| 【Presentation of Case】
A 35-year-old woman was referred to our endocrinologic clinic due to newly diagnosed hypertension with hypokalemia. She had been in her usual state of health until 2 months earlier, when excessive fatigability, bilateral leg weakness, and malaise developed. She had not sought medical care until she suffered from episodes of headache with hypertension for recent one month (systolic blood pressure around 160-190 mmHg and diastolic blood pressure exceeding 120 mmHg). Her family physician had treated her with a calcium channel antagonist, and angiotensin-receptor blocker. However, her blood pressure remained high. She was therefore referred to our clinic and then admitted. On physical examination, her blood pressure remained above 160/100 mmHg, and no discrepancies were noted when measurements were made in both arms. There was no moon face, buffalo hump, central obesity, purple striae, edema, abdominal mass, or bruit. Under the impression of secondary hypertension, serial surveys were performed, which are shown in Tables. Laboratory findings showed hypokalemia (3.1 mEq/L) and the blood gas analysis revealed metabolic alkalosis. Baseline hormone analysis showed increased plasma aldosterone concentration (PAC) with suppressed renin activity (PRA). Otherwise, plasma cortisol and ACTH levels, and 24 hour urine vanillylmandelic acid (VMA) all were within normal ranges. Primary aldosteronism was impressed. Repeat measurements of supine PRA and PAC after administration of 50 mg of captopril were 0.04 ng/ml/hr and 39.2 ng/dL, respectively. The PAC/PRA ratio was 980, which exceeded the level of 30. Subsequently, PAC before and after saline loading were 35.8 and 38.8 ng/dL, respectively, which confirmed the diagnosis of primary aldosteronism. Differentiation by posture test was done and the PAC did not increase after ambulation, which indicated the possibility of adenoma. Computerized tomography of the abdomen showed a low density mass approximately 2.2 cm in diameter at the left adrenal gland. She underwent laparoscopic adrenalectomy. Pathological finding revealed the adenomatous nature without malignancy. Two weeks later, follow-up data showed normal serum potassium levels and hormonal status (PAC and PRA). One month later, blood pressure normalized and she no longer needed to take any antihypertensive medication.
【Laboratory data】
1.Results of baseline data
Variable |
BUN |
CRE |
Na |
K |
ALB |
AST |
ALT |
CK |
unit |
mg/dL |
mg/dL |
mmol/L |
mmol/L |
g/dL |
U/L |
U/L |
U/L |
value |
11.4 |
1.3 |
137 |
3.1 |
3.8 |
37 |
32 |
112 |
2. Results of the baseline endocrine tests
Variable |
ACTH
(8:00 am) |
Cortisol
(8:00 am) |
Cortisol
(4:00 pm) |
24 hr urine
VMA |
PRA
(ng/ml/hr) |
PAC
(ng/dL) |
Reference
value |
10-65
pg/mL |
5-25
μg/dL |
2.5-12.5
μg/dL |
1-7μg/24h |
1-5 ng/ml/hr |
5-30ng/dL |
value |
12 |
13.8 |
6.8 |
2.6 |
0.04 |
39.2 |
*** ACTH= adrenocorticotropin
*** VMA= vanillylmandelic acid
*** PRA= plasma rennin activity
*** PAC= plasma aldosterone concentration
3. Captopril test ( 50 mg captopril )
Variable/Time |
PRA
(ng/ml/hr) |
PAC(ng/dL) |
PAC/PRA ratio
(ARR) |
0’ |
0.27 |
37.4 |
138.5 |
90’ |
0.04 |
39.2 |
980 |
***A positive screening test is considered when the aldosterone-renin ratio (ARR) is more than 30 (ng/dL per ng/mL/hr) and the plasma aldosterone concentration (PAC) is more than 15 ng/dL.
4. Saline loading test
Variable/Time |
PRA (ng/ml/hr) |
PAC
(ng/dL) |
PAC / PRA ratio (ARR) |
0’ |
0.41 |
35.8 |
87.3 |
120’ |
0.08 |
38.8 |
485 |
***A positive saline loading confirm test is considered when the PAC is still more than 10 (ng/dL) despite saline loading with 1250 ml normal saline for 2 hours.
5. Postural test
Variable/Time |
PRA (ng/ml/hr) |
PAC
(ng/dL) |
PAC/PRA ratio (ARR) |
Before |
0.32 |
47.2 |
147.5 |
After |
0.56 |
17.8 |
31.8 |
*** A positive postural test is defined by an ambulatory plasma aldosterone concentration that is either lower than the supine baseline level or that increases less than 30% above that value
【病例解析】
原發性皮質醛酮症( primary aldosteronism (Conn's disease) )是由於腎上腺皮質醛酮腺瘤或增生所造成，其血清中腎素(renin)的濃度是低的，並且血中皮質醛酮濃度(plasma aldosterone concentration, PAC)是不會因體液擴張而受抑制。在高血壓病人，原發性皮質醛酮症的盛行率達3~9%，是一種可治癒的次發性高血壓疾病(secondary hypertension)。好發在成人居多，多在30~50歲。分類分為︰(一)、分泌皮質醛酮的腎上腺皮質腺瘤(aldosterone-producing adenoma (APA))，約佔2/3；(二)、皮質醛酮增生(Idiopathic hyperaldosteronism (IHA)) ，約佔1/3；(三)、Glucocorticoid remediable aldosteronism (GRA)及aldosterone- producing adrenocortical carcinoma，比例不到百分之二。其中，腺瘤在女性較常發生；而雙側腎上腺增生症，在男生發生率較高，發生的年齡也高於腺瘤。原發性皮質醛酮症的症候，包括︰血壓升高、血鉀偏低、鹼血等造成倦怠、易疲勞、多尿、易渴、夜尿、肌肉抽搐、無力等非特異性症狀。
然而，部分病人可以沒有高血壓或低血鉀。一般在門診檢查若發現高皮質醛酮素 (aldosterone)、低腎素 (renin)的表現加上臨床懷疑的話，會先停掉可能影響抽血結果的藥物(例如︰降壓藥中的ß-blocker, ACEI, ARB, aldosterone antagonist)，改用不影響結果的藥物(例如︰calcium channel blocker,α-blocker)，另外補充鉀離子直到血鉀正常才抽血(坐或站著)檢查。PAC在15 ng/dL 以上，且aldosterone-renin ratio (ARR) 比例在30 (ng/dL per ng/mL/hr) 以上則為陽性。而為求更精確的篩檢結果，可加服50 mg captopril，而後於 90分鐘( captopril test )後再抽血檢驗，判讀結果同上所述。確定診斷則需要在2小時內注射生理食鹽水1250 ml (saline loading test)後再測PAC，其值若大於10 ng/dL 則確診。確診後需進一步鑑別診斷是APA或IHA，因兩者的治療方式不同: 單側皮質醛酮素瘤(APA)以手術去除腫瘤為主。大部分病人術後高血壓都能有明顯下降或恢復正常，約有10-40%的病人仍有高血壓。而腎上腺增生(IHA)以藥物治療(aldosterone blocker如spironolactone、eplerenone等)為主，手術切除腎上腺對血壓的控制效果都不佳。一般而言，會採postural test(整夜平躺後抽晨血，之後坐或走路4小時後再驗血)作實驗室上的鑑別診斷(腺瘤的PAC不會因站立而增加，倘若增加，其幅度也不會超過原先躺臥時數值的30% )配合影像學上的定位(adrenal gland CT是首選)確定是單側腺瘤或雙側的增生。若血液檢驗與影像學上無法相符的時候(如︰少數情況下，有一些實際上是雙側腎上腺增生的病人影像上看起來像單側的結節；而部分病人所罹患的腺瘤(APA)，影像上兩側卻都會看到腫大的腺體等)，才考慮作侵入性的腎上腺靜脈抽樣 (adrenal vein sampling )來決定最終的診斷與治療方向。
【參考文獻】
- Rossi GP, et al.Primary aldosteronism: an update on screening, diagnosis and treatment. J Hypertens 2008;26:613-21
- Young WF, et al.Minireview: primary aldosteronism--changing concepts in diagnosis and treatment. Endocrinology 2003;144: 2208-13.
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Case Discussion 
繼續教育考題