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<Chief
complaint>
Recurrent bilateral flank soreness for one year.
<Brief
History>
A 58-year-old woman had been healthy before
until one year ago when she suffered from bilateral flank
soreness, gross hematuria and dysuria. She characterized the
discomfort as a constant dull ache accompanied by mild nausea.
Besides, she also complained of polyuria and polydipsia for a
long time. She visited a local hospital where urinalysis
showed many neutrophils and red blood cells, while plain
abdominal roentogenograms showed bilateral renal opacities,
indicating the diagnosis of urolithiasis with urinary tract
infection (UTI). She received empirical antibiotic treatment
and then underwent extracorporeal shock wave lithotripsy
(ESWL). She had experienced another three episodes of flank
soreness related to urolithiasis since then. Because of
recurrent bilateral flank soreness, urolithiasis and UTI, she
visited a professional clinic where elevation of serum calcium
level (2.77 mmol/L) was noted. Under the impression of
hypercalcemia with recurrent urolithiasis, she was admitted
for further management.
Throughout her disease course, there was no
hypertension, peptic ulcer disease, fracture, constipation or
abdominal pain. She denied smoking, medication, alcohol
consumption, calcium or vitamin supplementation and a family
history of hypercalcemia.
Physical examination revealed a well-nourished
woman whose consciousness was clear, blood pressure was 120/80
mmHg, respiratory rate was 18/min, pulse rate was 82/min and
temperature was 36.5℃. The conjunctivae were pink, the sclerae
were anicteric and the pupils were isocoric with prompt light
reflex. The neck was supple without a goiter, palpable masses,
lymphadenopathy or engorged jugular veins. The chest, abdomen,
back, extremities and skin were all unremarkable.
<Laboratory
data>
1. CBC/DC
| WBC |
RBC |
HB |
HCT |
MCV |
MCHC |
PLT |
| K/μL |
M/μL |
g/dL |
％ |
fL |
g/dL |
K/μL |
| 5.38 |
3.87 |
12.0 |
33 |
91.6 |
33.4 |
348 | 2. BCS+e-
| ALB |
TP |
T-Bil |
AST |
ALT |
ALP |
γ-GT |
Glucose |
| g/dL |
g/dL |
mg/dL |
U/L |
U/L |
U/L |
U/L |
mg/dL |
| 4.1 |
7.0 |
0.4 |
27 |
25 |
430 |
25 |
90 |
| UN |
CRE |
Na |
K |
Ca |
P |
Cl |
iPTH |
| mg/dL |
mg/dL |
mmol/L |
mmol/L |
mmol/L |
mg/dL |
mmol/L |
pg/mL
(12-72) |
| 17.6 |
0.7 |
140 |
4.1 |
3.13 |
2.7 |
109 |
141 |
3. Urinalysis
| Appearance |
Sp. Gr |
pH |
Protein |
Glucose |
Ketone |
Crystal |
| |
|
|
g/dL |
|
mg/dL |
Ca-OX |
| Y;C |
1.024 |
6.0 |
- |
- |
- |
3+ |
| Urobilirubin |
Bilirubin |
Nitrate |
WBC |
RBC |
Epi |
Cast |
| |
|
|
|
|
HPF |
|
| 1.0 |
- |
- |
35-50 |
25-35 |
3-5 |
- |
<Course &
treatment>
The patient's serum biochemistries
revealed hypercalcemia and mild hypophosphatemia. Serum level
of intact parathyroid hormone (iPTH) inappropriately increased
(141 pg/mL), which was compatible with a primary
hyperparathyroidism. Intravenous hydration with normal saline
followed by loop diuretics was given immediately. Neck
sonograms showed enlargement of the right inferior parathyroid
gland (0.7 x 0.6 x 0.6 cm). Echo-guided aspiration cytology
reported typical chief cells. Parathyroid adenoma was
suspected. Pre-operation localization with 201T1
and 99m
Tc
subtraction scans showed a focal tracer accumulation in the
right lower pole of the thyroid (Fig
1 &
2
). Bone survey showed no evidence of osteolytic bone
lesions in the skull, spine, pelvic and long bones. She
underwent surgical exploration of the neck which revealed a
soft nodule about one centimeter in diameter located behind
the right lower pole of the thyroid gland. The right superior,
left superior, and left inferior parathyroid glands appeared
normal. The pathology of the nodule confirmed the diagnosis of
parathyroid adenoma. Post-operation course was smooth without
any hypocalcemic episode. She was discharged and followed up
in the OPD.
<Discussion>
副甲狀腺(parathyroid
glands)位於甲狀腺附近，通常是由4個腺體組成。原發性副甲狀腺機能亢進症(primary
hyperparathyroidism)是高血鈣最常見的原因，每年每十萬人約有42人發現此病，然而超過60歲的女人，每1000人便有4人有原發性副甲狀腺機能亢進症，女性為男性的2-3倍之多。過多的副甲狀腺素(parathyroid
hormone，PTH)會增加骨頭再吸收、增加腸道吸收鈣及降低腎臟排泄鈣，而導致高血鈣。
80%的原發性副甲狀腺機能亢進症是因為副甲狀腺瘤(parathyroid
adenoma)，15%是原發性過度增生(primary
hyperplasia)，而1-2%是副甲狀腺癌(parathyroid
carcinoma)造成的，後者因為常會有相當嚴重的高血鈣及可觸摸到的頸部腫塊，一般於手術前就可以確定。也有可能是家族性內分泌疾病造成4個腺體都過度增生，如多發性內分泌腫瘤(multiple
endocrine neoplasia 1 & 2A)及isolated familial
hyperparathyroidism。
高血鈣會影響身體許多器官，因此造成諸多症狀及疾病：如對中樞神經系統造成疲勞、憂鬱、精神病、步履不穩、僵呆及昏迷；對神經肌肉造成無力、近端肌病變；對心臟血管形成高血壓、心跳緩慢，縮短QT
interval；促進腎臟結石形成、降低腎絲球過濾率、多尿、高血氯性酸中毒、腎鈣化症(nephrocalcinosis)；對腸胃道的影響包括噁心、嘔吐、便秘及食慾不振；另可以發現眼睛有帶狀角膜病變(band
keratopathy)；骨頭會有囊狀纖維性骨炎(osteitis fibrosa
cystica)及骨質疏鬆症；也會造成全身轉移性鈣化(systemic metastatic
calcification)。然而隨著血液篩檢的普及，這些病人通常是沒有症狀且也大大降低其併發症的發生。
實驗室檢查可以發現高血鈣及低血磷，因為PTH會促進腎臟排泄磷，另外也會出現輕微的高血氯代謝性酸中毒，因此如果血氯與血磷的比值大於33則可以高度懷疑是原發性副甲狀腺機能亢進。當血中intact
PTH高於正常值或於正常值上限時就可以診斷為原發性副甲狀腺機能亢進，但是有一個例外－家族性良性低尿鈣高血鈣症(familial
benign hypocalciuric
hypercalcemia)，後者需要再測24小時尿鈣排泄量。因為高骨頭轉換率(high bone
turnover)，所以alkaline phosphatase值也會上升。
對於高血鈣症危象(hypercalcemia crisis)應該緊急給予治療，包括適當給予輸液及loop
diuretics，增加鈣由尿液中排出；再給予雙磷酸鹽類(bisphosphonate)及降鈣素(calcitonin)抑制骨骼之蝕骨作用。當然，最重要是治療潛在的疾病。
最確定的治療是副甲狀腺切除(parathyroidectomy)。有關手術前的定位，目前建議頸部超音波及Tc-99m
sestamibi為起始的定位方法，其他尚有核磁共振攝影、血管攝影、細針抽吸等，另外還有T1-201/Tc-99m
subtraction
scans，主要是由於T1-201可被甲狀腺和副甲狀腺攝取，而Tc-99m會被甲狀腺和唾液腺攝取，將前者的影像減掉後者即可觀察到副甲狀腺腺瘤，如同這位病人。手術切除的併發症包括反喉神經損傷及永久性副甲狀腺低能症，對有經驗的外科醫師而言，其發生率小於1%。
<References>
- Hyperparathyroid and
hypoparathyroid disorders. N Engl J Med 2000;343:1863.
- Hypercalcemia. Curr Probl Surg
2002;39:349.
- Therapeutic controversies in primary
hyperparathyroidism. J Clin Endocrinol Metab
1999;84:2275.
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Case Discussion
繼續教育考題