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A 44-year-old woman had been quite
well before until recent six months prior to the admission
when she had 4-5 episodes of syncope. She denied having
headache, visual deficit, seizures, stool or urine
incontinence, vertigo, limb weakness, dysphagia, dysarthria,
or an unstable gait while syncope occurred. There was no
associated chest tightness, palpitation, dyspnea. An image of
the central nervous system and a lumbar puncture were
performed and disclosed no significant abnormal findings.
However, unusual low fasting plasma glucose levels were noted
for several times (fasting plasma glucose, 32, 30, 55,
52 mg/dL at 1st, 2nd, 3rd, 4th day of
hospitalization, respectively).
She denied a history of drug
abuse, alcohol consumption, or a family history of endocrine
disorders.
On physical examinations, her
consciousness was clear, height was 162 cm and weight was 45
kg. The body temperature was 36.6°C, pulse rate was 88 beats
per minute, respiratory rate was 20 breaths per minute, and
the blood pressure was 136/80 mmHg. The conjunctivae were not
pink, sclera were not icteric, and the pupils were isocoric
with prompt light reflex. The neck was supple without a
goiter, palpable masses, engorged jugular veins or
lymphadenopathy. Examinations of the chest, heart, abdomen,
and back were normal. The extremities were freely movable
without edema.
< Laboratory data
>
1. Hemogram
|
WBC |
RBC |
HB |
HCT |
MCV |
MCHC |
PLT |
|
K/μL |
M/μL |
g/dL |
％ |
fL |
g/dL |
K/μL |
|
11.23 |
4.1 |
13 |
37.0 |
89.4 |
34.8 |
168 |
2. Biochemistries and electrolytes
|
ALB |
TP |
T-Bil |
AST |
ALT |
ALP |
γ-GT |
Glucose |
|
g/dL |
g/dL |
mg/dL |
U/L |
U/L |
U/L |
U/L |
mg/dL |
|
3.7 |
6.5 |
0.4 |
23 |
21 |
162 |
18 |
32 |
|
UN |
CRE |
Na |
K |
Ca |
Mg |
P |
CRP |
|
mg/dL |
mg/dL |
mmol/L |
mmol/L |
mg/dL |
mmol/L |
mg/dL |
mg/dL |
|
13.2 |
0.6 |
138 |
3.8 |
8.9 |
0.82 |
3.0 |
<0.8 |
3. The basal endocrinologic
results
|
Glucose |
Insulin |
C-peptide |
Cortisol |
|
mg/dL |
(uU/ml) |
(ng/ml) |
μg/dL |
|
34 |
4.54 |
1.33 |
37.8 |
4. The survey while hypoglycemia during the 72 hour
prolonged fasting
tests
|
Glucose |
Insulin |
C-peptide |
Cortisol |
|
mg/dL |
(uU/ml) |
(ng/ml) |
μg/dL |
|
23 |
6.11 |
1.05 |
37.8 |
< Course and treatment
>
Serum levels of cortisol, insulin,
C-peptide were measured while an episode of hypoglycemia
occurred. The results demonstrated a relatively high serum
insulin and C-peptide levels with an acceptable cortisol level
(37.8 ug/dl). A 72-hour prolonged fasting test was carried out
which showed a loss of insulin and C-peptide suppression after
definite hypoglycemia. The findings were compatible with
insulinoma. MEN-1 syndrome was excluded later after checking
pituitary hormone axis and parathyroid hormone levels. The
computed tomography of the pancreas with administration of
contrast media showed a hyperechoic lesion, measuring 1.2 cm
in maximal diameter, over the pancreatic body. Angiography
disclosed a hypervascular pancreatic tumor with blood supply
from a proximal gastroduodenal artery branch. En-nucleation of
the pancreas was performed and pathology disclosed insulinoma.
Fasting hypoglycemia improved one day after
operation.
< Discussion
>
低血糖的病因有很多種，而低血糖發作的時刻對於病因的探討的幫助很大。一般以飯後4-6小時為界定，分為飯後4-6小時以後才發生的低血糖
(又叫空腹(吸收後) 低血糖 (fasting ( post-absorptive)
hypoglycemia))，及飯後4-6小時之內便發生的低血糖 (又叫反應性 (飯後) 低血糖 (reactive
(post-prandial) hypoglycemia))。
空腹低血糖最常見的原因是藥物，多見於病患不當或誤服用降血糖藥；其他諸如：少見的是使用水楊酸 (salicylates)、磺胺
(sulfonamides)、抗生素，如：pentamidine；quinine亦有個案報導過；而在食物攝取不多的情況下，大量喝酒亦可能造成低血糖；另外，病人若同時處於較危急的情況下，如心臟衰竭、肝衰竭、急性腎衰竭、敗血症，也可能加重低血糖的發作；其他諸如一些非胰島beta細胞的大腫瘤，如：肝細胞癌
(hepatocellular
carcinoma)、腎上腺皮質癌、類癌等亦可能引起低血糖；而內分泌腺體方面，只要身體調控血糖相關的腺體出現問題，
便會發生低血糖。一般而言，負責危急情況下升血糖的荷爾蒙(如腎上腺皮質素 (cortisol)、生長激素 (growth
hormone) 功能不足或有內生性的胰島素分泌過多，如胰島細胞瘤 (
insulinoma)，都會造成低血糖。至於飯後低血糖，也就是一般發作在飯後4-6小時之內者，多見於胃腸道有開刀病史的患者，發生平均時間大概在飯後1.5-3小時。而糖尿病前期的患者，也因為胰島素分泌的量隨攝食對應分泌的量不穩定，也可能發生飯後低血糖。以上飯後低血糖的確定診斷可以藉由5小時內口服75g
糖水測試，若發生有症狀且服糖水可逆的低血糖狀況時( Whipple triads) 則可確診。
胰島細胞瘤是非常少見的腫瘤疾病，發生率約為每年每二十五萬人口有一個病例。
大約90%患者為良性腫瘤。一般而言，造成的低血糖多半可手術治癒。在臨床上可以是偶發的，也可以是體顯性遺傳的多發性內分泌腫瘤第一型(
MEN-I，包括：腦垂體腫瘤、胰島細胞腫瘤及副甲狀腺腺瘤)。分泌胰島素之腫瘤幾乎皆位在胰臟本身，但通常很小，就算在超音波、電腦斷層或磁振攝影下看不到，也不能排除其存在。常見的臨床表現包括：低血糖引起的交感神經症狀及神經學症狀。由於臨床低血糖症狀明顯，這些腫瘤在診斷時通常直徑都很小，只有將近五分之一的腫瘤在腹部電腦斷層可見。因此更增加定位的困難度。由於胰島細胞瘤缺乏低血糖時的生理性抑制，故在低血糖發生的時候，身體所分泌的胰島素及C-月太 ( C-peptide )
相對來講會較高。人體胰臟分泌的胰島素前趨為proinsulin, 之後會經過切割成比例1比1的胰島素及C-月太 (C-peptide)，其中以C-月太較穩定，
半衰期較長，一般在評估胰島功能時，兩者都會測量，以減少外來藥物及半衰期的影響。在低血糖發作(若住院期間無法”自然”地發生低血糖，則可進行72小時禁食以誘發之)時，若胰島素及C-月太均相對高
(即符合診斷標準，見表一)，則表示是內生性的高胰島素症，須排除口服降血糖藥的可能性，才能下診斷是胰島細胞瘤所引起。之後對腫瘤治本的方法便是手術摘除。但臨床上最困難的地方往往是手術前的定位。由於在診斷之初，腫瘤多半很小，有極大部分無法由電腦斷層去偵測出
(電腦斷層的主要角色在偵測腫瘤的轉移與否，為胰島細胞瘤常用的第一線影像檢查)，故必須仰賴更進一?的影像檢查。典型的腺瘤在血管攝影下為高血管性的均勻腫瘤
(敏感度約40%)，在超音波下表現為低回音(敏感度約10%)；也可藉經肝門靜脈取樣定位
(敏感度約為60-80%)或術中腹內超音波偵測
(敏感度最高，約為80-90%)；另外也可在血管攝影的同時經由供應腺瘤的動脈打入葡萄酸鈣刺激胰島素分泌進一步在左右兩邊肝靜脈去採樣胰島素濃度
(敏感度大約為80-90%，只不過可能有偽陽性)。整體而言,
似乎以術中腹內超音波的敏感度最高，但在未手術剖腹前可藉鈣刺激下的血管攝影採樣及肝門靜脈採樣嘗試去作剖腹前的定位。一般而言，手術是根除的方法,
但若真的無法在術前或術中定位，並不建議作盲目的部分胰臟切除 (subtotal pancreatectomy)
，因為腺瘤有可能位在胰臟頭。不能手術切除的腫瘤採內科治療，包括使用diazoxide及octreotide。我們的病人在術後的隔天血糖便已回升，且追蹤迄今一年止尚未復發。
表一:
| |
Service, 1999
(reference 2) |
Marks and Teale,
1996 (reference 3) |
|
Glucose
(mg/dl) |
<= 45
|
<54 |
|
Insulin
( uU/ml) |
>=6
|
>5 |
|
C-peptide
(ng/ml) |
>=0.6 |
>0.9 |
< References
>
- Williams textbook of
endocrinology, the !0th edition.
- Service FJ: Hypoglycemic disorders.
Endocrinol Metab Clin North Am. 1999; 467-661
- Marks V, Teale JD: Investigation of
hypoglycaemia. Clin Endocrinol (Oxf). 1996; 44(2):133-6
- Norton JA, Shawker TH, Doppman JL,
Miller DL, Fraker DL, Cromack DT, Gorden P, Jensen RT:
Localization and surgical treatment of occult insulinomas.
Ann Surg. 1990 Nov;212(5):615-20.
- Clark LR, Jaffe MH, Choyke PL, Grant
EG, Zeman RK: Pancreatic imaging. Radiol Clin North Am. 1985
Sep;23(3):489-501.
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Case Discussion
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