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<Chief
complaint>
Intermittent palpitations for one year.
<Case
presentation>
A 19-year-old girl had been healthy before until one year
ago when she suffered from intermittent palpitations. The
paroxysmal episodes were accompanied by profuse sweating and
headache, the duration and frequency of which were about 20-30
minutes and 2-3 times per day, respectively. There was no
known precipitating factor. She visited a hospital where
hypertension was noted (BP about 170/100 mmHg). Secondary
hypertension was impressed, and she underwent serial studies
to search the underlying causes.
Twenty-four-hour urine level of vanillylmandelic acid
(VMA) reported 182 μmole/day (normal < 31).
Pheochromocytoma was highly suspected, but both computer
tomography of the adrenal glands and
131I-metaiodobenzylguanidine (MIBG) scan were
negative. She took doxazosin (1.5 mg Q.D.) and nifedipine if
needed but the discomfort was only slightly alleviated. So she
visited a medical center for second opinion and was admitted
for further evaluation and management.
She was a student and denied smoking, alcohol consumption,
other systemic diseases and a family history of hypertension.
Physical examination revealed a 63 kg, 163 cm-tall girl
without a round face, acne or truncal obesity. Her temperature
was 36.9°C, pulse rate 76/min, respiratory rate 20 /min and
her blood pressure was 160/90 mmHg. Her conjunctivae were
pink, sclerae were anicteric and pupils were isocoric with
prompt light reflex. Her neck was supple without a goiter,
engorged jugular veins, or lymphadenopathy. The thoracic,
abdominal, and neurologic examinations were normal. There was
no gynecomastia, galactorrhea, buffalo hump or purple
striae.
<Laboratory
data>
Table1. Endocrine test
|
Renin |
Aldosterone |
Cortisol (8AM) |
Cortisol (4PM) |
DHEA-SO4* |
|
ng/mL/hr
(1-5) |
ng/dL
(5-30) |
μ g/dL
(5-25) |
μ g/dL
(2.5-12.5) |
μ mol/L
(4.6-15.4) |
|
6.40 |
66.75 |
10.3 |
6.87 |
4.7 | Table2. 24 HR urine catecholamine
|
Dopamine |
Epinephrine |
Norepinephrine |
VMA |
|
μ g/24h
(50-450) |
μ g/24h
(< 22.4) �� |
μ g/24h
(12.1-85.5) |
mg/24h
(1-7) |
|
361.4 |
15.2 |
1173.2 |
18.1 |
*DHEA-SO4: dehydroepiandrosterone
sulfate
<Course and
treatment>
She
discontinued all medications for two weeks. Complete blood
counts and biochemical studies, including serum electrolytes
were within normal ranges. Both 24-hr urine levels of VMA and
norepinephrine increased. Other endocrine studies were within
normal limits except serum rennin activity and aldosterone
level elevated. Computer tomography of chest, abdomen and
pelvis revealed a heterogeneous and moderately enhanced mass
about 4 cm around the pancreatic head (Fig 1
). Bilateral adrenal glands were
normal in size. Previous 131I-MIBG scan was negative, so she
received 2-[Flurine-18] fluoro-2-deoxy-D-glucose positron
emission tomography (PET) of whole body. The image showed a
large FDG hypermetabolic ring lesion at right sub-hepatic
region (Fig 2).
She got a magnetic resonance image to exclude vascular
invasion. She took phenoxybenzamine for pre-operative blood
pressure control and propranolol for tachycardia. She
successfully accepted an operation for tumor excision. No
vascular invasion was noted. The tumor was soft and well
encapsulated and the pathology confirmed the diagnosis of
paraganglioma (Fig 3
& 4
). Post-operative 24-hour urine
levels of VMA and norepinephrine decreased apparently. She
never had palpitation and hypertension after removal of the
tumor and needed no antihypertensive drugs, either. She
followed up regularly at
OPD.
<Discussion>
小於30歲或大於60歲出現高血壓的病人都需考慮續發性高血壓(secondary
hypertension)。嗜鉻細胞瘤(pheochromocytoma)是原因之一，90％的嗜鉻細胞瘤位於腎上腺，10％在腎上腺外，稱為副神經節瘤(paraganglioma)，後者從神經節長出，大部分可在腹腔內發現，但也可以位於後腹腔、骨盆腔、前後縱隔腔、心臟或主動脈旁。許多病人於診斷前就因心律不整或中風死亡，大多數的病人都有高血壓、頭痛、心悸及冒汗等症狀。15％的嗜鉻細胞瘤是惡性的，可以轉移到頭骨、肋骨、脊椎、胸管、腸繫膜和肺臟；副神經節瘤的惡性機會較高，約30-50％。大約30-60％的副神經節瘤是有功能的(functional)，可以分泌norepinephrine及normetanephrine，但是並不會因此影響生存。
除了臨床症狀外，仍需生化檢查輔助診斷，如血漿和尿液中的catecholamines及metanephrine
(catecholamine的代謝物)。目前以測尿液中的metanephrine的敏感性最高，但是基於實驗室的限制，我們的病人只測二十四小時尿液中的VMA及catecholamines。然而，有些藥物、食物(咖啡因、香蕉)、或疾病也都會影響血漿或尿液catecholamines的濃度，繼而干擾我們的診斷，所以應該仔細問診，如果允許，於檢查前應停止所有藥物至少兩星期。也可以測serum
chromogranin A
(CgA)，正常情況下，CgA早上八點時血中濃度最低，下午及晚上11點時濃度最高，且CgA的濃度和腫瘤大小有關，所以是一個有用的腫瘤標誌。因為catecholamines可以促進renin分泌，所以有些病人血中的renin及aldosterone也會上升，如同我們的病人。
臨床上利用metaiodobenzylguanidine (MIBG)
scans和電腦斷層檢查來定位。MIBG的敏感性約85％，但是對於偵測腎上腺外腫瘤時敏感性會下降。我們的病人於臨床上(包括症狀及檢驗)強烈懷疑是嗜鉻細胞瘤，但是腎上腺電腦斷層檢查及MIBG卻沒有找到腫瘤，此時就要考慮副神經節瘤，因此須多作胸腔、腹腔及骨盆腔電腦斷層。於電腦斷層檢查前，一定要先控制血壓，因為顯影劑會造成高血壓危象。懷孕病人首選的檢查是核磁共振造影，因為不需要打顯影劑，也沒有輻射線；加作血管攝影可以知道是否有血管侵犯。正子攝影(positron
emission
tomography，PET)對定位惡性嗜鉻細胞瘤轉移的敏感性不錯，但是特異性較MIBG差，好處是可以立即作不需事前準備。
治療以手術切除為主，內視鏡腎上腺切除(laparoscopic
adrenectomy)是目前的主流。然而要做好術前準備，以防高血壓危象或休克；建議使用α-blockers(如phenoxybenzamine、doxazosin或prazosin)，但是會增加catecholamines和metanephrine的合成，使得心跳加快，此時可以併用β-
blockers，對治療臉部潮紅也有效。有些專家建議使用鈣離子阻斷劑，因為術前水份不需要補充太多且病人的耐受性較好。由於catecholamines會刺激renin分泌且腫瘤細胞上有angiotensin-coverting
enzyme (ACE)的結合位置，所以可以同時使用ACE inhibitors或angiotensin receptor
blockers (ARBs)，但是孕婦禁用，因為會致畸胎。
腫瘤切除後仍有25％的病人會有高血壓。良性嗜鉻細胞瘤5年存活率為96％，惡性腫瘤只有44％。手術後2星期再追蹤尿液catecholamines及metanephrine，之後也要定期追蹤。
<References>
- Kebebew E, Duh QY: Benign and
malignant pheochromocytoma: diagnosis, treatment, and
follow-up. Surg Oncol Clin N Am 1998;7:765.
- Lenders JW et al: Biochemical
diagnosis of pheochromocytoma: which test is best? JAMA
2002;287:1427.
- Lenz T et al: Diagnosis of
pheochromocytoma. Clin Lab 2002;48:5.
- Roelants V et al: Iodine-131-MIBG
scintigraphy in adults: interpretation revisited ? J Nucl
Med 1998 ;39 :1007.
- Hoegerle S et al: Pheochromocytomas:
detection with 18F DOPA whole body PET-initial results.
Radiology 2002;222:507.
- Combemale F et al: Exclusive use of
calcium channel blockers and cardioselective beta-blockers
in the pre- and peri-operative management of
pheochromocytoma. 70 cases. Ann Chir 1998;52:341.
- Winfield HN et al: Technique of
laparoscopic adrenalectomy. Urol Clin North Am 1997;24:459.
- Tagaya N et al: Laparoscopic resection of a functional
paraganglioma in the organ of Zucherkandl. Surg Endosc
2002;16:219.
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Case Discussion
繼續教育考題