<Case
Presentation>
A 21-yer-old girl was admitted to this hospital because
of jaundice for 5 months and goiter for 3-4 month.
The patient had been in excellent health until two years
ago, when she began to have palpitation, hand tremor and easy
perspiration. About one year ago she began to experience loose
stools, heat intolerance, frequent insomnia, and yellowish
discoloration of sclera and skin. She also noticed a weight
loss from 58 kg to 40 kg and a decrease in duration and
frequency of menstruation in recent half a year. Insidious
onset of neck swelling and proptosis developed 2 months later.
She visited a local hospital, where hyperthyroidism, anemia
and hyperbilirubinemia were found. Propylthiouracil,
propranolol and estazolam were prescribed. Her diarrhea
improved after medication, but hand tremor, heat intolerance
and palpitation persisted. Besides, she felt congestion and
itching of both eyes. The patient was then admitted to this
hospital for further evaluation.
The temperature was 37.4℃, the pulse
was 120, and the respirations were 20. The blood pressure was
130/70 mmHg. Physical examination revealed that the patient
had mild icteric skin and sclera. The conjunctiva was slight
pale and the eyes were bulging out. The thyroid was diffusely
enlarged (grade II) with bruit. There was no cyanosis or edema
of extremities. Peripheral blood smear (Fig.
1)
and laboratory
tests were performed (Table 1~4)
Table 1. Hematologic Laboratory Values.
WBC K/μl |
RBC M/μL |
Hb g/dL |
Hct % |
MCV fL |
PLT K/μL |
Reticulocyte % |
8.35 |
2.59 |
9.4 |
27.5 |
106.2 |
320 |
17.79 | Reticulocyte
index: 4.26% Haptoglobin: <5.83 mg/dL
(64.81-157.48) Stool O.B.:
negative
Table 2. Blood chemical values.
BUN mg/dL |
Cre mg/dL |
Na mmol/L |
K mmol/L |
Cl mmol/L |
Ca mmol/L |
AST U/l |
11.4 |
0.76 |
141 |
3.9 |
104 |
2.14 |
35 |
T-BIL mg/dL |
D-BIL mg/dL |
LDH U/L |
TG mg/dL |
T-CHO mg/dL |
Glu AC mg/dL |
|
3.2 |
1.2 |
1194 |
129 |
163 |
102 |
| Table
3. Urinary Analysis.
Sp Gr
|
PH |
Protein mg/dL |
Glu g/dL |
O.B. |
Urobil EU/dL |
Bil |
RBC /HPF |
WBC /HPF |
Cast /LPF |
1.010 |
6.0 |
– |
– |
– |
1.0 |
– |
0-1 |
0-1 |
– | Table 4.
Thyroid function and immunologic profiles.
Free T4 (CIA) ng/dL |
HsTSH (CIA) μIU/mL |
T3 (RIA) ng/dL |
AMA |
ATA
|
0.87(0.6-1.75) |
0.002(0.4-4) |
185 (80-200) |
>20480 (<1:80) |
>20480 (<1:80) |
ANA |
C3 mg/dL |
C4 mg/dL |
Coombs test |
Anti-DNA IU/mL |
1:1280+ (Speckle) |
53.1(81.61-118.41) |
7.1(27.45±10.72) |
4+ (direct) 3+ (indirect) |
4.6
(<12)
|
After admission, propylthiouracil
100 mg tid and propranolol 20 mg tid were prescribed for
hyperthyroidism. The marked reticulocytosis, indirect
hyperbilirubinemia, the elevated lactate dehydrogenase and the
decreased haptoglobin level suggests that the patient had a
hemolytic anemia. The positive results of direct and indirect
Coombs tests led to the diagnosis of autoimmune hemolytic
anemia. Prednisolone 50 mg qd was given and her hemoglobin
returned to 15 g/dL in 1 month. She was in euthyroid status
during the last follow-up at out patient clinic.
病案分析
本病例為毒性彌漫性甲狀腺腫合併自體免疫性溶血性貧血的罕見病例。毒性彌漫性甲狀腺腫,
即所謂的葛雷夫茲氏病(Graves’ disease), 在診斷上相當直接。
病人的臨床表現加上生化檢查證實有甲狀腺機能亢進, 觸診可見甲狀腺腫, 外觀可見到眼球突出,
抗微粒體抗體常為陽性反應,
再加上本人或其親人有自體免疫疾病史時, 就可確定其診斷。當病人甲狀腺機能亢進, 但缺乏其他表現時,
最可靠的輔助診斷方式是核醫的甲狀腺131I 造影 (radionucleotide 131I scan) 。
甲狀腺131I造影在葛雷夫茲氏病為彌漫性的碘高量攝取, 可將之與其他引起甲狀腺機能亢進的狀況,
如甲狀腺毒性結節、破壞性的甲狀腺發炎如橋本氏甲狀腺炎、異位的甲狀腺組織、或人為製造的甲狀腺毒症,
做很好的區分。本病人臨床表現非常典型, 故而無須安排甲狀腺131I 造影即可確立診斷。在治療上,
通常使用抗甲狀腺藥物
(thionamides類如methimazole carbimazole propylthiouracil)
合併非選擇性乙型阻斷劑 (propranolol) 及抗焦慮藥物來治療病人。也可選擇131I或手術方式來減少甲狀腺的大小,
達到控制甲狀腺機能的目的。 必須注意的是, 抗甲狀腺藥物本身也有許多可能的副作用出現。如:
藥物過敏、皮膚紅疹、發燒、關節痠痛、白血球特別是嗜中性球低下、肝機能異常、血管炎, 甚至溶血性貧血等等。
本病例較為特殊的表現為其黃疸。由於黃疸的出現在用藥以前就已開始,
初步可排除為甲狀腺藥物所導致。其黃疸為非直接膽色素為主, 且不超過5 mg/dL,
加上血球容積正常的貧血、haptoglobin低下、及LDH上升, 可很快得到溶血性貧血的結論。Direct 及
indirect Coombs’ tests均呈陽性反應,
加上週邊血液檢查可見到spherocytosis及polychromasia,
證實為自體免疫性溶血性貧血(autoimmune hemolytic
anemia--AIHA)。治療方式為口服prednisolone (1 mg/kg/day), 通常在1-2星期後,
即可見到病人血色素的回升。此時再逐漸將類固醇的劑量調低, 並在之後的數個月, 慢慢將類固醇停掉即可。
若病人對類固醇反應不佳,
可考慮脾臟切除手術, 或使用其他免疫抑制劑如azathioprine 或 cyclophosphamide.
靜脈注射gamma球蛋白, 對急性控制溶血現象有幫助, 但長期效果不明。
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