19. Lavery GG, Ronconi V, Draper N, Rabbitt EH: Late-onset apparent mineralocorticoid excess caused by novel compound heterozygous mutations in the HSD11B2 gene. Hypertension 2003; 42: 123-9. 20. White PC, Mune T, Agarwal AK: 11- ß hydroxysteroid dehydrogenase and the syndrome of apparent mineralocorticoid excess. Endocr Rev 1997; 18: 135-56. 21. White PC, New MI, Dupont B: Congenital adrenal hyperplasia. N Engl J Med 1987; 316: 1519-24. 22. White PC, Curnow KM, Pascoe L: Disorders of steroid 11- beta-hydroxylase isozymes. Endocr Rev 1994; 15: 421-28. 23. Ruler A, Leiberman E, Cohen T: High frequency of congenital adrenal hyperplasia (classic 11-beta-hydroxylase deficiency) among Jews from Morocco. Am J Med Genet 1992; 42: 827-34. 24. Biglieri EG: 17-alpha-hydroxylase deficiency: 1963-1966. J Clin Endocrinol Metab 1997; 82: 48-50. 116 94 17 2