< Presentation of Case >
A 61-year-old female patient, previously healthy, was brought to our outpatient clinic because of progressive generalized pain, easy fatigability, and decreased appetite for 1 year. The past medical history of the patient and her family was unremarkable. On physical examination, her blood pressure was 138/86 mmHg. Her conjunctivae were pale, sclerae were anicteric. There was a palpable nodule in the inferior pole of the left lobe of the thyroid gland. Biochemical investigations showed elevated serum calcium and creatinine levels, decreased serum phosphate concentrations, together with an increased parathyroid hormone (PTH) level (Tables, laboratory data). Her 24 hour urine calcium excretion was 588 mg/day, with fasting urinary calcium/creatinine ratio being 0.56 (normal, <0.2). Thyroid ultrasonography disclosed a nodule adjacent to the inferior pole of the left lobe of the thyroid gland. Renal ultrasonography revealed a right renal stone. Technetium-99m sestamibi scan suggested a left-sided parathyroid adenoma (Figure 1). These above laboratory findings were compatible with primary hyperparathyroidism complicated with renal insufficiency and nephrolithiasis. She was then admitted for operation. Parathyroidectomy was performed and biopsy showed parathyroid adenoma. On the first postoperative day, the serum calcium level decreased to 7.1mg/dl and further fell to 6.7 mg/dL on the second day despite intermittent calcium supply administered by vein. Numbness over her circumoral region and tingling over her fingers and toes were experienced with positive Chvostek's sign and Trousseau's sign. She subsequently received continuous intravenous calcium infusion until the seventh postoperative day. She was discharged on the 15th day postoperatively with oral calcium supplement and calcitriol. Dosage of calcitriol and calcium supplement was gradually tapered and then stopped for five months after surgery, when her parathyroid hormone, serum calcium, and serum phosphate were within normal limits.
< Laboratory data >
Laboratory data before and after the parathyroidectomy
Lab test |
Ca
(mg/dl) |
Pi
(mg/dl) |
Cr
(mg/dl) |
iPTH
(pg/ml) |
Alk-p
(U/l) |
Spot Urine Ca/Cr |
Reference value |
8.2-10.6 |
2.5-4.5 |
<1.5 |
12-72 |
53-141 |
<0.2 |
Pre-OP |
12.2 |
2.1 |
1.7 |
1087 |
1614 |
0.56 |
Post-OP Day 1 |
7.1 |
1.9 |
1.7 |
1.2 |
NM |
NM |
Day 2 |
6.7 |
1.8 |
NM |
NM |
NM |
NM |
Day 7 |
9.2 |
1.6 |
NM |
NM |
NM |
NM |
Day 15 |
10.2 |
3.5 |
NM |
NM |
NM |
NM |
Fifth month |
9.8 |
4.2 |
1.7 |
48 |
307 |
0.08 |
***intact parathyroid hormone＝iPTH
***not measured = NM
< 病例解析 >
在非住院的人口中，高血鈣的原因最常見為副甲狀腺功能亢進。而當生化檢查出有高血鈣、高副甲狀腺素的時候，必須排除掉病人是否有服用鋰鹽、是否有家族遺傳性的低尿鈣高血鈣症( familial hypocalciuric hypercalcemia, FHH)之後，才可以認定是副甲狀腺功能亢進。一般由藥物史、尿液鈣 ( 24小時尿鈣> 4 mg/kg 或尿鈣排出分率> 2%即可排除FHH ) 便可排除前二者。至於原發性副甲狀腺功能亢進，當中大約有90%為腺瘤過量分泌副甲狀腺賀爾蒙，其他約10%的病人則是腺體增生引致功能亢進，極少數少於1%因為副甲狀腺惡性腫瘤所引起。 副甲狀腺素主要作用在骨骼和腎臟，能促進鈣離子自骨質再吸收(bone resorption)及腎小管再吸收鈣而釋出鈣到血液，同時增加磷在尿中之排除，當功能亢進時血鈣便會增多，磷則減少，骨鈣移至血液中，於是骨質變得疏鬆、疼痛，又因血鈣過高，使尿中鈣的排出量增加，甚至會形成腎結石。根據美國國家衛生總署2002年專家小組會議 (2002 NIH consensus conference)，病人如果只是血鈣稍高又無症狀，腎臟和骨骼都正常，可以暫不開刀，但需長期追蹤血鈣、腎功能、骨質密度及腹部x光等。 並應多喝水，常運動，避免服用某些利尿劑，如thiazides。根據美國國家衛生總署2002年專家小組會議，有明顯症狀如腎結石或纖維囊狀骨炎(osteitis fibrosa cystica)、血鈣濃度多出標準值上限1 mg/dl、腎功能(creatinine clearance)低於同年紀族群30%以上、24小時尿鈣大於400 mg、骨質疏鬆(骨密度T score < -2.5) 和年齡小於50歲等可以考慮開刀，但這些評估標的並非是絕對的，視病人與臨床情況為準。而因副甲狀腺切除術後所致之低血鈣的機率有13-30%之多，多半是暫時性的，可能是短暫性的數天，原被壓抑之正常副甲狀腺體即恢復功能、維持正常血鈣；也可能發生嚴重之低血鈣症，如同本文病人，稱之為骨頭飢餓症候群 (hungry bone syndrome)，在手術後便須積極治療，待一段時間後才能停止治療。另也可能因切除過多腺體造成永久性副甲狀腺功能低下，必須終身補充鈣片及維他命D。骨頭飢餓症候群的機轉可能是正常副甲狀腺腺體長期被腺瘤抑制而萎縮、或是術中副甲狀腺暫時性缺氧缺血造成，因術後還無法快速恢復功能、喪失原來促骨質再吸收的作用，導致骨頭大量再礦化 (remineralization)，而造成嚴重低血鈣、低血磷。危險因子包括較大的腺瘤、較高的術前BUN、較高的alkaline phosphatase、及較大的年紀。有些研究指出在術前給予雙磷酸鹽類可以預防此症候群的發生，但機轉不明。一般在副甲狀腺切除術後的48至72小時內須每4-6小時追蹤血鈣值，當血鈣值低於7.2 mg/dl時, 就應該立刻給予10% calcium gluconate 10 ml靜注點滴10 分鐘 (約含90 mg元素鈣)，而後維持連續靜脈滴注元素鈣100 mg/hr的速度治療，若在積極靜脈補充鈣時仍持續低血鈣，便須一併監測血鎂濃度。當病人可以使用口服藥物時，慢慢降低鈣針劑代之以口服，長期可以補充鈣片(每天至少1克元素鈣)及活性維生素D3 (1, 25-dihydroxy vitamin D3)(每天約0.5-2µg)來治療低血鈣直到腺體功能恢復。治療的目標以維持血鈣在8-8.6 mg/dl 左右，並儘可能保持尿鈣在30 mg/dl 以下，必要時可加上thiazide類利尿劑以增加鈣在腎臟之回收，以免腎結石。
< 參考文獻 >
- Fraser WD. Hyperparathyroidism. Lancet. 2009;374(9684):145-58.
- Iglesias P, Diez JJ.Current treatments in the management of patients with primary hyperparathyroidism. Postgrad Med J. 2009;85(999):15-23.
- Bilezikian JP, Khan AA, Potts JT Jr. Guidelines for the management of asymptomatic primary hyperparathyroidism: summary statement from the third international workshop.J Clin Endocrinol Metab. 2009;94(2):335-9.
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Case Discussion
繼續教育考題