Case Discussion <Case Presentation> A 75-year-old female patient was sent to emergency room (ER) due to consciousness disturbance for one day. She had diabetes mellitus, complicated with diabetic retinopathy and nephropathy, with oral antidiabetic agent treatment for 6-7 years. Besides, she had osteoporotic compression fracture of L1 and received calcium carbonate treatment since one month ago. She was noticed to have disorientation and agitated behavior abruptly one day prior to admission. There was no fever or head injury, but body weight loss (10 kgs/ 6 months) was noted. At ER, her consciousness was drowsy (Glasgow coma scale: E4V4M5). The blood pressure was 202/104 mmHg. The body temperature was 36.8 C, pulse rate was 89 beats per minute, and respiration rate was 18 per minute. Her skin was dry without petechiae. Her conjunctiva was pale and the neck was supple. The other physical findings were nonremarkable. The brain CT revealed no definite acute intracranial lesion. Laboratory data showed hypercalcemia (13.57 mg/dl), hypophosphatemia (1.8 mg/dl) and hyperglycemia (337.9 mg/dl). Other data are listed in Table 1 and 2. After admission, normal saline hydration, furosemide (Lasix) and clodronate sodium (Bonefos) infusion were given. Consciousness recovered after hypercalcemia improved. The plasma intact parathyroid hormone (i-PTH) level was found to be elevated (330 pg/ml). Thyroid echo showed left thyroid hypoechoic nodule and one hypoechoic nodule (0.9 x 0.4 cm) behind the right thyroid lobe (Figure 1). Parathyroid sestamibi scan revealed persistent abnormal accumulation of radioactivity at the inferior right thyroid bed in the early (15 min) and delayed (3 hr) imaging (Figure 2 ). Parathyroidectomy was done later and pathology report was adenoma of right lower parathyroid. She was discharged on the 4th day after operation when relative hypocalcemia (7.4 mg/dl) was noted. She was admitted again because progressive consciousness disturbance was found on the 7th day after operation when the serum calcium level was 5.29 mg/dl. She received oral calcium carbonate supplement and calcitriol treatment later. Table 1. Hematologic laboratory values on admission WBC K/μL RBC M/μL Hb g/dl Hct % MCV fL PLT K/μL Seg % Lym %  Mono % Eosin % Baso % 7.1 4.21 11.7 35.2 83.6 393 67.4 26.3 5.9 0.4 0.0 Table 2. Blood chemical values on admission BUN mg/dl Cre mg/dl Glu mg/dl Na mEq/L K mEq/L Ca mg/dl P mg/dl GPT IU/L NH3 μg/dl Alb g/dl Ketone body 12.7 0.71 337.9 138.2 3.10 13.57 1.8 26.6 32 4.59 Neg. Table 3. Endocrinology laboratory tests Cortisol (random) μg/dl (N: 3-25) T4 μg/dl (N: 5-12) Free T4 ng/dl (N: 0.9-1.8) T3 ng/dl (N: 70-190) TSH μIU/ml (N: 0.4-5.0)  PTH-intact pg/ml (N: 10-60) 15.63 4.91 1.09 48.39 0.41 330 EKG: non-specific ST-T change CXR: cardiomegaly, no active lung lesion 24-hrs urine calcium excretion: 811 mg/ day (normal range 100-300) CCr: 72.7 ml/ min Post-OP: serum i-PTH 3.5 pg/ml <病案分析> 這是一個原發性副甲狀腺功能亢進造成高血鈣症的案例，其臨床表現包括意識變化、骨折、體重減輕等。意識變化除了考慮腦血管病變、高低血糖的問題外，電解質不平衡亦應考慮。此案例曾因骨質疏鬆、腰椎骨折住院，沒有檢驗血中鈣離子濃度，而接受碳酸鈣補充治療。體內的總血鈣值受血中白蛋白的影響，所以要先校正或直接測量游離鈣。要鑑別診斷高血鈣症，要先檢查血中的完整型副甲狀腺素(i-PTH) 。除了副甲狀腺功能亢進，其他高血鈣症的原因還有惡性腫瘤、腎衰竭末期、內分泌疾病如甲狀腺功能亢進、腎上腺功能不足，肉芽腫病如結核病，藥物因素如Thiazide、Lithium及家族性低尿鈣高血鈣症等(familial hypocalciuric hypercalcemia)。原發性副甲狀腺功能亢進要尋找有無家族史，約有1-3%的病人是第一型多發性內分泌腫瘤(multiple endocrine neoplasia)。原發性副甲狀腺功能亢進有百分之八十以上是單一腺瘤所引起，15-20%為副甲狀腺增生，目前的標準療法是手術切除腺瘤或增生的腺體。高血鈣危症的治療除了大量的等張輸液灌注、視情形投與利尿劑，臨床上常用的降血鈣藥物為雙磷酸類(包括pamidronate、clodronate)及抑鈣素(calcitonin)。術前對副甲狀腺的定位檢查包括超音波、核醫攝影、電腦斷層、核磁共振等。有1-5%的病人術後因為骨骼的remineralization，會產生慢性低血鈣症，稱為hungry bone syndrome，須服用鈣片及維生素D治療。 繼續教育考題 1. (C) 1. 下列何者非為副甲狀腺素之主要作用器官 A 骨骼 B 腎臟 C 胰臟 D 以上皆是 E 以上皆非 2. (E) 下列何者可能是副甲狀腺機能亢進引起的症狀？ A 骨折 B 無力 C 尿路結石 D 意識改變 E 以上皆是 3. (C) 有一患者的血清calcium 7.5 mg/dl, glucose 540 mg/dl, sodium 135 mEq/L, BUN 28 mg/dl, albumin 2.5 g/dl，其血清鈣的修正值約為  A 7.2 mg/dl B 8.0 mg/dl C  8.7 mg/dl D  9.7 mg/dl E 6.7 mg/dl 4. (B) 副甲狀腺機能亢進大多是因為下列何者？ A 副甲狀腺增生 B 副甲狀腺腺瘤 C 副甲狀腺惡性腫瘤 D 家族性遺傳疾病 E 藥物引起 5. (E) 下列何種情況可能會產生高鈣血症？ A 原發性副甲狀腺機能亢進 B 惡性腫瘤 C 肉芽腫疾病 D  鋰鹽 E 以上皆會造成高鈣血症 6. (D) 下列何項對副甲狀腺機能亢進是最有效之治療？ A 補充生理食鹽水輸液 B 利尿劑 C 低鈣飲食 D 手術切除副甲狀腺 E 雙磷酸類Bisphosphate 7. (D) 副甲狀腺功能不足之患者除了補充鈣片外，還要補充何者維生素？ A 維生素A B 維生素B C 維生素C D 維生素D E 維生素E 8. (A) 上述維生素主要之作用器官為？ A 小腸 B 肝臟 C 骨頭 D 副甲狀腺 E 神經系統 9. (D) 副甲狀腺位於甲狀腺之後，請問一般人通常有幾顆副甲狀腺？ A 一顆 B 二顆 C 三顆 D 四顆 E 六顆 10. (C) 副甲狀腺的切除須要外科醫師的技術及良好的定位，請問下列何種方法較不可能幫助外科醫師判別是否正確切除副甲狀腺？ A 核醫攝影 B 超音波 C 醫師術前觸診頸部腫塊的位置 D 術中連續追蹤副甲狀腺素數值高低 E 術後追蹤鈣離子及副甲狀腺素 答案解說 (C)  副甲狀腺素可透過刺激骨骼的再吸收(resorption)、增加腎臟對鈣的重吸收(reabsorption)及促進活性維生素D的產生，以增加血清中的鈣濃度。 (E) 副甲狀腺功能亢進引起骨質疏鬆，容易骨折。高鈣血症使尿鈣的排泄量增加，易罹患尿路結石。高鈣血症也會影響腸胃道，甚至精神意識。 (C) 總血鈣值受血中白蛋白濃度的影響，可依下列公式修正: 總血鈣 [修正值(mg/dl)] =總血鈣 [測量值(mg/dl)] + 0.8 x [ 4.0 – 血中Albumin濃度(g/dl)] 。 (B ) 原發性副甲狀腺功能亢進有百分之八十以上是單一腺瘤所引起，15-20%為副甲狀腺增生，少於1%是因為副甲狀腺惡性腫瘤 (E ) 除了副甲狀腺功能亢進，其他高血鈣症的原因還有惡性腫瘤、內分泌疾病，肉芽腫病如結核病，藥物因素如Lithium及家族性遺傳疾病等 (D ) 手術切除腺瘤或增生的腺體是目前對於副甲狀腺機能亢進的標準療法，其他選項只是治療高鈣血症 (D)   副甲狀腺功能不足造成慢性低血鈣症，須服用鈣片及維生素D治療 (A ) 維生素D會增加腸胃道對鈣、磷的吸收 (D) 副甲狀腺一般是4個綠豆般大的腺體，藏於頸部甲狀腺的後面 (C)  術前對副甲狀腺的定位檢查包括超音波、核醫攝影、電腦斷層等，一般副甲狀腺功能亢進症摸不到頸部腫塊；術中或術後追蹤副甲狀腺素可評估是否已切除腺瘤或增生的腺體