# 108年內專(101-150題)

## Question 101:

一位76歲婦女因社區感染肺炎住院，接受氧氣補充，注射 ceftriaxone和azithromycin 共3天，血液及痰液培養均無細菌長出。她感覺比較舒服，食慾良好，咳嗽及呼吸急促都改善了，在住院第2天就退燒了。她沒有其他共病。身體 診察體溫37.8°C，血壓 120/74 mmHg，心跳90/min，呼吸18/min，未額外給氧氣 時氧飽和度為94%。她呼吸平穩，聽診兩側肺基底呼吸聲降低，叩診無濁音 (dullness)，心臟診察無特殊發現，雙下肢無水腫，實驗室檢查周邊血白血球 13000/cumm(入院時18000/cumm)，生化值正常。 請問下列最合適之抗生素治療 為何者?

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- A.持續ceftriaxone注射治療。
- B.改成口服抗生素並出院。
- C.改成口服抗生素並觀察 24小時。
- D.改成口服抗生素並與注射抗生素重疊 24小時。
- E.停用抗生素並出院。

### Correct Answer: B

**COMMUNITY-ACQUIRED PNEUMONIA**
Selecting antibiotic therapy
U.S. guidelines always target S. pneumoniae and atypical pathogens. Retrospective data suggest that this approach lowers the mortality rate.
Pts initially treated with IV antibiotics can be switched to oral agents when they can ingest and absorb drugs, are hemodynamically stable, and are improving clinically.
A 5-day course of a fluoroquinolone is sufficient for cases of uncomplicated CAP, but a longer course may be required for pts with bacteremia, metastatic infection, or infection with a particularly virulent pathogen (e.g., P. aeruginosa, community-acquired MRSA).
Fever and leukocytosis usually resolve within 2–4 days. Pts who have not responded to therapy by day 3 should be reevaluated, with consideration of alternative diagnoses, antibiotic resistance in the pathogen, and the possibility that the wrong drug is being given.

VS comment：
個人覺得題目是在考合理的降階。一般還會看一下 X-ray。 CAP 要 cover typical infection 就ATS 的 guideline 來說三個選擇： 1） Levofloxacin 單用 2) beta-lactam + macrolide 3) betalactam。如果病人有 organic heart disease 擔心 QT prolongation 就選加 doxycyline。病人不能口服的話實務上可以給 tigecycline。

延伸閱讀：
**Microbiology**
Although many bacteria, viruses, fungi, and protozoa can cause CAP, most cases are caused by relatively few pathogens. In >50% of cases, a specific etiology is never determined. Of CAP cases, 10–15% are polymicrobial and involve a combination of typical and atypical organisms.
Typical bacterial pathogens:
• S. pneumoniae, Haemophilus influenzae, Staphylococcus aureus, and gram-negative
bacteria such as Klebsiella pneumoniae and Pseudomonas aeruginosa.
• The incidence of pneumococcal pneumonia is decreasing because of the increasing use of
pneumococcal vaccines.

Atypical organisms:
• Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella spp., and respiratory viruses
(e.g., influenza viruses, adenoviruses, human metapneumovirus, respiratory syncytial viruses).
• A virus may be responsible for a large proportion of CAP cases that require hospital
admission, even in adults.
• The incidences of cases due to M. pneumoniae and C. pneumoniae are increasing,
particularly among young adults.
Involvement of anaerobes: only when aspiration precedes presentation by days or weeks, often results in significant empyemas.

**Deciding whether to hospitalize pts**
• Pneumonia Severity Index (PSI): Points are given for 20 variables, including age,
coexisting illness, and abnormal physical and laboratory findings. On this basis, pts are
assigned to one of five classes of mortality risk.
• CURB-65: Five variables are included: confusion (C); urea >7 mmol/L (U); respiratory
rate ≥30/min (R); blood pressure, systolic ≤90 mmHg or diastolic ≤60 mmHg (B); and age
≥65 years (65). Pts with a score of 0 can be treated at home, pts with a score of 1 or 2 (not
counting any point given for age ≥65 years) should be hospitalized, and pts with a score of
≥3 may require management in the ICU.

Empirical Antibiotic Treatment of Community-Acquired Pneumonia
**Outpatients**
1. Previously healthy and no antibiotics in past 3 months
o A macrolide (clarithromycin [500 mg PO bid] or azithromycin [500 mg PO once,
then 250 mg qd]) or
o Doxycycline (100 mg PO bid)
2. Comorbidities or antibiotics in past 3 months: select an alternative from a different class
o A respiratory fluoroquinolone (moxifloxacin [400 mg PO qd], gemifloxacin [320
mg PO qd], levofloxacin [750 mg PO qd]) or
o A β-lactam (preferred: high-dose amoxicillin [1 g tid] or amoxicillin/clavulanate [2
g bid]; alternatives: ceftriaxone [1–2 g IV qd], cefpodoxime [200 mg PO bid], or
cefuroxime [500 mg PO bid]) plus a macrolidea
3. In regions with a high rate of “high-level” pneumococcal macrolide resistance,b consider alternatives listed earlier for pts with comorbidities.
**Inpatients, Non-ICU**
• A respiratory fluoroquinolone (e.g., moxifloxacin [400 mg PO or IV qd] or levofloxacin
[750 mg PO or IV qd])
• A β-lactamc (e.g., ceftriaxone [1–2 g IV qd], ampicillin [1–2 g IV q4–6h], cefotaxime [1–2 g
IV q8h], ertapenem [1 g IV qd]) plus a macrolided (e.g., oral clarithromycin or azithromycin
as listed earlier or IV azithromycin [1 g once, then 500 mg qd])
**Inpatients, ICU**
• A β-lactame (e.g., ceftriaxone [2 g IV qd], ampicillin-sulbactam [2 g IV q8h], or cefotaxime [1–2 g IV q8h]) plus either azithromycin or a fluoroquinolone (as listed earlier for inpatients, non-ICU)
**Special Concerns**
If Pseudomonas is a consideration:
• An antipseudomonal β-lactam (e.g., piperacillin/tazobactam [4.5 g IV q6h], cefepime [1–2 g IV q12h], imipenem [500 mg IV q6h], meropenem [1 g IV q8h]) plus either ciprofloxacin (400 mg IV q12h) or levofloxacin (750 mg IV qd)
• The earlier β-lactams plus an aminoglycoside (amikacin [15 mg/kg qd] or tobramycin [1.7 mg/kg qd]) plus azithromycin
• The earlier β-lactamsf plus an aminoglycoside plus an antipneumococcal fluoroquinolone
If CA-MRSA is a consideration:
• Add linezolid (600 mg IV q12h) or vancomycin (15 mg/kg q12h initially, with adjusted
doses) plus clindamycin (300 mg q6h)

資料來源：
Harrison
Chapter 134: Pneumonia, Bronchiectasis, and Lung Abscess

## Question 102:

一位83歲男性，因為尿路感染併菌血症而住進加護病房。三天前他因為間斷性神智混亂、虛弱，解尿疼痛和血尿被送到急診，因為血流動力情況不穩而入住加護 病房，剛開始接受靜脈輸液，經驗性 meropenem。三天後低血壓和發燒都緩解， 身體診察體溫37.6°C，血壓 120/80 mmHg，心跳 94/min，呼吸18/min，心臟診察 正常，腰側和腹部無壓痛，尿液培養 Enterococcus faecalis 大於100000菌落，而 184 血液培養也是E. faecalis，抗生素感染性試驗對 ampicillin，vancomycin和 gentamicin具敏感性。 請問此時下列哪一項抗生素治療是適當的?

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- A.改成ampicillin
- B.改成ampicillin 和gentamicin
- C.改成vancomycin
- D.改成vancomycin和 gentamicin
- E.繼續使用meropenem

### Correct Answer: A

**Enterococcal Infections**
• Given low cure rates with β-lactam monotherapy, combination therapy with a cell wall–active agent (a β-lactam or a glycopeptide) plus gentamicin or streptomycin is recommended for serious enterococcal infections. High-level resistance to aminoglycosides (i.e., MICs of >500 and >2000 µg/mL for gentamicin and streptomycin, respectively) abolishes the synergism otherwise obtained by the addition of an aminoglycoside to a cell wall–active agent. This phenotype must be assessed in isolates from serious infections.

**VS comment**：
Ampicillin 有效可以用單方 amicillin、感染嚴重的話用 ampicillin+gentamicin 或是
ampicillin+ceftriaxone。其他如補充資料： teicoplanin, linezolid

資料來源：
Harrison
Chapter 90: Streptococcal/Enterococcal Infections, Diphtheria, and Infections Caused by Other
Corynebacteria and Related Species
Chapter 147: Dysuria, Urinary Tract Infections, Bladder Pain, and Interstitial Cystitis

## Question 103:

一位60歲男性因腹瀉和發燒3天而來就診，他沒有腹痛或嘔吐，糞便混有黏液，但沒有看到血便，他感覺疲勞和食慾變差，他從事市場工作。身體診察體溫 38°C，血壓146/68 mmHg，心跳82/min，呼吸22/min，腹部診察腸音增強，整個 腹部有輕微壓痛。實驗室檢查周邊血白血球 11400/mm^3，糞便有潛血反應。他接 受糞便培養及經驗性抗生素 levofloxacin 3 天後，糞便培養呈現 Campylobacter jejuni，對levofloxacin 有抗藥性。他來門診複查時，感覺病已好，腹瀉及發燒都已緩解。請問這時最適當的處理是?

---

- A.停levofloxacin
- B.採血液培養
- C.再採集糞便培養
- D.改成azithromycin
- E.改成ciprofloxacin

### Correct Answer: A

**CAMPYLOBACTERIOSIS**
Treatment
• Fluid and electrolyte replacement are the mainstay of therapy.
• Use of antimotility agents is not recommended, as they are associated with toxic megacolon.
• Antibiotic treatment (azithromycin, 500 mg PO daily for 3 days or 1000 mg PO given as a single dose) should be reserved for pts with high fever, bloody or severe diarrhea, persistence for >1 week, and worsening of symptoms. Fluoroquinolones are an alternative choice, although resistance to fluoroquinolones is increasing.

**VS comment：**
Campylobacter jejuni 如果沒有菌血症、 sepsis，可以停抗生素。

延伸閱讀：
**Microbiology**
Campylobacters are motile, curved gram-negative rods that are a common bacterial cause of gastroenteritis in the United States. Most cases are caused by Campylobacter jejuni.
**Epidemiology**
Campylobacters are common commensals in the GI tract of many food animals and household pets. In developed countries, ingestion of contaminated poultry accounts for 30–70% of cases. Transmission to humans occurs via contact with or ingestion of raw or undercooked food products or direct contact with infected animals.
**Clinical Manifestations**
An incubation period of 2–4 days (range, 1–7 days) is followed by a prodrome of fever, headache, myalgia, and/or malaise. Within the next 12–48 h, diarrhea (with stools containing blood in ∼10% of cases in adults), cramping abdominal pain, and fever develop.

• Most cases are self-limited, but illness persists for >1 week in 10–20% of pts and may be confused with inflammatory bowel disease.
• Species other than C. jejuni (e.g., C. fetus) can cause a similar illness in normal hosts or
prolonged relapsing systemic disease without a primary focus in immunocompromised pts.
o The course may be fulminant, with bacterial seeding of many organs, particularly vascular sites.
o Fetal death can result from infection in a pregnant pt.
• Three patterns of extraintestinal infection have been noted:
(1) transient bacteremia in a normal host with enteritis (benign course, no specific treatment needed);
(2) sustained bacteremia or focal infection in a normal host; and
(3) sustained bacteremia or focal infection in a compromised host.
• Complications include reactive arthritis (particularly in persons with the HLA-B27 phenotype) and Guillain-Barré syndrome (in which campylobacters are associated with 20–40% of cases).

資料來源：
Harrison
Chapter 85: Infectious Diarrheas and Bacterial Food Poisoning

## Question 104:

一位60歲女性因為呼吸急促和腳腫於 1天前被送到急診室，臨床判斷為失償性(decompensated)心衰竭，她接受導尿管置放，靜脈注射給予利尿劑並住院。她有高 血壓、糖尿病和慢性腎病等潛在疾病。她所使用的藥物包括 aspirin，carvedilol， insulin，lisinopril，rosuvastatin，spironolactone和視需要用 furosemide。身體診察體 溫36.5°C，血壓128/72 mmHg，心跳96/min，呼吸 18/min，聽診肺部雙側基底有 囉音，心音有S3，二側下肢有第二度水腫，由尿管流出的尿液是清澈的，實驗室 檢查血清Creatinine 2.8 mg/dL。 請問此時對病人導尿管最恰當的處理為何?

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- A.三天後拔導尿管
- B.換一支導尿管
- C.拔掉導尿管
- D.當腎功能回復到病人基礎值時拔導尿管
- E.等出院再拔導尿管

### Correct Answer: C

Beyond association with urinary tract infection and the attendant complications, inappropriate use of indwelling catheters has been associated with increased mortality, further highlighting the importance of catheter removal when it is no longer needed.

資料來源：
UpToDate
Placement and management of urinary bladder catheters in adults

## Question 105:

近年又興起麻疹群聚疫情，相關敘述請選出最正確之組合。
(1)傳統初次感染麻疹的臨床表現包括全身性皮膚斑丘疹，發燒 38.3°C 以上，以及coryza，cough 或 conjunctivitis，而曾施打過疫苗者得到麻疹則症狀常呈現不典型
(2)麻疹迄今並無 抗病毒藥物可治療，臨床處理採支持性治療如水份和退燒藥。而 vitamin A 治療可 降低麻疹morbidity 和 mortality
(3)麻疹嚴重合併症包括病毒直接侵犯呼吸道及續 發性細菌感染造成肺炎或中耳炎。極嚴重的腦脊髓炎發生率約為千分之一
(4)醫護人員若10至15年內有打過 MMR 疫苗，在未防護情況暴露到帶病毒量較高的 免疫抑制患者，不必擔心遭受感染
(5)急性 IgM 若呈陰性，也不可排除感染，而 鼻咽拭子PCR 檢測之陽性率會更高。

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- A.(1)+(3)+(5)
- B.(1)+(2)+(3)
- C.(1)+(2)+(3)+(4)
- D.(1)+(2)+(3)+(5)
- E.(1)+(2)+(3)+(4)+(5)

### Correct Answer: D

(1)(5)麻疹可由典型的病史及症狀診斷。 惟過去曾接種含麻疹之活性疫苗（Measles vaccine,MMR vaccine）的麻疹病毒感染者，急性期麻疹 IgM 抗體可能出現陰性，且其臨床病徵可能不典型需與德國麻疹、微小病毒 B19、或腺病毒等感染作鑑別診斷。因此，除進行血清抗體檢測外，採集尿液及鼻咽檢體進行病原體分子診斷及病毒培養，為現今診斷麻疹感染的重要實驗室診斷依據，且有助於病毒感染源追溯、群聚關聯比對與疫苗株感染的確認。

**DIAGNOSIS**
The characteristic rash and pathognomonic Koplik’s spots permit a clinical diagnosis.
⚫ Serologic testing is the most common method of laboratory diagnosis. Measles-specific IgM is usually detectable within 1–3 days of rash onset.
⚫ Viral culture and reverse-transcription PCR analysis of clinical specimens are used occasionally to detect measles.
**CLINICAL MANIFESTATIONS**
Approximately 10 days after infection with measles virus, pts develop fever and malaise, followed by cough, coryza, and conjunctivitis; the characteristic rash occurs 14 days after infection.
⚫ An erythematous, nonpruritic, maculopapular rash begins at the hairline and behind the ears,spreads down the trunk and limbs to include the palms and soles, can become confluent, and begins to fade (in the same order of progression) by day 4.
⚫ Koplik’s spots are pathognomonic for measles and consist of bluish-white dots ∼1 mm in diameter surrounded by erythema. They appear on the buccal mucosa ∼2 days before the rash appears and fade with the onset of rash.
⚫ Pts with impaired cellular immunity may not develop a rash and have a higher case–fatality rate than those with intact immunity.
⚫ Complications include giant-cell pneumonitis, secondary bacterial infection of the respiratory tract (e.g., otitis media, bronchopneumonia), and CNS disorders.
◼ Postmeasles encephalitis occurs within 2 weeks of rash onset in ∼1 in 1000 cases and is
characterized by fever, seizures, and a variety of neurologic abnormalities.
◼ Measles inclusion-body encephalitis (MIBE) and subacute sclerosing panencephalitis (SSPE) occur months to years after acute infection and are caused by persistent measles virus infection.
◆ MIBE is a fatal complication that primarily affects pts with defects in cellular
immunity.
◆ SSPE is a progressive disease characterized by seizures and deterioration of
cognitive and motor functions, with death occurring 5–15 years after measles virus
infection

延伸閱讀：
衛生福利部傳染病防治諮詢委員會「預防接種組」建議 1981 年（含）以後出生之醫療照
護工作人員，若不具有麻疹或德國麻疹免疫力，補接種 1 劑 MMR。判斷對麻疹及德國麻疹
具有免疫力的操作型條件如下：
(一) 曾經由實驗室診斷確認感染麻疹及德國麻疹者；或
(二) 至少曾注射過 2 劑麻疹、德國麻疹疫苗，且有疫苗接種紀錄者（須為出生滿 1 歲後曾
經注射過 2 劑含麻疹及德國麻疹的活性減毒疫苗，且 2 劑間隔 28 天以上，且最後一劑疫
苗接種距今<15 年）；或
(三) 具有麻疹、德國麻疹抗體檢驗陽性證明，且檢驗日期距今<5年

資料來源：
衛生福利部疾管局 – 麻疹防治手冊
https://www.cdc.gov.tw/File/Get/awThBLxVjvWdoVvmYFhwCw
Harrison
Chapter 104: Rubeola, Rubella, Mumps, and Parvovirus Infections

## Question 106:

有關登革熱的描述，最正確的組合為下列何者? (1)發疹約在頭痛、發燒第4至第7日，從軀幹散至頭部及四肢。 (2)發疹次序和麻疹類似。 (3)皮疹出現時，血 小板、白血球數目約降至最低點，而後再逐漸回升。 (4)皮疹初發顏色較潮紅， 而後漸暗消退，約4-7 天才消失。 (5)約有50%至90%的病人感染症狀不明顯。

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- A.(1)+(2)+(3)+(4)
- B.(1)+(3)+(4)+(5)
- C.(1)+(2)+(3)+(4)+(5)
- D.(3)+(4)+(5)
- E.(1)+(2)+(3)

### Correct Answer: B

(2) 麻疹典型的斑丘疹出現於耳後，再擴散至整個臉面，然後在第 2 天至第 3 天會慢慢向下移至軀幹和四肢；登革熱皮疹主要在四肢，病程中間會出現 white islets 是最特別的地方。
**登革熱皮疹及病理變化**
登革熱如同天花、麻疹、德國麻疹、水痘皆是具有特殊皮疹變化的病毒感染。 臨床上除發燒、頭痛、關節酸痛、腸胃不適外，伴隨有皮疹的出現，約在高燒後 4∼7 天，於四肢末端出現彌漫性紅斑及出血性丘疹，逐漸往手臂大腿蔓延，軀幹皮膚亦可出現。在施加外壓時，紅色小紅丘疹不會消褪，此點有別於麻疹、德國麻疹之紅色斑疹。此外病人手掌、腳掌出現紅斑輕度腫脹，手掌緊蹦感，掌心搔癢，其刺痛亦是一重要特徵。 一般在皮疹開始出現時，血小板、白血球數目約下降至最低點，而後逐漸回昇。 皮疹初發時，較為潮紅，伴隨不同程度的搔癢， 隨時間皮疹慢慢轉為暗紅、暗褐色，而逐漸消失，最後可能會留下輕微的色素沈著。皮疹依嚴重程度不同，約須 4∼7 天才會消失。 登革熱皮疹的主要病理變化，主要為真皮上層血管的擴張，內皮細胞輕微水腫，血管週圍中等程度淋巴球浸潤，出現細胞核碎片，紅血球自血管內外溢，血管壁無纖維蛋白變性，表皮無特殊變化，直接免疫螢光法檢查不會看到抗體、補體或纖維蛋白的沈積。

延伸閱讀：
登革熱在眼科的臨床表徵
登革熱的眼部表徵在文獻上很少提及，可能是由於其變化相當輕微而且恢復極快，所以容易被忽略。 登革熱在眼科的致病機轉可能可以分為兩大類，其中之一是病毒本身造成感染引起的發炎，從最表面的結膜炎到最深層的視神經炎等，都有可能發生。另外就是出血的問題，可能是病毒活化了單核細胞，使其釋出許多特質如蛋白酶、組織胺、血栓形成因子，使得血管通透性改變，而容易出血。從最表層的結膜到最深層的視網膜，都可以有出血的情形。 登革熱的眼睛徵兆有下列之情形：眼瞼腫脹、結膜充血、結膜炎、視網膜及玻璃體出血等，在疾病初期容易有眼球及眼球後之疼痛。一般而言治療效果很好，病人預後良好。切記不要濫用類固醇，以免不良副作用所造成的傷害。

登革熱對懷孕之影響
懷孕罹患登革熱時臨床上須考慮下列幾點重要事項：
1) 登革病毒對胎兒是否有 teratogenic effect？關於此點，據我們的查證到目前為止，世界上的文獻還未有完整的報告，故實際情況尚待往後的研究結果。然而母體的登革病毒抗體可經由胎盤傳給胎兒，故胎兒生下後若不幸感染登革病毒的話，極易形成dengue hemorrhagic fever (DHF)或 dengue shock syndrome (DSS)之嚴重疾病則已被證實。換句話說，曾經罹患過登革熱的母親，其生下的嬰兒須盡可能的避免登革病毒的感染。
2) 治療登革熱之藥物對胎兒是否有 teratogenic effect？ aspirin 及 indomethacin 已被證實有致畸形及 bleeding diathesis 作用，故懷孕時須極力避免使用。而 acetaminophen則被認為是較安全的解熱鎮痛劑。
3) 登革熱是否可造成流產或胎兒子宮內發育遲緩？根據我們的經驗及超音波檢查的結果，若是典型登革熱的話，目前的答案是否定的。
4) 宿主的免疫狀態被認為是決定登革熱之臨床過程及導致 DHF/DSS 與否的主要因素之一。而懷孕的母親其特異的與非特異的免疫能力均受到抑制，故懷孕罹患登革熱時須注意 DHF/DSS 或二次感染的發生。

登革熱病人之肝膽變化
噁心、嘔吐 、腹脹、腹痛、腹瀉為登革熱的主要腸胃道症狀，其表現與急性肝炎類似。大多數的病人在第三天起 GOT、 GPT 開始輕度或中度上昇，且 SGOT 較高。進入恢復期後，即漸漸回復正常沒有後遺症。臨床上表現噁心、嘔吐、腹脹、 腹痛、腹瀉，但無黃疸出現。超音波所見大部分正常，部份右上腹痛者可見膽囊壁肥厚，症狀消失後恢復正常，是急性肝炎所見影像相符，需謹慎的與膽囊炎及胰臟炎做鑑別診斷。

治療
本病的治療有三個原則：第一是臥床休息，第二是解熱和鎮痛，第三是適當地補充體液。罹患登革熱的痛苦是刻骨銘心的，再加上極度的疲勞，臥床休息是必需的。解除或減輕肢體的痛苦當然得靠解熱和鎮痛劑。不可使用阿斯匹靈以及非類固醇抗發炎藥物(NSAIDS)，否則將引起出血，加重病情。體液的補充在典型登革熱只要多喝水，保持不口渴即可，若有出血、休克、或脫水現象時，則以靜脈輸液為宜，大量出血時，應輸血治療。至於類固醇的使用，對登革熱治療沒有幫助。

資料來源：
https://osa.kmu.edu.tw/images/s_hs/f_hc/d_m.pdf

## Question 107:

有效降低中心靜脈導管感染的組合式方法已經在先進國家得到驗證，其中包括: (1)手部衛生，選擇適當置入部位 (2)使用2% chlorhexidine消毒劑消毒皮膚 (3)最大無 菌面防護 (4)每日評估儘早拔除不需要之導管 (5)組套式的供應包或置放車，採 checklist 以確定每一步驟之遵從。

---

- A.(1)+(2)+(4)
- B.(1)+(3)+(4)
- C.(1)+(3)+(4)+(5)
- D.(1)+(2)+(3)+(4)+(5)
- E.(1)+(2)+(3)+(4)

### Correct Answer: D

「組合式照護措施」 (care bundle)的概念首先由 John Hopkins University Dr. Peter Pronovost所提出，他與美國密西根州醫院協會(Michigan Health & Hospital Association, MHA)合作進行的 Keystone ICU project，在全州 103 個 ICU 推行美國疾病控制與預防中心(CDC)所建議之具實證結果的 5 項措施，包含選擇適當的置入部位(optimal catheter site selection)、手部衛生(hand hygiene)、選擇適當且有效的皮膚消毒劑(chlorhexidine skin antisepsis)、最大無菌面防護(maximal sterile barrier precautions)及每日評估是否拔除導管(daily review of line necessity)，檢視其對控制中心導管相關血流感染發生的成效。

資料來源：
中心導管組合式照護工作手冊 - 衛生福利部疾病管制署 編著・出版
https://www.cdc.gov.tw/Uploads/files/201511/b210316a-c7d5-4931-896c-850f352940cb.pdf

## Question 108:

手部衛生是預防院內交叉感染最有效之方法，有關酒精性乾洗手之描述，下列何者正確? (1)手部有明顯弄髒或血液汙染不可使用，應採洗手乳濕洗手 (2)在接觸病人 或旁邊環境前後使用 (3)病房有Clostridium difficile 群聚感染時使用 (4)腸病毒流行 時使用 (5)大部分的情況皆可使用。

---

- A.(1)+(2)+(5)
- B.(1)+(2)+(3)+(5)
- C.(1)+(2)+(4)+(5)
- D.(1)+(2)+(3)+(4)+(5)
- E.(2)+(3)+(4)+(5)

### Correct Answer: A

Clostridium 會有 spore，腸病毒沒有 envelope，酒精無效。
(4) 腸病毒消毒方法：
⚫ 腸病毒對酸及許多化學藥物具抵抗性，如抗微生物製劑、清潔消毒劑及酒精，均無法殺死腸病毒。
⚫ 醛類、鹵素類消毒劑（如市售含氯漂白水）可使腸病毒失去活性。
⚫ 腸病毒於室溫可存活數天，4℃可存活數週，冷凍下可存活數月以上，但在 50℃以上的環境，很快就會失去活性，所以食物經過加熱處理，或將內衣褲浸泡熱水，都可減少腸病毒傳播。
⚫ 乾燥可降低腸病毒在室溫下存活的時間。
⚫ 紫外線可降低病毒活性。

延伸閱讀：
手部衛生執行原則
(一) 當手部有明顯髒污或沾有血液/體液時，建議使用濕洗手。
(二) 若確定或懷疑可能暴露於具產芽孢能力的病原體(spore-forming pathogens)，包括困難梭狀桿菌(Clostridium difficile)等，建議使用濕洗手
(三) 前述適用情形下，當手部沒有明顯髒污的時候，建議優先使用酒精性乾洗手執行手部衛生。
(四) 進行費時較長的侵入性治療前，如胸部穿刺引流，放置中心靜脈導管等，建議使用酒精性乾洗手液或具去污作用的手部消毒劑和清水清潔雙手。
(五) 避免同時使用肥皂和酒精性乾洗手液。
(六) 上完廁所後，建議使用濕洗手。

資料來源：
手部衛生工作手冊 - 衛生福利部疾病管制署 編著・出版
https://www.cdc.gov.tw/Uploads/b00b689f-794f-449b-a1bd-e47400c336fd
腸病毒感染併發重症 - 衛生福利部疾病管制署
https://www.cdc.gov.tw/Category/Page/FgfRlDl6XxDkuqaOghuNfQ

## Question 109:

台灣地區 65 歲以上老人，建議接種疫苗為何? (1)肺炎球菌疫苗 (2)日本腦炎疫苗 (3)流感疫苗 (4)B 型嗜血桿菌疫苗(Hib vaccine) (5)破傷風及減毒白喉混合疫苗(Td)

---

- A.(2)+(3)+(4)
- B.(2)+(3)+(5)
- C.(1)+(2)+(3)
- D.(1)+(3)+(5)
- E.(1)+(3)

### Correct Answer: A


資料來源：
衛生福利部疾病管制署
https://www.cdc.gov.tw/Category/List/7NSDP7_u5whIcOEQHfLthQ

## Question 110:

有關抗生素之描述，下列哪一項不正確?

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- A.Fluoroquinolone 類抗生素在 QTc prolongation 的病人產生心律不整的風險增加
- B.老年人和同時用 steroid 的人使用 fluoroquinolone 會增加 tendinitis 副作用之風險
- C.懷孕婦人不建議使用 streptomycin， tetracycline 或 tigecycline (category D)
- D.使用 ceftriaxone 不可加入含鈣之點滴注射液
- E.Fluoroquinolone 對 MRSA 及 VRE 治療效果良好

### Correct Answer: E

A. Fluoroquinolones can prolong the QT interval by inhibiting cardiac KCHN2 potassium voltagegated channels, potentially leading to torsades de pointes (a life-threatening arrhythmia). When safe and effective alternatives are available, we avoid fluoroquinolone use for patients taking other QTprolonging drugs and patients with long QT syndromes or other significant risk factors for arrhythmia. Available clinical data suggest that, among available fluoroquinolones, moxifloxacin has the highest association with QT interval prolongation, arrhythmia, and cardiovascular mortality, followed by levofloxacin and then ciprofloxacin. Delafloxacin, which came to market in 2018, has not been associated with QT interval prolongation, but clinical experience is limited.

B. Risk factors associated with FQ- induced tendon disorders include age greater than 60 years, corticosteroid therapy, renal failure, diabetes mellitus, and a history of musculoskeletal disorders

C. Aminoglycosides may cause fetal harm if administered to a pregnant woman. There are several
reports of total irreversible bilateral congenital deafness in children whose mothers received another aminoglycoside (streptomycin) during pregnancy. Although serious side effects to the fetus/infant have not been reported following maternal use of all aminoglycosides, a potential for harm exists.

D. Ceftriaxone binds to calcium forming an insoluble precipitate. Fatal precipitation reactions in neonates due to coadministration of calcium-containing solutions have been reported; concurrent use in neonates is contraindicated

E. Fluoroquinolones for Gram-positive organisms – Levofloxacin, moxifloxacin, and delafloxacin are active against certain gram-positive organisms including Staphylococcus aureus, some streptococci, and some strains of coagulase-negative staphylococci. Delafloxacin is also active against methicillin-resistant S. aureus (MRSA), a unique feature among fluoroquinolones. Although some fluoroquinolones have in vitro activity against enterococci, they are generally not used for the treatment of enterococcal infections because achievable serum concentrations are frequently close to the minimum inhibitory concentrations and efficacy data are limited.

資料來源：
A, C, D, E. UpToDate: fluoroquinolone, aminoglycisides, ceftriaxone,
B. The Risk of Fluoroquinolone-induced Tendinopathy and Tendon Rupture
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2921747/pdf/jcad_3_4_49.pdf

## Question 111:

社區性抗藥性金黃色葡萄球菌(Community-acquired MRSA)肺炎感染，近年來有流行率上升的趨勢，下列相關的敘述，何者最不適當?

---

- A.肺部感染較易出現開洞性病灶(Cavitation)或壞死
- B.病人大多為慢性腎功能不全接受血液透析患者(Chronic dialysis)
- C.患者較為年輕，且多半之前健康狀況良好
- D.合併咳血、肌肉痠痛及皮疹
- E.除 oxacillin 抗藥之外，其他多數抗生素具有感受性(susceptible)

### Correct Answer: B

Methicillin-resistant S. aureus (MRSA) is an uncommon cause of CAP. Risk factors for MRSA have two patterns: health care associated and community acquired. The strongest risk factors for MRSA pneumonia include known MRSA colonization or prior MRSA infection, particularly involving the respiratory tract. Gram-positive cocci on sputum Gram stain are also predictive of MRSA infection. Other factors that should raise suspicion for MRSA infection include recent antibiotic use (particularly receipt of intravenous antibiotics within the past three months), recent influenza-like illness, the presence of empyema, necrotizing/cavitary pneumonia, and immunosuppression.
In contrast with health care-associated MRSA, community-acquired MRSA (CA-MRSA) infections tend to occur in younger healthy persons. Risk factors for CA-MRSA infection include a history of MRSA skin lesions, participation in contact sports, injection drug use, crowded living conditions, and men who have sex with men. CAP caused by CA-MRSA can be severe and is associated with necrotizing and/or cavitary
pneumonia, empyema, gross hemoptysis, septic shock, and respiratory failure.

資料來源：
UpToDate
Overview of community-acquired pneumonia in adults

## Question 112:

下列社區性肺炎致病原與宿主因子之配對， 何者最不適當?

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- A.Alcoholism - Streptococcus pneumoniae
- B.Bronchiectasis - Pseudomonas aeruginosa
- C.Post-Influenza illness - Stapylococcus aureus
- D.Exposure to bird - Chlamydia trochomatis
- E.Exposure to sheep - Coxiella burnetii

### Correct Answer: D

A. Risk factors for pneumococcal pneumonia Influenza infection, Alcohol abuse, Smoking, COPD and asthma, Hyposplenism or splenectomy, Immunocompromise and other factors, including homelessness, incarceration, pregnancy, crack cocaine use, opioid use, and welding as an occupation, especially if the welder is a tobacco smoker

B. Pseudomonas is also an uncommon cause of CAP and tends to occur more frequently in patients with known colonization or prior infection with Pseudomonas spp, recent hospitalization or antibiotic use, underlying structural lung disease (eg, cystic fibrosis or advanced chronic obstructive pulmonary disease [bronchiectasis]), and immunosuppression.

C. 見上題

D. Chlamydia trachomatis is the most common bacterial cause of sexually transmitted genital infections. The majority of affected persons are asymptomatic and, thus, provide an ongoing reservoir for infection. In infants born to mothers through an infected birth canal, conjunctivitis and pneumonia can occur. Moreover, both men and women can experience clinical syndromes due to infection at common epithelial sites, including the rectum and conjunctivae. (沙眼、 PID、 UTI 的致病菌)

E. Mammals, birds, and arthropods may be reservoirs for C. burnetii, but the main reservoir is ticks. The most commonly identified sources of human infection are farm animals, such as cattle, goats, and sheep. However, pets, including cats, rabbits, pigeons, and dogs may serve as sources of urban outbreaks of human disease.

資料來源：
UpToDate
Overview of community-acquired pneumonia in adults
Microbiology and epidemiology of Q fever

## Question 113:

一位 30 歲女性，開心搭乘郵輪出遊，但在船上進食後 24 小時左右開始出現發燒、腹痛、腹瀉之症狀，其他同行者也有多人出現腸胃不適，請問下列何者是最可能的致病原?

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- A.Norovirus
- B.Giardia lamblia
- C.Cryptosporidium
- D.Entameoba histolytica
- E.Escherichia coli

### Correct Answer: A

VS comment：
腸胃道的群聚大概猜 1） norovirus 2） rotavirus 3）食物中毒……

解題：
A. 腸胃炎係指胃、小腸或大腸的發炎，會導致病患嘔吐或腹瀉。有多種不同的病毒可導致病毒性腸胃炎，最常見的是輪狀病毒、諾羅病毒及腺病毒。台灣諾羅病毒及輪狀病毒主要流行季節為 11 月到隔年 3 月間，而腺病毒則一整年內都會發生。 輪狀病毒、腺病毒、沙波病毒及星狀病毒好發於 5 歲以下的兒童，輪狀病毒更是引起嬰兒和 5 歲以下幼童腹瀉最常見的原因；而諾羅病毒則是任何年齡層皆可能受到感染。諾羅病毒的爆發流行好發於學校、醫院、軍營、收容及安養機構等人口密集機構，但也常發生在餐廳、大型遊輪、宿舍和露營地等地方。

B. Symptoms usually develop after an incubation period of 7 to 14 days. Onset of acute gastrointestinal symptoms within one week of exposure is not likely attributable to infection with Giardia.

C. Cryptosporidium: Incubation period – In patients who develop symptoms, the incubation period is usually 7 to 10 days (range 2 to 28 days).

D. Clinical amebiasis generally has a subacute onset, usually over one to three weeks

延伸閱讀：
**GIARDIASIS**
**Microbiology and Epidemiology**
Giardia lamblia (also known as G. intestinalis or G. duodenalis) is a protozoal parasite that inhabits the small intestines of humans and other mammals.
⚫ Transmission occurs via the fecal–oral route, by ingestion of contaminated food and water, or from person to person in settings with poor fecal hygiene (e.g., day-care centers, institutional settings). Infection results from as few as 10 cysts.
⚫ Viable cysts can be eradicated from water by either boiling or filtration. Standard chlorination techniques used to control bacteria do not destroy cysts.
⚫ Young pts, newly exposed pts, and pts with hypogammaglobulinemia are at increased risk—a pattern suggesting a role for humoral immunity in resistance.

Clinical Manifestations
After an incubation period of 5 days to 3 weeks, the manifestations of infection range from
asymptomatic carriage (most common) to fulminant diarrhea and malabsorption.
⚫ Prominent early symptoms include diarrhea, abdominal pain, bloating, belching, flatus, nausea, and vomiting and usually last >1 week. Fever is rare, as is blood or mucus in stool.
⚫ Chronic giardiasis can be continual or episodic; diarrhea may not be prominent, but increased flatulence, sulfurous belching, and weight loss can occur.
⚫ In some cases, disease can be severe, with malabsorption, growth retardation, dehydration, and/or extraintestinal manifestations (e.g., anterior uveitis, arthritis).

Diagnosis
⚫ parasite antigen detection in feces
⚫ identification of cysts (oval, with four nuclei) or trophozoites (pear-shaped, flattened parasites with two nuclei and four pairs of flagella) in stool specimens
⚫ nucleic acid amplification tests
Given variability in cyst excretion, multiple samples may need to be examined.

TREATMENT
Cure rates with metronidazole (250 mg tid for 5 days) are >90%; tinidazole (2 g PO once) may be more effective. Nitazoxanide (500 mg bid for 3 days) is an alternative agent.
If symptoms persist, continued infection should be documented before re-treatment, and possible sources of reinfection should be sought. Prolonged therapy with metronidazole (750 mg tid for 21 days) has been successful.

**CRYPTOSPORIDIOSIS**
Microbiology and Epidemiology
Cryptosporidial infections are caused by Cryptosporidium hominis and C. parvum.
⚫ Person-to-person transmission of infectious oocysts can occur among close contacts and in day-care settings. Waterborne transmission is common.
⚫ Oocysts are not killed by routine chlorination.

Clinical Manifestations
After an incubation period of ∼1 week, pts may remain asymptomatic or develop watery,
nonbloody diarrhea, occasionally with abdominal pain, nausea, anorexia, fever, and/or weight loss lasting 1–2 weeks. In immunocompromised hosts (particularly those with CD4+ T cell counts <100/µL), diarrhea can be profuse and chronic, resulting in severe dehydration, weight loss, and wasting; the biliary tract can be involved.

Diagnosis
On multiple days, fecal samples should be examined for oocysts (4–5 µm in diameter, smaller than most parasites). Although conventional stool examination for ova and parasites does not detect Cryptosporidium, modified acid-fast staining, direct immunofluorescent techniques, and EIAs can facilitate diagnosis.

TREATMENT
Nitazoxanide (500 mg bid for 3 days) is effective for immunocompetent pts but not for HIVinfected pts; improved immune status due to antiretroviral therapy can alleviate symptoms in the latter pts.
In addition to antiprotozoal agents, supportive measures include replacement of fluid and electrolytes and use of antidiarrheal agents.

Entameoba histolytica
The majority of entamoeba infections are asymptomatic; this includes 90 percent of E.histolytica infections.
Factors that influence whether infection leads to asymptomatic or invasive disease include the E.histolytica strain and host factors such as genetic susceptibility, age, and immune status. Risk factors for severe disease and increased mortality include young age, pregnancy, corticosteroid treatment, malignancy, malnutrition, and alcoholism.
Clinical amebiasis generally has a subacute onset, usually over one to three weeks. Symptoms range from mild diarrhea to severe dysentery, producing abdominal pain (12 to 80 percent), diarrhea (94 to 100 percent), and bloody stools (94 to 100 percent), to fulminant amebic colitis.
Rarely, acute fulminant necrotizing amebic colitis presents with life-threatening lower gastrointestinal bleeding without diarrhea. Weight loss occurs in about half of patients, and fever occurs in up to 38 percent

E.coli
Escherichia coli are normal inhabitants of the human gastrointestinal tract. When E. coli strains acquire certain additional genetic material, they can become pathogenic. E. coli are among the most frequent bacterial causes of diarrhea.
⚫ Enterotoxigenic E. coli (ETEC) survives readily in water and food and is one of the most common bacterial causes of dehydrating diarrheal illness in children under two years of age in resource-limited regions. ETEC can also cause diarrhea among travelers to tropical regions and is emerging as a pathogen in resource-rich settings. ETEC infection has a short incubation period (one to three days), and the onset of symptoms and signs is rapid. Diarrhea is watery and may be mild or severe. Patients may report nausea, but vomiting is relatively uncommon.
The illness is self-limiting, lasting one to five days
⚫ Enteropathogenic E. coli (EPEC) has been associated with sporadic diarrheal illness and diarrhea outbreaks, most commonly among children under six months of age in resourcelimited countries. EPEC strains are defined by their characteristic "attaching and effacing" effect upon interaction with epithelial cells and by the fact that they do not produce Shiga toxin. The diarrhea associated with typical EPEC in children can be severe, with concomitant
vomiting and dehydration. Stools are typically watery without blood or pus. Fever may occur in a minority of patients. Diarrhea due to atypical EPEC is also watery and not as severe as that caused by tEPEC
⚫ Enterohemorrhagic E. coli (EHEC) strains are capable of producing Shiga toxin and, like EPEC strains, demonstrate an "attaching and effacing" lesion. EHEC strains, especially those belonging to serotype O157:H7 (and also O104:H4) have been responsible for large outbreaks of bloody diarrhea, some associated with hemolytic uremic syndrome.
⚫ Enteroinvasive E. coli (EIEC) infection appears to be uncommon. Clinical disease begins as watery diarrhea that may progress to bloody diarrhea and dysentery. EIEC is closely related to Shigella, and the same genes facilitate pathogenesis of both organisms. EIEC invades the intestinal cell, multiplies intracellularly, and extends into the adjacent intestinal cells.
⚫ Enteroaggregative E. coli (EAEC) is associated with persistent and acute diarrheal illness among many demographic groups in both resource-limited and -rich settings and may be
associated with linear growth retardation.

資料來源：
衛生福利部疾管署 - 病毒性腸炎
Harrison
Chapter 85: Infectious Diarrheas and Bacterial Food Poisoning
UpToDate
Intestinal Entamoeba histolytica amebiasis
Pathogenic Escherichia coli associated with diarrhea

## Question 114:

有關典型退伍軍人症(Legionnaires' disease)之病史，臨床表徵與檢驗結果之敘述，下列何者最不適當?

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- A.併有發高燒(>40℃)、腹瀉(Diarrhea)等
- B.尿液抗原反應之敏感度(Sensitivity)約為 70%
- C.併有高血鈉症(hypernatremia)及低血鉀症(hypokalemia)
- D.典型痰液可見中性球(neutrophils)浸潤增加但革蘭氏染色找不到細菌
- E.與有汙染的水源環境接觸有關

### Correct Answer: C

EPIDEMIOLOGY
⚫ Legionella is found in fresh water and human-constructed water sources. Outbreaks have been
traced to drinking water systems and rarely to cooling towers.
⚫ The organisms are transmitted to individuals primarily via aspiration, but can also be transmitted by aerosolization and direct instillation into the lungs during respiratory tract
manipulations.
⚫ Pts who have chronic lung disease, who smoke, and/or who are elderly, immunosuppressed, or recently discharged from the hospital are at particularly high risk for disease.

CLINICAL MANIFESTATIONS
Legionellosis manifests as either an acute, febrile, self-limited illness (Pontiac fever) or pneumonia(Legionnaires’ disease).
⚫ Pontiac fever is a flulike illness with a 24- to 48-h incubation period. Malaise, fatigue, and myalgias occur in 97% of cases. Fever, chills, and headaches are also very common, but pneumonia does not develop. The disease is self-limited and does not require antimicrobial treatment. Recovery takes place in a few days.
⚫ Legionnaires’ disease is more severe than other atypical pneumonias and is more likely to result in ICU admission.
◼ After a usual incubation period of 2–10 days, nonspecific symptoms (e.g., fever, malaise, fatigue, headache, anorexia) develop and are followed by a cough that is usually mild and only slightly productive. Chest pain and GI difficulties can be prominent.
◼ Radiologic findings are nonspecific, but pleural effusions are present in 28–63% of pts on hospital admission.
◼ Legionnaires’ disease is not readily distinguishable from pneumonia of other etiologies on the basis of clinical manifestations, but diarrhea, confusion, temperatures >39°C
(>102.2°F), hyponatremia, increased aminotransferase levels, hematuria, hypophosphatemia, and elevated CPK levels are documented more frequently than in other pneumonias
◼ Extrapulmonary infection results from hematogenous dissemination and most commonly affects the heart (e.g., myocarditis, pericarditis).

DIAGNOSIS
The use of Legionella testing—especially the Legionella urinary antigen test—is recommended for all pts with community-acquired pneumonia.
⚫ Urinary antigen testing is rapid, inexpensive, easy to perform, reasonably sensitive (70–90%), and highly specific (95–100%). It is useful only for L. pneumophila serogroup 1, which causes 80% of disease cases.
◼ Urinary antigen is detectable shortly after disease onset and for up to 10 months, even during antibiotic treatment.
◼ 常規的革蘭氏染色於退伍軍人桿菌感染時痰液不具有診斷價值，由於呈現陰性非
常淡染的紅色，故痰液進行革蘭氏染色時，只能看到許多多核性白血球的存在，
而細菌未被染色〈退伍軍人症之實驗室診斷與環境調查 - 衛生福利部疾病管制
署〉

VS comment：
肺外症狀多於肺內症狀，腸胃道症狀多、肝功能異常、 hyponatremia。 X 光會看到肺炎, 大多 lobar 或好幾個 lobe 看嚴重程度。

延伸閱讀：
TREATMENT
⚫ Newer macrolides (e.g., azithromycin at 500 mg/d IV or PO, with doubling of the first dose considered; or clarithromycin at 500 mg bid IV or PO) or fluoroquinolones(e.g., levofloxacin at 750 mg/d IV or 500 mg/d PO or moxifloxacin at 400 mg/d PO) are most effective.
◼ Rifampin (300–600 mg bid) combined with either class of drug is recommended in severe cases.
◼ Tetracyclines (doxycycline at 100 mg bid IV or PO) are alternatives.
⚫ Immunocompetent hosts should receive 10–14 days of therapy, but immunocompromised hosts and pts with advanced disease should receive a 3-week course.
◼ A 5- to 10-day course of azithromycin is adequate because of this drug’s long half-life.
◼ A clinical response usually occurs within 3–5 days after the initiation of parenteral therapy, at which point oral therapy can be substituted.

資料來源：
Harrison
Chapter 100: Mycoplasma pneumoniae, Legionella Species, and Chlamydia pneumoniae

## Question 115:

一位 30 歲的女性，吃了生豬肉之後發生明顯的腸胃炎症狀，且有發燒、右下腹痛
及腹瀉，急診室診查發現 terminal ileum 部位發炎(ileitis)，並有右下腹部反彈痛疑似盲腸炎，請問最有可能是下列哪一種腸道致病原?

---

- A.Vibrio cholera
- B.Salmonella typhi
- C.Yersinia enterocolitica
- D.E. coli O157
- E.Enterovirus 71 (EV71)

### Correct Answer: C

**YERSINIOSIS**
Microbiology and Clinical Manifestations Yersinia enterocolitica and Y. pseudotuberculosis are nonmotile gram-negative rods that cause enteritis or enterocolitis with self-limited diarrhea that lasts an average of 2 weeks as well as mesenteric adenitis (especially common with Y. pseudotuberculosis) and terminal ileitis (especially common with Y. enterocolitica), either of which can resemble acute appendicitis. Septicemia can occur in pts with chronic liver disease, malignancy, diabetes mellitus, and other underlying
illnesses. Infection has been linked to reactive arthritis in HLA-B27-positive pts.

Diagnosis
Stool culture studies for Yersinia must be specifically requested and require the use of special media.

TREATMENT
Antibiotics are not indicated for diarrhea caused by yersiniae; supportive measures suffice.

延伸閱讀：
霍亂（Cholera） 是一種猝然發作的急性細菌性腸炎，症狀為無痛性（ O139 型菌病患偶發腹痛）大量米湯樣水性腹瀉，偶而伴有嘔吐、快速脫水、酸中毒和循環衰竭。但 E1 Tor 型菌感染時常見無臨床症狀或輕微腹瀉（尤其小孩）。嚴重未治療的患者可在數小時內死亡，致死率可超過 50.0％，如加以適當治療，則可降至 1.0％以下。

致病原（ Infectious agent）
⚫ 產生腸毒素之霍亂弧菌血清型 O1（Vibrio cholerae serogroup O1）：該菌可分為cholera classical 和 E1 Tor 二種生物型，每一種生物型又包括稻葉（Inaba）、小川（Ogawa）和彥島（Hikojima）三種血清型。因分泌的腸毒素類似，故臨床 症狀也相似。大流行時多以其中一型為主，現在除了少數地區外，流行以 E1 Tor 型為主。
⚫ 產生腸毒素之霍亂弧菌血清型 O139（ Vibrio cholerae serogroup O139）：係新發現之菌種（非 O1 型亦非 non O1 之 O2～O138 型中任何一型），本型菌病例依霍亂病例有關規定通報及處理。
傳染窩（ Reservoir） 為人類。近年在美國和澳洲觀察顯示環境傳染窩亦可能存在。

傳染方式（ Mode of transmission）
攝食受病人（主要）或帶菌者（次要）糞便或嘔吐物污染的水或食物。霍亂弧菌可存在污水中相當長的時間。生食受霍亂弧菌污染海域捕獲的海鮮，曾導致數次爆發 流行。

潛伏期（ Incubation period）
數小時至 5 天，經常 2～3 天。

可傳染期（ Period of communicability）
糞便中仍呈霍亂弧菌陽性期間，通常只延至恢復期後幾天，有時也可持續至病癒後 數個月為帶菌狀態。 Tetracycline 可縮短傳染期。慢性膽道感染者，其帶菌狀態可持 續數年之久，並間斷性地排出霍亂菌。

感受性及抵抗力（ Susceptibility and resistance）
⚫ 個人感受性差異很大，胃酸缺乏者將增加發病的危險性，不過即使在嚴重的流行區域，侵襲率也甚少超過 2.0％。感染後數種抗體增加（殺弧菌抗體、抗毒素抗體和凝集抗體），可抵抗再次感染，尤其是對同一型細菌持續時間更長。在霍亂呈地方性流行的地區，大部分的人於成年早期均已獲得抗體。
⚫ O139 型菌之各種臨床症狀（嘔吐、腹瀉、脫水等）較 O1 型為嚴重且有腹痛之 主訴，但罹患者大部分都是成人群（小孩病例稀少）。

**沙門氏菌**
流行病學
沙門氏菌感染症屬全球分布，在已開發國家（除非有很好的通報系統）大部分的臨床病例沒有被通報，通報率低於 1%，病例最常發生於嬰兒和五歲以下小孩。大約 60%~80%的病例屬於散發病例，其他病例為爆發流行，小的流行通常發生於一般人群，大的流行則常見於兒童醫院或機構、餐廳及護理之家等人口密集機構，大部分的發生原因是食物來源遭受污染，少數是因帶菌者污染食物，或人與人直接糞口接觸引致。本病較易發生在 7 月~10月，氣候溫暖的季節，目前在世界許多國家的發生率有增加的趨勢。

傳染窩
動物及人類，動物例如：家禽、豬、羊、馬、牛、齧齒動物及寵物（鬣蜥蜴、烏龜、小雞、蛇、狗、貓…）等。人類慢性帶菌者較少，但在動物及鳥類較為普遍。

傳染方式
食入被動物或人類糞便污染的水或食物，受污染的食物例如：生的或未煮熟的雞蛋/雞蛋製品、牛奶/牛奶製品、肉類/肉類製品等，若食物保存不當，沙門氏菌易在高溫下大量繁殖，更易傳播。少數散發病例為接觸寵物而感染，有一些群突發與被污染的生菜或水果有關。農場的動物因食用被污染的飼料而感染，而在飼養或屠宰過程中散播病菌。人與人之間糞口傳染途徑也很重要，特別是在病人腹瀉時，如果是嬰兒或糞便失禁的成人，其傳染力比無症狀帶菌者更高。

臨床症狀
一般臨床症狀以急性腸胃炎表現，在感染後約 6-48 小時會有噁心、嘔吐及下痢等，伴隨發燒及腹部絞痛等症狀，通常發燒 72 小時內會好轉。嬰兒、老年人或免疫功能低下者症狀通常較嚴重，易因菌血症引發其他嚴重併發症

感受性及抵抗力
胃酸缺乏者、接受制酸劑治療者、胃切除者、服用廣效抗生素治療者、癌症患者、接受免疫抑制劑者、虛弱的人（包括營養不良）較易被感染。疾病的嚴重度和感染的血清型別、食入的菌量及宿主因素有關。

傳染期
糞便排菌的時間通常為數天到數週，有些可能數月（特別是嬰兒）。依所感染的血清型別不同而有差異，大約 1％的成人及 5％小於 5 歲的小孩可能排菌超過 1 年。

潛伏期
潛伏期 6-72 小時，通常是 12-36 小時。
E. coli O157 見 13 題

**腸病毒 71**
Hand-foot-and-mouth disease: generally due to coxsackievirus A16 and enterovirus 71. Pts present with fever, anorexia, and malaise, which are followed by sore throat and vesicles on the buccal mucosa, tongue, and dorsum or palms of the hands and occasionally on the palate, uvula, tonsillar pillars, or feet.
⚫ The disease is highly infectious, with attack rates of almost 100% among young children. Symptoms resolve within a week.
⚫ Epidemics of enterovirus 71 infection occurred in Taiwan in 1998 and have occurred annually in China since 2008, with hundreds of thousands of cases and hundreds of deaths each year.
These epidemics were associated with CNS disease (e.g., brain-stem encephalitis, seizures), myocarditis, and pulmonary hemorrhage. Deaths occurred primarily among children ≤5 years old.

資料來源：
衛生福利部疾病管制署 - 霍亂工作手冊, 沙門氏菌感染症
Harrison
Chapter 85: Infectious Diarrheas and Bacterial Food Poisoning
Chapter 105: Enterovirus Infections

## Question 116:

有關中東呼吸症狀群冠狀病毒感染症(MERS-CoV)，下列何者敘述為非？

---

- A.傳染途徑為飛沫及接觸傳染，潛伏期約為 7 至 14 天，已有出現局限性人傳人的群聚感染事件
- B.中東呼吸症狀群冠狀病毒感染症臨床表現包括發燒、咳嗽、呼吸急促與呼吸困難、通常會有肺炎，部分病人會出現腎衰竭、心包膜炎、血管內瀰漫性凝血(DIC)或死亡
- C.病患就醫或進行檢查時，病患需強制配戴 N95 口罩，住院重症插管病患死亡率約為 10%至 12%
- D.病患應入住負壓隔離病室，若無負壓隔離病室可暫時安置有衛浴設備的單人病室，且病室房門應維持關閉
- E.目前仍無有效治療藥物，主要以支持性療法為主

### Correct Answer: C

疾病概述（Disease description）
中東呼吸症候群冠狀病毒感染症（ MERS-CoV）為人畜共通傳染病。主要症狀包括發燒、咳嗽與呼吸急促等，另有部分病患可能出現噁心、嘔吐、腹瀉等腸胃道症狀。感染者胸部 X光通常會發現肺炎，部分重症則出現急性腎衰竭、心包膜炎、血管內瀰漫性凝血等併發症，死亡率約 35%。重症病患大多具有慢性疾病，如糖尿病、慢性肺病、腎病和免疫力缺陷。此外，研究指出部分病患僅出現輕微感冒症狀或無明顯症狀，且可合併其他呼吸道病毒或細菌同時感染。

傳染窩（Reservoir）
雖然 MERS-CoV的確實來源尚未能確定，但一般推測最可能的來源仍為動物。由於大部分beta 亞科冠狀病毒之天然宿主為蝙蝠，因此初期認為蝙蝠可能為 MERS-CoV 感染源，但多數個案並無蝙蝠接觸史，故研判可能有其他宿主。進一步研究發現自中東當地單峰駱駝可分離出 MERS-CoV，其基因序列與自確診個案檢體分離出之病毒基因序列高度相似。又血清學研究顯示其他國家駱駝亦曾感染該病毒，加上部分個案曾有駱駝接觸史，顯示駱駝為人類感染 MERS-CoV 之潛在感染源。目前尚無證據顯示其他動物可能傳播此病毒。

傳染方式（Mode of transmission）
一般冠狀病毒主要透過大的呼吸道飛沫顆粒，以及直接或間接接觸到感染者分泌物等方式傳播，但 MERS-CoV 確實傳播途徑仍不明。根據目前研究結果推測，個案可能因接觸或吸入患病駱駝之飛沫或分泌物而感染。人與人間的傳播主要透過親密接觸發生，例如照顧病患或與病患同住等，以院內感染為主，目前流行地區之社區中尚無持續性人傳人的現象。另曾有研究指出 MERS-CoV 病毒可在低溫(4℃)的駱駝生乳存活 72 小時，部分確診病例亦曾飲用駱駝乳。

潛伏期（ Incubation period）
2~14 天（中位數為 5~6 天）。

可傳染期（ Period of communicability）
目前尚無證據可以知道中東呼吸症候群冠狀病毒可傳染期為何。只要病人體液或分泌物可分離出病毒，則病人仍具有傳染力。易致嚴重併發症之高風險族群 (People at high risk of developing severe disease)男性、老年人（大於 60 歲）及具有慢性疾病如糖尿病、慢性肺 病、腎病和免疫力缺陷者，為受感染後易出現嚴重併發症的高風險族群。

個案處置
符合中東呼吸症候群冠狀病毒感染症通報定義者：
如果病人狀況允許，應戴上外科口罩，以預防病人的呼吸道分泌物噴濺，轉送人員或護送人員在轉送過程中應戴上 N95 等級(含)以上口罩；若預期過程中有接觸或噴濺到病人分泌物之風險，可視身體可能暴露之範圍及業務執行現況，使用手套、隔離衣及護目裝備。

治療：目前無特定抗病毒治療藥劑，應給予症狀治療及支持性療法。
(UpToDate: antiviral therapy was not associated with a change in 90-day mortality or with morerapid MERS-CoV RNA clearance)

資料來源：
衛生福利部疾病管制署- MERS-CoV 防治工作手冊
UpToDate
Middle East respiratory syndrome coronavirus: Treatment and prevention

## Question 117:

有關致病原感染與抗生素治療的配對,下列哪些組合是正確的?
(1) Bacteroides -metronidazole (2) Meningococcus - ceftriaxone (3) Staphylococcus - vancomycin or oxacillin (4) Enterococcus - cefazolin

---

- A.(1)+(2)+(3)
- B.(2)+(3)+(4)
- C.(1)+(3)+(4)
- D.(1)+(2)+(4)
- E.(1)+(2)+(3)+(4)

### Correct Answer: A

Regimens for treatment of bacteremia due to susceptible enterococci in adults
Options for monotherapy:
Preferred agents: Ampicillin or Penicillin G
Alternate agents: Vancomycin or Daptomycin

資料來源：
UpToDate
Treatment of enterococcal infections

## Question 118:

有一位 30 歲孕婦，想來門診施打疫苗預防感染，下列哪些疫苗屬於活性疫苗是孕
婦不建議注射的? (1) Influenza vaccine 流感疫苗 (2) MMR vaccine (Measles - Mump - Rubella vaccine) 麻疹-腮腺炎-德國麻疹疫苗 (3) Varicella vaccine 水痘疫苗 (4) Pneumococcal vaccine 肺炎鏈球菌疫苗

---

- A.(1)+(3)
- B.(2)+(3)
- C.(1)+(4)
- D.(1)+(2)+(3)
- E.(2)+(3)+(4)

### Correct Answer: B

Vaccine safety by type — When immunization is performed during pregnancy, the benefits to both mother and fetus should outweigh the risks. There is no evidence of harm to pregnant women or fetuses from administration of inactivated vaccines. However, live vaccines that are considered safe in children and adults may be harmful to a developing fetus. They are generally avoided during pregnancy. 故選選活性疫苗

資料來源：
UpToDate

## Question 119:

有關退伍軍人症(Legionella Infection)之治療藥物，下列何者是最完整的可選擇藥物組合? (1)Macrolides (2)Quinolones (3)Tetracyclines (4)Cephalosporins(5)Trimethoprim/ Sulfamethoxazle

---

- A.(1)+(2)
- B.(1)+(2)+(3)
- C.(2)+(3)+(4)
- D.(1)+(2)+(3)+(5)
- E.(3)+(4)+(5)

### Correct Answer: D

見 14 題延伸閱讀
(5)Harrison, UptoDate, 熱病都沒寫到 baktar，只好附上 paper 長知識
Antimicrobial agent susceptibilities of Legionella pneumophila MLVA-8 genotypes “clarithromycin (another macrolide) and trimethoprim with sulfamethoxazole (SXT) were the most effective antimicrobial agents towards L. pneumophila strains.”
資料來源：
Antimicrobial agent susceptibilities of Legionella pneumophila MLVA-8 genotypes

## Question 120:

以 Amiodarone 治療心律不整可能影響甲狀腺功能，以下哪一項描述最正確? (1)因為使用 amiodarone 而上升的碘含量，在停用 amiodarone 兩週後可以下降至正常 (2)使用每天一次 200 mg amiodarone 就可能使血碘及尿碘上升 40 倍 (3)與碘缺乏地區比較，碘充足地區因為使用 amiodarone 而造成甲狀腺功能低下(hypothyroidism)的發生率比較高 (4)使用 amiodarone 後造成的甲狀腺功能亢進 ( amiodarone-induced thyrotoxicosis (AIT) )第二型其發生率與 amidarone 的累積劑量無關 (5)使用amiodarone 造成甲狀腺功能低下，不需要停用 amiodarone。

---

- A.(1)+(3)
- B.(2)+(4)
- C.(2)+(3)+(5)
- D.(1)+(2)+(4)
- E.(1)+(3)+(5)

### Correct Answer: C

(1) Amiodarone is stored in adipose tissue, high iodine levels persist for>6 months after discontinuation of the drug. Amiodarone 會儲存在脂肪細胞內，體內濃度可維持 6 個月以上
(2) Amiodarone contains 39% iodine by weight. Thus, typical doses of amiodarone (200 mg/d), lead to greater than 40-fold increases in plasma and urinary iodine levels Amiodarone 有 39%的成分是碘，因此 200 mg/d 劑量的 Amiodarone 即可使血液、尿液中的
碘濃度增加 40 倍
(3) The incidence of hypothyroidism from amiodarone apparently correlates with iodine intake. Hypothyroidism occurs in up to 13% of amiodarone-treated patients in iodine-replete countries (USA) but is less common (<6% incidence) in areas of lower iodine intake(Italy or Spain)
Pathogenesis appears to involve an inability of the thyroid gland to escape from the Wolff-Chaikoff effect in autoimmune thyroiditis. Amiodarone 造成的甲狀腺低下，於碘攝取高的地區較常見，其病生理學可能與 WolffChaiokoff effect 有關(甲狀腺組織在碘濃度增加時，會抑制甲狀腺賀爾蒙的有機化，造成甲狀腺素的製造與釋放降低)
(4) Type I AIT: associated with an underlying thyroid abnormality
(preclinical Graves’ disease or nodular goiter)
Type II AIT: no intrinsic thyroid abnormalities and is the result of drug-induced lysosomal activation leading to destructive thyroiditis with histiocyte accumulation in the thyroid; the incidence rises as cumulative amiodarone dosage increases第二型 AIT 通常為藥物引起。使用 Amiodarone 引起的第二型 AIT 與累積劑量呈正相關
(5) It is usually unnecessary to discontinue amiodarone for hypothyroidism, because levothyroxine can be used to normalize thyroid function.
發生 Amiodarone 造成之甲狀腺低下，可選擇不停藥，以口服甲狀腺素補充

延伸閱讀：
De Leo S et al: Hyperthyroidism. Lancet 388:906, 2016
資料來源：
Harrison 20th ed, Page 2710 (Hyperthyroidism-Amiodarone effects on thyroid function)

## Question 121:

一位 28 歲女性病人，已懷孕 8 週，有心悸、怕熱、體重下降等症狀，身體診察顯
示有凸眼、甲狀腺瀰漫性腫大，抽血檢查顯示 free thyroxine (fT4) 2.92 ng/ dL、thyroid stimulating hormone (TSH) <0.001 μIU/mL (參考值: fT4 0.70~1.48 ng/dL、hsTSH 0.35~4.94 μIU/mL)，下列哪一項選擇最正確? (1)懷孕前期使用 methimazole或 carbimazole 可能影響胚胎發育，因此最好選擇使用 propylthiouracil 治療(2)propylthiouracil 可能有肝毒性，因此懷孕中期以後若仍需要抗甲狀腺藥物，最好改用 methimazole 或 carbimazole (3)抗甲狀腺藥物不會穿透胎盤影響胎兒 (4)授乳期禁用抗甲狀腺藥物以免影響嬰兒 (5)為避免抗甲狀腺藥物之副作用，建議安排甲狀腺切除手術

---

- A.(1)+(2)
- B.(3)+(4)
- C.(2)+(3)+(4)
- D.(1)+(2)+(5)
- E.(1)+(3)+(5)

### Correct Answer: A

(1) If available, propylthiouracil should be used until 14–16 weeks’ gestation because of the association of rare cases of methimazole/carbimazole embryopathy, including aplasia cutis, choanal atresia and tracheoesophageal fistulae
孕期 14-16 週前建議使用 PTU，因 Methimazole 及 Carbimazole 有少量報告指出會造成胚胎病變
(2) Because of its rare association with hepatotoxicity, propylthiouracil should be limited to the first trimester and then maternal therapy should be converted to methimazole (or carbimazole) at a ratio of 15–20 mg of propylthiouracil to 1 mg of methimazole. 孕期 14-16 週後，因胚胎發展已較穩定，考慮到 PTU 之肝毒性，應將 PTU 換藥成methimazole
(3) Because transplacental passage of antithyroid drugs may produce fetal hypothyroidism and goiter if the maternal dose is excessive, maternal antithyroid dose titration should target serum free or total T4 levels at or just above the pregnancy reference range Antithyroid drug 會穿過胎盤
(4) Breast-feeding is safe with low doses of antithyroid drugs.Antithyroid drug 哺乳期使用是安全的
(5) Total or near-total thyroidectomy is an option for patients who relapse after antithyroid drugs and prefer operation to radioiodine. 若使用 antithyroid drugs 後仍復發再考慮手術

延伸閱讀：
Ross DS et al: 2016 American Thyroid Association guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis. Thyroid 26:1343, 2016.
資料來源：
Harrison 20th ed, Page 2707 (Treatment of Grave’s disease)

## Question 122:

藥物可能影響 renin、 aldosterone 的定量以及 Aldosterone-renin ratio (ARR)，下列哪一項描述最正確??
(1)β-blocker 可能使 renin 下降、 aldosterone 上升、 ARR 上升 (2)α-blocker 不會影響 renin、 aldosterone、 ARR (3)Angiotensin-converting enzyme inhibitors (ACEI) 可能使 renin 下降、 aldosterone 上升、 ARR 上升 (4)Calcium antagonists 應該先停用一週，以避免影響 renin、 aldosterone 的定量 (5)Saline infusion test 時，如果 aldosterone 為 10 ng/dL，可以排除原發性高醛固酮症 (primary aldosteronism)

---

- A.(1)+(3)+(5)
- B.(2)+(4)
- C.(1)+(2)
- D.(3)+(5)
- E.(1)+(2)+(4)

### Correct Answer: C


前四選項同表格對照
(5)Diagnostic confirmation of mineralocorticoid excess in a patient with positive ARR screening result should be undertaken by an endocrinologist as the tests lack optimized validation. The most straightforward is the saline infusion test, which involves the IV administration of 2 L of physiologic saline over a 4-h period. Failure of aldosterone to suppress <140 pmol/L (5 ng/dL) is indicative of autonomous mineralocorticoid excess. (Saline infusion test 後 plasma aldosterone 應小於 5ng/dL，若大於 5ng/dL 表示 mineralocorticoid 過多)

延伸閱讀：
Young WF Jr: The management of primary aldosteronism: Case detection, diagnosis, and treatment: An endocrine society clinical practice guideline. J Clin Endocrinol Metab 101:1889, 2016.
資料來源：
Harrison 20th ed, Page 2730 Table 379-4 (Effects of Antihypertensive Drugs on the AldosteroneRenin Ratio (ARR))
Harrison 20th ed, Page 2729 (MIneralocorticoid excess- Diagnosis)

## Question 123:

一位 58 歲男性病人有體重下降、倦怠、姿態性低血壓等症狀，他的血鈉是 125
mmol/L，血糖是 60 mg/dL，懷疑有腎上腺功能不全，請問下列哪一項描述最正確?

---

- A.如果病人外表黑、乾、瘦，則其 ACTH、 cortisol 都應該比正常值低
- B.如果病人的乳頭顏色較淡，應該同時使用 glucocorticoid 及 mineralocorticoid 治療
- C.如果病人有月亮臉、中樞性肥胖、紫斑、腹部紫色斑紋等外表特徵，則其ACTH、 cortisol 都應該比正常值高
- D.如果病人的 fT4 及 TSH 都偏低，應該優先使用甲狀腺素治療
- E.不管是原發性或次發性腎上腺功能不全，腎上腺雄性素( adrenal androgen) 的分泌都有可能受到影響

### Correct Answer: E


(A) A distinguishing feature of primary adrenal insufficiency is hyperpigmentation, which is caused by excess ACTH stimulation of melanocytes.
原發性腎上腺功能不全: High ACTH, high renin, low aldosterone
(B) In secondary adrenal insufficiency, the skin has an alabaster-like paleness due to lack of ACTH secretion。 In secondary adrenal insufficiency, only glucocorticoid deficiency is present, as the adrenal itself is intact and thus still amenable to regulation by the RAA system
根據 flow chart, 單用 glucocroticoid replacement
(C) Cushing’s syndrome can be ACTH-dependent (e.g.,pituitary corticotrope adenoma, ectopic secretion of ACTH by nonpituitary tumor) or ACTH-independent (e.g., adrenocortical
adenoma,adrenocortical carcinoma [ACC], nodular adrenal hyperplasia)如題描述為 Cushing syndrome， ACTH 濃度不一定高
(D) Pituitary-adrenal function should be assessed, usually by a corticotropin (ACTH) stimulation test, before levothyroxine therapy is begun in all patients with central hypothyroidism. If adrenal insufficiency is present, glucocorticoid therapy should be given concomitantly with T4. Central hypothyroidism 的病人都應先確認 pituiary-adrenal function.
(E) Adrenal androgen secretion is disrupted in both primary and secondary adrenal insufficiency primary and secondary adrenal insufficiency 都可能影響 androgen 分泌

延伸閱讀：
Bancos I et al: Diagnosis and management of adrenal insufficiency.
Lancet Diabetes Endocrinol 3:216, 2015.
Bornstein SR et al: Diagnosis and treatment of primary adrenal insufficiency: An Endocrine
Society Clinical Practice Guideline. J Clin
Endocrinol Metab 101:364, 2016.
資料來源：
ABE 選項： Harrison 20th ed, Page 2734 (Adrenal insufficiency-Clinical manifecstation )
C 選項: Harrison 20th ed, Page 2723 (Cushing’s syndrome)
D 選項： Uptodate-Central hypothyroidism-Treatment

## Question 124:

一位 38 歲女性病人，因為陣發性高血壓、頭痛、心悸來診，懷疑有嗜鉻細胞瘤
(pheochromocytoma)，請問下列哪一項描述最適當?

---

- A.因為血壓太高，下肢有輕微水腫，應該限制水分攝取
- B.檢查尿液中的 fractionated metanephrines 及 catecholamine 對於嗜鉻細胞瘤的診斷有最高的特異性( specificity)
- C.病人曾經使用三環抗憂鬱藥物及利尿劑，三環抗憂鬱藥物可能造成偽陽性(false positive)的 catecholamine 檢驗結果，但利尿劑則不會影響檢驗結果
- D.為減少壓力，做電腦斷層或核磁共振等影像學檢查時應該避免使用顯影劑
- E.嗜鉻細胞瘤或副神經節細胞瘤 ( paragangliomas) 大約有 5-10% 是惡性的

### Correct Answer: E

(A)Because patients with pheochromocytoma are volume-constricted, liberal salt intake and hydration are necessary to avoid severe orthostasis 嗜鉻細胞瘤患者通常處於相對體液缺乏的狀態，限水限鹽容易造成姿勢性低血壓
(B)
Sensitive: 24hr spot urine metanephrine, plasma free metanephrine Specific: 24hr total urine metanephrine
詳見 Table 380.2
(C)
withdrawal of levodopa or use of sympathomimetics, diuretics, tricyclic antidepressants, alpha and beta blockers might cause false-positive results of catecholamine三環抗憂鬱藥物、利尿劑、交感神經促進及拮抗劑皆會影響 catecholamine 檢驗結果
(D)
CT and MRI are similar in sensitivity and should be performed with contrast. T2-weighted MRI with gadoliniumcontrast is optimal for detecting pheochromocytomas and is somewhat better than CT for imaging extraadrenal pheochromocytomas and paragangliomas. CT 及 MRI for pheochromocytoma 需打顯影劑
(E) About 5–10% of pheochromocytomas and paragangliomas are malignant


延伸閱讀：
Neumann, H. P., Young, W. F., & Eng, C. (2019). Pheochromocytoma and Paraganglioma. New
England Journal of Medicine, 381(6), 552–565.

資料來源：
(A) Harrison 20th ed, Page 2743 (Treatment of pheochromocytoma)
(B)(C) Harrison 20th ed, Page 2741 (Pheochromocytoma-Biochemical Testing)
(D) Harrison 20th ed, Page 2741 (Pheochromocytoma-Diagnostic Imaging)
(E) Harrison 20th ed, Page 2743 (Malignant pheochromocytoma)

## Question 125:

一位 50 歲男性病人，有肢端肥大、關節炎、睡眠呼吸中止等症狀，他的生長激素
（Growth hormone, GH）為 10 ng/mL (參考值 < 8 ng/mL)、 insulin-like growth factor-1 (IGF-1) 為 300 ng/mL (參考值 48.1~209 ng/mL)，請問下列哪一項描述正確?

---

- A.青春期時 IGF-1 的參考值通常較年紀大時為高
- B.單次隨意(single random) 的血清 GH 值與肢端肥大症疾病嚴重度有正相關
- C.給予口服 75 公克葡萄糖後 GH 的最低值為 4 ng/mL，可以排除肢端肥大症
- D.生長激素瘤的首選治療為手術切除，術前禁忌給予 somatostatin analogues
- E.生長激素瘤的放射性治療(radiotherapy)，通常在一年左右可以看到生化指標(biochemical parameter)正常化

### Correct Answer: A

(A) 青春期和 acromegaly 病患生長激素分泌增加， IGF-1 level 也增加。正確
Age-matched serum IGF-I levels are elevated in acromegaly. Consequently, an IGF-I level provides a useful laboratory screening measure when clinical features raise the possibility of acromegaly.
(B)因生長激素呈波動性分泌，單次 GH 濃度並不能代表疾病嚴重程度
Owing to the pulsatility of GH secretion, measurement of a single random GH level is not useful for the diagnosis or exclusion of acromegaly and does not correlate with disease severity.
(C)口服 75g 葡萄糖後 1-2 小時 GH level 未降至 4 ng/mL（ 0.4 μg/L）可以診斷肢端肥大症。但 GH level 降至 4 ng/mL 以下並不能排除
The diagnosis of acromegaly is confirmed by demonstrating the failure of GH suppression to<0.4 μg/L within 1–2 h of an oral glucose load (75 g). When newer ultrasensitive GH assays are
used, normal nadir GH levels are even lower (<0.05 μg/L).
(D)治療包含 surgery, somatostatin analogues, GH receptor antagonist and radiation. 手術治療為首選。教科書沒有直接說明 somatostatin analogues 是手術前禁忌，但提到手術治療就可以讓 GH level 在一小時內恢復正常， IGF-1 level 在 3-4 天恢復正常。
Transsphenoidal surgical resection by an experienced surgeon is the preferred primary treatment for both microadenomas (remission rate ~70%) and macroadenomas (<50% in remission). Soft tissue swelling improves immediately after tumor resection. GH levels return to normal within an
hour, and IGF-I levels are normalized within 3–4 days. In ~10% of patients, acromegaly may recur several years after apparently successful surgery; hypopituitarism develops in up to 15% of patients after surgery.
(E)放射治療後隨著腫瘤體積減小 GH level 也逐漸下降，約需八年時間才會回到正常值，期間需配合藥物治療
External radiation therapy or high-energy stereotactic techniques are used as adjuvant therapy for acromegaly. An advantage of radiation is that patient compliance with long-term treatment is not required. Tumor mass is reduced, and GH levels are attenuated over time. However, 50% of patients require at least 8 years for GH levels to be suppressed to <5 μg/L; this level of GH reduction is achieved in ~90% of patients after 18 years but represents suboptimal GH suppression. Patients may require interim medical therapy for several years before attaining maximal radiation benefits. Most patients also experience hypothalamic-pituitary damage, leading to gonadotropin, ACTH, and/or TSH deficiency within 10 years of therapy.

延伸閱讀：


資料來源：
Harrison's Principles of Internal Medicine, 20e
Chapter 373: Pituitary Tumor Syndromes/ HYPOTHALAMIC, PITUITARY, AND OTHER
SELLAR MASSES/ acromegaly

## Question 126:

下列哪一項可能使副甲狀腺荷爾蒙濃度(parathyroid hormone, PTH)上升?

---

- A.Calcium-sensing receptor (CaSR) agonists such as cinacalcet
- B.Vitamin D
- C.Fibroblast growth factor 23 (FGF23)
- D.Phosphates
- E.Severe intracellular magnesium deficiency

### Correct Answer: D

(A)(B) CaSR 和 vitamin D 會降低 PTH level Calcium, acting through the calcium-sensing receptor (CaSR), and vitamin D, acting through its nuclear receptor, reduce PTH release and synthesis.
(C) FGF23 會抑制 PTH secretion Additional evidence indicates that fibroblast growth factor 23 (FGF23), a phosphaturic hormone, can suppress PTH secretion.
(D) Phosphates 濃度上升會刺激 PT。正確
(E)Mg 和 Ca 濃度上升會刺激 PTH 分泌，反之抑制
The effects of magnesium on PTH secretion are similar to those of calcium; hypermagnesemia suppresses and hypomagnesemia stimulates PTH secretion. The effects of magnesium on PTH secretion are normally of little significance, however, because the calcium effects dominate
資料來源：
Harrison's Principles of Internal Medicine, 20e
Chapter 403: Disorders of the Parathyroid Gland and Calcium Homeostasis

簡易記法:


## Question 127:

一位 25 歲男性病人因為第二性徵不明顯來求診，經病史詢問及身體診察後確認有
性腺功能低下(hypogonadism)、嗅覺異常、色盲、顎裂，請問以下哪一項描述正確?

---

- A.此病人之睪丸小而硬
- B.此病人之濾泡刺激素（ follicle-stimulating hormone, FSH）及黃體化激素(luteinizing hormone, LH) 較參考值高
- C.此病人可能有 X-linked KAL gene 突變
- D.若此病人急於結婚生子，應該趕快給予 testosterone 治療
- E.核磁共振檢查發現有腦下垂體微小腫瘤(microadenoma)

### Correct Answer: C

根據臨床症狀描述，此應為 Kallmann syndrome（症狀包含色盲、視神經萎縮、神經性耳聾、顎裂、腎功能異常、隱睪症等）
Classically, the syndrome may also be associated with color blindness, optic atrophy, nerve
deafness, cleft palate, renal abnormalities, cryptorchidism, and neurologic abnormalities such as
mirror movements.
(A)(E) 未提及
(B) FSH 及 LH 較正常值低
Kallmann syndrome and other causes of congenital GnRH deficiency are characterized by low luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels and low concentrations of sex steroids (testosterone or estradiol).
(C)此疾病最初的基因突變就是 X-linked KAL gene mutation。正確
The initial genetic cause was identified in the X-linked KAL gene, mutations of which impair embryonic migration of GnRH neurons from the hypothalamic olfactory placode to the hypothalamus.
Since then, at least a dozen additional genetic abnormalities, in addition to KAL mutations, have been found to cause isolated GnRH deficiency. Autosomal recessive (i.e., GPR54, KISS1) and dominant (i.e., FGFR1) modes of transmission have been described, and there is a growing list of genes associated with GnRH deficiency.
(D)反覆給予 GnRH 可使下視丘對 gonadotropins 恢復反應。男性的長期治療應使用 hCG 或 testosterone 來恢復性成熟及第二性徵；女性的治療應使用 estrogen 及 progesterone。要恢復生育能力則應給予 gonadotropins 或 pulsatile GnRH Repetitive GnRH administration restores normal pituitary gonadotropin responses, pointing to a hypothalamic defect in these patients.
Long-term treatment of males with human chorionic gonadotropin (hCG) or testosterone restores pubertal development and secondary sex characteristics; women can be treated with cyclic estrogen and progestin. Fertility may be restored by the administration of gonadotropins or by using a
portable infusion pump to deliver subcutaneous, pulsatile GnRH.
資料來源：
Harrison's Principles of Internal Medicine, 20e
Chapter 372: Hypopituitarism
Developmental Hypothalamic Dysfunction/KALLMANN SYNDROME

## Question 128:

下列有關泌乳激素瘤(prolactinoma)的描述，哪一項正確？

---

- A.一公分以上的 prolactinoma,男女比約為 1:3
- B.女性病人有 prolactin microadenoma (< 1 cm) 但無症狀，不須治療，追蹤即可
- C.血液中泌乳激素(Prolactin)濃度與腫瘤大小無關
- D.Prolactinoma 病人如果以 dopamine agonists 治療，最好維持其 prolactin 濃度於參考值之 1 至 1.5 倍
- E.女性病人有小於 1 公分的 prolactinoma，如果以 dopamine agonists 治療後懷孕，不可以停藥，應該持續使用 dopamine agonists

### Correct Answer: B

(A)prolactinoma在女性盛行率為十萬分之10-30。<1 cm稱為microadenoma，>1cm稱為 macroadenoma。Macroadenoma男女比例為1:1 Tumors arising from lactotrope cells account for about half of all functioning pituitary tumors, with a population prevalence of ~10/100,000 in men and ~30/100,000 in women. Mixed tumors that secrete combinations of GH and PRL, ACTH and PRL, and rarely TSH and PRL are also seen.
Microadenomas are classified as <1 cm in diameter and usually do not invade the parasellar region. Macroadenomas are >1 cm in diameter and may be locally invasive and impinge on adjacent structures. The female-to-male ratio for microprolactinomas is 20:1, whereas the sex ratio is near 1:1 for macroadenomas.
(B)沒有症狀的microadenoma不用治療。正確 Because microadenomas rarely progress to become macroadenomas, no treatment may be needed if patients are asymptomatic and fertility is not desired; these patients should be monitored by regular serial PRL measurements and MRI scans.
(C)腫瘤大小與PRL濃度相關。PRL values >250 μg/L多見於macroadenoma Tumor size generally correlates directly with PRL concentrations; values >250 μg/L usually are associated with macroadenomas.
(D)dopamine agonists 如cabergoline and bromocriptine可用來治療prolactinoma，目標是 讓PRL 正常。Bromocruptine起始劑量0.625–1.25 mg HS，可逐步上調至2.5mg TID Oral dopamine agonists (cabergoline and bromocriptine) are the mainstay of therapy for patients with micro- or macroprolactinomas. Dopamine agonists suppress PRL secretion and synthesis as well as lactotrope cell proliferation.
The ergot alkaloid bromocriptine mesylate is a dopamine receptor agonist that suppresses PRL secretion. Because it is short-acting, the drug is preferred when pregnancy is desired. In microadenomas, bromocriptine rapidly lowers serum PRL levels to normal in up to 70% of patients, decreases tumor size, and restores gonadal function. In patients with macroadenomas, PRL levels are also normalized in 70% of patients, and tumor mass shrinkage (≥50%) is achieved in most patients. Therapy is initiated by administering a low bromocriptine dose (0.625–1.25 mg) at bedtime with a snack, followed by gradually increasing the dose. Most patients are controlled with a daily dose of <7.5 mg (2.5 mg tid).
(E)懷孕期間應停用 When pregnancy is confirmed, bromocriptine should be discontinued and PRL levels followed serially, especially if headaches or visual symptoms occur.

延伸閱讀：


資料來源： Harrison's Principles of Internal Medicine, 20e Chapter 373: Pituitary Tumor Syndromes/ HYPERPROLACTINEMIA/ PROLACTINOMA

## Question 129:

自體免疫多發性內分泌症候群第一型(Autoimmune Polyendocrine Syndromes type 1, APS-1) 有下列特徵，哪一項不正確?

---

- A.Candidiasis
- B.牙釉質增生 (Hyperplasia of the dental enamel)
- C.Hypoparathyroidism
- D.Addison's disease
- E.為 AIRE gene 的體染色體隱性突變

### Correct Answer: B

(A)如下所述。正確 It has also been called autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED) (B) 未提及此現象
(C) APS-1表現包含Hypoparathyroidism。正確
(D) APS-1及APS-2表現包含Addison's disease。正確
(E) 是AIRE gene 的體染色體隱性突變。正確 The classical form of APS-1 is an autosomal recessive disorder caused by mutations in the AIRE gene (autoimmune regulator gene) found on chromosome 21. This gene is most highly expressed in thymic medullary epithelial cells (mTECs) where it appears to control the expression of tissue-specific self-antigens (e.g., insulin). Deletion of this regulator leads to decreased expression of tissue-specific self-antigens and is hypothesized to allow autoreactive T cells to avoid central deletion, which normally occurs during T cell maturation in the thymus. The AIRE gene is also expressed in epithelial cells found in peripheral lymphoid organs, but its role in these extrathymic cells remains controversial.

延伸閱讀：



資料來源： Harrison's Principles of Internal Medicine, 20e Chapter 382: Autoimmune Polyendocrine Syndromes/APS-1

## Question 130:

糖尿病與肥胖組成糖胖症(Diabesity)，在新陳代謝疾病的範疇內，彼此密切相關，下列之有關此兩類疾病敘述中，何者有誤?

---

- A.長期的研究中，計畫性飲食及規律之足量運動，可以降低糖尿病發病之機率，其關鍵機轉為控制體重
- B.運動對於體重之控制非常重要，運動強度愈強，研究之資料顯示可以降低糖尿病發病率，也可以降低心臟血管疾病之死亡率
- C.除了身體質量(body mass index, BMI)之外，與心血管疾病密切相關的肥胖型態是中心性腹部肥胖 (central abdominal obesity)
- D.依照糖尿病飲食控制原則，預防疾病進展時，計畫性飲食及運動降低的體重，主要是脂肪組織
- E.美國國衛院進行之生活型態研究 LOOKAHEAD，針對糖尿病的患者安排營養諮詢及體重管理，雖然可以改善血糖及 HbA1c 之控制，但是研究結果顯示並無法降低糖尿病患者之心臟血管疾病 死亡率

### Correct Answer: B

- A. 藉由生活型態的改變，如經由飲食與運動來減輕體重，除可改善胰島素阻抗和高胰島 素血症外，也可改善葡萄糖耐受性和其它心血管疾病的風險因子
- B. 第 2 型糖尿病人，體能活動建議每週 >150分鐘的中等強度有氧運動，或是每週至少 3日，每日至少 20分鐘，較中等強度稍強的體能活動。 The amount of exercise made a larger difference on plasma lipoprotein concentrations than the intensity of exercise.
- C. Waist circumference and waist-to-hip ratio are surrogate estimations of visceral adiposity, which is linked to insulin resistance, dyslipidemia, and increased CVD risk
- D. Compared with a weight loss diet alone, diet coupled with either exercise or exercise and resistance training is associated with a greater reduction in body fat and enhanced preservation of body lean mass
- E. 於 Look AHEAD 研究中發現積極的生活型態介入減重，有助於改善血糖控制，體適 能及心血管疾病的風險因子，雖然未能顯著減少心血管疾病發生的風險 － 中華民國 內分泌暨糖尿病學會 2018糖尿病臨床照護指引

延伸閱讀：

資料來源： Uptodate, 中華民國內分泌暨糖尿病學會 2018糖尿病臨床照護指引

## Question 131:

糖尿病用藥的機轉，與病患空腹或飯後血糖控制密切相關，口服降血糖藥物中，有些與胰島素分泌或胰島素阻抗性有關，有些則無直接關聯(non-insulin dependent)，以下降血糖藥物中，何項藥物為非胰島素相關(non-insulin dependent)之機轉?

---

- A.Sulfonylurea
- B.Biguanide
- C.Dipeptidyl dipeptidase 4 inhibitor (DPP4 inhibitor)
- D.Sodium-glucose co-transporter 2 inhibitor (SGLT 2 inhibitor)
- E.Glucagon like peptide 1 receptor agonist (GLP 1 RA)

### Correct Answer: D

A. The sulfonylurea receptor is a component of the adenosine triphosphate (ATP)-sensitive potassium channel (K-ATP channel) in the pancreatic beta cells. The K-ATP channel regulates the release of insulin from pancreatic beta cells. Sulfonylurea binding leads to inhibition of these channels, which alters the resting potential of the cell, leading to calcium influx and stimulation of insulin secretion.
B. Metformin's major effect is to decrease hepatic glucose output by inhibiting gluconeogenesis. In addition, metformin increases insulin-mediated glucose utilization in peripheral tissues (such as muscle and liver), particularly after meals.
C. DPP-4 inhibitors are a class of oral diabetes drugs that inhibit the enzyme DPP-4. DPP-4 is a ubiquitous enzyme expressed on the surface of most cell types that deactivates a variety of other bioactive peptides, including glucose-dependent insulinotropic polypeptide (GIP) and GLP-1(參閱選項E)
D. The SGLT2 is expressed in the proximal tubule and mediates reabsorption of approximately 90 percent of the filtered glucose load. SGLT2 inhibitors promote the renal excretion of glucose and thereby modestly lower elevated blood glucose levels in patients with type 2 diabetes.
E. GLP-1 exerts its main effect by stimulating glucose-dependent insulin release from the pancreatic islets. It has also been shown to slow gastric emptying, inhibit inappropriate post- meal glucagon release, and reduce food intake.
延伸閱讀：
資料來源： uptodate

## Question 132:

糖尿病的治療，生活型態管控飲食及運動之外，口服或注射型藥物也是關鍵控制因子，下 D 列有關糖尿病藥物之敘述，何者為錯誤之描述? (1) Metformin可以安全地使用於eGFR < 30 的糖尿病患者 (2)Sulfobnylurea類之降血糖藥物，容易造成病患之低血糖及體重上升 (3) 國內糖尿病學會之建議中，HbA1c糖化血色素應控制於 < 6% (4) Sodium glucose co-transporter 2 inhibitor (SGLT2 inhibitor) 在降低血糖之時，通常也會伴隨減輕病患之體重 (5) 腎功能不 佳，eGFR < 60時，應避免使用胰島素及GLP-1 receptor agonist之針劑藥物。

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- A.(2)+(4)+(5)
- B.(1)+(3)+(4)
- C.(1)+(4)+(5)
- D.(1)+(3)+(5)
- E.(3)+(4)+(5)

### Correct Answer: D

1. Metformin is contraindicated in patients with Impaired renal function ( [eGFR] <30 mL/min/1.73 m2)→ may induce lactic acidosis
2. Hypoglycemia is a common side effect of Sulfonylureas. Hypoglycemia may be less common with shorter- (gliclazide, glipizide) than longer-acting (glyburide) sulfonylureas. Modest weight gain is a common side effect of sulfonylureas. Other, infrequent side effects that can occur with all sulfonylureas include nausea, skin reactions, and abnormal liver function tests
3. 我國糖尿病學會HbA1C的建議值目前也為低於 7.0 %，並建議空腹血糖目標值為 80- 130mg/dl，餐後血糖目標值為≤160 mg/dl。 ◼ 針對 65 歲以上的老年人，如果健康狀態正常者 (很少共病症，認知及身體機能 正常)，HbA1C的建議值為<7.5%。 ◼ 如果健康狀態中等者(多種共病症，認知及身體機能輕微至中等異常)，HbA1C的 建議值為 <8%。 ◼ 而健康狀態較差者(末期慢性病，認知及身體機能中等至嚴重異常)，HbA1C的建 議值為<8.5%。
4. Weight loss — SGLT2 inhibitors decrease weight. In 12-week trials of dapagliflozin, canagliflozin, and empagliflozin, weight loss of 2 to 3 kg was reported
5. Exenatide(one of GLP-1) should not be used in patients with a creatinine clearance below 30 mL/min. In patients with moderate renal impairment (creatinine clearance 30 to 50 mL/min), monitoring of serum creatinine is warranted when initiating therapy and after the usual dose increase from 5 to 10 mcg. There is limited experience in using liraglutide, dulaglutide, and semaglutide in patients with severe renal impairment (eGFR 15 to 29 mL/min/1.73 m2).
延伸閱讀：
資料來源： 中華民國內分泌暨糖尿病學會 2018糖尿病臨床照護指引, uptodate

## Question 133:

Sodium glucose co-transporter 2 inhibitor (SGLT 2 inhibitor) 是近幾年來使用於糖尿病患者之新型口服降血糖藥物，降血糖之機轉是經由尿液將葡萄糖排出體外，以下有關本項藥品之敘述，何者為錯誤的?

---

- A.SGLT 2 inhibitor 所形成之高尿糖， 增加泌尿道及生殖器感染之風險
- B.臨床試驗研究顯示 SGLT 2 inhibitor 可以降低糖尿病患者因心臟衰竭住院的機率
- C.SGLT 2 inhibitor 對糖尿病患者而言，在降低血糖之際，也同時降低了病患產生酮酸中
毒(diabetic ketoacidosis) 的機率
- D.目前之研究顯示 SGLT 2 inhibitor 可以與胰島素同時合併使用來控制血糖
- E.eGFR > 60 以上之糖尿病患者，都可以使用 SGLT 2 inhibitor

### Correct Answer: C

- A. SGLT2 inhibitors increase the rate of urinary tract infections (8.8 versus 6.1 percent). In addition, the US Food and Drug Administration (FDA) has received reports of potentially fatal: 1. Urosepsis and pyelonephritis 2.Necrotizing fasciitis of the perineum (Fournier's gangrene)
- B. In meta-analyses of the three major CVD outcome trials, SGLT2 inhibitors compared with placebo reduced the risk of major adverse cardiovascular events (86.9 versus 99.6 events per 1000 patient-years, hazard ratio [HR] 0.89, 95% CI 0.83-0.96) and a composite outcome of CV death or hospitalization for heart failure
- C. "Euglycemic" (usually meaning plasma glucose <250 mg/dL) diabetic ketoacidosis has been reported in patients with type 2 diabetes taking SGLT2 inhibitors. Serum ketones should be obtained in any patient with nausea, vomiting, or malaise while taking SGLT2 inhibitors, and SGLT2 inhibitors should be discontinued if acidosis is confirmed
- D. For patients with a prior history of myocardial infarction or stroke, GLP-1 receptor agonists (liraglutide, semaglutide, or dulaglutide) or SGLT2 inhibitors (empagliflozin or canagliflozin) are reasonable choices (to be added to metformin and insulin), based on the results of cardiovascular outcomes studies. Insulin dose requirements can decrease precipitously with the addition of these medications, requiring patient education and close follow-up in the short term to reduce the risk of hypoglycemia.
- E. Use of SGLT 2 inhibitor is not recommended with an eGFR of <45 to 60 mL/min/1.73 m2, and they are contraindicated with an eGFR of <30 mL/min/1.73 m2, including patients with ESRD who are on dialysis
延伸閱讀：
資料來源： uptodate

## Question 134:

在內科糖尿病血糖之控制中，胰島素(lnsulin)及 GLP-1 receptor agonist (GLP-1 RA)注射型製劑是重要的控制藥物，以下有關胰島素及 GLP-1 RA 治療之描述，何者為錯誤的?

---

- A.Basal insulin (基礎胰島素) 使用之起始劑量(initial dose) 的原則為 0.2 unit/kg/day
- B.Basal insulin 可以合併 GLP-1 RA，協同控制病患之血糖
- C.GLP-1 RA 常見的副作用為腹脹噁心感，胰島素最常見之副作用為低血糖
- D.GLP-1 RA 可以合併胰島素治療第一型糖尿病，並可減少胰島素使用之劑量
- E.臨床試驗研究之結果顯示， GLP-1 RA 之使用，在降低血糖時，也會同時減輕病患之體重

### Correct Answer: D

- A. For patients with type 2 diabetes, the initial dose of insulin (whether in addition to oral agents, in place of oral agents, or as initial treatment) is similar. The initial dose for NPH, detemir, or glargine is 0.2 units per kg (minimum 10 units) daily.
- B. GLP-1 RA is available for use as monotherapy as an adjunct to diet and exercise or in combination with oral agents and basal insulin in adults with type 2 diabetes. It is not considered a first-line therapy.
- C. Gastrointestinal side effects, including nausea and vomiting, are common. Other side effects include diarrhea, low blood sugar, and anorexia. Serious but less common side effects include pancreatitis, gallbladder disease, and renal impairment.
- D. The addition of the glucagon-like peptide 1 (GLP-1) receptor agonists (RAs) liraglutide and exenatide to insulin therapy caused small (0.2%) reductions in A1C compared with insulin alone in people with type 1 diabetes and also reduced body weight by ~3 kg. The risks and benefits of adjunctive agents continue to be evaluated, but only pramlintide in Noninsulin Treatments for Type 1 Diabetes is approved for treatment of type 1 diabetes.
- E. The side effects of GLP-1 receptor agonists are predominantly gastrointestinal. Weight loss may be due, in part, to gastrointestinal side effects directly or through suppression of appetite.
延伸閱讀：
資料來源： Uptodate, ADA Standards of Medical Care in diabetes—2020

## Question 135:

陳先生， 40 歲，身高 173 公分，體重 84 公斤，近一年來，體重增加了 6 公斤。並無糖尿病之家族及個人病史，半年來，曾經有數次不明原因的昏倒，都在 30 分鐘內甦醒過來。門診病無心律不整或異常神經血管之異常狀況。本次因再度於工作時昏倒，但是意識持續不清，因此送到急診。急診之血壓為 110/68 mmHg，脈搏為規律的 72 bpm，急診之血糖顯示為 35 mg/dL，給予 50%之葡萄糖輸液後，恢復意識。建議住院診察，在病房無點滴輸液的前提下，空腹 8 小時後，抽血報告為: 空腹血糖 84 mg/dL， Insulin 3.6 mIU/mL ， Cpeptide 2.6 ng/mL， ACTH 62.2 pg/mL， Cortisol 24.3 ug/dL， IGF-1 198 ng/mL， TSH 1.2mIU/mL，此時應考慮之優先檢查項目為何?

---

- A.24 小時心電圖
- B.腦下垂體磁振攝影(MRI)
- C.腹部電腦斷層
- D.75 公克葡萄糖耐受試驗 (Oral glucose tolerance test)
- E.72 小時之 Prolonged fasting test

### Correct Answer: E

✓ Plasma normal C-peptide range is 0.5 to 2.0 nanograms per milliliter.( distinguishes endogenous from exogenous hyperinsulinemia.)
✓ Plasma insulin normal range < 25 mIU/L 228
✓ Plasma corticotropin (ACTH) concentrations are usually between 10 and 60 pg/mL (2.2 and 13.3 pmol/L) at 8 AM.
✓ Normal IGF-1: 36-40 years: 48-292 ng/mL
✓ TSH normal range: 0.4 and 4.0 (mIU/l) ➔ Mild elevated C peptide, normal insulin level, no adrenal insufficiency Patients who are fortuitously observed during an episode of symptoms and are found to have hypoglycemia at that time should have the following blood tests:
✓ Glucose
✓ Insulin
✓ C-peptide
✓ Beta-hydroxybutyrate (BHOB)
✓ Proinsulin
✓ Sulfonylurea and meglitinide screen
Fasting evaluation — There are patients in whom symptoms occur after only a short period of food withdrawal. In such patients, continued observation in the office or clinic, especially if they have fasted overnight, may result in an episode of symptomatic hypoglycemia. If symptoms occur and hypoglycemia is documented (plasma glucose <55 mg/dL [3 mmol/L]), the other tests described above should be performed. The results may obviate the need for a provocative test, such as the 72-hour fast.
延伸閱讀： 資料來源： uptodate

## Question 136:

Glitazone(TZD)類之降血糖藥物，屬於胰島素增敏劑，可以改善胰島素在人體內之敏感度，但是也有些藥物之副作用，以 Pioglitazone 為例，使用相關藥物副作用包括下列何者? (1)骨質疏鬆 (2)認知障礙 (cognitive dysfunction) (3)水腫 (4)腦中風 (Storke) (5)體重及脂肪組織增加。

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- A.(1)+(2)+(3)
- B.(1)+(3)+(5)
- C.(3)+(4)+(5)
- D.(1)+(2)+(5)
- E.(2)+(3)+(5)

### Correct Answer: B

adverse effects including increased risk of weight gain, fluid retention, heart failure, fractures, and the potential small increased risk of bladder cancer (pioglitazone). → 1,3,5
資料來源：
uptodate

## Question 137:

李先生， 56 歲，糖尿病病史為 10 年，兩年前因冠狀動脈疾病進行心導管置放支架，目前使用藥物包括: 預混型胰島素 (Premix insulin)，高血壓藥物為每日 valsatan 160mg 及amlodipine 5mg ，膽固醇藥物為 rosuvastatin 每日 20mg。目前 HbA1c 為 6.8%， LDL cholesterol 為 50 mg/dL， HDL cholesterol 31 mg/dL， Triglyceride 為 828 mg/dL，尿液檢查正常，無微量白蛋白尿，輕微背景型視網膜病變 (Background retinopathy)，目前應該增加使用下列哪一項藥物?

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- A.Pioglitazone
- B.Nicotic acid
- C.Fenofibrate
- D.Acarbose
- E.Cholestyramine

### Correct Answer: C

Hypertension:
✓ 合併高血壓的糖尿病人，血壓控制於140/90 mmHg以下
✓ 合併高血壓與蛋白尿的糖尿病人，血壓控制於130/80 mmHg以下 第一線的降血壓藥物，從減緩腎病變的角度來看，建議考慮 ACEI 或 ARB。 Dyslipidemia: ✓ 沒有心血管疾病的糖尿病人，LDL的治療目標是低於100 mg/dl，或是降低30-40%。 (證據等級:高，強烈建議)
✓ 罹患心血管疾病的糖尿病人，LDL的治療目標是低於 70 mg/dl，或降低30-40%。(證 據等級:中，中等建議)
✓ TG的治療目標最好能低於150 mg/dl，HDL的治療目標最好能：男性高於40 mg/dl， 女性高於50 mg/ dl。(證據等級: 低，中等建議) 如果沒有禁忌症，建議糖尿病人使用statins類藥物來降低LDL。(證據等級:中，強烈建議) Fibrates: 主要用來降低TG(約 20-50％)與提升HDL(約 10-20％)，當糖尿病人有TG增高與 HDL降低，血糖的控制及飲食的調整應該先進行，當TG> 500 mg/dl 時，需要馬上給予 Fibrates，以減少急性胰臟炎的風險。

資料來源： 中華民國內分泌暨糖尿病學會 2018糖尿病臨床照護指引

## Question 138:

低血糖的發生，有時與糖尿病之治療密切相關，但非糖尿病之疾病也可能發生低血糖，下列敘述的病症中，何者為低血糖發生的原因? (1)使用胰島素或 sulfonylurea 類降血糖藥物(2)庫欣氏症候群 (Cushing's Syndrome) (3)胃切除手術後 (Post-gastric bypass survey) (4)腎上腺機能不足 (Adrenal insufficiency) (5) 肢端肥大症 (Acromegaly)。

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- A.(1)+(2)+(3)
- B.(3)+(4)+(5)
- C.(1)+(3)+(5)
- D.(2)+(3)+(4)
- E.(1)+(3)+(4)

### Correct Answer: E

✓ Drugs –
Insulin and insulin secretagogues →(1) other drugs such as ACEI and ARB, β-adrenergic receptor antagonists, quinolone antibiotics, indomethacin, quinine, and sulfonamides.
✓ Hormone Deficiencies occur with prolonged fasting in patients with primary adrenocortical failure (Addison’s disease) or hypopituitarism. →(4)
✓ Post-gastric bypass survey Although endogenous hyperinsulinemic hypoglycemia is rare, there have been several reports of it occurring after Roux-en-Y gastric bypass (RYGB) surgery.
Several hypotheses have been proposed for the etiology of islet cell hyperplasia following RYGB surgery: hormonal changes (possibly involving GLP-1, GIP, or ghrelin), unidentified factors from the proximal intestine, or disruption in the presurgery homeostasis of insulin resistance and hyperinsulinemia with rapid weight loss. →(3)

延伸閱讀：
**Hypoglycemia without diabetes**
✓ Drugs –
Insulin and insulin secretagogues →(1) other drugs such as ACEI and ARB, β-adrenergic receptor antagonists, quinolone antibiotics, indomethacin, quinine, and sulfonamides.
✓ Critical Illness Serious illnesses such as renal, hepatic, or cardiac failure; sepsis
✓ Hormone Deficiencies occur with prolonged fasting in patients with primary adrenocortical failure (Addison’s disease) or hypopituitarism. →(4)
✓ Non-a-Cell Tumors Fasting hypoglycemia, often termed non–islet cell tumor hypoglycemia, occurs occasionally in patients with large mesenchymal or epithelial tumors
✓ Endogenous Hyperinsulinism Hypoglycemia due to endogenous hyperinsulinism can be caused by
◼ a primary β-cell disorder—typically a β-cell tumor (insulinoma) ◼ an antibody to insulin or to the insulin receptor ◼ a β-cell secreta-gogue such as a sulfonylurea; ◼ ectopic insulin secretion
✓ Accidental, surreptitious, or malicious hypoglycemia
✓ Inborn errors of metabolism causing hypoglycemia

資料來源：Harrison 20e, uptodate

## Question 139:

10 以下有關糖尿病、高血壓及高血脂治療藥物的敘述，何者為錯誤的? (1)隨著年齡的老化，血糖控制的HbA1c及血壓控制範圍，高齡的糖尿病病患會較年輕的糖尿病患者寬鬆些 (2)目 前糖尿病高血壓治療的首選藥物為 Angiotensin converting enzyme inhibitor (ACEI)或 angiotension receptor blocker (ARB) (3)糖尿病患者如需藥物控制治療高血脂，其低密度膽固 醇(LDL-cholestrol) 之治療標的為低於130 mg/mL (4)糖尿病患者之高血壓控制目標，基本上 定在低於120/80 mmHg，如果合併蛋白尿時，血壓控制建議為低於110/70 mmHg (5)當 HbA1c、血壓及血脂均達到控制標準時，戒菸已無助於進一步降低糖尿病血管併發症之風 險。

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- A.(3)+(4)+(5)
- B.(1)+(3)+(5)
- C.(1)+(2)+(3)
- D.(1)+(4)+(5)
- E.(2)+(4)+(5)

### Correct Answer: A

(1) 我國糖尿病學會HbA1C的建議值目前也為低於 7.0 %，並建議空腹 血糖目標值為 80- 130mg/dl，餐後血糖目標值為≤160 mg/dl。 針對65歲以上的老年人
◼ 如果健康狀態正常者 (很少共病症，認知及身體機能正常 )，HbA1C的建議值為 <7.5%
◼ 如果健康狀態中等者 (多種共病症，認知及身體機能輕微至中等異常 )，HbA1C 的建議值為 <8%。
◼ 健康狀態較差者(末期慢性病，認知及身體機能中等至嚴重異常)，HbA1C的建議 值為 <8.5%。
(2) 第一線的降血壓藥物，從減緩腎病變的角度來看，建議考慮 ACEI 或 ARB。 (3) 糖尿病患者如需藥物控制治療高血脂，其(LDL-cholestrol) 之治療標的
◼ 未罹患心血管疾病: 低於100 mg/dl
◼ 罹患心血管疾病的糖尿病人，LDL的治療目標是低於 70 mg/dl
(4) 糖尿病患者之高血壓控制目標，基本上定在低於血壓控制於140/90 mmHg以下，合併 高血壓與蛋白尿的糖尿病人，血壓控制於130/80 mmHg以下
(5) Smoking cessation — A meta-analysis of many of the cardiovascular risk reduction trials showed that cessation of smoking had a much greater benefit on survival than most other interventions. These findings suggest that discontinuation of smoking is one of the most important aspects of therapy in patients with diabetes who smoke.

延伸閱讀： 資料來源： 中華民國內分泌暨糖尿病學會 2018糖尿病臨床照護指引, uptodate

## Question 140:

下列敘述何者為正確？
(1)類風濕性關節炎(RA)易肌腱骨接合點發炎(enthesitis)，乾癬性關節炎(Psoriatic arthritis,PSA)易關節滑膜炎(synovitis) (2)類風濕性關節炎(RA)易 侵犯遠端指間關節(Distal interphalangeal joint,DIP)，乾癬性關節炎(PSA)易侵犯近端 指端節(proximal interphalangeal join,PIP) (3)類風濕性關節炎(RA)易引起骨侵蝕，乾癬 性關節炎(PSA)易引起肌腱骨接合點發炎 (4)類風濕性關節炎(RA)大部分會產生自體 抗體，乾癬性關節炎(PSA)大部分不會產生自體抗體 (5)類風濕性關節炎(RA)主要是 機械性引起之發炎(Mechanical inflammation)，乾癬性關節炎(PSA)主要是自體免疫反 應造成(Autoimmune)

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- A.(1)+(2)
- B.(2)+(3)
- C.(3)+(4)
- D.(4)+(5)
- E.(1)+(5)

### Correct Answer: C

1. 相反。類風濕性關節炎(RA) 易關節滑膜炎(synovitis)，乾癬性關節炎(Psoriatic arthritis,PSA) 易肌腱骨接合點發炎(enthesitis)
2. 相反。類風濕性關節炎(RA) 易侵犯近端指端節(proximal interphalangeal join,PIP)及 MCP 掌指骨關節，乾癬性關節炎(PSA) 易侵犯遠端指間關節(Distal interphalangeal joint,DIP)
3. Correct
4. Correct
5. PsA is almost certainly immune-mediated and presumably shares pathogenic mechanisms with psoriasis. The pathogenesis of RA is built upon the concept that self- reactive T cells drive the chronic inflammatory response.

資料來源： Harrison's Principles of Internal Medicine, 20e Chapter 351/355

## Question 141:

下列藥物被建議在所有紅斑性狼瘡(SLE)病人長期使用？

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- A.endoxan
- B.hydroxychloroquine
- C.azathioprine
- D.高劑量類固醇 glucocorticoid
- E.抗生素以預防感染

### Correct Answer: B

A. C 用在狼瘡性腎炎病人治療有其角色。但毒性副作用強，僅能謹慎使用，不會用在所有紅斑性狼瘡(SLE)病人長期使用。
D. 在狼瘡性腎炎、狼瘡性腦炎、發血管炎或一些狼瘡活性引發的狀況時會短時間使用高劑量類固醇。
E.“抗生素以預防感染”顯然錯。

資料來源： Harrison's Principles of Internal Medicine, 20e Chapter 349

## Question 142:

下列抗體常合併間質肺疾病(interstitial lung disease)並快速影響生命危險？

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- A.anti- melanoma differentiation-associated protein 5(MDA5)Ab
- B.anti-Sm Ab
- C.anti-RNP Ab
- D.anti-dsDNA Ab
- E.anti histone Ab

### Correct Answer: A

anti-MDA5 antibodies are associated with amyopathic DM with severe palmar rash, digital ulcers, and rapidly progressive ILD…

延伸閱讀： Detection of anti-MDA5 antibodies was found to correlate with DM, and especially CADM, in the meta-analysis we performed. Moreover, anti-MDA5 antibodies showed good value in diagnosing CADM and were associated with an unfavorable prognosis in DM patients.

資料來源： Harrison's Principles of Internal Medicine, 20e Chapter 358 Li L, Wang Q, Yang F, et al. Anti-MDA5 antibody as a potential diagnostic and prognostic biomarker in patients with dermatomyositis. Oncotarget. 2017;8(16):26552–26564. doi:10.18632/oncotarget.15716

## Question 143:

一位65歲女性因全身無力及虛弱，深褐色小便及吞嚥困難而住院，三十五年前病人接受變性手術從男變女，此後就長期使用雌激素，一年半前有心臟引起的腦中風後 開始服用atorvastatin 及 Aspirin及利尿劑，身體檢查顯示上下肢近端肌肉無力，下列 主要檢查將最有可能於疾病診斷此病? (1)CK (2)anti-HMGCR (3)anti-sm (4)anti- topoisomerase 1 (5)anti-Ro Ab

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- A.(1)+(2)
- B.(1)+(3)
- C.(1)+(4)
- D.(1)+(5)
- E.(2)+(5)

### Correct Answer: A

The most important aspect of assessing individuals with neuromuscular disorders is taking a thorough history of the patient’s symptoms, disease progression, past medical and family history as well as performing a detailed neurologic examination. Based on this and additional laboratory workup (e.g., serum creatine kinase [CK], electromyography [EMG]) one can usually localize the site of the lesion to muscle (as opposed to motor neurons, peripheral nerves, or neuromuscular junction) and the pattern of muscle involvement. Ps.近端肌肉無力在風濕免疫科要注意多發性肌炎及皮肌炎的診斷，此題為 Drug induced myopathy會稍難些。


資料來源： Harrison's Principles of Internal Medicine, 20e Chapter 441

## Question 144:

承接上題，此病人最有可能患有？

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- A.紅斑性狼瘡(SLE)
- B.類風濕性關節炎(RA)
- C.感染心內膜炎
- D.藥物引起肌炎
- E.硬皮症

### Correct Answer: D


資料來源： Harrison's Principles of Internal Medicine, 20e Chapter 441

## Question 145:

一位60歲男性因急性痛風多次住院，他有腎結石、慢性腎病之病史，經檢查屬於尿酸製造增加之病人。下列敘述何者正確? (1)最好的降尿酸藥物為 allopurinol (2)此病 人目前急性痛風發作應可馬上給予 allopurinol 300mg/day (3)病人開始使用降尿酸藥 時，可同時給予colchicine 預防發作 (4)此病人最好的降尿酸藥物是 benzbromarone (5)此病人應長期服用降尿酸藥

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- A.(1)+(2)
- B.(1)+(3)
- C.(1)+(4)
- D.(2)+(4)
- E.(2)+(5)

### Correct Answer: B

(1) allopurinol 為用於治療抑制尿酸生成的降尿酸藥物。 (2)此病人急性痛風發作不適合馬上給予降尿酸藥物 allopurinol 屬於抑制尿酸生成的 降尿酸藥物。 (3)病人開始使用降尿酸藥時，可同時給予 colchicine預防發作 。colchicine可用於急 慢性痛風發作。 (4) benzbromarone屬於促進尿酸排泄的降尿酸藥物，不適合尿酸製造增加之病人。 (5)應先改善生活方式(如控制體重, 低嘌呤飲食, 減少酒精食用等), 不行再使用降尿 酸藥物控制

資料來源： Harrison's Principles of Internal Medicine, 20e Chapter 365

## Question 146:

一位45歲女性因手指及腳趾腫痛三年，其兩腳大拇指及右腳第二腳趾及左第三腳趾為像香腸樣的腫脹(Sausage-like)，anti-CCP 抗體及類風濕性固皆陰性，她的腳跟腱 (Achilles tendon)長期腫脹及疼痛，此病人最有可能之診斷為？

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- A.類風溼性關節炎(RA)
- B.紅斑性狼瘡(SLE)
- C.乾癬性關節炎(PSA)
- D.硬皮症(SSc)
- E.多發性肌炎(Polymyositis)

### Correct Answer: C

解 Dactylitis 表現為香腸樣的腫脹(Sausage-like) 。整個手指的軟組織腫脹，並且可能具 有類似香腸的外觀。 常見原因包括牛皮癬性關節炎，脊椎關節炎，少年型脊柱炎， 混合性結締組織病，硬皮病，結節病和鐮狀細胞病（sickle cell disease）。
**Psoriatic arthritis**:
clinical feature:
**arthropathy**
a.arthritis of DIP joints
b.asymmetric oligoarthritis
c.symmetric polyarthritis similar to RA
d.axial involvement(spine and sacroiliac)
e.arthritis mutilans

**nail change**
a. pitting
b. horizontal ridging
c. oncholysis
d. yellowishdiscoloration of nail margins
e. dystrophic hyperkeratosis

**eye involvement**
a. conjunctivitis
b. uveitis

資料來源：Harrison's Principles of Internal Medicine, 20e Chapter 55/363

## Question 147:

免疫抑制劑常用於治療自體免疫疾病及器官移植病人，下列敘述何為正確? (1)類固醇(corticosteroid)常引起骨質疏鬆(Osteoporosis) (2)Tacrolimus 及cyclosporine會引起 肌肉減少 (3)使用免疫抑制劑較少引起感染 (4)使用免疫抑制劑較不會引起乾癬 (5) 使用免疫抑制劑較不會造成腎臟破壞

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- A.(1)+(2)
- B.(1)+(3)
- C.(1)+(4)
- D.(1)+(5)
- E.(2)+(4)

### Correct Answer: A

(1) corticosteroid — Osteoporosis is a well-known adverse effect of glucocorticoid use (2) Tacrolimus/Cyclosporin — May cause musculoskeletal pain and weakness (3) Immunosuppressive agent — Increasing infection risk (4) 詳細請見延伸閱讀 (5) MTX, cyclosporin, tacrolimus…etc. — relative with nephrotoxicity 延伸閱讀：


資料來源： 1.UPTODATE: Overview of immunosuppressive agents used for prevention and treatment of graft-versus-host disease 2.UPTODATE: Psoriasis: Epidemiology, clinical manifestations, and diagnosis 3.MICROMEDEX

## Question 148:

一位30歲女性患有紅斑性狼瘡(SLE)多年，最近有三次流產並被診斷有抗磷脂抗體 症候群(Antiphospholipid Syndrome)下列敘述何者正確? (1)可以Aspirin 100mg/day 治 療 (2)可以Aspirin 330mg/day 治療 (3)可以服用避孕藥 (4)抽煙不影響病情 (5)再次懷孕時可打低劑量(heparin)

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- A.(1)+(3)
- B.(1)+(4)
- C.(1)+(5)
- D.(2)+(3)
- E.(2)+(5)

### Correct Answer: C

After the first thrombotic event, APS patients should be placed on warfarin for life, aiming to achieve an international normalized ratio (INR) ranging from 2.5 to 3.5, alone or in combination with 80 mg of aspirin daily. Pregnancy morbidity is prevented by administering low-molecular-weight heparin with aspirin 80 mg daily. 資料來源： Harrison's Principles of Internal Medicine, 20e Chapter 350

## Question 149:

硬皮症腎危急(scleroderma renal crisis, SRC)是嚴重且致命之急症其首選之治療藥物？

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- A.ACE-inhibitors (angiotensin-converting enzyme inhibitor)
- B.corticosteroids
- C.endoxan (cyclophosphamide)
- D.Immuran (azathioprine)
- E.methotrexate (MTX)

### Correct Answer: A

Scleroderma renal crisis is a medical emergency. Once other causes of renal disease are excluded, treatment should be started promptly with titration of short-acting ACE inhibitors, with the goal of achieving rapid normalization of the blood pressure. In patients with persistent hypertension, addition of angiotensin II receptor blockers, calcium channel blockers, endothelin-1 receptor blockers, prostacyclins, and direct renin inhibitors should be considered.

資料來源：Harrison's Principles of Internal Medicine, 20e Chapter 353

## Question 150:

下列有關 SLE 自體抗體與臨床表現之間的相關性，何者最為正確？

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- A.Anti-dsDNA 與 disease activity 有正相關
- B.Anti-SSB 與 nephritis 有正相關
- C.Anti-cardiolipin 與 neonatal lupus 的發生有關
- D.Anti-ribosomal P 與 mononeuritis multiplex 有正相關
- E.Anti-histone 與 thrombocytopenia 有正相關

### Correct Answer: A

(A)選項無誤 解 (B)anti-SSB(anti-La) 與 nephritis 是負相關 (C)anti-cardioplipin與fetal loss, thrombocytopenia 相關 (D)mononeuritis multiplex: Vasculitic neuropathy classically presents as multiple mononeuropathy (also called mononeuritis multiplex), which refers to an anatomic pattern of peripheral neuropathy that affects two or more noncontiguous named nerves simultaneously or sequentially Antni-ribosomal P 主要與CNS lupus有相關性 (E)anti-histone 跟drug induced lupus有關連性

資料來源： 1. Harrison’s principles of internal medicine 18th edition, chapter 319, p.2726, table 319-1 2. Uptodate ”Clinical manifestations and diagnosis of systemic lupus erythematosus in adults” 3. Uptodate “Clinical manifestations and diagnosis of vasculitic neuropathies”