|
<Chief
complaint>
Progressive enlargement of the nose
for 8 months.
<Brief
history>
A 68-year-old housewife had had hypertension for 13 years
with regular medication control. Eight months prior to the
admission, she noted that her nose enlarged gradually.
Besides, increased sweating, weight gain, an increase in shoe
size and lethargy were noted. She increased the frequency and
duration of exercise with an intention to lose weight but was
in vain. Acomegaly was suspected by her physician during the
monthly OPD follow-up of hypertension. Serum level of growth
hormone was only mildly elevated (hGH 5.6 ng/mL). Because she
had typical symptoms of acromegaly, she was admitted for
further evaluation and treatment.
Throughout her whole disease course, there was no visual
deficit, headache, joint pain or paresthesis. She denied a
history of smoking, drug abuse, alcohol consumption, operation
and a family history of endocrine disorders.
On physical examinations, her consciousness was clear,
height was 162 cm and her weight was 74kg. The body
temperature was 36.6°C, pulse rate was 88 /min, respiratory
rate was 20/min and the blood pressure was 136/80 mmHg. The
supraorbital ridges were mildly prominent, the nose was
enlarged and the mandible was protruding downward and forward.
The conjunctivae were pink, sclerae were anicteric and the
pupils were isocoric with prompt light reflex. The neck was
supple without a goiter, palpable masses, engorged jugular
veins or lymphadenopathy. Chest, heart, abdomen and back were
normal. The extremities were freely movable without edema. The
hands and feet were large, thickened and bulky, with blunt,
spade-like fingers and toes. Neither hypertrichosis nor
acanthosis nigricans was noted. Neurological examinations were
unremarkable.
<Laboratory
data>
1.Hemogram
| WBC |
RBC |
HB |
HCT |
MCV |
MCHC |
PLT |
| K/μL |
M/μL |
g/dL |
％ |
fL |
g/dL |
K/μL |
| 6.32 |
4.31 |
13.3 |
39.8 |
92.3 |
33.4 |
289 |
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 |
| 4.1 |
6.3 |
0.6 |
20 |
17 |
179 |
15 |
110 |
| UN |
CRE |
Na |
K |
Ca |
P |
Cl |
Mg |
| mg/dL |
mg/dL |
mmol/L |
mmol/L |
mmol/L |
mg/dL |
mmol/L |
mmol/L |
| 25 |
1.0 |
140 |
4.1 |
2.2 |
4.4 |
109 |
0.9 |
3. Basal endocrine
tests
| hsTSH |
free T4 |
ACTH(A) |
Cortisol(A) |
Prolactin |
hGH |
IGF-I |
0.4- 4
IU/mL |
0.60-1.75
ng/dL |
10-65
pg/mL |
5-25
g/dL |
87-390
mIU/L |
0.06-5.0
ng/mL |
48-225
g/dL |
| 1.27 |
0.9 |
42.5 |
12.5 |
224 |
5.6 |
821 | *high
sensitivity thyroid-stimulating hormone＝hsTSH, free
thyroxine＝FT4, corticotropin＝ACTH, A＝8AM, growth hormone＝hGH,
insulin-like growth factor-I＝IGF-I
4. Oral glucose tolerance test
| Time |
0 min |
30 min |
60 min |
90 min |
120 min |
| Glucose(mg/dL) |
116 |
236 |
295 |
290 |
220 |
| hGH(ng/mL) |
5.9 |
5.2 |
4.2 |
4.8 |
3.9 |
<Course and
treatment>
Serum levels of growth hormone and
IGF-I were elevated and could not be suppressed in an oral
glucose tolerance test (100 g glucose). The result
demonstrated a loss of growth hormone suppressibility after a
glucose load that was compatible with acromegaly. The visual
fields were intact. The skull X-ray showed a slight increase
in size of the frontal sinuses and mandibular prognathism and
an enlarged sellar turcica with bony erosion. Magnetic
resonance imaging (MRI) displayed an enlarged sellar turcica
with a mass lesion at the left sellar which invaded downward
to the sphenoid sinuses(Fig
1 &
2 ).
Acromegaly caused by a pituitary tumor was diagnosed.
Abdominal echo revealed some gall bladder stones. However, she
hesitated to undergo an operation and decided to receive the
first dose of octreotide injection and the treatment caused no
obvious side effects. She was discharged and was followed-up
regularly at our OPD undergoing a monthly intramuscular
injection of 20 mg of Sandostatin LAR. Eight months later,
follow-up brain MRI showed a marked decrease in tumor size.
She continued Sandostatin treatment thereafter during OPD
follow-up.
<Discussion>
肢端肥大症(acromegaly)是因為生長素過多所導致的疾病，最常見的原因是分泌生長素(growth hormone，GH)之腦下垂體腺瘤，發生率約為每年每百萬人口有三到四個病例；其他原因包括異位性分泌生長素、類癌或胰島細胞瘤分泌異位性生長素釋素(ectopic GH-releasing
hormone)及下視丘、腦下垂體神經節細胞瘤或下視丘錯構瘤過度分泌外生性的生長素釋素。分泌生長素的腦下垂體腺瘤約佔所有原發性腦下垂體腺瘤的20%，少有病人是因為腦下垂體腺瘤本身的空間填塞或破壞作用死亡，多因長期生長素過度分泌影響身體許多系統而增加罹病率及死亡率。
分泌生長素之腦下垂體腺瘤通常從外側翼長出。由於臨床症狀的緩慢惡化，這些腫瘤在診斷時通常直徑都大於一公分(巨大腺瘤，macroadenoma)，小於10%的病例是微小腺瘤(microadenoma)。病人之生長素分泌仍有週期性，但是增加分泌的次數、期間和幅度，且缺乏特徵性的夜間起伏；缺乏葡萄糖的生理性抑制及低血糖刺激生長素分泌作用；更甚者，正常狀態下不會刺激生長素分泌的下視丘釋素(如甲釋素和性釋素)都可能促進生長素釋放。給予健康人dopamine agonists
(如bromocripitine和apomorphine)會刺激生長素分泌，然而令人驚奇的是約有70%到80%的肢端肥大症病人卻會抑制生長素分泌。
慢性生長素過度分泌使得成人出現肢端肥大症，主要以局部的骨頭過度生長為特徵，尤其是顱骨和下頜骨。而在小孩和未成年人會造成巨人症，主要是因為相關連的續發性性腺低能症延遲骨閉合。通常，症狀發生在診斷之前五到十年，如肢端變大、軟組織過度生長、多汗、疲倦、體重增加、感覺異常、關節疼痛、畏光、乳突瘤、多毛症、甲狀腺腫、黑色棘皮症、高血壓、心臟肥大、頭痛、視野缺損及腎結石等。除了典型的表徵外，因生長素引起的胰島素阻抗所產生的葡萄糖耐受性不良和高胰島素血症是常見的，發生率分別是 50%和70%。60%的女性病人和46%的男性病人會有性腺低能症，其由多重原因導致，包括腦下垂體或腦垂腺柄被腫瘤壓迫時直接破壞性腺激素的分泌或干擾性腺釋素經由垂體門脈系統的傳送、高乳促素血症或過多生長素分泌的類似促乳素作用；然而甲狀腺低能症和腎上腺機能不全並不常見，分別只發生在13%和4%的病人身上；大約15%的病人會發生乳溢。雖然少見，肢端肥大症可能是第一型多發性內分泌瘤之一。
併發症包括漸進性的外觀變形、殘廢的退化性關節炎以及癌症的發生率增加，尤其是大腸息肉和大腸癌，因此建議病人應接受大腸鏡的篩檢。除此之外，包括心臟血管和大腦血管粥狀硬化以及呼吸疾病死亡率是健康人口的兩倍。 診斷除了須有典型的臨床症狀外，仍須靠實驗室檢查生長素值來確定診斷。超過90%的病人其基礎的空腹生長素值大於10 ng/mL(正常範圍是1到5 ng/mL)，然而單次的測定值並不完全可靠，其他情況如焦慮、運動、急性疾病、慢性腎衰竭、肝硬化、飢餓，蛋白質熱量營養不良，厭食症，和第一型糖尿病皆可以增加生長素的分泌，也需要排除。口服葡萄糖無法抑制生長素分泌是診斷肢端肥大症最簡單且最具專一性的機能性檢查。健康人口服100公克的葡萄糖可以在60分鐘後將生長素抑制至小於5 ng/mL(大部份是小於2 ng/mL)，肢端肥大症的病人則否。測定IGF-I(insulin-like growth
factor-I)值上升對診斷肢端肥大症是另一種有用的檢驗，因其有極好的特性可以和糖尿病病人鑑別診斷。
所有肢端肥大症病人都需接受治療，以阻止疾病的進行和預防晚期的併發症。治療的目標包括去除或破壞腦下垂體腫瘤，停止生長素過度分泌和維持正常的前腦下垂體和後腦下垂體功能。目前以經蝶竇切除腺瘤(transsphenoid surgery)為治療的初始選擇，於術前須以核磁共振檢查定位，嚴重的手術併發症或破壞到正常腦下垂體只發生在1%到2 %的病人身上；少數病人需要頭顱切開術(craniotomy)。傳統的放射治療劑量4500到5000cGy可以預防腫瘤惡化，並且成功地降低60%到80%病人生長素的過度分泌，但是通常需要數年的時間，因此一般建議已經接受腦下垂體顯微手術後生長素仍持續過度分泌的病人才接受放射線治療。Bomocriptine可以降低70%到80%病人的生長素值，然而只有少數病人可達10 ng/mL以下且只有少數可減少腫瘤大小，治療中斷後很快地就會再復發，因此，建議手術或放射治療後生長素還沒降低的病人才使用bromocriptine。Octreotide acetate是一種長效性的體抑素類似物(somatostatin
analogue)，可以有效治療肢端肥大症，使多數病人的GH和IGF-I降低至正常，且使某些腺瘤顯著萎縮，但是副作用包括腹痛、脂瀉症和膽石症。
術後須評估生長素分泌、腦下垂體功能及腺瘤大小。如生長素仍高者須併用octreotide；如低於2
ng/mL，應每半年檢查一次，連續兩年，然後每年追蹤一次。接受放射治療者，應每年檢查生長素二次和腦下垂體功能一次，因其導致的遲發性腦下垂體低能症發生率偏高。
<References>
-
Ezzat S et al: Octreotide treatment of acromegaly:
A randomized multicenter study. Ann Intern Med
1992;117:711.
-
Newman CB: Medical therapy
for acromegaly. Endocrinol Metab Clin North AM
1999;28:171.
-
Melmed S et
al: Clinical Review 75: Recent advances in pathogenesis, diagnosis and
management of acromegaly. J Clin Endocrinol Metab
1995;80:3395.
-
Chang-DeMoranville BM, Jackson MD: Diagnosis and endocrine testing in
acromegaly. Endocrinol Metab Clin North Am 1992;
21:649. | 
Case Discussion
繼續教育考題