Case Discussion <Brief History>    The 37-year-old gentleman was hospitalized because of hypertension with hypokalemia for 9 years. He firstly experienced a sudden onset of severe throbbing headache in 1991 when he was teaching. Hypertension with blood pressure up to 180/100 mmHg was found. Therefore, he visited hospital A. After a series of examinations, hypokalemia (less than 3 mEq/L) and a small left adrenal tumor were detected. He took medication since then. However, his blood pressure was not well controlled. He still had intermittent headache and he remained hypokalemic. He did not have symptoms of hypokalemia, such as malaise, fatigue or constipation except occasional leg weakness after rigorous exercise.     He visited hospital B on February 3, 1993. A CT scan of the abdomen demonstrated a nodule in the left adrenal gland. An 13I I-NP59 scan showed symmetrically increased uptake in both adrenals. Then, adrenal venous sampling was performed. The aldosteorone and cortisol levels were 283/65.8 in the right adrenal vein, 198/21.3 in the left adrenal vein, and 357/42.8 in the inferior vena cava, respectively (aldosterone in ng/dl, cortisol in μg/dl). No definite diagnosis was made. Thereafter, he took various drugs, including labetalol, prazocin, hydralazine, and spironolactone, from different hospitals.    General weakness, headache, and epistaxis developed on January 9, 2000. On the next day, he suffered from headache, palpitation, and flushing sensation. So, he was admitted to hospital C. Again, hypertension was noted (SBP over 200 mmHg). He received several examinations, including 24-hr urine potassium excretion, a postural test, and a CT scan of the abdomen, which demonstrated a 1.3 cm tumor in the left adrenal gland (Figure 1 ). Then, he was hospitalized to our hospital on March 2 for adrenal venous sampling after spironolactone was discontinued for one week. Physical findings were unremarkable except hypertension.  <Lab Data> 1. CBC+DC (2/23): RBC Hb Hct MCV Plt WBC 4.55M 13.1 37.4 82.2 187K 4.97K 2. BCS:   Na K Cl Ca Mg 2/23 140 3.1 106 2.4 -- 2/25 142 2.7 103 2.19 0.93 A/G Bil (T/D) GOT/GPT ALP g-GT BUN/Cre 4.2/3.5 1.0/0.3 14/14 127 22 15.4/1.1 3.ABG: pH PaCO2 PaO2 HCO3 7.45 40.8 94.4 27.7 4. Urine: VMA Dopamine Epinephrine NE pH 5.5 (1--7) 301 (50--45) 23.8 (<22.4) 90 (12--85) 6.5 Amount Cl K Na Osm 3,000 cc 22 13.5 27 245 5. Postural test:   8 AM 12 noon Plasma renin activity (ng/ml/hr) 0.26 0.21 Aldosterone (ng/dl) 92.40 47.20 Cortisol (μg/dl) 16.34 6.99 6. Adrenal venous sampling:   PRA (ng/ml/hr) Aldo (ng/dl) Cortisol (μg/dl) Ratio Peripheral 0.09 84.2 15.84 5.3 IVC above 0.07 134.2 20.78 6.5 IVC below 0.12 101.3 18.39 5.5 Left adrenal 0.08 442.1 57.1 7.7 Right adrenal 0.13 90.9 14.26 6.4 <Course and Treatment>    After admission, 24-hr urine was collected for measuring the excretion amount of potassium, VMA, and catecholamines. Bilateral adrenal sampling was performed smoothly on February 25, 2000. Ophthalmologists were consulted and his eye ground was found to be normal. Left adrenalectomy was performed on April 1. Macroscopically, a 1.3-cm yellow soft tumor was found. Microscopically, it was an adrenocortical adenoma(Figure2 ).  His BP was 130/90 mmHg before discharge. Enalapril 5 mg qd was prescribed. He returned to the urology clinic 6 days later. His blood pressure was 150/110 mmHg. The serum potassium level was 4.4 mEq/L. 病案分析 由高血壓與低鉀血症可懷疑此病例有續發性高血壓，進一步的檢查雖發現左側腎上腺有一腫瘤，但131I -NP59 scan與第一次adrenal venous sampling並未證明該腫瘤具有分泌功能。此次住院，從plasma renin activity與aldosterone的變化可推測病人罹患primary aldosteronism，再由postural test配合電腦斷層攝影結果更加支持病人左側腎上腺有aldosterone-producing tumor，故開刀切除之。 繼續教育考題 1. (C) His average baseline blood pressure was 182/112 mmHg if he did not take anti-hypertensives. Which stage of hypertension it is？（Based on the sixth report of the Joint National Committee on Detection, Evaluation and Treatment of High Blood Pressure） A Stage 1 B Stage 2 C Stage 3 D Stage 4 2. (D) Evaluation for secondary hypertension is indicated in the following conditions, EXCEPT： A Hypertension refractory to three-drug regimen B Hypokalemia C Continued creatinine rise while on appropriate antihypertensive therapy D None of the above 3. (D) Hypokalemia may cause all of the following signs, EXCEPT： A Hyporeflexia or areflexia B Impaired urine concentrating ability C Paralytic ileus D None of the above 4. (D) This hypertensive patient was found to have hypokalemia. Which of the followings can NOT explain his hypokalemia？ A Taking thiazides B Renin-secreting tumor C Renovascular hypertension D None of the above 5. (A) Which of the following diseases may cause decreased plasma renin activity and increased plasma aldosterone level？ A Conn's syndrome B Liddle's syndrome C Bartter's syndrome D Congenital adrenal hyperplasia 6. (C) Which one(s) support(s) the presence of primary aldosteronism？  A Decreased plasma renin activity after normal saline infusion B Elevated plasma aldosterone level after furosemide injection C Elevated plasma aldosterone level despite of taking captopril D All of the above 7. (A) Which of the following data supported that this patient had an aldosterone-producing adenoma rather than idiopathic hyperaldosteronism due to bilateral adrenal hyperplasia？ A Postural test B  131I－NP59 scan C Urine catecholamine data D None of the above 8. (C) Which of the following data did not support the decision of left adrenalectomy in this patient？ A Abdominal CT scan  B Plasma renin activity and aldosterone level C 13I I－NP59 scan D Postural test 9. (D) Which of the following statements about glucocorticoid remediable aldosteronism（GRA）is WRONG？ A An autosomal dominant inherited disorder B Resulting from chimeric 11 beta-hydroxylase /aldosterone synthase gene C Confirmed by genetic testing D ACTH injection can suppress this subset of primary aldosteronism 10. (A) What is the most appropriate therapy for bilateral adrenal hyperplasia？ A Spironolactone B Bilateral adrenalectomy C Low-dose dexamethasone D None of the above

題目解析

1. 根據JNC-VI對高血壓的分類，收縮壓小於130mmHg且舒張壓小於85mmHg為正常血壓，收縮壓130-139mmHg或舒張壓85-89mmHg為高正常血壓，收縮壓140-159mmHg或舒張壓90-99mmHg為stage 1高血壓，收縮壓160-179mmHg或舒張壓100-109mmHg為stage 2高血壓，收縮壓大於180mmHg或舒張壓大於110mmHg為stage 3高血壓。不同stage的高血壓處置方式略有差異。(Arch Intern Med 157:2413, 1997) 2. 三種情況皆需考慮secondary hypertension之可能性。 3. 三選項皆可以是低鉀血症之表現。  4. 前三選項皆可以造成高血壓加低鉀血症之表現。  5. Plasma aldosterone上升而plasma renin activity下降，可推論答案應選一種造成primary aldosteronism之狀況，所有選項中僅第一項符合。  6. 前二選項乃是生理現象無法判斷是否有primary aldosteronism。服用ACEI後，plasma renin activity與aldosterone應下降，若aldosterone未被壓抑便可支持有primary aldosteronism存在。  7. Postural test乃是讓受試者直立四小時，比較之前之後plasma renin activity、aldosterone與cortisol的變化。通常bilateral adrenal hyperplasia患者之aldosterone會上升而 aldosterone-producing tumor患者之aldosterone會下降或不變。  8. 從 plasma renin activity 與 aldosterone level 再配合 postural test 的變化，支持此病患有 aldosterone-producing tumor，而 CT scan 支持 tumor 在左側，需考慮 left adrenalectomy。  9. Glucocorticoid remediable aldosteronism會造成primary aldosteronism，以autosomal dominant方式遺傳，複合的11beta-hydroxylase/aldosterone synthase gene無法以正常方式調控之，但可以用glucocorticoid抑制此基因之表現來治療此種primary aldosteronism。診斷上依賴分子生物學檢測異常基因之存在。  10. Bilateral adrenal hyperplasia是primary aldosteronism的一種subset，治療上可考慮使用spironolactone或amiloride，無法開刀治療。