網路內科繼續教育
有效期間:民國 95年01月16日 95年01月31日

    Case Discussion

< 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。

< References > 

  1. Greger NG, Kirkland RT, Clayton GW, et al: Central diabetes insipidus. 22 years' experience. Am J Dis Child 1986;140:551-4.
  2.  Maghnie M, Cosi G, Genovese E, et al: Central diabetes insipidus in children and young adults. N Engl J Med 2000;343:998-1007.
  3. Maghnie M, Villa A, Arico M, et al: Correlation between magnetic resonance imaging of posterior pituitary and neurohypophyseal function in children with diabetes insipidus. J Clin Endocrinol Metab 1992;74:795-800.
  4. Mootha SL, Barkovich AJ, Grumbach MM, et al: Idiopathic hypothalamic diabetes insipidus, pituitary stalk thickening, and the occult intracranial germinoma in children and adolescents. J Clin Endocrinol Metab 1997;82:1362-7.
  5. Imura H, Nakao K, Shimatsu A, et al: Lymphocytic infundibuloneurohypophysitis as a cause of central diabetes insipidus. N Engl J Med 1993;329:683-9.
  6. Fujisawa I, Asato R, Okumura R, et al: Magnetic resonance imaging of neurohypophyseal germinomas. Cancer 1991;68:1009-14.
  7. Leger J, Velasquez A, Garel C, et al: Thickened pituitary stalk on magnetic resonance imaging in children with central diabetes insipidus. J Clin Endocrinol Metab 1999;84:1954-60. 
        

繼續教育考題
1.
(E)
對於一個多尿的患者,下列何者檢查可以排除滲透性利尿?
A尿液滲透壓
B尿液比重
C血液滲透壓
D血中鈉離子濃度
E(A)、(B)均可
2.
(B)
下列何者最不可能是尿崩症患者(尚未治療)的資料?
A血漿滲透壓 280 mosm/kg
B尿液滲透壓 280 mosm/kg
C尿液比重 1.002
D血液鈉離子濃度140 meq/mL
E血漿滲透壓 300 mosm/kg
3.
(C)
限水試驗時,下列何者最不可能是尿崩症患者的資料?
A血漿滲透壓290 mosm/kg
B尿液滲透壓 100 mosm/kg
C尿液比重 1.012
D血液鈉離子濃度140 meq/mL
E每小時尿量200 mL
4.
(D)
下列何者可以區分中樞性尿崩症和腎性尿崩症?
A血漿滲透壓
B尿液滲透壓
C每小時尿量
D限水及血管加壓素試驗(dehydration-vasopressin tests)
E病史
5.
(D)
下列敘述何者有誤?
A雖然診斷為中樞性尿崩症,仍需檢驗腦下腺前葉功能
B作限水及血管加壓素試驗時,除了測血漿滲透壓、尿液比重及滲透壓、 尿量外,仍需監測病人的血壓及體重
C尿崩症也可能是遺傳造成的
D生殖細胞瘤通常會使得腦下腺前葉變小且伴隨著柄變厚
E滲透性利尿患者之尿液滲透壓較高
6.
(B)
有關原發性多飲症患者的敘述何者有誤?
A從病史很難和尿崩症患者區分
B可以從血液及尿液滲透壓與尿崩症患者區分
C需要作限水試驗來與尿崩症區分
D作試驗期間應全程有醫護人員在場
E原發性多飲症病人的血漿和尿液是較稀釋的。
7.
(A)
中樞性尿崩症在影像檢查有何特色?
A在核磁共振檢查時,腦下腺後葉缺乏高訊號
B在電腦斷層檢查時,腦下腺後葉密度增加
C在電腦斷層檢查時,為空蝶鞍(empty sella)
D腦下腺前葉變大且伴隨著柄變厚
E以上皆非
8.
(C)
下列何者是中樞性尿崩症最常見的原因?
A神經系統腫瘤
B發炎反應
C不明原因
D結節病
E組織細胞增生症X
9.
(E)
使用desmopressin需要注意哪些?
A體重
B鈉離子濃度
C血壓
D水量攝取
E以上皆是
10.
(A)
下列何者非desmopressin的副作用?
A高血鉀
B腹痛
C低血鈉
D口乾
E頭痛

答案解說

  1. E】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。
  2. B】在正常飲食的情況下,尿崩症和原發性多飲症患者的尿液滲透壓遠低於 血漿滲透壓。
  3. C】限水試驗時,完全性尿崩症的病人仍會有大量的尿液,而且尿液的比重仍然會小於1.005。
  4. D】尿崩症分為中樞性尿崩症及腎性尿崩症(nephrogenic),前者是因為缺乏血 管加壓素,而後者是腎臟對血管加壓素有抗性。因此藉由限水及血管加壓素試驗(dehydration-vasopressin tests)可以確定診斷。
  5. D】生殖細胞瘤通常會使得腦下腺前葉變大且伴隨著柄變厚。
  6. B】(A)尿崩症和原發性多飲症患者均有多喝及多尿症狀,因此無法從病史來區分。(B)(C)限水試驗才能區分原發性多飲症及尿崩症患者。(D)尿崩症病患因為尿量多但是又無法喝水可能會出現低血壓,而原發性多飲症患者可能會禁不住而喝水,因此需要全程有醫護人員陪伴。
  7. A】核磁共振(T1-weighted)影像檢查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。
  8. C】約30%到50%的中樞性尿崩症是不明原因(idiopathic)的。
  9. E】使用desmopressin需注意fluid intake, serum Na, weight and blood pressure.
  10. A】Desmopressin的副作用包括headache, abdominal pain, nausea, hyponatremia, dizziness, peripheral edema, daytime polyuria, stomach pain, dry mouth, weight gain, emotional disturbance in children, allergic skin reactions.


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