高血鈣

簡介:

    -血鈣由副甲狀腺, 骨骼細胞,促鈣三醇, 腎小管及小腸共同維持在一狹小範圍內。
    -在血中之攜鈣蛋白正常下, 血鈣高於正常 ( > 10.2 mg/dL) 就應警覺。
    -生理具活性的鈣是 free or ionized (iCa)
    -serum Ca reflect total Ca (bound + unbound), it influenced by albumin (主要與鈣結合的蛋白)

    -白蛋白下降1, 血鈣需向上校正0.8
    *Corrected Ca = 測得Ca + ( 0.8 x (4-albumin))
    -Alkalosis 會導致更多的鈣與albumin結合 (造成total Ca可能正常, 但測iCa卻是下降的)
    -直接測 iCa 是最好的方法

診斷:
    -副甲狀腺亢進及癌症占90%
          -無症狀or 慢性高血鈣 ->↑副甲狀腺亢進
          -有症狀, overt or 急性(數月內)高血鈣 ->  癌症
    -check Ca, albumin, iCa, iPTH, PO4
    -依結果, 考慮測: PTHrP, 25-(OH)D, 1,25-(OH)2D, ALK P, Uca, SPEP, UPEP, ACE, CXR/CT, mammogram

Ca	iPTH	PO4	dz
↑	↑↑	↓	副甲狀腺亢進 (1°, 3°)
	↑or nl	↓	Familial hypocalciuric hypercalcemia
	↓	Var.	癌症
		↑	Vit D excess
		↓	Milk-alkali synd, thiazides
		↑	↑Bone turnover
↓	↑↑	↑	Pseudohypoparathyroidism
	↑	↓	Vit D defi
		↑	Chronic renal failure ( 2°hyperpara-)
	Var.	var.	Acute Ca sequestration
	↓	↑	副甲狀腺低下

高血鈣	病因
Hyperparathyroidism (HPT)	-1°: (80% asx, 20% 腎結石, 骨質疏鬆) -adenoma (85%) -Hyperplasia (15-20%; spont vs. MEN 1, MEN2A) -Carcinoma (<1%) -3°:   -長期腎衰竭 (2° hyperparathyroidism後) -> 副甲狀腺結節 (autonomous nodule) dev (需手術) -鋰鹽 (->↑PTH)
Familial hypocalciuric hypercalcemia (FHH)	Inactivate 副甲狀腺/腎臟細胞內Ca-sensing R的突變-> ↑Ca set point ±↑PTH, Acquired form, due to autoAb vs. Ca-sensing R (rare) FEca < 0.01 [(24h UCa/serum Ca) / (24h UCr/ serum Cr)
Malignancy	-分泌PTHrP (鱗狀細胞癌, 腎,乳,膀胱癌) -血液癌 (cytokines & 1,25-(OH)2D3 -乳癌,骨髓癌 (local osteolysis)
Vit D excess	Granulomas (sarcoid, TB, histo, Wegener’s) ->↑1-OH ->↑1,25-(OH)2D
↑Bone turnover	甲狀腺亢進, Immobiliztion + Paget’s dz, Vit A,
Misc	-Thiazide, -含鈣制酸劑 or 食入大量乳製品(milk-alkali synd) -Adrenal insuff
住院病人高血鈣	45% - 癌症 25% - 1°HPT 10% - CKD ->3°HPT

臨床表現: (bones, stones, abdominal groans and psychic moans)

  -Hypercalcemic crisis (當血鈣 > 13): 多尿,脫水,意識改變
      -過高血鈣毒害腎小管
         ->阻斷ADH活性,
               ->導致血管收縮,↓GFR,
               ->多尿
        ->增加血鈣再回收->高血鈣->腎毒性, CNS症狀

  -骨骼: 骨質疏鬆 (osteopenia), 骨折,
              Osteitis fibrosa cystica (只見於嚴重的副甲狀腺亢進
                 ->↑osteoclast活性->骨X-ray: cysts, fibrous nodules, "salt&pepper樣")
  -泌尿道: 腎結石, nephrocalcinosis, nephrogenic DI (多尿)
  -腸胃道: N/V/A, 腹痛',便秘,胰臟炎,消化性潰瘍
  -中樞:  疲倦, 無力, 憂鬱, 混亂, 昏迷, ↓DTRs
  -心臟:  short QT interval
  -血管:  皮膚壞死
     Calciphylaxis (calcific uremic arteriopathy)
      -真皮層/皮下脂肪之小~中型血管的media層鈣化 ->造成皮膚缺血/壞死 (NEJM 2007;356:1049)
      -a/w uremia
      -↑(PTH, Ca, PO4, (Ca x PO4) product)
      -診斷: by biopsy
      -治療:
           -aggressive wound care
           -降血鈣, keep Ca x PO4 nl (goal < 55)
           -避免給予 vit D 及 鈣片
       * iv Na thiosulfate & 副甲狀腺切除 controversial
      -預後: poor

---------------------------------------------------
   -副甲狀腺亢進可見:
        -osteitis fibrosa cystica (纖維性骨炎骨囊腫)樣放射線學變化
        -尿路結石,
   -其他原因之高血鈣表現:
        -多尿 (腎性尿崩)
        -噁心,食慾差,消瘦,無力,便秘
        -消化性潰瘍,
        -意識障礙,
   -EKG: QT 縮短, PR prolong


---------------------------------------------------
治療:

高血鈣急性治療 (NEJM 2005;352:373)
Treatment	onset	duration	NOTE
N/S (4-6L/d)	h		Natriuresis ->增加腎臟Ca排出
± Lasix	h		Volume 過多時才用
雙磷酸鹽	1-2d	Var.	-抑制破骨細胞 -只對癌症高血鈣有用 -腎衰竭病人要小心 -[副]: 下巴骨壞死(危險)
Calcitonin	h	2-3d	很快造成 tachyphylaxis
Steroid	days	days	? 用於某些癌症, 肉芽腫疾病, vit D中毒

無症狀 1° HPT高血鈣之治療

 -OP, if

    1) 50歲以下

2) 血鈣比正常上限高出 1mg/dL

3) 腎功能差 (CrCl < 60)

4) 骨質疏鬆嚴重 (DEXA T score < -2.5)

 -未達手術標準者:

    -每年抽血Ca, Cr, 做BMD

    -? 給予雙磷酸鹽, estrogen, SERMs, calcimimetic

 

治療:
    N/S (4-6L/day)
    Lasix (20mg iv q6h)
    Steocin (calcitonin)(50U/支=117元): 4u/kg (q12-q8-q6h)
        -200u q12h (ivd (in N/S 100ml), im, sc, 鼻噴劑)
        -150u SC q8h (450u/d)
        -50u IM qd

    Bonefos (clodronate)(300mg/支)
        -1-2支/day, ivd (in N/S500ml x4h) (x3d (7d max)
        -2# bid
       [忌]: 勿併 鎂制酸劑, 錳, 鐵

    Steroid (for 血液癌 only)
      Rinderone (4mg, 1支 bid)
      Methasone (solumedrol) (4mg) 1# bid

    急洗 .