臨床醫學概論

九十六學年度第一學期

授課老師：林朝順老師

九十六年九月

臨床醫學概論 授課大綱

上課對象：營養系三

上課地點：民生學院 教室 時間：每週二 13:40-15:30

週次

月

日

課程進度及綱要:

講師

ㄧ

9

18

臨床病歷結構說明

閱讀病歷的工具書及網站

林朝順

二

9

25

中秋節 放假一天

林朝順

三

10

2

身體檢查的描述與意義

林朝順

四

10

9

特殊檢驗介紹

林朝順

五

10

16

口頭報告示範

馬漢平

六

10

23

病例：1. Mucormycosis

2.胃腫瘤

馬漢平

七

10

31

病例：3.低血糖

4.多尿

林秋梅

八

11

6

專題演講：營養師在醫院的角色

曾筱晴

九

11

13

期中考

林朝順

十

11

20

病例：5.乳促素瘤

6.嗜鉻細胞瘤

林朝順

十ㄧ

11

27

病例：7.眼內炎

8.系統性紅斑狼瘡併抗磷酯症候群

林朝順

十二

12

4

病例：9.阻塞性細支氣管炎合併器質化肺炎

10.胰臟炎

馬漢平

十三

12

11

病例：11.傳染性單核球過多症

12.急性病毒性E型肝炎

林朝順

十四

12

18

病例：13.泌尿道結核

14.腎上腺功能不足

林朝順

十五

12

25

聖誕節 放假一天

十六

97/1

1

開國紀念日 放假一天

十七

1

8

專題演講：中醫美容

林秋梅

十八

1

15

期末考

林朝順

目錄

1一、病歷結構

3二、英文住院病歷樣本

8七、Mucormycosis (8/1~8/15)

10八、胃腫瘤 (9/1~9/15)

13九、低血糖 (12/16~12/31)

16十、多尿 (1/16~1/31)

18十一、乳促素瘤 (2/1~2/15)

21十二、嗜鉻細胞瘤 (3/16~3/31)

25十三、眼內炎 (5/1~5/15)

28十四、系統性紅斑狼瘡併抗磷酯症候群(6/1~6/15)

33十五、阻塞性細支氣管炎合併器質化肺炎 (7/1~7/15)

37十六、胰臟炎（7/1）

40十七、傳染性單核球過多症（5/16）

43十八、急性病毒性E型肝炎（5/1）

46十九、泌尿道結核（4/1）

50二十、腎上腺功能不足（3/16）

52附錄一、期末測驗試題樣本

54附錄二、臨床醫學概論口頭及書面報告之進行方式

(資料出處: http://www.sim.org.tw/ )

一、病歷結構

病歷的格式每家醫院皆有制訂，形式或有不同但寫作原則及要點一致，說明如下：

1、 門、急診部份（概分初診及複診）：

(1) 初診病歷：

初診病人的病歷應按照S.O.A.P原則書寫。

1. S（Subjective Data）：自覺徵候，包括病人主訴、症狀及發病時間、現在病史及個人史。

2. O（Objective Data）：醫師檢查發現，包括診察發現及各種檢查報告。

3. A（Assessment）：診斷評估，包括診斷（Diagnosis）或臆斷（Impression）。

4. P（Plan）：治療或檢查計劃，包括各種處置、檢查、醫令或處方。

(2) 複診病歷

應記錄病人之主訴及各種理學檢查之重要項目，看診時檢查結果若已知曉，應記錄於病歷上，若病人久未來看診，或未看過本科，則應視同初診病歷詳實記載。

(3) 急診病歷

必須要有SOAP之實際的記錄內容（其內容比照初診病歷書寫），於病人處理後，應有追蹤記錄，離院時應有離院狀況記錄；任何處置需有詳細時間記錄。

(4) 用藥必須與所記錄之病情與診斷相符合，劑量亦需註明。

(5) 避免處方之外一切空白。

(6) 記錄之字跡必須清晰可辨，處方完後住院醫師級以上必須簽名及蓋章。

2、 住院部份：

(1) 住院病歷首頁（Front sheet）：

應記載病人基本資料、入（出）院日期、診斷、手術、病理診斷及各級醫師之簽名；診斷應以英文或中文全名書寫，不可只用英文縮寫。

(2) 出院病歷摘要：

應包括病人基本資料、入出院日期、入院診斷、出院主要及次要記錄、簡要病史、理學發現、重要實驗室及放射線檢查結果、手術及病理報告、病程及主要治療、重要會診記錄、出院醫囑等；住院醫師完成摘要記錄，應由主治醫師簽名；上述寫作得以打字完成。

(3) 入院記錄（Admission note）：應包括—

1. 前言（General statement）：病人簡介，含年齡、性別、婚姻狀況等。

2. 主訴（Chief complaint）：病人主要問題之簡單陳述，包括duration，且儘可能引用患者本身表達的自覺症狀。

3. 現在病史（Present illness）：應以主訴症狀為中心，再包括相關症狀含生病之期間及部位、特殊症狀以及由疾病所造成其他生理機能之影響。

4. 過去病史（Past illness）：現症以前的重要既往史（含住院、手術、外傷等事宜）全部需記載。

5. 個人病史（Personal history）：如職業、煙酒、習慣、家庭環境、經濟狀況等。

6. 家族病史（Family history）：若有遺傳性之疾病應對家族做查詢，必要時以畫圖（family tree，pedigree）表示。

7. 身體理學檢查（Physical examination）：包括身體各系統的視診、聽診、問診和觸診等之檢查，必要時亦應以圖表示。

a. 生命徵象（Vital signs）：包括體溫、脈博、呼吸（T.P.R.）及血壓（B.P.）。

b. 一般檢查（General examination）：整體之觀感及診察，包括營養狀態、發育、疾病嚴重度、神智和情緒狀態等。

c. 局部檢查（Local examination）：對於特殊部位器官之檢查。

8. 診斷，臆斷或鑑別診斷（Diagnosis，Impression或Differential diagnosis）：醫師完成以上記錄後就要下診斷，診斷名稱需書寫正確完整，不能使用縮寫詞，若不明確者，應以R/O表示。

9. 採取之診療計畫。

以上諸項若有合乎病人病情需要或檢查結果是陽性反應者，應詳細記錄。

(4) 病程記錄（Progress notes）：

應於住院期間完成，原則上每日一記，病情變化大時，隨時記錄之；病情變化不大時，做一期間之記錄。若住院超過一週時，每週應有一週摘要（Weekly summary），轉病房時轉出單位應有轉科記錄（Transfer note），接受轉科單位應有收診記錄（Accept note），主治醫師迴診時應有迴診記錄。手術前、手術後記錄亦應詳細紀錄於此。病程記錄應對每一問題以SOAP之方式書寫，活動性之問題應勤予記錄。

二、英文住院病歷樣本

X X　醫　院

ADMISSION HISTORY

Hospital Reg. No. 1234567

Bed No. A701-1 Date Admitted： 2006-07-02

Patient： 黃大一（Hung） Age： 35 Sex： M Martial Status： Married

CHIEF COMPLAINTS：Previously well unemployed man who presents with one weeks of progressive anorexia, malaise and darkening urine on a background of increased alcohol consumption.

PRESENT ILLNESS：

In good health with no major problems up to Jan. 20 previously when he was sacked from his job on Far-Eastern electric factory.

He had worked for Far-Eastern since left school at age 15 years. He was very distressed by losing his job-felt like he had “been kicked in the guts” after all the years of hard work he had put in at Far-Eastern. He was actively looking for work but had been unable to find anything. In the last 8 weeks, he has stopped looking for work and has increased his alcohol consumption from 2 cups per day to 1 bottle of Rice wine per day.

Three weeks prior to admission, he started to feel unwell – flat, tired, general unwellness and noted that his urine was darker than usual （”like strong tea”）. Over this 3 week period, his appetite fell, and he feels he lost approximately 3Kg in weight prior to admission.

Associated with the general malaise, he experienced some vague discomfort in his upper abdomen, particularly under the right costal margin. Three days before his presentation to Cardinal Tien Hospital, he consulted his family physician, who noted the presence of jaundice （yellowing of sclerae）and ordered a biochemical screen. This confirmed the hyperbilirubinaemia （bilirubin total 5.3 mg/dl）and demonstrated an elevation of serum alkaline phosphatase （400 units/l）and a mild elevation of transaminase （AST 102 units/l）.

His wife and children had been in very good health, and to his knowledge there had been no friends or neighbors with jaundice over the past three months. He had noticed no change in the frequency of micturition or defecation, and there had been no change in stool color. He had mild morning nausea over the three weeks before admission, but no vomiting. He had noticed no pruritis, and had not felt sweaty or febrile.

PERSONAL HISTORY：

Habits：Alcohol （＋）: 2 cups per day, 8 weeks ago increased bottle of Rice wine per day；

Tobacco（＋）0.5 pack/day since age 16. Recent increase to 1 pack/day (last 6 weeks)

Allergy：scanal, rash no anaphylasix

Worked on production line at Far-Eastern until Jan. 20, 2006.

Two children – male age 8, female age 6.

Both live with partners.

Wife – part time cleaner,.

Live in Hsin – Chung - own house – mortgage paid off four years ago.

Hobbies – fishing, sports (watching).

Occasional Aspirin for headaches

PAST MEDICAL HISTORY：

Illness/Operation/Injury

Age

Date

.Description/Diagnosis/Management

Hospital/clinic

16 Appendicectomy

FAMILY HISTORY：

1. Father + age 75 – stroke

2. Mother – age 70 – hypertension

3. Sister alive and well – age 46

4. No family history of allergic disorders, asthma, diabetes or liver disease.

5. No family history of heart disease.

6. Children in good health

※SYSTEM REVIEW：

General：

Fever - Chils - weight loss - Fatigue - Anorexia -

Neuro-

Headache - Seizure - Dizziness - Syncope - Paralysis -

psychiatric：Loss of sphincter control - Difficulty sleeping -

Eye：

Loss of visiion - Diplopia - Eye ain - Sotomate -

Cardio-

Cough - Sputum - Hemoptysis - Chest pain - Palpitation -

respiratory：Dyspnea - Orthopnea - Edema - Cyanosis -

Catro-

Change in appetite ＋ Nausea ＋ Vomiting ＋ Diarrhea -

intetinal：Constipation - Jaundice ＋ Abdominal pain ＋ Bleeding -

Genito-

Frequency - Dysuria - Hematuria - Urethral discharge -

urinary：

Nocturia - Acute urinary retention - Flank pain -

Musculo-

Backpain - Bone infections - Joint ain or swelling -

skeletal： Varicose vein -

Skin：

Rashes - Eruption - Ulceration - Pruritis -

Skin pigmentation -

Endocrine：Heart cold intolerance - Thyroid problems - Thirsty -

Polyuria - Polydipsia - Hirsutism - Delayed puberty -

OB-GYN：

Graida Para Living children Menarche Menopause

L.M.P. Cycle Duration Regular Amount of flow

Leukorrhea Method of contraceptives

※Place (＋) to indicate a positive response

XX 　醫　院

ADMISSION PHYSICAL EXAMINATION

Age:35 Sex:MHeight:168 Weight:75 T: 37(C P: 90/min R:20/minBP:140/95 mmHg

General appearance: Acute-illlooking

Neck: Supple ＋ Stiffiness -

Skin: mild yellowish discoloration

Thyroid: not palpable

Head: normal

Venous engorgement: negative

Ears: normal

Mouth and Throat: normal

Nose: normal

Eyes:

Fundi: normal

Visual acuity: normal

Discs

Sclera: Yellow

Vessels

Conjunctiva:no pale

Retina

Cornea: normal

Pupils: equal

React to light

Lymh nodes:no LN enalrgement

Breasts: normal

Submandibular

Mass

Postauriclar

Discharge

Occipital Retraction

Supraclavicular

Ulceration

Axillary

Gyneomastia

Inguinal

Tenderness

Chest:

Deformities: no deformity

Auscultation:no rales, no wheezing

Percussion: no dullness

Heart:

Rate 90/min

Phythm: regular

PMI at 5 ICS cm at or beyond LMCL

Heart sunds: S1 Normal ＋

Accentuate Decrease in intensity

S2 Normal ＋

Splitting-fixed Paradoxical .

S3, S4

Cardiac murmur: Systole - Diastole - Thrill - Ventricular gllop -

Pulses:normal

Vascular: 0=Absent + = Decreased ++ = Normal +++ = Hyperactive Br = Brult

Pulses

Carotid

Brachial

Radial

Femoral

Popllteal

Dor pedls

Post tibial

Right

Left

Abdoment: Appendicectomy scar

Distended （-）

Ascites

Bowel movement : normal Liver: palpable 2cms below RCM-tender to palpation (liver scan 16cms) –smooth, firm

Tenderness: No Tenderness

Spleen: just palpable

Rigidity:soft

Hernia orifices – normal

Masses: No lymph nodes palpable in groin or axillae

Gentilia:

Spine and extremities

Male

Pensis

Testes

Tenderness

Scrotum and Epididymis

Clubbing and cyanosis

Female

Edema

Joints

Deformities

Rectal: not done

Posture

Local heat

Limitated range of movement

Nervous system

Consciousness

Mental status

Cranial nerves

Motor

Sensory

Reflexes

(0 to ++++)

Deep tendon reflex

Muscle power

Specific findings:

Impression:

1. Excessive Alcohol Consumption

2 Jaundice – alcoholic liver disease with abnormal liver enzymes.Alcoholic hepatitis likely.

Plan of management

1..Refer Alcohol Service

2.Refer Social Worker umemployment benefits etc

3.Biliary ultrasound to Rule out extra-hepatic obstruction.LFTS,CBP, ROTHROMBIN

Examiners Data:

XX醫院

病情進展記錄

MEDICAL PROGRESS NOTES

日期DATE

記事NOTES

95.07.03

S: Felling a little better

O: Obs stable, T 36.5

Jaundiced

Liver still tender, 2cm below RCM

A:1. Alcoholism

Seen by Social Worker (Miss Lee) – will discuss problems of unemployment with

Family this pm

2. Jaundice – Alcoholic Liver Disease

Continue biochemical work-up

P: -Liver biopsy desirable

-normalise coagulation

95-07-11

S: c/o pain (L) great toe

T 37.2

O: (L) great toe –red, tender to light touch and with any movement

A:1. Alcoholism

2. Jaundice

P: Repeat LFTs

Consider liver biopsy next week if INR allows

A:3. Gout

P: Serum uric acid

Colchicine if pain perists.

95-07-12

Jaundice – Alcoholic Liver Disease

Seen by Dr Lin “Most consistent with Alcoholic Hepatitis”. INR now 1.3, platelets

170,000 – liver biopsy tomorrow am.

七、Mucormycosis (8/1~8/15)

A 51-year-old woman has been diagnosed as having diabetes mellitus with insulin control and end stage renal disease (ESRD) with regular hemodialysis for 12 and 10 years respectively. She was found to have iron overload by routine monthly blood check. The iron overload was suspected to be resulted from frequent blood transfusion and she was treated with deferoxamine (DFO). During the treatment of DFO, she had suffered from progressive left frontal headache and low-grade fever. Besides, progressive left orbital swelling with exophthalmos and erythematous change in skin color developed one week after the onset of headache. Sinusitis was diagnosed initially by LMD. However, a few nodules were noted on her nose, and they enlarged and coalesced gradually, associated with yellowish, mucus-like discharge. She visited another hospital and chronic paranasal sinusitis was impressed, too. Functional Endoscopic Sinus Surgery (FESS) was performed immediately, but was complicated with high fever and dyspnea. She was transferred to medical ward for further care. Physically, her conscious ness was clear. The temperature was 38.1°C, the pulse was 100 per minute, and the respiration rate was 28 per minute. The blood pressure was 141/76mmHg. The conjunctiva was pink and the pupils were isocoric. The neck was supple without jugular venous engorgement or lymphadenopathy. The chest wall was symmetrically expanded. The breath sounds were coarse with diffuse wheezes. The heart sounds were regular without murmur. The abdomen was flat and soft with normoactive bowel sound. No pitting edema was noted in both arms and legs. Marked swelling and erythematous skin lesions on the left forehead and periorbital areas were noted. Besides, two nodules measuring 3 x 1cm and 2 x 1cm were found in the left eye and on the nasal ridge, respectively, associated with local tenderness, local heat and fragile bony structure on palpation. (Fig. 1 )

1.CBC/DC:

 

WBC(/μl)

RBC(M/μl)

Hb(g/dl)

Hct(%)

MCV(fl)

PLT(k/μl)

CRP(mg/d)

921028

11340

2.22

6.9

19.8

89.2

98

10.32

921104

10090

3.36

10.5

28.7

85.4

76

13.29

921116

30470

2.69

8.5

25.5

94.8

116

 

 

Blast(%)

Band(%)

Seg(%)

Eos(%)

 Baso(%)

Mono(%)

921028

0

0

92.9

0.2

0.1

3.4

3.4

2.Biochemistry

 

UN

Cr

T-bili

D-bili

Alb

AST

ALT

ALP

 r-GT

HbA1c

Glucose

 

mg/dL

mg/dL

mg/dL

mg/dL

g/dL

U/L

U/L

U/L

U/L

 %

mg/dL

921028

59

5.7

0.9

0.84

3.5

110

56

587

562

6.6

287

921104

53.6

4.9

2.6

2.05

2.8

 

 

 

 

 

 

921116

58.2

5.0

3.8

3.6

 

462

247

 

 

 

 

 

Na

K

Ca

Mg

Cl

P

CK/MB  

TG

CHO

 

mmol/L

Mmol/L

mmol/L

mmol/L

mmol/L

mg/dL

U/L

mg/dL

mg/dL

921028

130

2.8

2.36

1.06

 

4.4  

117/9.5

344

110

921104

133

4.3

2.42

1.3

93

 4.0

<20/<1

 

 

ABG: nasal cannula 3L/min: pH 7.42, pCO2 27.5, pO2 69, HCO3 17.63. Urine analysis:

 

Sp.Gr

pH

Protein

Glu.

Ketone

O.B

Urobil

Bil

Nitrite

RBC

WBC

Epith

Cast

921103

1.025

7.5

>300

-

+/-

3+

1.0

1+

+

25-30

>100

15-20

-

The biopsy revealed mucormycosis and MRI disclosed mucormycosis with invasion into paranasal sinus, and penetration of nasal cartilage, nasal floor and hard palate (Fig 2A &Fig 2B&Fig 3 ). During admission, she was treated with amphotericin B (100mg/day) and Tazocin. Because of the patient’s impending respiratory failure, intubation was performed. Otolaryngeal specialist was consulted but only palliative debridement was performed due to the severe bleeding tendency. She was transferred to ICU and tracheostomy was performed due to difficulty in weaning. A second debridement was scheduled but was postponed due to frequent ventricular tachycardia refractory to DC shocks. Her family refused further aggressive treatment, and she passed away on November 16, 2004, 19 days after admission.

Mucormycosis is an aggressive, opportunistic infection caused by fungi in the class of Phycomycetes. The genera most commonly responsible for mucormycosis usually are Mucor or Rhizopus. Orbitorhinocerebral mucormycosis, the most common type, generally occurs in conjunction with sinus or nasal involvement. Mucormycosis also may affect other parts of the body, including the lungs, GI tract, or skin. Most cases of mucormycosis are acute surgical emergencies. The fungus gains entry into the body through the nasopharynx and can be inhaled into the lungs, or it can extend to the sinuses, orbit, and brain. The occurrence of mucormycosis depends on host immunity. The overall mortality rate in adults is 50%. Survival rates are largely determined by early diagnosis and resolution of the underlying condition.

The most common symptoms of rhinocerebral mucormycosis include altered mental status, fever, and pain over the involved site. Most characteristic feature of mucormycosis is hyphal invasion of blood vessels, leading to hemorrhage, thrombosis, infarction & necrosis. It may lead to cavernous sinus and internal carotid artery thrombosis. Diagnosis based on direct morphologic identification of broad, irregular, perpendicular angle branching, nonseptate hyphae or tissue culture, CT/MRI etc.

The predisposing factors for mucormycosis are including: -Immunosuppression: neutropenia, corticosteroid therapy, transplantation, HIV infection. -Metabolic: DKA, uncontrolled DM, chronic metabolic acidosis, deferoxamine therapy. -Skin or soft tissue breakdown: burn, traumatic or surgical wounds. -Iron overload: phagocytic, chemotatic, bactericidal dysfunction. -Others: IVDU, prematurity, malnutrition, malt and lumber workers. Mucoraceae synthesizes siderophore (rhizoferrin), and Deferoxamine behaves like siderophore, uptake by Mucoraceae and then stimulates its growth.

Treatments includeantifungal therapy with Amphotericin B (1-1.5mg/kg/d), hyperbaric oxygen, surgical therapy or frozen section-guided debridement. The best outcomes are achievable with combined surgical and medical approaches. The lipid-based Amphotericin B appears to be the best medical option considering length of therapy and need for very high doses. But Deferoxamine-related mucormycosis still has very high mortality which had been reported to be around 89% in dialysis patients from international registry. Immunocompromised status plus prolonged half-life of DFO are all possible mechanism of high mortality in dialysis patients.

八、胃腫瘤 (9/1~9/15)

     Progressive left flank dull pain for two weeks

     A 76-year-old man visited emergent department because of progressive left flank pain for two weeks. The pain was dull in character and was persistent. It was not associated with postural change and there were no radiation nor obvious aggravating and relieving factors. He experienced malaise, poor appetite, and body weight loss of 5Kg in one month. There were no hematuria and dysuria. He had history of urolithiasis and underwent extracorporeal shock wave lithotripsy (ESWL) two years ago. He denied history of psychiatric illness, smoking, drinking, or illicit drug use. The stool passage was normal. He was admitted to urology ward under the suspicion of urolithiasis. However, two episodes of hematemesis (about 150-200ml fresh blood in each episode) happened on the 4th day of hospitalization. Ketoprfen (intramuscular) was ever given three times for pain control during hospitalization. Gastroenterologists were consulted for further evaluation and management.

     On consultation, physical examination revealed a thin but well-developed man with acute ill-looking. Heart rate was 114 bpm, temperature was 36.7 ℃, blood pressure was 106/70 mmHg. Conjunctiva was pale and a 1.5cm hard lymphadenopathy was noted at submandibular region. Auscultation of the abdomen showed hyperactive bowel sounds. There was no shifting dullness or hepatosplenomegaly. Knocking pain was noted at left flank area.

1. CBC/DC

WBC

RBC

MCV

MCHC

Hb

Hct

PLT

K/μL

M/μL

fL

g/dL

 g/dL

%

K/μL

6.2

3.83

80.6

31.2

8.1

31.6

141

Seg

Mono

Eos

Baso

 Lym

%

%

 %

%

%

70.4

7

3

0

20

 

2. Biochemistry

BUN

Cr

Na

K

AST

ALT

Glu

CRP

mg/dL

mg/dL

meq/L

meq/L

U/l

U/l

mg/dL

 mg/dL

30

2.0

138

4.1

26

30

106

1.4 

3. Urine analysis:

Appearance

Sp.gr

PH

Protein

Glu

Ketone

Clear

1.006

6.0

--

--

--

OB

Urobilinogen (EU/dL)

WBC (/HPF)

RBC (/HPF)

Cast (/LPF)

Crystal (/LPF)

--

0.1

50-60

3-5

--

-- 

Abdominal plain film: normal.

Renal ultrasonography: enlargement of bilateral kidneys and mild hydronephrosis of left kidney.

Ureteroscopic examination: narrowing of bilateral ureteral lumens without urolithiasis nor tumor.

     Double J tube was inserted to the left ureter.

     Emergent upper endoscopy revealed multiple doughnut–like tumors at gastric body and antrum (Figure 1A , Figure1B). Giant gastric folds were also noted. As the bleeding was minimal (from gastric tumors) during endoscopy and there were no visible bleeding vessels in the stomach and duodenum, endoscopic hemostasis was not done. The bleeding stopped after NPO and intravenous omeprazole injection. Computed tomography (CT) of abdomen and pelvis showed perirenal mass enveloping bilateral kidneys and segmental bowel wall thickening at jejunum (Figure 2A ,  Figure2B). There was neither lymphadenopathy nor mass lesion compressing the ureters. Small bowel barium study showed segmental filling defects with thumb-printing appearance at jejunum and ileum (Figure 3 ).

     However, acute renal failure progressed (serum urea and creatinine levels elevated to 59.4 mg/dL and 4.0 mg/dL, respectively). Histological evaluation of the gastric biopsy specimen revealed intermediate to large-size lymphoid cells crowding between glands in a classical starry-sky pattern. The cellular proliferation rate was extremely high, which was identified by nearly 100% Ki-67 positivity. Special stains for tumor cells showed CD20(+), CD21(-), and CD3(-). These findings were compatible with Burkitt’s lymphoma. Tumor cells were negative for Epstein-Barr virus (EBV) encoded RNAs. Serology test showed positive for EBV-VCA IgG and negative for human immunodeficiency virus (HIV). Both the urine cytology and cerebral spinal fluid (CSF) analysis disclosed lymphoblastic cells. Bone marrow aspiration and biopsy did not show marrow involvement of lymphoma.

     Systemic chemotherapy with rituximab, BCNU, vincristine, methotrexate, etoposide, and methylprednisolone and intrathecal injection of methotrexate were administered after establishing the diagnosis of Burkitt's lymphoma. After two courses of systemic chemotherapy and intrathecal injection of methotrexate, his general condition improved remarkably and nearly complete remission was noted by follow-up panendoscopy, endoscopic ultrasonography, small bowel series, CT scan of abdomen, and cerebral spinal fluid cytoloty. Dramatic normalization of renal function was also noted soon after initiation of chemotherapy. Unfortunately, the patient died of pneumonia during the 3rd course of chemotherapy.

        此病人的胃腫瘤的特色為多發性甜甜圈狀的腫瘤，同時可見持續性少量的滲血。這類型腫瘤的鑑別診斷包括Burkitt's 淋巴瘤，轉移至胃的腫瘤（常見的有黑色素瘤、肺癌、乳癌等），Gastrointestinal stromal tumor（GIST），或Kaposi's肉瘤等等。胃鏡下胃的distensibility還不錯，同時看到有巨大胃皺摺，電腦斷層及小腸攝影發現小腸亦有區段性增厚。頸部亦有淋巴結結腫大，加上LDH升高，而其他腫瘤指數正常，故臨床診斷為淋巴瘤，而病理檢查更進一步診斷為Burkitt's淋巴瘤。胃出血常見的原因包括消化性潰瘍、食道或胃之靜脈瘤或Mallorg-Weiss症候群。胃腫瘤引起的大量出血較不常見，胃淋巴瘤有15-30﹪會發生上消化道出血，但是僅有少數病例引發大量吐血。有些報告指出胃腫瘤引起之出血可利用內視鏡治療達到止血的效果。但在這個病人其胃腫瘤之出血是廣泛的、緩慢性的滲血，亦無看到明顯的血管，所以並未利用內視鏡進行止血治療。在支持性療法及化學治療之後，病人未再發生上消化道出血。

      Burkitt's 淋巴瘤是Non-Hodgkin's lymphoma（NHL）的其中一種，占NHL的1-2﹪，最早是由Dennis Burkitt 在1958年時所發表，他發現烏干達的小孩易患有這類的淋巴瘤，它們腫瘤細胞生長得相當快速，而且，對化學治療的反應相當的好，但病人的預後較一般淋巴瘤差。後來在美洲也有發現Burkitt's 淋巴瘤的病例，但發生率較低，且好發在腸胃道及腹部淋巴結，與EB-virus的關聯性也較小。Burkitt's 淋巴瘤約有30-50﹪會侵犯到腎臟，常見的影像學包括單個或多個腎臟腫瘤，或瀰漫性腎臟浸潤，或從腎臟周圍包住腎臟（此病人的電腦斷層顯示為此類）。在治療方面，目前仍以化學治療為主，此病人使用之處方為R-BOMES（Rituximab BLNU ,Vincristine ,Methotrexate,Etoposide and methylprednisolone）治療後二個月，胃、小腸、頸部以及腎臟之病變幾乎完全消失。當發現多發現胃腫瘤時，應仔細找尋是否有淋巴結腫大或其他器官，如皮膚、肺部、乳房等等是否有腫瘤。腫瘤指數、胸部X光、腹部超音波掃描、電腦斷層掃描、上、下消化道及小腸攝影等檢查均可幫忙進一步診斷。    

九、低血糖 (12/16~12/31)

< Chief complaint >     A 62-year-old housewife with frequent attacks of confused consciousness for 5 years

< Brief history >     This 62-year-old woman had been in good state of health until 5 years ago, when she began to have frequent attacks of general weakness, cold sweating and confused consciousness which mostly happened in the late afternoon and evening and sometimes in the early morning. Those episodes could be relieved by eating and deteriorated with starvation and exercise. Most of the attacks last for several minutes and could recover spontaneously. Because of confused consciousness and syncope, she was brought to a local hospital where hypoglycemia was noted. She regained her consciousness after intravenous dextrose infusion. She was suggested to admission for further study but she refused. In recent months, both the frequency and severity of hypoglycemic attacks increased. It took longer time to regain her muscle power and consciousness (several minutes in past 5 years compared to one hour recently). Besides, she was noted to have involuntary movement of limbs during the hypoglycemic episodes. She had a weight gain of 25 kg in recent four years. 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 pituitary or pancreatic tumor, bone disease, thyroid disease, parathyroid disease, nephrolithiasis or diabetes mellitus.

< Physical examination >     On physical examinations, she had clear consciousness but was in anxious state. She was obese in general appearance. Her body height was 153 cm and body weight was 86.5 kg. The body temperature was 37°C, the pulse rate 88 per minute and the respiratory rate 20 per minute. Her blood pressure in supine position was 120/84 mmHg. Her conjunctivae were pink and the sclerae were anicteric. The pupils were isocoric with prompt light reflexes. There was no moon face, acne nor buffalo hump. The neck was supple without lymphadenopathy, engorged jugular veins, palpable thyroid gland or carotid bruit. The chest was symmetric expansion and breath sounds were bilaterally clear. The heart beats were regular without audible murmur. The abdomen was distended but soft without purple striae. Normoactive bowel sounds and impalpable liver and spleen were noticed. Her extremities were freely movable without edema. There was no cyanosis, petechiae, purpura or pigmentation.

< Laboratory data >1. CBC/DC

WBC

RBC

HB

HCT

MCV

MCHC

PLT

  K/μL

M/μL

g/dL

％

 fL

g/dL

K/μL

5.17

 4.6

13.4

42.8

29.1

31.3

271

2. BCS+e- (Overnight fasting)

ALB

TP

T-Bil

AST

ALT

ALP

ACTH

Cortisol

g/dL

g/dL

mg/dL

U/L

U/L

U/L

pg/mL

μg/dL

3.7

6.9

 0.4

27

39

226

60(10-65)

25 (5-25) 

UN

CRE

Na

K

Ca

Glucose

Insulin

C-peptide

mg/dL

mg/dL

mmol/L

mmol/L

mmol/L

mg/dL

 μU/mL

μg/mL

16.1

0.7

146

4.2

2.22

39

31.6

10.8 

3. Urine analysis 

Appearance

Sp. Gr

pH

Protein

Glucose

Ketone

OB

 

 

 

g/dL

 mg/dL

 

 

Y;C

1.028

6.0

-

-

-

 -  

Urobilirubin

 Bilirubin

Nitrate

WBC

RBC

Epi

Cast

 

 

 

HPF

 

1.0

 -

-

-

-

3-5

- 

4. Prolonged fasting test 

Glucose

Insulin

C-peptide

Cortisol

mg/dL

μU/mL

ng/mL

μg/dL

33

31 (5-20)

 7.9 (0.5-3)

25 (5-25)  

< Course and treatment >       Overnight fasting plasma glucose was 39 mg/dL. Prolonged fasting tests showed hypoglycemia (glucose 33 mg/dL) with inappropriate high serum insulin and C-peptide levels (insulin 31 μU/mL, C-peptide 7.9 ng/mL ). Elevation of amended insulin-glucose ratio (AIGR＝1030)* proved hyperinsulinemic hypoglycemia. Insulinoma was highly suspected. Endoscopic ultrasound study showed a tumor about 0.5 cm at the pancreatic neck（Fig 1）. Both abdominal computer tomography scan （Fig 2）and magnetic resonance cholangiopancreatography（Fig 3）reported negative finding. She received exploratory laparotomy with intraoperative ultrasonography but the excised nodule turned out to be only a lymph node. Medical therapy with diazoxide was suggested. Diazoxide 3 ml bid was adjusted with 90 mg/dL of serum fasting glucose level. Loop diuretics were administered for fluid retention. Antacids were prescribed for GI upset. She was discharged in a stable condition and followed up at our OPD.  

*AIGR＝serum insulin (μU/mL) × 100 ÷ (plasma glucose (mg/dL)－30)＝31×100÷(33-30)＝1030 When AIGR is more than 30, insulinoma is suggested.

< Discussion >     低血糖除了會出現腎上腺症狀（adrenergic symptoms），包括心悸、緊張、手抖、冒汗及心跳加快外，也會出現神經性低血糖症狀（neuroglycopenic symptoms），如無力、倦怠、頭痛、語言不清、行為改變、意識改變、甚至癲癇發作，因此容易被當成是精神方面的問題。發生低血糖時須先區分是空腹低血糖（fasting）或飯後低血糖（postprandial）。完全符合Whipple's triad時就可以診斷為空腹低血糖，包括出現低血糖的症狀及徵兆，血糖值45 mg/dL以下，及給予葡萄糖後症狀立刻緩解。因此我們的病人符合空腹低血糖的診斷。

      造成空腹低血糖的原因很多，包括肝臟疾病、腎臟疾病、藥物作用、升糖荷爾蒙缺乏或血中胰島素量增加。外源性胰島素的使用、降血糖藥物、胰島素抗體或胰島素接受體抗體以及內生性胰島素量增加，均會造成空腹低血糖。然而健康成人出現自發性空腹低血糖最常見的原因是胰島素瘤（insulinoma）。

     80％的胰島素瘤是單一且良性的；10％是惡性的；剩下的是多發且散在性腺瘤（multiple with scattered micro- or macroadenomas），需嚴密監控是否為惡性。超過99％的胰島素瘤位於胰臟內，尤其是胰臟頭。雖然最常發生在30到40歲，但是可以在任何年紀出現，沒有性別上的差異，然而有些研究顯示女性較多。 臨床表現主要以亞急性神經性低血糖（subacute neuroglycopenia）為主，而非腎上腺症狀，因此容易以為是精神疾病而延遲診斷。常常在運動或空腹時出現反覆性的中樞神經系統功能失常。吃含糖食物可以減輕症狀，因此約30％的病人有肥胖的問題。

     當血糖值小於45 mg/dL且血中胰島素量大於5 μU/mL時就要高度懷疑是胰島素瘤。臨床上最常使用抑制性試驗（prolonged fasting test）來作診斷。正常人在禁食72小時後血糖也不會低於55 mg/dL，而此時的胰島素濃度會低於10 μU/mL。有些正常女性甚至血糖可以低至30 mg/dL，胰島素下降到小於5 μU/mL而仍然沒有症狀，因為酮體形成（ketogenesis）可以提供足夠的燃料給中樞神經。以前會使用胰島素與血糖的比值（正常非肥胖的人小於0.25 μU/mL），但是目前少用。大部分胰島素瘤的病人在禁食24至36小時後會出現進行性低血糖症狀併血中胰島素上升，但是沒有酮尿。

      也可以使用刺激試驗（stimulation tests）來作診斷。靜脈注射1 mg的升糖素（glucagon）或鈣離子，之後每五分鐘抽一次血，共15分鐘，當血中胰島素濃度大於130 μU/mL時，50％是胰島素瘤，但是如缺乏過多的胰島素分泌並不能完全排除胰島素瘤的可能性。也可以測前胰島素（Proinsulin），正常人前胰島素與胰島素的比值小於20％，但是胰島素瘤的病人比值為30-90％，因此對於胰島素瘤而言，測前胰島素有較高的特異性。

     臨床上仍需測C胜(月太)（C-peptide）、磺醯尿素（sulfonylurea）及胰島素抗體來排除外源性胰島素、降血糖藥物及自體免疫疾病的可能性。

     然而，臨床上最重要的仍是腫瘤的定位，包括腹部超音波、電腦斷層、核磁共振、血管攝影、內視鏡超音波（endoscopic ultrasound）及手術中超音波使用，後者常用於小腫瘤，被認為是目前最有效的方法。手術中外科醫師仔細的觸摸配合手術中超音波使用，成功率可以高達97%。但是因為這些腫瘤通常太小而找不到(平均直徑為1.5 cm)，因此常需要重新開刀。

     治療胰島素瘤主要以手術切除腫瘤為主，然而2-5％的病人即使有術中超音波的輔助也無法找到腫瘤。這些腫瘤大部分位於胰臟的頭，因此不建議盲目的切除胰臟遠端三分之二，也不建議將胰臟完全切除。這時可以先以內科治療。手術後會有數天出現高血糖，原因為術後胰臟水腫及發炎無法分泌胰島素、手術使得一些反調節荷爾蒙升高（counterregulatory hormone）、胰島素受體因為長期高胰島素而降低調節（chronic down regulation of insulin receptors）、長期的低血糖抑制正常胰臟B細胞的功能；給予外源性胰島素治療，大部分胰島素的分泌會在48至72小時之後恢復。內科治療胰島素瘤首用diazoxide（每天300-400 mg），副作用為腸胃不適、多毛、水腫、體重增加及高血鉀，腎臟及心臟功能不良的病人應小心使用。通常建議並用利尿劑（hydrochlorothiazide，每天25-50 mg）。如果無法忍受副作用，可以選擇鈣離子阻斷劑（如verapamil 80 mg，每天三次），長效體制素（octreotide）的效果有限，streptozocin用於胰島細胞癌。 

十、多尿 (1/16~1/31)

Chief complaint >     Polyuria for three years

< Case presentation >     This 21-year-old previously health girl presented with polyuria for three years, which made her to urinate every hour. The urine was clear and light-colored. She also felt thirsty frequently, and had water intake of up to 10 liters per day. Nocturia and ensuing disturbed sleeping developed, which resulted in easy-anxiety and daytime somnolence. She denied history of head trauma, surgery, eating disorder or medication use before. She had no family history of polyuria, either.

< Physical examination >     Physical examination revealed a 55 kg, 155 cm-tall woman with blood pressure 120/70 mmHg. She appeared anxious and thirsty. Her respirations and temperature were normal and her pulse rate was 80 beats per minute. The pupils were isocoric (3/3 mm) with prompt light reflex. Neither facial deformity nor oropharyngeal lesion was found. The neck was supple without goiter or lymphadenopathy. Chest, abdominal and extremity examinations were normal. Neurological examinations including visual field, motion of eye balls and hearing function were normal.

< Course and treatment >     Biochemical studies and complete blood count were within the normal range. Daily water intake and urine volume were approximately 13 liters, respectively. Urinalysis revealed a specific gravity of 1.002. Urine and plasma osmolality were 73 and 282 mosm/kg, respectively. Baseline serum hormone levels were as follows: high sensitivity thyroid-stimulating hormone (hsTSH) 2.5 μIU/mL (normal, 0.1-4.5), free thyroxine (FT4) 0.95 ng/dL (normal, 0.6-1.75), corticotropin (ACTH) 20 pg/mL (normal, 10-65), cortisol 19 μg/dL (normal, AM 5-25), prolactin 7.8 ng/mL (normal, 1.4-24.2), growth hormone (hGH) 0.09 ng/mL (normal, 0.06-5.0), follicle-stimulating hormone (FSH) 9.69 IU/L (normal, 3.4-10), luteinizing hormone (LH) 7.67 IU/L (normal, 1.6-8.3) and estradiol 120 pg/mL (normal in follicular phase, 73.4-367). Both microsomal antibodies (MA) and thyroglobulin antibodies (TA) were negative. Electrocardiogram was normal. Roentgenologic examinations, including chest films and skull films with stereoscopic views of the sella turcica were unremarkable. Magnetic resonance imaging (MRI) demonstrated normal-sized pituitary gland with mildly prominent pituitary stalk and absence of the high signal of the posterior pituitary lobe（Fig 1 & Fig 2 ）. Dehydration test containing hourly measurements of urine volume, urine specific gravity, urine and plasma osmolality was carried out. The test was terminated after four hours when the weight decreased by 3%. She then received an intramuscular injection of 2 μg desmopressin acetate. The dehydration-desmopressin tests revealed no increase in urine concentration during dehydration but prompt response to vasopressin (table 1). The patient was treated with oral desmopressin twice daily. Her daily urine volume decreased to two liters. She regularly followed up at our hospital.

< Laboratory data >

Table 1. Dehydration-vasopressin tests (Dehydration since 8am; stop water deprivation with desmopressin acetate (DDAVP) 2 μg  IM given at noon)

Time

 BW(kg)

UA(ml/h)

 Sp. Gr

Uosm (mosm/kg)

 Posm (mosm/kg)

 P[Na+] (meq/L)

BP(mmHg)

8am

55

300

1.002

73

282

144

136/80

9am

55

600

1.002

72

282

 

124/78

10am

54

510

1.002

80

287

144

144/92

11am

53.5

540

1.002

90

292

 

142/86

0pm

53

400

1.003

128

295

147

140/80

1pm

54

100

1.012

440

284

 

144/96

2pm

55

60

1.013

470

282

141

143/86

3pm

55

90

1.012

430

279

 

138/84

4pm

55

35

1.012

398

279

138

136/86

BW = body weight; UA= urine amount; Sp. Gr. = specific gravity of urine; Uosm:= urine osmolality; Posm = plasma osmolality; P[Na+] = plasma sodium concentration; BP = systolic blood pressure / diastolic blood pressure   

< Discussion >     每天尿量大於3公升稱為多尿（polyuria）。多尿的原因很多，包括尿崩症（diabetes insipidus），原發性多飲症（primary polydipsia）和滲透性利尿（osmotic diuresis）。滲透性利尿患者之尿液滲透壓接近血漿滲透壓；而尿崩症和原發性多飲症患者的尿液滲透壓就會遠低於血漿滲透壓。尿液的比重小於1.005 (滲透壓小於200 mosm/kg)時，通常可以排除滲透性多尿。尿崩症患者血中鈉離子濃度和滲透壓經常是正常或增加的，而原發性多飲症病人的血漿和尿液則是較稀釋的。接受限水試驗（dehydration test）時，完全性尿崩症(complete DI)的病人仍會有大量的尿液，而且尿液的比重仍然小於1.005；但是，在原發性多飲症的病人身上可以看到尿液滲透壓隨著時間持續上升至超過血液的滲透壓。因此我們的病人診斷為尿崩症而非原發性多飲症。

      尿崩症分為中樞性尿崩症(central )及腎性尿崩症(nephrogenic)，前者是因為缺乏血管加壓素(vasopressin)，而後者是腎臟對血管加壓素有抗性。藉由限水及血管加壓素試驗(dehydration-vasopressin tests)可以確定診斷。我們的病患注射desmopressin後，尿液的滲透壓增加超過50%，因此可以診斷為中樞性尿崩症而非腎性尿崩症。造成中樞性尿崩症的原因不少，包括浸潤(包括結節病和組織細胞增生症 X，sarcoidosis and histiocytosis X)、發炎（lymphocytic hypophysitis）、自體免疫或血管性疾病、中樞神經系統腫瘤(如生殖細胞瘤，germinoma)、頭部手術或意外造成的傷害，及其他非常少見的病因，如因為遺傳基因缺損造成血管加壓素合成異常。然而，約30%到50%是不明原因(idiopathic)的。

     核磁共振影像檢查（T1-weighted）會發現腦下腺後葉缺乏高訊號，這是中樞性尿崩症一個非專一性的特點。雖然不具專一性，但是如果同時出現漏斗或腦下腺柄變厚，則表示有局部發炎、浸潤或自體免疫疾病或生殖細胞瘤。生殖細胞瘤通常會使得腦下腺前葉變大且柄變厚；然而，如果是發炎反應或自體免疫疾病反而會使得腦下腺前葉變小而柄變厚。但是浸潤或慢性發炎疾病常常會同時影響身體其他器官而伴隨著其他系統的症狀。雖然不能完全排除自體免疫疾病造成我們的病人出現尿崩症，但是目前的診斷仍為不明原因中樞性尿崩症。 有些不明原因之中樞性尿崩症也會伴隨有腦下腺前葉荷爾蒙缺乏，所以這些病患應該同時檢查腦下腺前葉功能。治療通常是給予血管加壓素(desmopressin)，有口服或鼻噴劑可以選擇。治療時應隨時注意體重、血壓及電解質是否平衡。

十一、乳促素瘤 (2/1~2/15)

< Chief complaint >      A 47-year-old man with a progressive decrease in libido and sexual activity for 2 months

< Case presentation >      This 47-year-old married man is a patient with essential hypertension for 2 years and had regular medical control with amlodipine besylate 5 mg QD. He had two children. Two months prior to admission, he noted a progressive decrease in libido and frequency of sexual activity. He almost totally lost libido axillary hair, pubic hair, eyebrow and moustache. He visited an outpatient department where bilateral atrophic testes were noted. He had neither headache nor visual problems. Under the impression of androgen deficiency, he was admitted for further management.

< Physical examination >     Physical examination revealed a 70 kg, 173 cm tall man with blood pressure 130/80 mmHg, respiratory rate 20/min, pulse rate 84/min and temperature 37℃. The consciousness was clear, the conjunctivae were pink, and the sclerae were anicteric. The pupils were isocoric (3/3 mm) with prompt light reflex. The neck was supple without goiter, lymphadenopathy or engorged jugular veins. Chest, abdominal and extremity examinations were normal. The areolae were hypopigmented, No gynecomastia, galactorrhea, or purple striae was noted. The testes were atrophic with size of 1.5×1.0 cm. The eyebrow, moustache, axillary hair, and pubic hair were scanty. Neurological examinations including visual fields, motion of eye balls and hearing function were normal.

< Laboratory data >Table 1. Basal endocrine test level

hsTSH

free T4

ACTH(A)

Cortisol(A)

ACTH(P)

Cortisol(P)

0.4- 4 μIU/mL

0.60-1.75ng/dL

10-65 pg/mL

5-25 μg/dL

10-65 pg/mL

2.5-12.5 μg/dL

2.98

0.37

9.9

1.4

8.0

＜ 1

hGH

FSH

LH

Prolactin

DHEA-SO4

Androstenedione

0.06-5 ng/mL

3.4-10 mIU/mL

1.6-8.3 mIU/mL

1.4-24.2ng/mL

4.6-15.4μmol/L

1.75-8.7 nM

0.08

0.37

＜ 0.7

3938

＜ 0.81

＜ 0.35     

 

 E2

P4

Testosterone

MA

TA

73.4-367 pg/mL

0.2-1.4 ng/mL

10-50 ng/mL

 

 

21.4

＜ 0.2

＜ 0.2

1：40(-)

1：40(-)     

**high sensitivity thyroid-stimulating hormone＝hsTSH, free thyroxine＝FT4, corticotropin＝ACTH, A＝8AM, P＝4PM, growth hormone＝hGH, follicle-stimulating hormone＝FSH, luteinizing hormone＝LH, DHEA-SO4＝dehydroepiandrosterone sulfate, E2＝estradiol, P4＝ progesterone, MA＝microsomal antibodies, TA＝thyroglobulin antibodies.    

< Course and treatment >     Biochemistry studies and complete blood counts were within  normal ranges. Baseline serum hormone levels revealed hyperprolactinemia, hypogonadotropic hypogonadism and panhypopituitarism. Skull films showed an enlarged sellar turcica（Fig 1）. Prolactinoma was suspected. Magnetic resonance imaging (MRI) demonstrated an enlarged sellar turcica with a mass lesion(about 2.5 × 2 × 2cm) at the sellar and suprasellar region which invaded to left cavernous sinus（Fig 2, 3, 4 & 5 ）. The optic chiasm was elevated and the posterior lobe of the pituitary gland was absent. Pituitary macroadenoma was impressed. He received hormone replacement therapy including thyroxin 100 μg QD, prednisolone 5- 2.5 mg B.I.D, and testosterone enanthate depot 125 mg per month. Initially, bromocriptine 2.5 mg QD was prescribed for reducing tumor size and prolactin level. The dose gradually increased to 2.5 mg T.I.D. He could tolerate the mild nausea and dizziness related to the medications. Follow-up prolactin level decreased to 30 ng/mL. Surgical resection of the tumor was suggested but he refused. He regularly followed up at our hospital.

< Discussion >     乳促素瘤（prolactinoma）是腦下腺腺瘤（pituitary adenoma）中最常見的，約佔60％左右。乳促素瘤通常從腦下腺前葉的側翼（lateral wings）長出，隨著時間漸漸充滿整個蝶鞍，甚至壓迫腦下腺前葉及後葉。腫瘤大小可以多變，從微腺瘤（microadenoma，直徑小於1公分）到巨大腺瘤（macroadenoma，直徑1公分以上），甚至往蝶鞍外侵犯都有可能，大部份在診斷時是微腺瘤。一般而言，乳促素瘤的生長是很慢的，甚至有些研究顯示大部分的微腺瘤是不會長大的。其發生率沒有性別上的差異。

      女性以無月經（amenorrhea）及乳溢（galactorrhea）為主要表現，男性則以性慾降低（decreased libido）和陽萎為主（impotence）。女性病患在診斷時通常腫瘤較小，可能是因為症狀較早出現，而男性因為起始症狀不明顯而常常延遲診斷，因此發現時腫瘤通常較大，就像我們的病人。

      大部分的女性病人都會出現乳溢症狀，可以持續存在，也可以短暫或間歇性出現；少部份病人雖然血中乳促素很高卻沒有乳溢症狀，可能是因為同時缺乏性腺激素（gonadal hormones）。90％的女性病人會有無月經、月經稀少、無排卵或是不孕，這些病人可以同時、之前或之後出現乳溢。造成性腺功能低下（hypogonadism）不是因為破壞促性腺激素分泌細胞（gonadotropin-secreting cells），因為當血中乳促素濃度回到正常值後，月經週期也會恢復正常。雖然基礎的促性腺激素（gonadotropins）常常在正常範圍內，但是乳促素會抑制促性腺激素正常的脈動性分泌及促黃體生成素高峰（LH surge），導致不排卵，也會抑制雌激素（estrogen）不分泌。因此這些病人是缺乏雌激素的，很容易會出現骨質疏鬆症。

      過多的乳促素偶而會使得男性病人出現乳溢，然而，大部分卻是造成性腺功能低下。最初的症狀通常是性慾降低，因此常常被認為是精神上的問題，使得病人難以開口，也容易讓醫師失去警覺，造成診斷延遲，以致男性病人經常有較高的乳促素（乳促素大於200 ng/mL）及蝶鞍變大，甚至頭痛、視力不良或性腺功能低下。雖然血中睪固酮濃度很低，但是造成陽萎的原因不明，如果沒有矯正乳促素濃度，即使注射睪固酮也無法改善。許多情況都會造成血中乳促素增加，應該進一步鑑別診斷，包括一些生理性反應，如懷孕、哺乳、刺激乳頭、運動、壓力（低血糖）、睡眠、癲癇發作、新生兒時期；疾病，如脊柱疾病、下視丘及腦下腺柄疾病、原發性甲狀腺功能低下、慢性腎衰竭及嚴重肝疾病；還有一些藥物也會造成乳促素增加，如estrogen、dopamine antagonists (phenothiazines, haloperidol, risperidone, metoclopramide)、cimetidine、verapamil；臨床上尤其常見藥物造成乳促素增加，因此詢問病史時要小心藥物。

      在診斷方面，除了典型的症狀外，就是測量血中乳促素濃度和影像檢查（包括頭部X光和核磁共振）。除了少數例外，當血中乳促素大於200 ng/mL，可以確定是乳促素瘤而且是巨大腺瘤；血中乳促素介於100到200 ng/mL，通常病人是乳促素瘤，可以是微腺瘤或巨大腺瘤；乳促素大於100 ng/mL的腺瘤通常可以在影像上清楚顯示；如果乳促素介於20至100 ng/mL之間，通常診斷較困難，此時需要依賴核磁共振檢查。

      所有的病人都應該接受治療以防腫瘤長大、骨質疏鬆、及性腺功能低下。治療包括內科治療、手術切除及放射線治療。對於微腺瘤通常建議以內科治療為主，可以用dopamine agonist，可以直接抑制乳促素分泌，包括bromocriptine及cabergoline，前者副作用較多，包括頭暈、噁心、嘔吐、姿勢性低血壓，建議從低劑量開始；後者較長效（一星期一到兩次）、較有效且副作用較少。對於巨大腺瘤一般建議手術治療，但是應該先使用內科治療，手術之後通常須輔以藥物治療甚至放射線治療。

      為了能早期診斷，所以病人如果有乳溢、無月經、性慾減低、陽萎、不孕、蝶鞍變大、或懷疑腦下腺腫瘤時，都應該測乳促素濃度。

十二、嗜鉻細胞瘤 (3/16~3/31)

< Chief Complaint >     Intermittent palpitation and headache for two months.

< Brief History >     This 54 year-old man, a boss of a factory, is a patient with diabetes mellitus diagnosed for 1 year. He took oral hypoglycemic agents (glimeperide 4 mg Q.D, metformin 500 mg T.I.D) and his average fasting plasma glucose level was around 110 mg/dL. Two months prior to admission, he developed intermittent palpitation and headache. Each episode of which lasted several minutes and resolved spontaneously without overt precipitating or aggravating factors. Occasionally the episode happened at bedtime and was accompanied by pallor, dizziness and perspiration. There was no chest tightness, vomiting or abdominal pain. He had ever visited a local medical clinic where hypertension was noted. Because these episodes were paroxysmal, he refused to take any medication. He denied a family history of hypertension.

     Because the frequency of headache increased recently, he underwent a health examination. Whole body magnetic resonance imaging revealed a left adrenal tumor measuring 3.2 cm in diameter which presented with hyperintense signal on T2-weighted image (fig 1& 2 ). Whole body positron emission tomography (PET) showed negative findings. Secondary hypertension which was related to a pheochromocytoma was highly suspected and he was admitted for further study.

< Physical examination >     Physical examination revealed a 76 kg, 169 cm tall man without round face, acne or truncal obesity. His blood pressure was 120/80 mmHg, respiratory rate was 18/min, pulse rate was 88/min and his temperature was 36.2℃. His consciousness was clear, conjunctivae were pink, and his sclerae were anicteric. The pupils were isocoric with prompt light reflex. The neck was supple without goiter, lymphadenopathy, engorged jugular veins or carotid bruit. Chest, abdominal and extremity examinations were normal. There was no gynecomastia, galactorrhea, buffalo hump or purple striae.

< Laboratory Examination >

Table1. Endocrine test

Renin

Aldosterone

Cortisol (8AM)

Cortisol (4PM)

DHEA-SO4*

 ng/mL/hr

 ng/dL

μg/dL

μg/dL

μmol/L

3.48 (1-5)

19.5 (5-30)

10 (5-25)

6 (2.5-12.5)

 4.2 (4.6-13.4)

   

Table 2. 24 HR urine catecholamines

Dopamine

Epinephrine

 Norepinephrine

VMA**

μg/24h

μg/24h

μg/24h

mg/24h

286.72 (50-450)

213.37 (< 22.4)

175.93 (12.1-85.5)

8.25 (1-7)

*DHEA-SO4: dehydroepiandrosterone sulfate; **VMA: vanillylmandelic acid

< Course and Treatment >     During hospitalization, he experienced another two episodes of palpitation and headache which were accompanied by concomitant elevation of blood pressure (systolic/diastolic 170/100 mmHg). Complete blood counts and biochemical studies, including serum electrolytes, were within normal ranges except for an overnight fasting glucose of 130 mg/dL. Twenty-four-hour urine exam revealed elevated VMA (8.25 mg) and catecholamine levels (epinephrine 213.37μg, norepinephrine 175.93μg). Plasma renin activity, aldosterone and cortisol levels were all within normal limits. The laboratory test confirmed the diagnosis of pheochromocytoma. Doxazosin 2 mg daily initially was prescribed and the dose was gradually increased to 16 mg daily for better blood pressure control. He received laparoscopic adrenalectomy smoothly. The pathology proved the diagnosis of pheochromocytoma (fig 3 & 4 ). Both his blood pressure and fasting blood glucose levels gradually returned to normal ranges without necessitating any medications. He was discharged and regularly followed up at out-patient department.  

< Discussion >       嗜鉻細胞瘤(pheochromocytoma)是一種少見的腫瘤，每年每一百萬人約有兩位，是造成續發性高血壓(secondary hypertension)的原因之一，佔所有高血壓少於0.1％。沒有性別上的差異，可以發生在任何年紀，尤其常見於30至40歲。90％的成人及70％的小孩位於腎上腺，右側又比左側常見，右側的嗜鉻細胞瘤較常出現陣發性(paroxysmal)高血壓，約10％的成人及35％的小孩兩側腎上腺皆有腫瘤。大部分偶發性嗜鉻細胞瘤是有包膜的(encapsulated)，很少會侵犯周邊組織，但是有時腫瘤會進入腎上腺靜脈、下腔靜脈，造成肺栓塞。嗜鉻細胞瘤的大小變異很大，可以很微小(microscopic)也可以大至3600克，平均直徑約4.5公分，重約100克。Paragangliomas是腎上腺外的嗜鉻細胞瘤(extra-adrenal pheochromocytomas)，從神經節長出，佔成人嗜鉻細胞瘤約10％，其中85％可以在腹部發現。

       大部分的嗜鉻細胞瘤是偶發的(sporadic)，但是超過10％可以是遺傳的，這些病人需要作基因篩檢，如multiple endocrine neoplasia type 2 (MEN 2)是因為ret proto-oncogene突變，造成嗜鉻細胞瘤、甲狀腺髓質癌(medullary thyroid carcinoma)及副甲狀腺機能亢進(hyperparathyroidism)或黏膜神經瘤(mucosal neuroma)；又如Von Hipple-Lindau disease是因為VHL tumor suppressor gene突變等。大部分偶發性腫瘤是良性的，而有15％的嗜鉻細胞瘤是惡性的，可以轉移到頭骨、肋骨、脊椎、肺、胸管、腸繫膜和肺臟。MEN 2的惡性機會較高，paragangliomas有30-50％是惡性的。腎上腺外嗜鉻細胞瘤、大腫瘤(直徑6公分以上)、腫瘤有融合性壞死、血管侵犯或廣泛性局部侵犯則惡性機會較大。

      雖然有些嗜鉻細胞瘤不會分泌catecholamine，但是大部分都可以製造catecholamine ，甚至高於正常的27倍。然而因為無法回饋抑制，所以造成持續且過度分泌，而增加心臟輸出量(cardiac output)、週邊血管阻抗(peripheral resistance)及腎素(renin)分泌，繼而造成高血壓。但是，血中catecholamine的濃度和腫瘤大小不一定相關，因為大腫瘤可能會有內部出血性壞死。腫瘤內自發性出血、生理性刺激如排尿(micturation)、身體疼痛、心煩意亂、插管、麻醉都可能引起高血壓危象(hypertensive crisis)。除此之外，嗜鉻細胞瘤還會分泌neuropeptide Y (NPY，非常強的血管收縮劑，引起高血壓)、neuron-specific enolase (NSE，良性腫瘤血中濃度會正常，一半的惡性嗜鉻細胞瘤濃度會上升)、ACTH(造成庫欣症候群)、erythropoietin(紅血球生成素，造成紅血球過多)、parathyroid hormone- related peptide (PTHrP，造成高血鈣)、IL-6 (發燒)。

      超過三分之一的病人於診斷出嗜鉻細胞瘤前就已經因為心律不整或中風死亡。90%的成人有高血壓，然而腎上腺素也可能引起偶發性低血壓及昏厥。80％的病人有頭痛，70％會冒汗，60％有心悸，50％會焦慮不安，40％會手抖，甚至出現感覺異常、心絞痛、腹痛或視覺改變。但是，MEN 2和VHL的病人血壓常常是正常而沒有症狀。因為血管運動腎上腺接收器去敏感(vasomotor adrenergic receptor desensitization)造成血管內容積減少會導致姿勢性低血壓；有些病人因為去敏感、耐受(tolerance)、或tachyphylasix，即使血中catecholamine過高血壓也正常。此外，血中catecholamine濃度過高也會導致左心室肥大、心肌炎、擴張型心肌病(dilated cardiomyopathy)，如果沒有造成心肌纖維化，於腫瘤切除後可以完全恢復。

      生化檢查通常是測血漿和尿液中的catecholamine及metanephrine(catecholamine的代謝物)。目前以測尿液metanephrine的敏感性最高，為97％，但是因為實驗室的限制，我們的病人只有測尿液norepinephrine、epinephrine、VMA及dopamine，卻也已經足夠診斷了。MEN 2的病人血漿metanephrine會上升，VHL disease的病人血漿norepinephrine會上升。測serum chromogranin A (CgA)對診斷也有幫助；正常情況下，CgA有晝夜節律，早上八點時血中濃度最低，下午及晚上11點時濃度最高，CgA的濃度和腫瘤大小有關，所以是一個有用的腫瘤標誌，正常人的CgA是48 ng/mL，良性嗜鉻細胞瘤為188 ng/mL，惡性嗜鉻細胞瘤是2932 ng/mL。CgA的敏感性為83-90％，而特異性為96％。除此之外，有些病人會出現白血球(主要是中性球)、紅血球、或紅血球沉降速度(ESR)增加、高血鈣，35％的病人有高血糖，如同我們的病人。有些藥物、食物(咖啡因或香蕉)、或疾病都會影響血漿或尿液catecholamine的濃度，因此會干擾我們對嗜鉻細胞瘤的診斷，所以應該仔細問診。

      臨床上主要使用metaiodobenzylguanidine (MIBG) scans來定位嗜鉻細胞瘤，benzylquanidine是quanethidine的衍生物，是一種假性神經傳導物質，會累積在分泌catecholamine的細胞中，因此可以定位嗜鉻細胞瘤。為了阻斷甲狀腺攝取放射碘，必須事先給予potassium iodide。如要做電腦斷層檢查，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，因為不需要打顯影劑，也沒有輻射線，75％的病人於T2-weighted image會呈現hyperintense signal，比肝臟亮，但是特異性差。正子攝影(positron emission tomography，PET)對定位惡性嗜鉻細胞瘤的轉移敏感性不錯，但是特異性較MIBG差，好處是可以立即作不需事前準備，但是很貴。如果強烈懷疑有paragagliomas或轉移，尤其是MIBG scans無異常時，應該考慮somatostatin receptor imaging。

      治療以手術切除為主，目前外科醫師傾向內視鏡腎上腺切除(laparoscopic adrenalectomy)，但是術前要先做好準備，以防發生高血壓危象或休克。血壓的控制比較建議使用鈣離子阻斷劑，因為術前水份不需要補充太多，而且病人的耐受性較好。但是α-blockers仍舊是最廣泛被使用的降壓藥，一般常用phenoxybenzamine，但是其會增加catecholamines和metanephrine的合成，使得心跳加快；也可以使用doxazosin或prazosin。由於catecholamine會刺激腎素分泌且嗜鉻細胞瘤上有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。一般不建議使用β- blockers，除非是為了治療潮紅、心跳過速，但是要在α-blockers使用後。Metyrosine (α-methylparatyrosine)少用，因為副作用多，通常用於已經轉移了。可以使用NSAIDs來治療嗜鉻細胞瘤引起的發燒。

      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％。即使切除腫瘤10天或更久後，仍舊可以在血液及尿液中測得高濃度的catecholamine，因此術後2星期再追蹤24小時尿液catecholamine及metanephrine，之後第一年每三個月追蹤一次，之後每6個月，然後每年，至少持續五年。腎功能正常的病人可以追蹤CgA；惡性腫瘤或有轉移的病人要在手術後數個月追蹤第一次MIBG scan。

      嗜鉻細胞瘤雖然罕見，但是卻很危險，所以臨床醫師應該有高度的警覺，那麼何時需要篩檢呢？年輕高血壓病人、嚴重高血壓、頭痛、心悸、冒汗、無法解釋的腹部或胸口疼痛、有家族史、無法使用降壓藥控制血壓等。

十三、眼內炎 (5/1~5/15)

Abdominal pain, diarrhea and fever for ten days.

This 73-year-old male patient, a case of diabetes mellitus (DM) for 20 years without regular medical control, has suffered from diarrhea and abdominal pain since July 10, 1999. He took some medication to relieve the pain. However, diarrhea about 2-3 times a day persisted. His stool was loose, neither bloody nor mucoid and was accompanied by low abdominal cramping pain. He did not pay much attention to it since the diarrhea was not very severe. Nevertheless, severe chills and high spiking fever developed in the afternoon of July 17. His fever subsided after he taking some antipyretics. However, progressive abdominal pain, diarrhea and fever relapsed and he came to the emergency room on July 19, where lower abdominal cramping pain, equivocal bloody and mucoid stool, leukocytosis with left shift were noted. Cefotiam was administered empirically under the impression of diverticulitis. Abdominal sonography showed wall thickening in the rectosigmoid colon. General surgeon was consulted and colonoscopy or abdominal computed tomography (CT) was suggested. Abdominal and pelvic CT showed wall thickening in the rectosigmoid colon without hollow organ perforation. The abdominal pain, diarrhea and fever improved gradually with antibiotics, but blurred vision occurred on July 21. Ophthalmological examination showed that his visual acuity was only of counting finger/ 50 cm (od). Proliferative diabetic retinopathy (PDR) (od) with macular hemorrhage was also diagnosed and Fluorecein anigiography (FAG) was performed on July 22, which revealed vitreous hemorrhage and transamin was administered for hemostasis. Colonoscopy performed on July 23 showed 4-5 mass lesions with hyperemia, small holes and pus in rectum and rectosigmoid junction and a polyp at upper rectum. Biopsy and culture were done. Under the suspicion of diverticulitis or amebic colonic abscess, he was admitted on July 23.

The consciousness was clear. The blood pressure was 157/91 mmHg, body temperature was 36.8°C, pulse rate was 85/min, and respiratory rate was18/min. Conjunctiva was not pale, anicteric sclera, clear breath sound and regular heart beat without murmur were noted.

There was distended abdomen with hypoactive bowel sound, tenderness and rebound tenderness.over lower abdomen. Muscle guarding was also noted. Liver and spleen were both impalpable.

WBC

 RBC

 Hb

MCV

Plat

Seg

Eos

Baso

 Mono

 Lym

/ul

106/ul

G/dl

fl

103/ul

%

%

%

 %

%

9430

4.10

13.0

92.0

53k

92.0

0.3

0.1

3.4

4.2

A/G

Bil(T/D)

AST

ALT

ALP

r-GT

BUN

Cre

Amy

Lip

Na

K

Ca

g/L/g/L

mg/dl

U/L

U/L

U/L

U/L

mg/dl

mg/dl

U/L

U/L

mM

mM

mM

2.8/3.5

1.3

39

43

223

168

20

1.1

<46

102

137

4.3

2.07

PT

PTT

Glu.AC

sec

sec

mg/dl

 12.3/11.2

36.9/33.9 

306

Urinalysis: negativeStool : occult-blood (+/-), pus cell (-) Stool culture: No Salmonella, Shigella, Campylobacter, ClostridiumColonoscopic abscess culture: no pathogen, many neutrophil. Biopsy: no malignant cell, polyp IHA test: 8x (-) Vitreous culture & smear: no pathogen Vitreous culture & smear: numerous PMN

Abdominal Ultrasonography;Colonic wall thickening over rectosigmoid junction, fatty liver, fat-free area of the liver.

CT of Abdomen & pelvis: Long segmental narrowing and wall thickening of the rectum and sigmoid colon. There is dirty fat plane at mesosigmoid colon. This may be inflammatory change or neoplastic process of the rectosigmoid colon.

Colonoscopy: There were 4-5 submucosal masses with hyperemia, and small holes with pus in rectum and rectosigmoid junction. Other areas of the rectum were edematous. A polyp at upper rectum and multiple inflammatory masses in the rectum and rectosigmoid junction were found and biopsy for pathology and culture was performed. Diverticulitis or ameba was suspected.

After admission, intravenous cefoxitin was administered empirically, and the bowel symptoms and the fever improved. However, ophthalmological examination of the right eye on the admission showed 4+ cells in the anterior chamber. The fundus was obscured because of dense vitreous opacity. His visual acuity was of hand movement at 30 cm. There was 3+ chemosis but the extraocular muscle movement was full and free. Vitreous paracentesis was done and amikacin and vancomycin were injected intravitreously on July 24. Culture of the specimen yielded no pathogen. His vision improved initially but became deteriorated gradually. Pars plana vitrectomy and intravitreous injection of vancomycin and amikacin were done on July 29. Ceftriaxone was administered instead to provide a more effective blood-retina barrier penetration. Elevated intraocular pressure and eye pain were noted, and cryotherapy was performed on August 6 to decrease the intraocular pressure. He was transferred to Ophthalmological department for further care. Trans-sclera cyclophotocoagulation (TSCPC) was done on Aug 16 due to persistent eye pain and elevated intraocular pressure. The eye pain subsided but he became totally blind in the right eye. He was discharged on Aug 28 and followed at OPD.

眼內炎（endophthalmitis）是定義為眼內液及眼內組織的發炎。而如果引起的原因為微生物感染，則最後常常造成嚴重視力減退，甚至失明。

眼內炎可分為1. 眼科手術後眼內炎；2. 創傷後眼內炎；3. 內源性眼內炎三類。這樣分類的好處可用以預測致病微生物及培養確認前的抗生素使用。前二類多為革蘭氏陽性菌，第三類多為革蘭氏陰性菌。

約70%的眼內炎是屬於眼科手術後眼內炎，25%是創傷後眼內炎。內源性眼肉炎佔不到5%，是其中最不常見的，然而值得注意的是罹患內源性眼內炎的病患大多是免疫力差或者是靜脈藥物濫用的患者。

臨床上診斷眼內炎可分為兩部分：一是臨床症狀，一是微生物確認。臨床症狀方面包括視力減退、紅眼、眼痛、明顯的眼內發炎症候（包括hypopyon，conjunctival congestion及corneal haze）。微生物確認必須做vitrectomy取得眼內液，可放在culture media或blood culture瓶送檢。

內源性眼內炎的特色是發生時程快（acute onset），進展很快（rapid progression）及對抗生素反應差（refractory response）。宿主因子則常常和糖尿病（diabetes mellitus）有關。在台灣第一名的致病菌是克雷白氏菌（Klebsiella pneumoniae）。若以原發器官論，則以腸道感染原預後為最差。所以，只要一發現，盡快做致病菌的確認以及給予適合的抗生素是唯一方針。但即使如此，失明的機會仍然很高。

十四、系統性紅斑狼瘡併抗磷酯症候群(6/1~6/15)

(antiphospholipid syndrome, Hughes syndrome)

Chief complaintA 34 year-old female was admitted to the infectious disease ward because of fever, swelling of bilateral lower legs and a wound on the lateral malleolus of her left foot for more than one week

Past history

1. Drug allergy(-), Food allergy(-)

2. Smoke(-), Alcohol(-)

3. Hypertension(-),DM(-)

4. Surgical intervention(-)

5. Occupation: nil

6. Education: 高職農工

Clinical course:  

· 1994-April: She was admitted to our neurology ward due to incoherent, irrelevant speech and mild fever for 2~3 weeks. Cerebrospinal fluid (CSF) study and immunological data showed normal results. Major depression was suspected

· 1994-May: She was admitted to our ophthalmology ward due to blurred vision. Optic neuritis R/O multiple sclerosis was suspected. But MRI showed ischemic change at left thalamus and bilateral hypothalamus. Vasculitis such as systemic lupus erythematous (SLE) was suspected.

· 2003-April: She was admitted to our neurology ward due to intermittent numbness around the trunk associated with an unstable gait and urinary incontinence for 6 months. Agarose gel electrophoresis of CSF showed oligoclonal bands. The evoked potential response test was abnormal. MRI revealed multiple spinal cord lesions that were consistent with multiple sclerosis involving the spinal cord below C1 level. Multiple sclerosis was diagnosed. She received one course of interferon treatment. The sequelae were paraplegia and nearly total blindness. She lost to follow-up for more than 2 years and received herb drug treatment intermittently.

· 2005-September: She got a wound on the lateral malleolus of left foot accidentally, then fever and swelling of bilateral lower legs developed. She was admitted to a local hospital due to suspected cellulitis. However after receiving antibiotics for three days, the fever persisted and the lower leg edema aggravated. Hence she was referred to our infectious disease department for further treatment.

Physical examinationConsciousness: clear, E4V5M6Vital sign: BT:37.8, BP:112/70mmHg, RR: 18/min PR:76/minConjunctiva: not pale sclera: not ictericNeck: supple, LAP(-) , JVE(-), goiter(-)Chest: symmetric expansion,   BS: decrease over bilateral lungs   HS: regular heart rate, Gr II/VI Systolic murmur over LLSBAbdomen: soft & obese   L/S: impalpable    Shifting dullness(-)   No tenderness, no rebound painExtremities: paraplegia(+) but only light touch sensation(+), pain sensation(-)   pitting edema of bilateral lower legs and feet(+)   a wound on the lateral malleolus of left foot: erythema(+), local heat (+), yellow   discharge with foul odor(+)   Palpable inguinal LAPs(-)

Laboratory data 

· WBC: 2830 Hb:11.1 MCV: 92.3 Platelet:140000 ESR: 96mm/1h

· Urine protein(-) OB(-) sugar(-) RBC: 0-2/HPF, WBC: 2-5/HPF, Epi: 5-10/HPF

· Stool OB(-)

· TP: 6.5, albumin: 2.5, GOT:31, GPT:15, LDH: 149, BUN: 20, Cr:1.47, Na: 138, K: 4.8, CL: 107, AC sugar: 87, Cholesterol: 134, TG: 224, UA: 10.02

· CRP: 17.5 D-dimer: <324 mg/dl

· S-iron: 47 mg/dl, UIBC: 143 mg/dl, Ferritin: 393.5 mg/dl

· Immunological data: as the following table

 

1994-03

2003-04

2005-09

ANA

-

-

>1:2560

Anti-DS-DNA

-

-

>400

RA factor

14.1

139

167

VDRL

-

-

-

LE cell

-

-

 

C3

 

94

22.8

C4

 

11.6

5.67

IgG

1510

 

3370

IgA

 

 

328

IgM

 

 

101

PT

 

11.5/12.3

11.1/11.1

INR

 

0.88

0.94

PTT

 

31.6/27.1

30.2/29.1

aCL IgG

 

 

+ (79)

LAC

 

 

<1.2

Anti-Ro

 

 

(+) (>240)

Anti-La

 

 

(-)

Anti-Sm

 

 

(+) (>120)

Anti-RNP 

 

 

(+)(>240)

Anti-Jo-1

 

 

(-)

Anti-Scl-70

 

 

(-)

Chest PA: cardiomegaly R/O pericardial effusion,                                       R/O pleural effusion

Cardiac echo

· Moderate pericardial effusion

· Moderate TR

· Pulmonary hypertension

Classification criteria of SLE that this patient met:

1. ANA(+)

2. Oral ulcer(-)

3. Malar rash(-)

4. Discoid rash(-)

5. Photosensitivity(-)

6. Serositis(+)

7. Renal disorder (-): urine protein(1+)

8. Neurological disorder(+)

9. Hematological disorder: WBC 2830

10. Immunological disorder: anti-DS-DNA(+) anti-Sm(+), anti-phospholipid Ab(+)

11. Arthritis(+)

Final diagnosis: 

1. Systemic lupus erythematosus with CNS involvement

2. Antiphospholipid syndrome

< Analysis>

      多發性硬化症，被認為是一種侵犯神經系統的自體免疫疾病。其特徵是發炎、去髓鞘化 (demyelination)、及gliosis。病人的症狀可能緩解、復發或者持續的惡化。

      多發性硬化症和大多數自體免疫疾病一樣，女性居多，男女比約一比二，好發年齡約20~40歲。病人的血中可能存在一些對抗髓鞘抗原的自體抗體，例如anti-MOG抗體(myelin oligodendrocyte glycoprotein)。臨床症狀的出現可能是abrupt或insidious。

      多發性硬化症的臨床症狀包括肌肉無力、運動之後肌肉更無力、甚至伴隨著pyramidal signs例如spasticity、hyperreflexia 及Babinski's sign。此外還有ataxia、視神經炎、視力減退、複視、感覺神經異常或喪失、眩暈、膀胱及大腸功能失常導致無法解尿、尿失禁或便秘等等。

表一：Initial symptoms of MS

Symptom

Percent of cases

Symptom

Percent of cases

Sensory loss

37

Lhermitte

3

Optic neuritis

36

Pain

3

Weakness

35

Dementia

2

Paresthesias 

24

Visual loss

2

Diplopia

15

Facial palsy

1

Ataxia

11

Impotence

1

Vertigo

6

Myokymia

1

Paroxysmal attacks

4

Epilepsy

1

Bladder

4

Falling

1

Source: Harrison's principles of internal medicine 16th ed. P2462.

表二則是多發性硬化症的診斷標準，目前MRI已是診斷多發性硬化症必備的檢查工具。

表二：Diagnostic criteria for MS

1. Examination must reveal objective abnormalities of the CNS.

2. Involvement must reflect predominantly disease of white matter long tracts, usually including (a) pyramidal pathways, (b) cerebellar pathways, (c) medial longitudinal fasciculus, (d) optic nerve, and (e) posterior columns.

3. Examination or history must implicate involvement of two or more areas of the CNS.

a. MRI may be used to document a second lesion when only one site of abnormality has been demonstrable on examination. A confirmatory MRI must have either four lesions involving the white matter or three lesions if one is periventricular in location. Acceptable lesions must be >3 mm in diameter. For patients older than 50 years, two of the following criteria must also be met: (a) lesion size>5mm, (b) lesions adjacent to the bodies of the lateral ventricles, and (c) lesions present in the posterior fossa.

b. Evoked response testing may be used to document a second lesion not evident on clinical examination.

4. The clinical pattern must consist of (a) two or more separate episodes of worsening involving different sites of the CNS, each lasting at least 24 h and occurring at least one month apart, or (b) gradual or stepwise progression over at least 6 months if accompanied by increased IgG synthesis or two or more oligoclonal bands. MRI may be used to document dissemination in time if a new T2 lesion or a Gd-enhancing lesion is seen or more months after a clinically isolated syndrome.

5. The patient's neurologic condition could not better be attributed to another disease.

Diagnostic categories

1. Definite MS: All five criteria fulfilled.

2. Probable MS: All five criteria fulfilled except (a) only one objective abnormality despite two symptomatic episodes or (b) only one symptomatic episodes despite two or more objective abnormalities.

3. At risk for MS: Criteria 1, 2, 3, and, 5 fulfilled; patient has only one symptomatic episode and one objective abnormality.

      抗磷酯症候群(antiphospholipid syndrome, Hughes syndrome)於1983首先由英國G.R.V. Hughes教授所描述，例經多年研究及國際會議討論，於1999年提出抗磷酯症候群的preliminary classification criteria，如附表：(Arthritis Rheum 42: 1309, 1999)

      抗磷酯症候群因是否伴隨其他自體免疫疾病之有無而分為原發性及次發性，次發性抗磷酯症候群經常伴隨著系統性紅斑狼瘡。其臨床特徵主要是靜脈或動脈血栓或流產及血中有存在抗磷酯抗體。臨床症狀依血栓發生部位而有不同症狀，例如腦中風、肺栓塞、腸子壞死、急性腎衰竭、急性心肌梗塞等等，除此之外有些病人還會出現網狀青斑(livedo reticularis)、自體免疫溶血性貧血、舞蹈症、肺動脈高壓、心臟瓣膜病變引起心衰竭等，實驗室檢查除了抗磷酯抗體外，有時可看到血小板低下、抗核抗體陽性、抗去氧核糖核甘酸抗體陽性、蛋白尿、VDRL陽性等。本病例抗磷酯抗體IgG高達79 GPL/ml，因此病患可能合併有次發性抗磷酯症候群。不過依據歐洲1000位抗磷酯症候群病人的統計資料，抗磷酯症候群較少發生myelopathy (0.4%)及視神經病變 (0.1%)。

      系統性紅斑狼瘡併中樞神經系統侵犯，主要分為神經(neurological)及精神 (psychiatric)兩方面，臨床症狀包括癲癇、頭痛、腦中風、腦出血、胡言亂語等等，此外有時會引起tranverse myelitis，造成paraplegia，甚至呼吸衰竭。

      本例剛開始因視神經炎被懷疑是多發性硬化症，事實上很多自體免疫疾病例如系統性紅斑狼瘡、修格連症候群等都可能引起視神經炎。因此必須從實驗室檢查的結果及長期追蹤病程才能確定病人的診斷。

      多發性硬化症、抗磷酯症候群及系統性紅斑狼瘡併中樞神經系統侵犯等三種病，其臨床症狀非常相似，很難鑑別診斷。G.R.V. Hughes教授等學者於2005年於Rheumatology這本雜誌發表了一篇文章，探討三者之間的差異，其結論如附表：(Rheumatology 44:434-442, 2005)

MS: multiple sclerosis PAPS: primary antiphospholipid syndrome NPLE/APS: neuropsychiatric lupus with/without APS

十五、阻塞性細支氣管炎合併器質化肺炎 (7/1~7/15)

主訴(Principal Description):

Dry cough with intermittent fever and progressive dyspnea for 1 month

病史(Brief History):

The 27-year-old man was a previously healthy student. He suffered from traumatic fracture of right fibula and tibia in a traffic accident 2 months ago and received only traditional bone manipulation. About 1 month ago, he began to develop a dry cough. Fever occurred several days later but there was only mild dyspnea. He visited the ER of a medical center in Taipei on April 8th, 2005. He did not have myalgia, anorexia or diarrhea. The CxR revealed bilateral interstitial infiltrates. The WBC count was 21600, with 84% of neutrophils. He was then admitted and antibiotics (Augmentin and Zithromax) were given. His fever gradually subsided and cough almost resolved, but the CxR lesions did not improve. The sputum acid-fast staining was negative. He was discharged on April 13 and continued to take oral antibiotic (levofloxacin). Nine days after discharge, however, fever relapsed and he was sent back to the ER. Some IV antibiotics were administered and the fever subsided in 2 days. Unfortunately, his cough and fever recurred on May 1. The CxR showed diffuse reticular pattern, especially in the right upper lung field. Morxifloxacin was given, and fever subsided in 2 days and his cough also improved. However, progressive dyspnea developed after discharge. It progressed rapidly in 3-4 days, and nonproductive cough also worsened. He went to the ER in another medical center on May 6 where mild hypoxemia was found. The CxR (Figure 1) and Chest CT