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< Present illness
>
This 68-year-old woman had been in
good state of health until one year earlier before this
admission, when she began to have frequent episodes of general
weakness, dizziness, cold sweating and palpitation, which
mostly developed 2-4 hours after meals, especially 3 hours
later; the symptoms did not develop while she was in fasting
state. Those episodes could be relieved by eating but became
worsening later. Most of the episodes lasted for several
minutes and could recover spontaneously. There was no facial
flush, chest tightness, dyspnea, or hypertension during these
episodes. She did not lose or gain a significant weight. There
was no thirst, polyuria, polydipsia or polyphagia. She visited
a local clinic where hypoglycemia was noted. Under the
impression of recurrent symptomatic hypoglycemia, she was
admitted for further evaluation.
She denied any use of alcohol,
tobacco or other medication. There was no family history of
diabetes mellitus, pancreatic tumor, thyroid disease, liver or
renal disease. She had not undergone stomach or duodenum
surgery.
On examination, she had clear
consciousness. Her height was 154 cm and weight was 56 kg. The
temperature was 36.8oC, the pulse rate 72 beats per minute and
the respiratory rate 18 breaths per minute. Blood pressure
while in supine position was 120/70 mmHg. There was no
cyanosis, petechiae, purpura, skin rash, or pigmentation. Her
conjunctivae were pink, the sclerae were anicteric and the
pupils were isocoric with prompt light reflexes. The neck was
supple without lymphadenopathy, engorged jugular veins,
carotid bruits or goiter. The chest wall expansion was
symmetric and breath sounds were bilaterally clear. The heart
beats were regular without audible murmur. The abdomen was
soft and bowel sounds were normoactive. The liver and spleen
were impalpable. The liver span was estimated 10 cm at the
right mid-clavicular line. The extremities were freely movable
without edema.
< Laboratory data
>
1. CBC/DC
|
WBC |
RBC |
HB |
HCT |
MCV |
MCHC |
PLT |
|
K/μL |
M/μL |
g/dL |
％ |
fL |
g/dL |
K/μL |
|
7.22 |
3.6 |
11.2 |
32.8 |
94.3 |
34.1 |
266 |
2. Biochemistry and electrolytes (Overnight fasting)
|
ALB |
TP |
T-Bil |
AST |
ALT |
ALP |
UN |
CRE |
|
g/dL |
g/dL |
mg/dL |
U/L |
U/L |
U/L |
mg/dL |
mg/dL |
|
3.7 |
7.0 |
0.4 |
26 |
35 |
216 |
16 |
0.6 |
|
Na |
K |
Glucose |
Insulin |
C-peptide |
ACTH |
Cortisol |
|
mmol/L |
mmol/L |
mg/dL |
5-20
μU/mL |
0.5-3
μg/mL |
10-65
pg/mL |
5-25
μg/dL |
|
142 |
4.1 |
90 |
6 |
1.1 |
30 |
21 |
3. During the hypoglycemic episode
|
Glucose |
Insulin |
C-peptide |
Cortisol |
|
mg/dL |
μU/mL |
ng/mL |
μg/dL |
|
46 |
48.3 |
> 7.9 |
30.3 |
< Course and treatment
>
Overnight
fasting plasma glucose was 90 mg/dL. She received prolonged
fasting tests. However, she had cold sweating, palpitation and
dizziness 2 hours after meal. After the blood sample was
obtained, intravenous glucose was prescribed, and her symptoms
were relieved. The blood tests showed hypoglycemia (glucose 46
mg/dL) with inappropriate high serum insulin and C-peptide
levels (insulin 48.3 μU/mL; C-peptide > 7.9 ng/mL ). Endogenous
hyperinsulinemic hypoglycemia was diagnosed. Angiography,
computerized tomography of the abdomen, magnetic resonance
cholangiopancreatography and endoscopic ultrasound study all
showed negative findings. She underwent exploratory
laparotomy. There was no obvious nodule or tumor by both
intraoperative ultrasonography and palpation. Frozen pathology
of the distal pancreas showed islet cell hyperplasia. She was
treated successfully by pancreatectomy to remove 85% of the
pancreas. The pathology of the distal pancreas reported islet
cell hyperplasia (figure 1)
and ductulo-insular complex (figure
2 ). Adult nesidioblastosis was diagnosed.
Post-operative course was smooth without any hypoglycemic
episode. She was discharged in a stable condition and followed
up regularly at our OPD with normal plasma glucose
levels.
< Discussion
>
發生低血糖時身體會出現警訊症狀，通常會先出現腎上腺症狀(adrenergic
symptoms)，如心悸、緊張、手抖、冒汗及心跳加快等；當血糖值更低時甚至會出現神經性低血糖症狀
(neuroglycopenic
symptoms)，如無力、倦怠、頭痛、語言不清、行為或意識改變，甚至癲癇發作。當出現低血糖的症狀或徵兆、血糖值45
mg/dL以下，且給予葡萄糖後症狀立刻緩解，即符合Whipple's triad，可以確診為低血糖。
低血糖發作時，除了緊急的處理外，最重要的是確定病因，防止再發。首先須區分是空腹(fasting)或飯後低血糖(postprandial)；後者還可以根據飯後時間長短分為早期
(飯後2-3小時內)及晚期(飯後3-5小時)。成人飯後低血糖原因，包括：胃手術後低血糖 (postgastrectomy
alimentary hypoglycemia)、功能性低血糖 (functional alimentary
hypoglycemia)、酒精性低血糖 (ethanol hypoglycemia)、胰島母細胞增殖症
(pancreatic islet hyperplasia，nesidioblastosis)及隱性糖尿病 (occult
diabetes)。
胰島母細胞增殖症是指胰臟小島細胞瀰漫或擴散性的增生，為造成嬰兒和小孩內源性高胰島素低血糖最常見的原因(50%)，機轉與胰島β細胞膜上磺醯尿素接受體ATP-敏感性鉀離子通道
( sulfonylurea receptor ATP-sensitive potassium channel )的KIR
6.2及SUR1基因突變有關，成人則少見，也被稱為非胰島素瘤胰原性低血糖症候群 (noninsulinoma
pancreatogenous hypoglycemic syndrome；NIPHS
)。成人的內源性高胰島素低血糖以胰島素瘤 (insulinoma)為最常見，成人胰島母細胞增殖症 (adult
nesidioblastosis)只佔0.5 - 5%，目前認為與KIR
6.2及SUR1基因突變無關，但是似乎會與第1型多發性內分泌腫瘤(multiple endocrine neoplasia
type 1)共存。
胰島母細胞增殖會過度分泌胰島素導致低血糖，雖然也會於空腹時出現低血糖，但是通常發生於飯後四小時內，72小時禁食不會發生低血糖，可與胰島素瘤區分；反應性低血糖(reactive
hypoglycemia)，如胃手術後低血糖及功能性低血糖的病人主要是出現腎上腺症狀，而胰島母細胞增殖症患者會出現嚴重的神經性低血糖症狀，可與之作鑑別診斷。和胰島素瘤一樣，胰島母細胞增殖患者抽血檢查時可發現低血糖，但是血中胰島素和C-peptide的濃度均升高。
在影像學檢查，包括：腹部超音波、斷層掃描、血管攝影、核磁共振造影、核醫及經食道超音波，在成人胰島母細胞增殖症患者，應該都找不到任何腫塊，其目的是要排除胰島素瘤的可能性。幾乎所有的患者其選擇性動脈鈣輸注試驗(selective
arterial calcium stimulation)，結果都呈陽性反應，代表著胰臟β細胞的異常分泌。
胰島母細胞增殖症治療以切除胰臟為首選，可以根據在不同血管給予刺激時所測得的胰島素濃度梯度來決定切除的範圍。在成人，大於90%的胰臟切除引起術後糖尿病的發生率可達40%；切除60%至89%，有50%的病患可以維持正常血糖濃度，19%需要加上藥物
(如diazoxide)治療，8%病患發生糖尿病；若切除小於60%，則有高達67%患者出現復發性低血糖，所以一般建議切除80%，如同我們的病人。藥物可以選用diazoxide、鈣離子通道阻斷劑或octreotide作為術前或術後復發時的治療方法。
< 參考資料
>
1. Kaczirek K, Niederle B: Nesidioblastosis: an old term
and a new understanding. World J Surg 2004; 28(12):1227-30.
2. Tanaka Y, Asakawa T, Asagiri K, Akiyoshi K, Hikida S,
Mizote H: Nesidioblastosis treated successfully by 85%
pancreatectomy. Kurume Med J. 2004; 51(1):99-103.
3. Arao T, Okada Y, Hirose A, Tanaka Y: A rare case of
adult-onset nesidioblastosis treated successfully with
diazoxide. Endocr J. 2006; 53(1):95-100.
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Case Discussion
繼續教育考題