Case Discussion < Chief complaint >      Intermittent fever for 3 days. < Brief History >      A 58-year-old woman had had type 2 DM for more than ten years with regular anti-diabetic medication control. She suffered from nervousness, excessive sweating, palpitations, insomnia and weight loss (5 kg in 2 months) without loss of appetite in recent two months. Three days prior to admission, intermittent low grade fever developed accompanied by lower abdominal dull pain, mild diarrhea, and dysuria. There was no cough, sputum, rhinorrhea or sore throat. Because of progressive dyspnea, orthopnea and a decrease in daily urine volume, she visited our ER where hyperthermia, irregular tachycardia with a pulse rate of 110/min, a grade II goiter, leukocytosis and pyuria were noted. Sudden onset of hypotension developed, after fluid resuscitation and inotropic support, she was admitted to ICU for further management.      She denied smoking, drug abuse, alcohol consumption, any systemic diseases and a family history of endocrine disorders.      Physical examination revealed a 54 kg, 156 cm-tall, woman with a blood pressure of 96/60 mmHg after infusion of inotropic agents. She appeared anxious and pale with clear consciousness. The temperature was 38.2°C, the pulse rate was 110 /min with irregular rhythm, and the breath was deep and fast with a respiratory rate of 27/min. The conjunctivae were pink, the sclerae were anicteric and the pupils were isocoric with prompt light reflex. There was no exophthalmos. The neck was supple without engorged jugular veins or lymphadenopathy. A grade II diffuse goiter with bruit was noted. The heart beat was irregular without significant murmurs. The thoracic, abdominal and back examinations were unremarkable. The extremities were freely movable without edema. < Laboratory data > 1. CBC/DC WBC RBC HB HCT MCV MCHC PLT K/μL  M/μL g/dL ％ fL g/dL K/μL 26.82 4.15 13 37.0 89.4 34.8 141 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 3.7 6.5 0.4 42  43 226 25  89 UN CRE Na  K Ca  Mg P CRP mg/dL mg/dL mmol/L mmol/L mmol/L mmol/L mg/dL mg/dL 12.2 0.5 134 3.4 2.1 0.82 3.0 12 3. Urine analysis Appearance Sp. Gr pH Protein Glucose Ketone Bacteria       g/dL mg/dL     Y;C 1.028 6.0 - - - 3+ Urobilirubin Bilirubin Nitrate WBC RBC Epi Cast       /HPF /HPF /HPF   1.0 - - 50-60 6-8 3-5 - 4. The results of basal endocrine and cosyntropin tests (250μg ACTH injection) hsTSH FT4 ACTH(0) Cortisol(0) Cortisol(30) MA TA  0.1-4.5 μIU/mL 0.60-1.75 ng/dL 10-65 pg/mL 5-25 μg/dL μg/dL     0.02 1.77 19.4 9.1 14.8 1:40(-) 1:40(-)  *high sensitivity thyroid-stimulating hormone＝hsTSH; free thyroxine＝FT4; corticotropin＝ACTH; 0 ＝ 0 min; 30 = 30 minutes after cosyntropin test; MA＝microsomal antibodies; TA＝thyroglobulin antibodies.   < Course and treatment >       Empirical antibiotics and continuous inotropic agent infusion were administrated, but the hemodynamic status was still instable. As adrenal insufficiency was suspected, hydrocortisone was injected after cosyntropin test, the result of which revealed that the adrenal cortex had inadequate response to ACTH stimulation. Clinical symptoms and signs, and thyroid function tests proved the diagnosis of thyroid storm. Propranolol and propylthiouracil followed by diluted Lugol's solution were administered. Both urine and blood cultures yielded E. coli. Thyroid echograms demonstrated a multinodular goiter, and renal echograms showed negative findings. Fever and tachycardia subsided gradually later and the dose of diluted Lugol's solution was tapered off gradually. She was discharged in a stable condition and was followed up regularly at our OPD with anti-thyroid drugs and steroid control. < Discussion >       甲狀腺毒性危象或甲狀腺風暴(thyrotoxic crisis或thyroid storm)是指所有甲狀腺功能亢進(hyperthyroidism)的症狀急劇惡化，這是非常少見的併發症，死亡率相當高。雖然偶而可以發生於甲狀腺手術後，但是通常發生在甲狀腺功能亢進病患未接受治療或控制不良，而又併發重病、手術、放射線碘治療或孕婦生產時。       典型的臨床表現包括顯著代謝率增加及過度腎上腺素反應。最常見的症狀為體溫上升，可以從38至41℃，並有皮膚潮紅和大汗淋漓。其他包括心跳過速(通常是心房纖顫，atrial fibrillation)、頻繁嘔吐及腹瀉、體重減輕、黃疸、極度消耗、譫妄、極度躁鬱不安、昏迷，最後死於休克、心肺功能衰竭及電解質紊亂(約半數患者有低血鉀症)。小部分患者臨床表現不典型，如表情淡漠、嗜睡、反射降低、低熱、惡病質、明顯無力、心率慢、及脈壓小，而突眼和甲狀腺腫常是輕度的，最後陷入昏迷而死亡，臨床上稱為淡漠型甲狀腺功能亢進(apathetic hyperthyroidism)。       有關甲狀腺風暴的致病機轉尚未完全闡明，目前認為可能與下列因素有關：有人認為導因於大量甲狀腺素(thyroid hormone)被釋放至血液中，但是實際上這些病人血中T4(thyroxine)及T3(triiodothyronine)值並沒有比其他甲狀腺功能亢進病人更高；相反的，卻有證據顯示這些患者增加了與catecholamine結合的位置，以致於心臟和神經組織增加敏感；除此之外，感染、疾病和手術都會使得甲狀腺素與甲狀腺結合球蛋白(thyroxine binding globulin，TBG)結合的濃度減少，而游離T3及T4增加。診斷除了依賴臨床症狀和表徵外，實驗室檢查包括T4、FT4及T3 上升，併有thyroid stimulating hormone (TSH)低下。      所有的病患都需要非常積極的治療：(一)抑制甲狀腺素的製造和分泌：抗甲狀腺藥物(propylthiouracil)可抑制甲狀腺素合成。給抗甲狀腺藥物約1小時後再給予碘劑，無機碘能迅速抑制TBG的水解而減少甲狀腺素釋放。(二)降低周邊組織對甲狀腺素的反應：碘和抗甲狀腺藥物只能減少甲狀腺素的合成和釋放，對於控制甲狀腺風暴的臨床表現作用不大。一般使用β腎上腺素阻斷劑(propranolol)來控制心律不整，如果病患有心臟衰竭或氣喘，可以改用verapamil。(三)支持性治療：保護體內各臟器系統，防止功能衰竭；發燒者給予acetaminophen，但是不可使用aspirin，因為會提高病人代謝率；高燒者可積極使用物理降溫，必要時考慮人工冬眠。由於高熱、嘔吐及大量出汗，患者易發生脫水及低鈉，應補充液體及電解質。另外，補充葡萄糖、大量維生素，尤其是B群；積極處理心衰竭(包括oxygen、diuretics及digitalis)。不建議所有的病患都給予腎上腺皮質素，因為大部分患者無腎上腺皮質功能不全，但是在危象時病患對腎上腺皮質素的需求量增加，故對有高熱及(或)休克的患者可加用腎上腺皮質素，除此之外，腎上腺皮質素還可抑制甲狀腺素釋放及T4轉變為T3。(四)積極控制誘因：有感染者應給予積極抗菌治療，伴有其他疾患者應同時積極處理。只有少數情況下才需要plasmapheresis或peritoneal dialysis。       迅速診斷及積極治療可以降低死亡率。如有高血壓、心臟擴大、心房纖顫、黃疸及低血鉀者則死亡率高。 < References > Alsanea O, Clark OH: Treatment of Graves's disease: the advantages of surgery. Endocrinol Metab Clin North Am 2000;29:321. Woeber KA: Update on the management of hyperthyroidism and hypothyroidism. Arch Intern Med 2000;160:1067. 繼續教育考題 1. (E) 下列何者可能是thyroid storm的臨床表徵？ A  Hyperpyrexia B  Atrial fibrillation C  Jaundice D  Hypotension E  all of above 2. (D) 下列何者非apathetic hyperthyroidism特色？ A 嗜睡 B 反射降低 C 心率慢 D 易發生於年輕人 E 體重減輕 3. (B) 下列何者非診斷thyroid storm所需條件？ A TSH低下 B T3非常高 C 心跳快 D 體溫高 E 代謝率快 4. (B) 下列何者非給予thyroid storm患者腎上腺皮質素的好處？ A 矯正腎上腺皮質功能不全 B 改善預後 C 矯正低血壓 D 抑制甲狀腺素釋放 E 抑制T4轉變為T3 5. (A) 建議使用抗甲狀腺藥物propylthiouracil來治療thyroid storm而非 methimazole之主要原因？ A 前者可以抑制T4轉變成T3 B 前者較長效 C 前者副作用少 D 前者可以大劑量服用 E 前者也可經肛門給予 6. (B) Thyroid strom的治療何者為非？ A  Propylthiouracil B  Aspirin C  Phenobarbital D  Propranolol E  Saturated solution of potassium iodide