Case Discussion Case Presentation A 42-year-old woman was admitted to the hospital because of hypertension and a left adrenal mass. The patient was diagnosed with hypertension about 5 years ago, and it was difficult to control with regular medication. She felt anxious and intermittent palpitation 3 months prior to hospitalization. She visited another hospital where a plasma renin activity <0.1 ng/mL/h and an aldosterone level 111 ng/dL were found. Abdominal CT (Fig. 1) also disclosed a suspicious left adrenal mass. She was then referred to this hospital for further evaluation. She was a housewife and denied consumption of cigarettes or alcohol. Some of her relatives have hypertension that usually developed after the 5th decade of life. The patient’s anti-hypertensive medications included nifedipine 20 mg bid, nadolol 80 mg qd, doxazocin 2 mg qd and lisinopril 10 mg qd. The patient appeared obese. The temperature was 36.7oC, pulse was 70 bmp, and respiration was smooth. The blood pressure was 141/ 103 mmHg. The other physical examinations were unremarkable. Her average blood pressures were 143/91 mmHg and 142/92 mmHg, respectively for daytime and nighttime. The maximal BP was 158 mmHg in systole and 110 mmHg in diastole during daytime. The systolic BP > 140 mmHg was found in 69% of daytime monitoring and 51% of nighttime ones. The diastolic BP > 90 mmHg was observed in 54% and 61% of the corresponding periods, respectively. The circadian change of BP was not evident. The electrocardiography on admission was shown (Fig. 2) . Table 1. Hematologic laboratory values   WBC /mL RBC M/mL Hb g/dL MCV fL Plt k/mL On admission 5890 4.34 13.0 88.7 286 Table 2. Blood chemical values   Glusose mg/dL Bilirubin mg/dL AST U/L BUN mg/dL Creatinine mg/dL Na mM K mM On admission 104 0.7 14 14.7 0.7 139 3.3   Cl mM Ca mM Mg mM P mg/dL pH HCO3- mEq/L    On admission 102 2.26 0.94 2.9 7.44 23.2   Table 3. Urinalysis   PH Pro mg/dL Glu mg/dL Ketone OB Urobil EU/dL RBC /HPF WBC /HPF Epi /HPF  On admission 5.5 +/- - - 1+ 0.1 - 0-2 5-10 Table 4. Endocrinologic laboratory values   On Admission 10th admission day 10th admission day 17th admission day 17th admission day Status Baseline High-salt diet Postural test Adrenal vein(right/ left) Primperan test (right/ left) Renin activity (ng/mL/hr) 0.01 0.26 0.54 0.04/0.04 0.05/0.01 Aldosterone (ng/dL) 13.8 30.1 25.8 11.8/32.8 26.6/640.6 (Reference level: renin activity 0.5~5ng/mL/h; aldosterone 5~20 ng/dL) After admission, serial laboratory studies were performed (Table 1~3). Adrenal venous blood sampling via bilateral femoral venous approach was performed smoothly on 17th admission day (Table 4). Under the impression of adrenal adenoma, she underwent laparoscopic adrenalectomy of left adrenal gland on June 30, 2001. The pathology revealed adrenal adenomatous hyperplasia (Fig. 3). Her post-operative plasma renin activity was 0.79 ng/mL/h and aldosterone 23.5 ng/dL. No obvious electrolyte derangement was found. However, hypertension with systolic pressure 160~170 mmHg and diastolic pressure 105 mmHg was still noted at OPD under valsartan 80 mg and ateolol 10 mg daily. <病案分析> 本病例為一個難以用一般藥物控制的高血壓患者, 同時合併有低血鉀的情況。 此時應考慮到原發性或次發性高醛酮血症 (primary or secondary hyperaldosteronism) 的可能性。 一個有效區分這兩種情況的方式,就是測量血漿腎素活性 (plasma renin activity)。 若是次發性高醛酮血症所引起之高血壓,血漿腎素活性會高; 反之若是原發性高醛酮血症, 則血漿腎素活性會低下。 事實上,若病人有自發性的低鉀血症, 亦即, 在停用利尿劑兩週以上仍有鉀離子低於2.5 mmol/L 的情況, 再加上血漿中aldosterone與renin activity的比值很高時, 幾乎就可以下原發性高醛酮血症的診斷。 當aldosterone 的單位為ng/dL, 而plasma renin activity 的單位以 ng/ml/hr 表示時, 其比值若超過30以上, 就強烈暗示病人有原發性高醛酮血症。 本例之患者即屬於此種狀況。 確認為原發性高醛酮血症之後, 最重要的就是區分病人是屬於腺瘤(adenoma) 或是自發性結節增生 (idiopathic bilateral nodular hyperplasia) 所導致。 區分這兩者非常重要, 是因為後者在開刀之後常不會有改善; 反之, 前者則可在切除adenoma之後, 高血壓可獲得改善, 或甚至完全不需藥物治療。 然而僅從臨床症狀及基本的實驗數據, 很難將二者完全區分開來。 要做正確的區分, 除了在影像學上清楚見到單一側的腫瘤之外, 雙側腎上腺靜脈導管插入 (bilateral adrenal venous catheterization) 並抽血檢查, 是最準確的區分方式。 若兩側同時抽血的aldosterone levels 比值超過2~3倍以上, 就可確立adenoma的診斷。 繼續教育考題 1. (E) In patients with primary aldosteronism, which of the following statements is wrong? A A benign aldosterone-producing adenoma accounts for 75% of cases of primary aldosteronism. B Idiopathic hyperaldosteronism accounts for about 20 % of cases. C In idiopathic hyperaldosteronism the adrenals are either normal in appearance or reveal bilateral micro- or macronodular adrenal hyperplasia. D After 2-4 hrs in upright posture, 90% of patients with adenoma will show no significant change or a frank decrease in plasma aldosterone levels. E After 2-4 hrs in upright posture, aldosterone levels almost always decrease in those with idiopathic hyperaldosteronism. 2. (D) Which of the following is not a common ECG change of hypokalemia? A Flattening or inversion of the T wave. B A prominent U wave. C ST segment depression. D A shortened QU interval. E A prolonged PR interval. 3. (A) For diagnosing secondary causes of hypertension, which of the following patients with hypertension should have a workup beyond routine laboratory studies (blood urea nitrogen, glucose, creatinine, calcium, uric acid, potassium, cholesterol, triglyceride, ECG and CxR)? A A 45-year-old man with an unknown prior history that presents with a BP of 160/100-mmHg and left ventricular heave on physical examination. B A 35-year-old woman with a prior history of normotension who presents with a BP of 160/105 and an abdominal bruit. C A 60-year-old man with a prior history of normotension who presents with a BP of 160/100. D A 40-year-old woman with a prior history of normotension who presents with a BP of 160/105 unresponsive to captopril and hydrochlorothiazide. E A 22-year-old man with a prior history of normotension who presents with a BP of 160/105 but otherwise normal physical examination. 4. (B) Patients with primary aldosteronism typically come to medical attention because of symptoms of followings, except: A Fatigue and weakness. B Clinical edema. C Increased thirst and polyuria. D Increased diastolic blood pressure. E All of the above statements are correct. 5. (E) Persistent post-operative hypertension may related to: A The chronicity of hypertension. B The presence of end-organ damages. C The coexistence of essential hypertension. D Idiopathic hyperplasia of bilateral adrenals E All of the above are correct. 6. (C) 6. About the mechanisms by which mineralocorticoids produce hypertension, which of the following statements is incorrect? A The initiating events are the physiologic consequences of mineralocorticoid-induced expansion of plasma and extracellular fluid volume. B After gaining 1-2 L of extracellular fluid, the phenomenon of Na+ “escape” follows. C The chronic phase of mineralocorticoid excess is characterized by an increase in stroke volume and cardiac output. D The chronic phase of mineralocorticoid excess is characterized by an increase in peripheral vascular resistance. E A direct central action of aldosterone. 7. (C) In the diagnosis of diastolic hypertension with hypokalemia, if no tumor is seen in adrenal CR or MRI, measuring plasma aldosterone level after dexamethasone administration is intended to rule out which of the following disease? A Liddle’s syndrome. B 11 beta-hydroxysteroid dehydrogenase deficiency. C Glucocorticoid-remediable aldosteronism. D Chronic licorice ingestion. E Aldosterone-producing adrnocortical carcinoma 8. (C) Which is the accurate pathway of aldosterone synthesis? (1) Cholesterol (2) Corticosterone (3) Deoxycorticosterone (4) Pregnenolone (5) Progesterone (6) Aldosterone A (1)(4)(2)(3)(5)(6) B (1)(4)(5)(2)(3)(6) C (1)(4)(5)(3)(2)(6) D (1)(4)(2)(5)(3)(6) E (1)(4)(3)(5)(2)(6) 9. (B) Which of the following is not included in pseudohyperaldosteronism, in which the clinical features are consistent with mineralocorticoid excess yet endogenous mineralocorticoid secretion is abnormally low? A Liddle’s syndrome. B Bartter’s syndrome. C Syndrome of apparent mineralocorticoid excess D 11 beta-hydroxysteroid dehydrogenase deficiency E Chronic ingestion of licorice. 10. (A) About the treatment options of primary aldosteronism, which of the following is incorrect? A Subtotal adrenalectomy usually corrects hypokalemia and hypertension in patients with idiopathic aldosteronism. B Unilateral adrenalectomy is recommended in patients with an aldosterone-producing adenoma. C The surgical cure rate of hypertension associated with adenoma is excellent. D Patients with idiopathic aldosteronism should not be routinely sent to surgery. E Spironolactone reduces the volume of the expanded extracellular fluid toward normal and promotes potassium retention, is suitable for preoperative preparation of these patients.

答案解說 (E)The answers A to D are correct. The differences between adenoma and idiopathic hyperplasia after posture tests are due to (1) the profound suppression of the renin system by excess aldosterone production in patients with an adenoma. (2) the adenoma is usually ACTH-responsive, while ACTH usually declines between 8AM and 12 noon, after posture tests.。 (D)A prolonged QU interval is correct. If severe K+ depletion occurs, a prolonged PR interval may ensue, followed by decreased voltage and widening of the QRS complex, which will increase the risk of ventricular arrhythmias especially in patients treated with digoxin. (A)The abrupt onset of severe hypertension or the onset of high blood pressure of any severity in a person under age 25 or after age 50 warrants additional tests to exclude secondary hypertension such as renovascular hypertension, primary aldosteronism, Cushing’s syndrome or pheochromocytoma. The presence of an abdominal bruit should prompt a workup for renovascular hypertension. Any patient whose hypertension is not controlled by a two-drug regimen at adequate dose should undergo further studies. The existence of left ventricular hypertrophy suggests a long-standing hypertension and dose not necessarily imply the presence of secondary hypertension. (B)Patients with primary aldosteronism characteristically do not have edema, since they exhibit an “escape” phenomenon from the sodium-retaining aspects of mineralocorticoids. The hypokalemia may results in nephrogenic diabetes insipidus in patients with primary aldosteronism. (E)All of these statements about persistent hypertension after surgical intervention of aldosteronism are correct. (C)Initially, sodium and fluid retention may increase the body weight and cardiac output. However, in chronic stage a new steady state is achieved, and normalization of stroke volume and cardiac output ensues. (C)Glucocorticoid-remediable aldosteronism is a rare form of genetic hypertension inherited in an autosomal dominant fashion. The primary defect is gene duplication that results form an unequal crossing over event that fuses the regulatory region of the 11 beta-hydroxylase genes to the coding sequence of aldosterone synthase. Aldosterone secretion is then ACTH-dependent, such that small doses of glucocorticoid (1-2 mg/day of dexamethasone) can ameliorate hypertension and hypokalemia of these patients. (C) (B)Bartter’s syndrome is characterized by hyperaldosteronism but normal blood pressure and no edema. The pathogenesis involves a defect in the renal conservation of sodium or chloride. The renal loss of sodium is thought to stimulate renin secretion and aldosterone production, which produces potassium depletion and profound hypokalemia. (A)In patients with idiopathic aldosteronism, subtotal adrenalectomy will correct hypokalemia, but hypertension is rarely cured. Other antihypertensive measures should be used to control hypertension, and such patients should not be routinely sent to surgery, unless there is significant and symptomatic hypokalemia that cannot be controlled with medical therapy. Top of Page