甲狀腺亢進 hyperthyroidism and Graves' disease

甲狀腺腫大常見原因
1. Graves' disease 葛瑞夫茲氏病
2. 單純性甲狀腺腫
3. 甲狀腺炎
4. 甲狀腺腫瘤

甲狀腺亢進診斷, 通常是抽 TSH + free T4
1. 血液中之T3及T4 (或FT4) 上升
2. TSH下降
3. 頸部均勻腫大
如果出現心律不整, 最常見的是 Af 心房顫動

甲狀腺亢進是一種自體免疫疾病 ( Graves disease)
90% 病患血中會出現TSH receptor Ab (甲促素接受器抗體)
(另一篇文獻是說, 70% 是 Graves disease)
抗體作用在甲狀腺上, 會刺激甲狀腺製造過多甲狀腺素

追蹤檢查
1. 需定期追蹤 free T4, 有時候也可以加驗 T3
2. TSH 判讀需謹慎, 因為剛開始治療的前幾周, 即使病患甲狀腺功能已經恢復, TSH 不會很快上升, 仍會維持在較低數值一段時間, 甚至病患已經發生甲狀腺功能低下, TSH 還會偏低
Thyroid function tests — Whatever treatment is used, initial monitoring should consist of periodic clinical assessment and measurements of serum free T4 and often total T3 levels. Serum TSH concentrations should be interpreted with caution since they may remain low for several weeks after the patient becomes euthyroid and may even remain low transiently in patients who have become hypothyroid.

開始服用 thionamides 之後, 每 4-6 周需再次評估, 以調整劑量

穩定之後每 3 到 6 個月追蹤一次

如果治療六個月之後, 病患TSH仍偏低, 則停藥之後疾病緩解的機率極低

如果經過一年至數年治療, 病患的甲促素接受器抗體濃度仍偏高, 也不太可能在停藥之後疾病緩解

即使病患沒有症狀, 且甲促素受器抗體濃度低, 停藥之後仍有 20% 機率復發

如果想停用抗甲狀腺素藥物 , 必須先想好復發之後的治療應如何進行

例如使用放射性碘治療, 或手術治療

或再次服用 thionamide 1-2 年

Euthyroid 沒有甲狀腺相關症狀的狀態(但TSH, free T4未必正常)

●Thionamides – Patients should have their thyroid function assessed at four- to six-week intervals until stabilized on maintenance thionamide therapy, then at three- to six-month intervals. Patients with persistently low serum TSH concentrations after more than six months of therapy with a thionamide are unlikely to have a remission when the drug is stopped. Patients with persistently high levels of TSH-receptor antibodies (TRAb, thyroid-stimulating immunoglobulins [TSI]) after one or more years of treatment are also unlikely to remain euthyroid if thionamides are discontinued [17]. Even patients who are euthyroid and have low levels of TRAb have a 20 percent risk of relapse. Therefore, before trying to discontinue the thionamide, a plan should be established for subsequent treatment of recurrent hyperthyroidism, either definitive therapy (radioiodine or surgery) or another one- to two-year course of a thionamide.

放射性碘, 治療之後 4-6 周抽血檢驗 free T4, T3, TSH

之後每 4-6 周追蹤一次, 連續追蹤六個月, 或追縱到甲狀腺功能低下, 且開始服用 levothyroxine 為止
●Radioiodine – For patients treated with radioiodine, we measure free T4, total T3, and TSH four to six weeks after treatment, and then free T4 and TSH (and total T3 if still hyperthyroid) at four- to six-week intervals for up to six months, or until hypothyroid and on stable doses of levothyroxine.

手術, Graves' disease 經切除全部或將近全部的甲狀腺之後, 如果病患已經沒有甲狀腺亢進症狀,出院前需補充甲狀腺素, 6-8 周後抽血追蹤 TSH , 目標是將 TSH 維持在正常範圍
●Surgery – For patients with Graves' disease who undergo near-total or total thyroidectomy, thyroid hormone should be initiated prior to discharge in a euthyroid patient and serum TSH should be measured six to eight weeks later to adjust the dose to maintain the TSH in the normal reference range.

手術後病患如果仍有甲狀腺功能亢進, 則甲狀腺素補充需延後, 直到數值回到正常, 間隔需考慮 T4 的血中半衰期
If the patient is still hyperthyroid at the time of surgery, thyroid hormone replacement should be delayed until levels fall into the normal range; the interval can be estimated based on the week-long half-life of T4.
診斷甲狀腺亢進之後, 至少服藥(thionamides)治療六個月, 通常一年到兩年可以考慮停藥
停藥(thionamides)之後約一半至三分之二的患者會復發
抗甲狀腺藥物(thionamides)至少需服用三周以上才會出現效果
通常需 6-8 周, 甲狀腺素才會降低

抗甲狀腺藥物(thionamides)副作用
皮膚癢、起疹 5%
肝功能異常
白血球過低 0.5 %
(因此甲亢症服用抗甲狀腺藥物, 如果出現發燒或喉嚨痛, 需考慮白血球低下合併感染)

放射性碘療法, 約 7-8% 會發生甲狀腺功能低下

手術治療甲狀腺, 併發症(後遺症)包括
1. 甲狀腺機能亢進復發 recurrent 5%
2. 甲狀腺功能低下症 hypothyroidism 15%
3. 副甲狀腺功能受損 hypoparathyroidism : 需終身口服鈣片及維生素D , 以免低血鈣及肌肉抽筋

原子碘治療 (即碘131治療)

1. 通常一次療程就夠, 但有些病患需 2-3 個療程

2. 需有核子醫學科的醫院才能使用

3. 吃藥之後 6-8 周才會出現最大療效, 所以開始服藥前 6-8 周仍建議口服抗甲狀腺藥物

4. 經放射性碘治療, 長期追蹤並沒有發現罹癌機率上升

5. 治療之後發生甲狀腺功能低下的機率

~~ 五年約20%

~~ 十年約40%~50%

~~ 功能低下會持續終身, 需口服甲狀腺素治療

甲狀腺亢進的治療, 先控制症狀

1. 診斷甲狀腺亢進之後立即使用 beta blocker, 不須等到確定診斷為 Graves' disease 

一般劑量 atenolol 25-50 mg QD. 好處是一天一次即可, 且為選擇性 beta-1 阻斷劑

所有的 beta blocker 都可以降低甲狀腺亢進的症狀

乙型阻斷劑可降低因 beta-adrenergic tone 上升引起的症狀, 包括 心悸 心跳快  顫抖  焦慮  不耐熱, 也可以改善容易疲勞及呼吸短促的症狀

Symptom control — A beta blocker should be started (assuming there are no contraindications to its use) in most patients as soon as the diagnosis of hyperthyroidism is made, even before confirming that the cause of hyperthyroidism is Graves' disease. We usually give atenolol (25 to 50 mg/day), which has the advantages of single daily dosing and beta-1 selectivity; however, all beta-adrenergic blocking drugs effectively diminish hyperthyroid symptoms. Beta blockers ameliorate the symptoms of hyperthyroidism that are caused by increased beta-adrenergic tone [2]. These include palpitations, tachycardia, tremulousness, anxiety, and heat intolerance. Fatigability and shortness of breath were also improved in patients who were treated with a beta blocker and a thionamide versus a thionamide alone [3]. 

個案
30歲女,雙腳發抖無力三個月, 無法正常上公車, NAUSEA

甲狀腺亢進
好發於20-40歲族群
免疫疾病, 與遺傳和體質相關, 壓力常是誘發疾病關鍵

壓力大會導致免疫系統製造抗體增加,造成甲狀腺發炎, 甲狀腺過度分泌
壓力減輕可能會不藥而癒