Resistant Hypertension - Primary Aldosteronism - 내분비 대사 내과 R3 송 란

Resistant, or refractory, hypertension Patients with diabetes or renal disease : antihypertensive medications (including a diuretic) : full doses of at least three  blood pressure : at least140/90 mm Hg or at least 130/80 mm Hg  Secondary causes (including exogenous substances)

- Approach to evaluation of resistant hypertension - - N Engl J Med 2006; 355

Among 4000 patients with resistant hypertension  Secondary causes –10 % of patients overall –17 % of patients over the age of 60 years Chronic renal parenchymal disease : M/C Atherosclerotic renovascular disease Primary aldosteronism Pheochromocytoma sleep apnea The effect of age on prevalence of secondary forms of hypertension in 4429 consecutively referred patients - J Hypertens. 1994; 12

DiagnosisDiagnostic test Chronic kidney diseaseEstimated GFR Coarctation of aortaCT angiography Cushing syndrome and other glucocorticoid excess states, including chronic steroid therapy History/dexamethasone suppression test Drug-induced/related causesHistory; drug screening Pheochromocytoma24-h urinary metanephrine and normetanephrine Primary aldosteronism and other mineralocorticoid excess states 24-h urinary aldosterone level or specific measurements of other mineralocorticoids Renovascular hypertensionDoppler flow study; magnetic resonance angiography Sleep apnea Sleep study with O2 saturation Thyroid/parathyroid diseaseTSH; serum PTH

Primary Aldosteronism 2 % of all hypertensives patients  5 ~ 10 % Screening test –plasma aldosterone to renin ratio (ARR) test Diagnosis : missed  No hypokalemia Type of primary aldosteronism TypesRelative frequency, % Solitary adrenal adenoma65 Bilateral adrenal hyperplasia30 Unilateral adrenal hyperplasia2 Glucocorticoid-remediable aldosteronism <1 Bilateral solitary adrenal adenomas<1 Adrenal carcinoma<1

Demographic and Clinical Characteristics of Patients with Various Types of Primary Aldosteronism ( Continued )

Continued.. - N Engl J Med, 1998; 339

Screening  strong indicator of aldosteronism But, 20 % : low normal serum potassium level Plasma aldosterone(ng/dL) to renin(ng/mL per hour) ratio: ARR –Timing of the tests : morning –The posture before blood sampling : upright –Unit of measurement –Cutt off value > 30 – 경희의료원 : plasma aldo.  pg/ml  계산값 X 0.1 Spontaneous HypokalemiaHTN +

345 patients of Hypertension Essential hypertension (EH) (n=260) Primary aldosteronism (PA) (n=49) Secondary HTN other than PA (n=36)

ARR –affected by antihypertensive drug use  no anti-hypertensive therapy or taking medications least likely to affect it (e.g. calcium-channel blockers or α-blockers) - Nat Clin Pract Endocrinol Metab,2005;1

Definitive Biochemical Diagnosis Diet high in sodium chloride (2 to 3 g with each meal for two to three days)  high rate of urinary aldosterone excretion  < 14 μg in 24 hours : rules out primary aldosteronism Intravenous infusion of normal saline (1.25 liters over a 2 hours period or 2 liters over a 4 hours period, preferably between 8 a.m. and noon)  high plasma aldosterone level  < 8.5 ng/dL(240 pmol/L) (performed in the morning) : rules out primary aldosteronism

Adrenal venous blood sampling with adrenocorticotropic hormone infusion  unilateral excess of aldosterone secretion : aldosteronoma, unilateral adrenal hyperplasia Computed tomographic (CT) scanning –Detect most aldosteronomas ( except very small ) –large adrenal tumor (>3 cm in diameter)  Possibility adrenal carcinoma : adrenal steroids (androgens, cortisol, estrogen) in the plasma or urine : measured Localizing Test

Algorithm for diagnosis and management of primary aldosteronism - Nat Clin Pract Endocrinol Metab,2005;1