剛剛門診病患抽血報告. TSH 過低. free T4 正常
TSH 0.148 (0.55-4.78)
free T4 1.27 (0.89~1.76)
早期或輕度甲亢可能表現為持續低 TSH 和正常 fT4 激素水平. 又稱為亞臨床甲狀腺功能亢進症，長期未經治療的亞臨床甲狀腺功能亢進症. 可能會加重骨質疏鬆症. 或導致心律異常
下面參考資料來自 uptodate. 中文是用google翻譯.
uptodate Laboratory assessment of thyroid function-
TSH 有很多中文翻譯的名稱: 促甲狀腺激素, 促甲狀腺分泌激素, 甲狀腺刺激素. 這些都是講同一個東西. 為了避免造成混淆. 下面都使用英文縮寫.
Serum TSH(這一段google沒有翻譯成中文. 只好自己翻譯)
目前使用廣泛的是第三代化學冷光免疫分析法, 可測劉到最低濃度 0.01 mU/L
即使在輕微甲亢(hyperthyroidism) 也能被測出.
因為能精確測TSH, 所以能準確的區分出"亞臨床型甲狀腺機能亢進 overt hyperthyroidism" 及 "甲狀腺正能病症 euthyroid patients"
(下面這一段google也沒有翻譯成中文)
●Assays – Third-generation TSH chemiluminometric assays, currently in wide use, have detection limits of approximately 0.01 mU/L. They can therefore provide detectable TSH measurements even in mild hyperthyroidism [5]. Because of the considerably lower detection limit, even with poor quality control, serum TSH values in patients with overt hyperthyroidism are easily distinguished from those in euthyroid patients [6].
(google 翻譯從這裡往下開始)
第二代 TSH 免疫分析法能偵測到濃度 0.1mU/L 以上的. 還有些檢驗單位用這個篩選甲狀腺機能低下症. 但如果患者的血中濃度接近最低可測濃度, 無法用這個區分甲亢的程度.
實驗室如果品管(QC)沒做好. 會得到錯誤的數值.
Second-generation TSH immunometric assays have detection limits of approximately 0.1 mU/L, and they are still used in some laboratories as screening tests to distinguish hyperthyroidism from euthyroidism and to assess the degree of hypothyroidism [7]. However, values near or at the detection limit do not distinguish the degree of hyperthyroidism, and poor quality control in many laboratories can lead to erroneous values [8].
第二代TSH免疫測定法的檢測限約為0.1 mU/L，一些實驗室仍將其用作篩選試驗，以區分甲狀腺功能亢進與甲狀腺功能正常並評估甲狀腺功能減退的程度[7 ]。然而，接近或處於檢測限的值並不能區分甲狀腺功能亢進的程度，並且許多實驗室的質量控制不良可能導致錯誤的值[ 8 ]。
●參考範圍——對於血清TSH正常值的適當上限存在相當大的爭議。大多數實驗室使用的值約為 4.5 至 5.0 mU/L。人群中 TSH 值的分佈因年齡而異。儘管沒有廣泛實施，但我們和其他人傾向於使用基於年齡的 TSH 正常範圍 [ 9]。
●Reference range – There is considerable controversy as to the appropriate upper limit of normal for serum TSH. Most laboratories have used values of approximately 4.5 to 5.0 mU/L. The distribution of TSH values in the population differs by age. Although not widely implemented, we and others favor using aged-based normal ranges for TSH [9].
在對國家健康和營養檢查調查III (NHANES III) 中的16,533 名個體進行的分析中，老年患者中存在與年齡相關的TSH 濃度變化，當排除抗甲狀腺抗體陽性患者時，這種變化仍然存在[ 10 ]。例如，20至29歲或80歲以上成年人的TSH 97.5百分位數分別為3.56和7.49 mU/L。老年組中 70% 的 TSH 大於 4.5 mU/L 的人在其年齡的正常範圍內。在其他前瞻性隊列研究中也發現了類似的與年齡相關的血清 TSH 濃度升高 [ 9,11-13]。老年人中較高的 TSH 水平可能與健康益處相關，而不是健康問題，並且對於血清 TSH 值在 5 至 10 mU/L 之間的患者是否需要治療存在爭議。
In an analysis of 16,533 individuals in the National Health and Nutrition Examination Survey III (NHANES III), there was an age-related shift toward higher TSH concentrations in older patients, which persisted when those with positive antithyroid antibodies were excluded [10]. For example, the 97.5 centile for TSH in adults aged 20 to 29 years, or over age 80, was 3.56 and 7.49 mU/L, respectively. Seventy percent of the individuals in the older group with a TSH greater than 4.5 mU/L were within the normal range for their age. Similar age-associated increases in serum TSH concentrations were found in other prospective cohort studies [9,11-13]. Higher TSH levels in older adults may be associated with health benefits rather than health problems, and controversy exists as to whether patients with serum TSH values between 5 and 10 mU/L require treatment.
美國國家臨床生物化學研究院出版的一篇專著認為，甲狀腺功能正常參考範圍的正常上限應降至2.5 mU/L，因為95% 的經過嚴格篩選的甲狀腺功能正常志願者中，血清值在 0.4 至 2.5 mU/L 之間 [ 14 ]。然而，德國的一項人群研究排除了有陽性家族史、甲狀腺腫、結節或抗甲狀腺過氧化物酶 (TPO) 抗體陽性的患者，發現正常參考範圍為 0.3 至 3.63 mU/L。15 ]。使用 2.5 mU/L 作為血清 TSH 正常上限將大幅增加美國診斷為亞臨床甲狀腺功能減退症的患者數量。在有數據證明血清 TSH 值在 2.5 至 5.0 mU/L 之間具有不良生物學意義之前，將此類患者標記為甲狀腺功能減退是否明智值得懷疑。
A monograph published by the National Academy of Clinical Biochemistry argued that the upper limit of normal of the euthyroid reference range should be reduced to 2.5 mU/L because 95 percent of rigorously screened euthyroid volunteers have serum values between 0.4 and 2.5 mU/L [14]. However, a population study from Germany, which excluded patients with a positive family history, goiter, nodules, or positive antithyroid peroxidase (TPO) antibodies, found a normal reference range of 0.3 to 3.63 mU/L [15]. The use of 2.5 mU/L as the upper limit of normal for serum TSH will increase substantially the number of patients in the United States diagnosed with subclinical hypothyroidism. Until there are data demonstrating an adverse biologic significance for serum TSH values between 2.5 and 5.0 mU/L, the wisdom of labeling such patients as hypothyroid is questionable.
據報導，II 級或 III 級肥胖人群中 TSH 參考範圍與體重相關的上升[ 16 ]。NHANES III 研究發現，非洲人後裔的 TSH 分佈向下移動，因此 3% 至 4% 的正常黑人的血清 TSH <0.4 mU/L [10 ]。
A weight-related shift upward in the reference range for TSH among people with class II or class III obesity has also been reported [16]. The NHANES III study found that persons of African descent have a TSH distribution that is shifted downward, so that 3 to 4 percent of normal Black individuals have a serum TSH <0.4 mU/L [10].
血清總 T4 和 T3
●檢測——血清總T4通常通過自動競爭性結合化學發光檢測來測量。較舊的競爭性結合放射免疫測定法仍然可用。幾乎所有（99.97%）的血清 T4 都與 TBG（甲狀腺素結合球蛋白）、運甲狀腺素蛋白（也稱為 TBPA [甲狀腺素結合前白蛋白]）和白蛋白結合。血清總 T4 測定可測量結合和未結合（“游離”）T4。
Serum total T4 and T3
●Assays – Serum total T4 is usually measured by automated competitive binding chemiluminometric assays. Older competitive binding radioimmunoassays are still available. Virtually all (99.97 percent) of serum T4 is bound to TBG (thyroxine-binding globulin), transthyretin (also called TBPA [thyroxine-binding prealbumin]), and albumin. Serum total T4 assays measure both bound and unbound ("free") T4.
血清總 T3 通常也通過自動競爭性結合化學發光測定來測量。與 T4 相比，T3 與 TBG 和 TBPA 的結合不太緊密，但與白蛋白的結合更緊密。
Serum total T3 is also usually measured by automated competitive binding chemiluminescent assays. T3 is less tightly bound to TBG and TBPA but more tightly bound to albumin than T4.
●參考範圍——不同實驗室的正常範圍有所不同；總 T4 的典型參考範圍是 4.6 至 11.2 mcg/dL（60 至 145 nmol/L）。實驗室中總 T3 的正常範圍比總 T4 的正常範圍變化更大；典型範圍約為 75 至 195 ng/dL（1.1 至 3 nmol/L）。
●Reference range – Normal ranges vary among laboratories; a typical reference range for total T4 is 4.6 to 11.2 mcg/dL (60 to 145 nmol/L). The normal range for total T3 is even more variable among laboratories than that for total T4; a typical range is approximately 75 to 195 ng/dL (1.1 to 3 nmol/L).
血清游離 T4 和 T3 — 游離激素假說指出，未結合或游離激素是可被細胞攝取並與核受體相互作用的部分 [17 ]。另一方面，結合的激素代表一個循環存儲池，不能立即被細胞吸收。
Serum free T4 and T3 — The free hormone hypothesis states that the unbound or free hormone is the fraction that is available for uptake into cells and interaction with nuclear receptors [17]. The bound hormone, on the other hand, represents a circulating storage pool that is not immediately available for uptake into cells.
由於藥物和疾病會改變結合蛋白的濃度或結合蛋白與 T4 或 T3 的相互作用（表 1），游離激素和總激素濃度可能不一致。一個例子是雌激素引起的TBG 過量，其中由於TBG 結合激素增加，總T4 濃度很高，但生理上重要的游離T4 濃度正常（參見“甲狀腺功能正常的高甲狀腺素血症和低甲狀腺素血症” ）。因此有必要估計游離激素濃度。
Since drugs and illness can alter concentrations of binding proteins or interaction of the binding proteins with T4 or T3 (table 1), the free and total hormone concentrations may not be concordant. An example is estrogen-induced TBG excess, in which total T4 concentrations are high due to increased TBG-bound hormone, but the physiologically important free T4 concentrations are normal
●測定 – 大多數實驗室通過“直接”測量來測量游離 T4 和游離 T3。
●Assays – Most laboratories measure free T4 and free T3 by "direct" measurement.
•“直接”免費 T4 – 直接免費 T4 測量可以自動化，並且商業實驗室已使用不同的方法 [ 18]; 然而，這些方法實際上都不能直接測量未結合的 T4，因為游離激素僅佔血清總 T4 的 0.03%。直接游離 T4 測量的明顯優點是，通過提供據稱考慮了結合異常的值，可以減輕與結合蛋白異常相關的混亂。缺點是目前沒有可用的檢測方法可以為已描述的所有結合異常提供正確的游離 T4 值。由於低白蛋白和其他因素，直接游離 T4 測量在懷孕期間可能不可靠（參見“甲狀腺疾病和妊娠概述”），而在營養不良或危重患者中，由於結合蛋白水平較低（參見“非甲狀腺疾病中的甲狀腺功能”））。正常範圍也因所使用的方法而異。
•"Direct" free T4 – Direct free T4 measurements can be automated, and varying methodologies have been used by commercial laboratories [18]; however, none of these actually measure unbound T4 directly since free hormone represents only 0.03 percent of serum total T4. The perceived advantage of direct free T4 measurement is that confusion related to binding protein abnormalities is mitigated by providing values that allegedly take binding abnormalities into account. The disadvantage is that no currently available assay provides correct free T4 values for all the binding abnormalities that have been described. Direct free T4 measurements may be unreliable during pregnancy due to low albumin and other factors (see "Overview of thyroid disease and pregnancy") and in malnourished or critically ill patients due to low levels of binding proteins
•“直接”游離T3 – 直接游離T3 測量使用類似的方法並且越來越多地可用，但這些測定顯示出比游離T4 測定更高的變異性，並且我們同意美國甲狀腺協會的指南，即使用總T3 測量更可靠[ 19 ]。
•"Direct" free T3 – Direct free T3 measurements use similar methodology and are increasingly available, but these assays demonstrate even higher variability than the free T4 assays, and we agree with American Thyroid Association guidelines that the use of total T3 measurements are more reliable [19].
•游離T4指數，使用T3攝取（或THBI）計算——這種估計游離T4濃度的舊方法仍在使用。計算游離 T4 指數的優點是臨床醫生可以獲得總 T4 和 T3 攝取或甲狀腺激素結合指數 (THBI)，從而清楚地了解患者何時存在潛在的結合蛋白異常。缺點是：(1) 許多臨床醫生對計算方法了解甚少，(2) 游離 T4 指數與直接游離 T4 測量一樣，無法為許多描述的結合蛋白異常提供正確的值。
•Free T4 index, calculated using the T3 uptake (or THBI) – This older method for estimating the free T4 concentration is still in use. Calculation of the free T4 index has the advantage that the clinician is given both a total T4 and a T3 uptake or thyroid hormone binding index (THBI), making it clear when the patient has a potential binding protein abnormality. The disadvantages are: (1) the calculation is poorly understood by many clinicians, and (2) the free T4 index, as with direct free T4 measurements, fails to give correct values for many described binding protein abnormalities.
傳統的T3 攝取測試是通過將患者的血清與放射性標記的T3 示踪劑一起孵育，然後添加不溶性物質（葡聚醣塗層的木炭或“樹脂”）來捕獲剩餘的未結合的放射性標記的T3 。報告的值是與樹脂結合的示踪劑的百分比，其與 T3 可用的游離結合位點的數量成反比。游離結合位點的數量由結合蛋白水平和內源激素產生決定。
The traditional T3-uptake test is performed by incubating the patient's serum with radiolabeled T3 tracer and subsequently adding an insoluble substance (dextran-coated charcoal or "resin") that traps the remaining unbound radiolabeled T3. The value reported is the percent of tracer bound to the resin, which varies inversely with the number of available free binding sites for T3. The number of free binding sites is determined by both binding protein levels and endogenous hormone production.
不同實驗室的正常範圍差異很大。雖然許多實驗室仍然報告 T3 攝取的實際測量值，但最好計算 THBI，它只是標準化的 T3 樹脂攝取值 [20] ： THBI
= 患者的 T3 攝取 ÷ 正常池 T3 攝取
因此，根據定義，平均 THBI 為 1.00，正常範圍約為 0.83 至 1.16。一些實驗室將 THBI 稱為甲狀腺激素結合比 (THBR)。
游離 T4 指數是通過 T3 攝取或 THBI“校正”總 T4 來計算的：
游離 T4 指數 = 總 T4 x T3 攝取，或游離 T4 指數 = 總 T4 x THBI
如果該指數是使用 T3 攝取計算的，結果是一個無單位的數字，其正常範圍對於實驗室來說是不同的。如果使用 THBI 計算該指數，則該指數應具有與實驗室總 T4 值大致相同的正常範圍。
The normal range varies considerably among laboratories. While many laboratories still report the actual measured value for the T3 uptake, it is preferable to calculate a THBI, which is simply a normalized T3-resin uptake value [20]:
THBI = patient's T3 uptake ÷ normal pool T3 uptake
The mean THBI is, therefore, by definition 1.00, with a normal range of approximately 0.83 to 1.16. Some laboratories call the THBI the thyroid hormone-binding ratio (THBR).
The free T4 index is calculated by "correcting" the total T4 by the T3 uptake or THBI:
Free T4 index = total T4 x T3 uptake, or free T4 index = total T4 x THBI
If the index is calculated by using the T3-uptake, the result is a unitless number with a normal range distinct for the laboratory. If the index is calculated using the THBI, the index should have approximately the same normal range as the total T4 values for the laboratory.
T3 攝取旨在區分 TBG 過多和缺乏與甲狀腺功能亢進和甲狀腺功能減退：
-甲狀腺功能亢進 – 血清總 T4 高、T3 攝取或 THBI 高、游離 T4 指數高
-TBG 過量 – 血清總 T4 高、T3 攝取或 THBI 低、游離 T4 指數正常 -
甲狀腺功能減退– 血清總T4 低、T3低 -攝取或 THBI，低游離 T4 指數
-TBG 缺乏 – 血清總 T4 低，高 T3 攝取或 THBI，游離 T4 指數正常
然而，該指數可能無法完全糾正結合蛋白異常的極端情況。
•平衡透析——只有少數參考實驗室可以通過平衡透析測量游離T4。經典技術測量平衡狀態下游離 T4 在透析膜上的分佈，以估計未結合的分數。該方法對於日常使用來說過於繁瑣且昂貴。
The T3-uptake was designed to distinguish TBG excess and deficiency from hyperthyroidism and hypothyroidism:
-Hyperthyroidism – High serum total T4, high T3-uptake or THBI, high free T4 index
-TBG excess – High serum total T4, low T3-uptake or THBI, normal free T4 index
-Hypothyroidism – Low serum total T4, low T3-uptake or THBI, low free T4 index
-TBG deficiency – Low serum total T4, high T3-uptake or THBI, normal free T4 index
However, the index may not fully correct at the extremes of binding protein abnormalities.
•Equilibrium dialysis – Measurement of free T4 by equilibrium dialysis is available only in a few reference laboratories. The classic technique measures the distribution of free T4 at equilibrium across a dialysis membrane to estimate the unbound fraction. The method is too tedious and expensive for routine use.
反向 T3 — 反向 T3 (rT3) 是甲狀腺素的無活性代謝物。它被替代性健康從業者廣泛測量，以證明使用 T3 療法和補充劑的合理性，這些補充劑被認為可以增強 T4 向 T3 的轉化。對於傳統醫生來說，它在評估罕見疾病（例如消耗性甲狀腺功能減退症、MCT8 或 SBP2 突變）或可能區分危重住院患者的中樞性甲狀腺功能減退症和非甲狀腺疾病方面的效用極其有限[21 ]。
Reverse T3 — Reverse T3 (rT3) is an inactive metabolite of thyroxine. It is widely measured by alternative health practitioners to justify the use of T3 therapy and supplements thought to enhance the conversion of T4 to T3. It has extremely limited utility for conventional medical practitioners for assessing rare conditions such as consumptive hypothyroidism, MCT8 or SBP2 mutations, or possibly distinguishing central hypothyroidism from nonthyroidal illness in critically ill hospitalized patients [21].
甲狀腺功能測試的臨床應用
甲狀腺功能測試在各種臨床環境中用於評估甲狀腺功能障礙、評估左旋甲狀腺素治療的充分性以及監測甲狀腺功能亢進症的治療（表 2）。假設穩態條件且不存在垂體或下丘腦疾病，最好通過測量血清 TSH 來評估甲狀腺功能。然而，血清 TSH 和甲狀腺激素水平的測量對於可能有甲狀腺功能障礙症狀的患者仍然很重要，因為血清 TSH 正常並不能明確排除 TSH 分泌腫瘤導致中樞性甲狀腺功能減退或中樞性甲狀腺功能亢進的可能性。
“篩查”是指對有患甲狀腺疾病風險且目前未知患有甲狀腺疾病的無症狀患者進行甲狀腺功能測試的測量。關於對明顯無症狀患者進行篩查或病例發現的成本效益存在一些爭議。該主題已在別處詳細討論。
CLINICAL USE OF THYROID FUNCTION TESTS
Thyroid function tests are used in a variety of clinical settings to evaluate thyroid dysfunction, assess the adequacy of levothyroxine therapy, and monitor the treatment of hyperthyroidism (table 2). Assuming steady-state conditions and the absence of pituitary or hypothalamic disease, thyroid function is best assessed by measuring serum TSH. However, measurement of serum TSH and thyroid hormone levels remains important in patients with symptoms of possible thyroid dysfunction since a normal serum TSH does not unequivocally exclude the possibility of central hypothyroidism or central hyperthyroidism from a TSH secreting tumor.
"Screening" refers to the measurement of thyroid function tests in asymptomatic patients at risk of having thyroid disease who are presently not known to have thyroid disease. There is some debate over the cost effectiveness of screening or case finding in apparently asymptomatic patients. This topic is reviewed in detail elsewhere.
評估甲狀腺功能障礙
●門診環境 – 在門診環境中進行評估時，許多實驗室使用以下策略來限制不必要的實驗室檢測： •血清 TSH 正常 – 不進行進一步檢測•血清TSH 高– 添加游離T4 以確定程度甲狀腺功能減退症的症狀
Evaluating for thyroid dysfunction
●Outpatient setting – When evaluation is performed in the outpatient setting, many laboratories use the following strategies to limit unnecessary laboratory testing:
•血清 TSH 低 – 添加游離 T4 和 T3 以確定甲狀腺功能亢進的程度
當用於評估個體患者可能的甲狀腺功能障礙時，我們對此策略進行了兩項修改：
•Serum TSH normal – No further testing performed
•Serum TSH high – Free T4 added to determine the degree of hypothyroidism
•Serum TSH low – Free T4 and T3 added to determine the degree of hyperthyroidism
•如果患者儘管TSH 結果正常但仍出現甲狀腺功能亢進或甲狀腺功能減退症狀，我們會測量血清游離T4。
We make two amendments to this strategy when used to assess possible thyroid dysfunction in an individual patient:
•如果垂體或下丘腦有甲狀腺功能障礙，我們會測量血清TSH 和游離T4懷疑患有疾病（例如年輕女性閉經和疲勞）。
•We measure both serum TSH and free T4 if pituitary or hypothalamic disease is suspected (eg, a young woman with amenorrhea and fatigue).
•如果患者儘管TSH 結果正常但仍出現甲狀腺功能亢進或甲狀腺功能減退症狀，我們會測量血清游離T4。
•We measure serum free T4 if the patient has symptoms of hyper- or hypothyroidism despite a normal TSH result.
然而，一些專家建議出於評估目的，對所有患者同時測量血清TSH 和游離T4，因為在繼發性或中樞性甲狀腺功能減退症或TSH 介導的甲狀腺功能亢進症患者中僅測量TSH 可能會出現錯誤。這種方法增加了相當大的篩查成本，並且可能會發現少數未被懷疑的垂體疾病病例。例如，在一項針對 4843 名社區居民的研究中，測量 TSH 僅會漏掉 3.8% 游離 T4 異常的患者，而這些患者中 85% 的游離 T4 濃度僅有最低限度的高或低 [24 ]。
Serum TSH assays are both more sensitive and specific than serum free T4 measurements for outpatients if a single test is utilized [22,23]. However, some experts recommend that both serum TSH and free T4 be measured in all patients for evaluation purposes since errors may be made when only TSH is measured in patients with secondary or central hypothyroidism or TSH-mediated hyperthyroidism. This approach adds considerable cost to screening and is likely to pick up few cases of unsuspected pituitary disease. As an example, in a study of 4843 community-dwelling individuals, measuring a TSH only would have missed 3.8 percent of patients with an abnormal free T4, and 85 percent of these patients had only minimally high or low free T4 concentrations [24].
●住院環境——在住院環境中評估甲狀腺功能是一個更困難的問題，除非強烈懷疑甲狀腺疾病，否則不建議這樣做，因為在嚴重的非甲狀腺疾病中，甲狀腺激素、結合蛋白和TSH濃度會發生變化（參見“甲狀腺疾病” ）在非甲狀腺疾病中發揮作用”）。這些變化可能包括[ 25 ]：
●Inpatient setting – Evaluating thyroid function in the inpatient setting is a more difficult problem, and it is not recommended unless thyroid disease is strongly suspected, since changes in thyroid hormones, binding proteins, and TSH concentrations occur in severe nonthyroidal illness ). These changes may include [25]:
所有三種結合蛋白濃度均低
• 游離脂肪酸濃度高，可取代結合蛋白中的甲狀腺激素
• 獲得性中樞性甲狀腺功能減退症
• 患者可能正在接受影響甲狀腺功能的藥物（表 1）
雖然有人主張血清 TSH 或游離 T4 對住院患者更有用，但大多數專家建議血清 TSH 和游離 T4 或總 T4 對於評估住院患者的甲狀腺功能都是必要的 [26-28 ]。
監測左旋甲狀腺素治療 — 評估甲狀腺功能的更常見原因之一是評估左旋甲狀腺素治療的充分性。
•Low concentrations of all three binding proteins
•High concentrations of free fatty acids that displace thyroid hormones from binding proteins
•Acquired central hypothyroidism
•The patient may be receiving medications that affect thyroid function (table 1)
While there are advocates for either serum TSH or free T4 being more useful in inpatients, most experts suggest that both serum TSH and free T4 or total T4 are necessary to assess thyroid function in hospitalized patients [26-28].
Monitoring levothyroxine therapy — One of the more common reasons for assessing thyroid function is to assess the adequacy of levothyroxine therapy.
原發性甲狀腺功能減退症——正在服用左旋甲狀腺素的原發性甲狀腺功能減退症患者可以僅通過評估血清 TSH 來監測替代治療。一般來說，無血清 T4 測量對於評估左旋甲狀腺素劑量的適當性非常不敏感。左旋甲狀腺素劑量比最佳劑量高出 40% 可能會導致血清 TSH 濃度低於正常水平，但血清游離 T4 濃度通常仍保持在正常範圍內 [ 29 ]。然而，當 TSH 非常高或非常低時，游離 T4 測量可用於確定適當的劑量增加或減少。
●Primary hypothyroidism – Patients with primary hypothyroidism who are taking levothyroxine replacement therapy can be monitored by assessing the serum TSH only. In general, serum free T4 measurements are very insensitive for assessing the appropriateness of the levothyroxine dose. Doses of levothyroxine that are 40 percent higher than optimal may result in subnormal serum TSH concentrations, yet serum free T4 concentrations frequently remain within the normal range [29]. Nevertheless, free T4 measurements can be useful to determine appropriate dose increases or decreases when TSH is very high or low, respectively.
（T3，Cytomel）通常不推薦用於治療甲狀腺功能減退症。然而，對於接受左旋甲狀腺素單藥治療但出現持續性甲狀腺功能減退症狀的患者，有時會添加 T3。在這種情況下，我們不會定期監測 T3 水平。目前的含T3製劑，由於其胃腸道吸收快，且循環半衰期相對較短（約1天），因此全天T3濃度波動較大。
Liothyronine (T3, Cytomel) is generally not recommended for treating hypothyroidism. However, in patients with persistent hypothyroid symptoms on levothyroxine monotherapy, T3 is sometimes added. In this setting, we do not routinely monitor T3 levels. With the currently available T3-containing preparations, there are wide fluctuations in T3 concentrations throughout the day due to its rapid gastrointestinal absorption and its relatively short half-life in the circulation (approximately one day).
●繼發性甲狀腺功能減退症——應使用血清游離T4值來滴定甲狀腺激素劑量的一種情況是，由於垂體或下丘腦疾病而導致TSH釋放缺失或受損的繼發性甲狀腺功能減退症患者。在這種情況下，游離 T4 水平應維持在正常範圍的 50% 以上。(參見“中樞性甲狀腺功能減退症”，關於‘治療’一節)
●Secondary hypothyroidism – The one setting in which the serum free T4 value should be used to titrate the thyroid hormone dose is in patients with secondary hypothyroidism due to pituitary or hypothalamic disease who have absent or impaired TSH release. In this situation, the free T4 level should be maintained in the upper 50 percent of the normal range.
●甲狀腺癌——對於服用左旋甲狀腺素抑制TSH分泌以預防甲狀腺癌復發的
患者來說，監測的目標和要求是不同的。
●Thyroid cancer – The goal and requirement for monitoring are different in patients taking levothyroxine for suppression of TSH secretion to prevent recurrence of thyroid cancer.
●甲狀腺結節和甲狀腺腫——很少使用左旋甲狀腺素輕度抑制TSH來防止甲狀腺腫組織的生長或再生。
●Thyroid nodules and goiter – Rarely, mild suppression of TSH with levothyroxine is used to prevent growth or regrowth of goitrous tissue.
甲狀腺功能亢進症治療的監測 — 在使用抗甲狀腺藥物、放射性碘或手術治療甲狀腺功能亢進症的早期過程中，血清 TSH 可能會持續數週，很少持續數月。因此，治療的初始監測應包括定期臨床評估、血清游離 T4 的測量以及經常測量的總 T3 水平。在許多類型的甲狀腺功能亢進症中，血清 T3 濃度可能不成比例地高於血清 T4 濃度。此外，抗甲狀腺藥物治療可使血清游離 T4 水平恢復正常，而血清 T3 水平可能持續升高。一旦穩態條件得到保證，血清 TSH 的測量只能用於評估治療效果。
Monitoring treatment of hyperthyroidism — During the early treatment of hyperthyroidism with antithyroid drugs, radioiodine, or surgery, serum TSH may remain subnormal for several weeks and rarely for several months. Initial monitoring of therapy, therefore, should consist of periodic clinical assessment, measurements of serum free T4, and often measurements of total T3 levels. Serum T3 concentrations may be disproportionately higher than serum T4 concentrations in many types of hyperthyroidism. Also, serum free T4 levels may normalize with antithyroid drug therapy, while serum T3 levels may remain persistently elevated. Once steady-state conditions are assured, measurement of serum TSH only can be used to assess the efficacy of therapy.
實驗室如果品管(QC)沒做好. 會得到錯誤的數值.
Second-generation TSH immunometric assays have detection limits of approximately 0.1 mU/L, and they are still used in some laboratories as screening tests to distinguish hyperthyroidism from euthyroidism and to assess the degree of hypothyroidism [7]. However, values near or at the detection limit do not distinguish the degree of hyperthyroidism, and poor quality control in many laboratories can lead to erroneous values [8].
第二代TSH免疫測定法的檢測限約為0.1 mU/L，一些實驗室仍將其用作篩選試驗，以區分甲狀腺功能亢進與甲狀腺功能正常並評估甲狀腺功能減退的程度[7 ]。然而，接近或處於檢測限的值並不能區分甲狀腺功能亢進的程度，並且許多實驗室的質量控制不良可能導致錯誤的值[ 8 ]。
●參考範圍——對於血清TSH正常值的適當上限存在相當大的爭議。大多數實驗室使用的值約為 4.5 至 5.0 mU/L。人群中 TSH 值的分佈因年齡而異。儘管沒有廣泛實施，但我們和其他人傾向於使用基於年齡的 TSH 正常範圍 [ 9]。
●Reference range – There is considerable controversy as to the appropriate upper limit of normal for serum TSH. Most laboratories have used values of approximately 4.5 to 5.0 mU/L. The distribution of TSH values in the population differs by age. Although not widely implemented, we and others favor using aged-based normal ranges for TSH [9].
在對國家健康和營養檢查調查III (NHANES III) 中的16,533 名個體進行的分析中，老年患者中存在與年齡相關的TSH 濃度變化，當排除抗甲狀腺抗體陽性患者時，這種變化仍然存在[ 10 ]。例如，20至29歲或80歲以上成年人的TSH 97.5百分位數分別為3.56和7.49 mU/L。老年組中 70% 的 TSH 大於 4.5 mU/L 的人在其年齡的正常範圍內。在其他前瞻性隊列研究中也發現了類似的與年齡相關的血清 TSH 濃度升高 [ 9,11-13]。老年人中較高的 TSH 水平可能與健康益處相關，而不是健康問題，並且對於血清 TSH 值在 5 至 10 mU/L 之間的患者是否需要治療存在爭議。
In an analysis of 16,533 individuals in the National Health and Nutrition Examination Survey III (NHANES III), there was an age-related shift toward higher TSH concentrations in older patients, which persisted when those with positive antithyroid antibodies were excluded [10]. For example, the 97.5 centile for TSH in adults aged 20 to 29 years, or over age 80, was 3.56 and 7.49 mU/L, respectively. Seventy percent of the individuals in the older group with a TSH greater than 4.5 mU/L were within the normal range for their age. Similar age-associated increases in serum TSH concentrations were found in other prospective cohort studies [9,11-13]. Higher TSH levels in older adults may be associated with health benefits rather than health problems, and controversy exists as to whether patients with serum TSH values between 5 and 10 mU/L require treatment.
美國國家臨床生物化學研究院出版的一篇專著認為，甲狀腺功能正常參考範圍的正常上限應降至2.5 mU/L，因為95% 的經過嚴格篩選的甲狀腺功能正常志願者中，血清值在 0.4 至 2.5 mU/L 之間 [ 14 ]。然而，德國的一項人群研究排除了有陽性家族史、甲狀腺腫、結節或抗甲狀腺過氧化物酶 (TPO) 抗體陽性的患者，發現正常參考範圍為 0.3 至 3.63 mU/L。15 ]。使用 2.5 mU/L 作為血清 TSH 正常上限將大幅增加美國診斷為亞臨床甲狀腺功能減退症的患者數量。在有數據證明血清 TSH 值在 2.5 至 5.0 mU/L 之間具有不良生物學意義之前，將此類患者標記為甲狀腺功能減退是否明智值得懷疑。
A monograph published by the National Academy of Clinical Biochemistry argued that the upper limit of normal of the euthyroid reference range should be reduced to 2.5 mU/L because 95 percent of rigorously screened euthyroid volunteers have serum values between 0.4 and 2.5 mU/L [14]. However, a population study from Germany, which excluded patients with a positive family history, goiter, nodules, or positive antithyroid peroxidase (TPO) antibodies, found a normal reference range of 0.3 to 3.63 mU/L [15]. The use of 2.5 mU/L as the upper limit of normal for serum TSH will increase substantially the number of patients in the United States diagnosed with subclinical hypothyroidism. Until there are data demonstrating an adverse biologic significance for serum TSH values between 2.5 and 5.0 mU/L, the wisdom of labeling such patients as hypothyroid is questionable.
據報導，II 級或 III 級肥胖人群中 TSH 參考範圍與體重相關的上升[ 16 ]。NHANES III 研究發現，非洲人後裔的 TSH 分佈向下移動，因此 3% 至 4% 的正常黑人的血清 TSH <0.4 mU/L [10 ]。
A weight-related shift upward in the reference range for TSH among people with class II or class III obesity has also been reported [16]. The NHANES III study found that persons of African descent have a TSH distribution that is shifted downward, so that 3 to 4 percent of normal Black individuals have a serum TSH <0.4 mU/L [10].
血清總 T4 和 T3
●檢測——血清總T4通常通過自動競爭性結合化學發光檢測來測量。較舊的競爭性結合放射免疫測定法仍然可用。幾乎所有（99.97%）的血清 T4 都與 TBG（甲狀腺素結合球蛋白）、運甲狀腺素蛋白（也稱為 TBPA [甲狀腺素結合前白蛋白]）和白蛋白結合。血清總 T4 測定可測量結合和未結合（“游離”）T4。
Serum total T4 and T3
●Assays – Serum total T4 is usually measured by automated competitive binding chemiluminometric assays. Older competitive binding radioimmunoassays are still available. Virtually all (99.97 percent) of serum T4 is bound to TBG (thyroxine-binding globulin), transthyretin (also called TBPA [thyroxine-binding prealbumin]), and albumin. Serum total T4 assays measure both bound and unbound ("free") T4.
血清總 T3 通常也通過自動競爭性結合化學發光測定來測量。與 T4 相比，T3 與 TBG 和 TBPA 的結合不太緊密，但與白蛋白的結合更緊密。
Serum total T3 is also usually measured by automated competitive binding chemiluminescent assays. T3 is less tightly bound to TBG and TBPA but more tightly bound to albumin than T4.
●參考範圍——不同實驗室的正常範圍有所不同；總 T4 的典型參考範圍是 4.6 至 11.2 mcg/dL（60 至 145 nmol/L）。實驗室中總 T3 的正常範圍比總 T4 的正常範圍變化更大；典型範圍約為 75 至 195 ng/dL（1.1 至 3 nmol/L）。
●Reference range – Normal ranges vary among laboratories; a typical reference range for total T4 is 4.6 to 11.2 mcg/dL (60 to 145 nmol/L). The normal range for total T3 is even more variable among laboratories than that for total T4; a typical range is approximately 75 to 195 ng/dL (1.1 to 3 nmol/L).
血清游離 T4 和 T3 — 游離激素假說指出，未結合或游離激素是可被細胞攝取並與核受體相互作用的部分 [17 ]。另一方面，結合的激素代表一個循環存儲池，不能立即被細胞吸收。
Serum free T4 and T3 — The free hormone hypothesis states that the unbound or free hormone is the fraction that is available for uptake into cells and interaction with nuclear receptors [17]. The bound hormone, on the other hand, represents a circulating storage pool that is not immediately available for uptake into cells.
由於藥物和疾病會改變結合蛋白的濃度或結合蛋白與 T4 或 T3 的相互作用（表 1），游離激素和總激素濃度可能不一致。一個例子是雌激素引起的TBG 過量，其中由於TBG 結合激素增加，總T4 濃度很高，但生理上重要的游離T4 濃度正常（參見“甲狀腺功能正常的高甲狀腺素血症和低甲狀腺素血症” ）。因此有必要估計游離激素濃度。
Since drugs and illness can alter concentrations of binding proteins or interaction of the binding proteins with T4 or T3 (table 1), the free and total hormone concentrations may not be concordant. An example is estrogen-induced TBG excess, in which total T4 concentrations are high due to increased TBG-bound hormone, but the physiologically important free T4 concentrations are normal
●測定 – 大多數實驗室通過“直接”測量來測量游離 T4 和游離 T3。
●Assays – Most laboratories measure free T4 and free T3 by "direct" measurement.
•“直接”免費 T4 – 直接免費 T4 測量可以自動化，並且商業實驗室已使用不同的方法 [ 18]; 然而，這些方法實際上都不能直接測量未結合的 T4，因為游離激素僅佔血清總 T4 的 0.03%。直接游離 T4 測量的明顯優點是，通過提供據稱考慮了結合異常的值，可以減輕與結合蛋白異常相關的混亂。缺點是目前沒有可用的檢測方法可以為已描述的所有結合異常提供正確的游離 T4 值。由於低白蛋白和其他因素，直接游離 T4 測量在懷孕期間可能不可靠（參見“甲狀腺疾病和妊娠概述”），而在營養不良或危重患者中，由於結合蛋白水平較低（參見“非甲狀腺疾病中的甲狀腺功能”））。正常範圍也因所使用的方法而異。
•"Direct" free T4 – Direct free T4 measurements can be automated, and varying methodologies have been used by commercial laboratories [18]; however, none of these actually measure unbound T4 directly since free hormone represents only 0.03 percent of serum total T4. The perceived advantage of direct free T4 measurement is that confusion related to binding protein abnormalities is mitigated by providing values that allegedly take binding abnormalities into account. The disadvantage is that no currently available assay provides correct free T4 values for all the binding abnormalities that have been described. Direct free T4 measurements may be unreliable during pregnancy due to low albumin and other factors (see "Overview of thyroid disease and pregnancy") and in malnourished or critically ill patients due to low levels of binding proteins
•“直接”游離T3 – 直接游離T3 測量使用類似的方法並且越來越多地可用，但這些測定顯示出比游離T4 測定更高的變異性，並且我們同意美國甲狀腺協會的指南，即使用總T3 測量更可靠[ 19 ]。
•"Direct" free T3 – Direct free T3 measurements use similar methodology and are increasingly available, but these assays demonstrate even higher variability than the free T4 assays, and we agree with American Thyroid Association guidelines that the use of total T3 measurements are more reliable [19].
•游離T4指數，使用T3攝取（或THBI）計算——這種估計游離T4濃度的舊方法仍在使用。計算游離 T4 指數的優點是臨床醫生可以獲得總 T4 和 T3 攝取或甲狀腺激素結合指數 (THBI)，從而清楚地了解患者何時存在潛在的結合蛋白異常。缺點是：(1) 許多臨床醫生對計算方法了解甚少，(2) 游離 T4 指數與直接游離 T4 測量一樣，無法為許多描述的結合蛋白異常提供正確的值。
•Free T4 index, calculated using the T3 uptake (or THBI) – This older method for estimating the free T4 concentration is still in use. Calculation of the free T4 index has the advantage that the clinician is given both a total T4 and a T3 uptake or thyroid hormone binding index (THBI), making it clear when the patient has a potential binding protein abnormality. The disadvantages are: (1) the calculation is poorly understood by many clinicians, and (2) the free T4 index, as with direct free T4 measurements, fails to give correct values for many described binding protein abnormalities.
傳統的T3 攝取測試是通過將患者的血清與放射性標記的T3 示踪劑一起孵育，然後添加不溶性物質（葡聚醣塗層的木炭或“樹脂”）來捕獲剩餘的未結合的放射性標記的T3 。報告的值是與樹脂結合的示踪劑的百分比，其與 T3 可用的游離結合位點的數量成反比。游離結合位點的數量由結合蛋白水平和內源激素產生決定。
The traditional T3-uptake test is performed by incubating the patient's serum with radiolabeled T3 tracer and subsequently adding an insoluble substance (dextran-coated charcoal or "resin") that traps the remaining unbound radiolabeled T3. The value reported is the percent of tracer bound to the resin, which varies inversely with the number of available free binding sites for T3. The number of free binding sites is determined by both binding protein levels and endogenous hormone production.
不同實驗室的正常範圍差異很大。雖然許多實驗室仍然報告 T3 攝取的實際測量值，但最好計算 THBI，它只是標準化的 T3 樹脂攝取值 [20] ： THBI
= 患者的 T3 攝取 ÷ 正常池 T3 攝取
因此，根據定義，平均 THBI 為 1.00，正常範圍約為 0.83 至 1.16。一些實驗室將 THBI 稱為甲狀腺激素結合比 (THBR)。
游離 T4 指數是通過 T3 攝取或 THBI“校正”總 T4 來計算的：
游離 T4 指數 = 總 T4 x T3 攝取，或游離 T4 指數 = 總 T4 x THBI
如果該指數是使用 T3 攝取計算的，結果是一個無單位的數字，其正常範圍對於實驗室來說是不同的。如果使用 THBI 計算該指數，則該指數應具有與實驗室總 T4 值大致相同的正常範圍。
The normal range varies considerably among laboratories. While many laboratories still report the actual measured value for the T3 uptake, it is preferable to calculate a THBI, which is simply a normalized T3-resin uptake value [20]:
THBI = patient's T3 uptake ÷ normal pool T3 uptake
The mean THBI is, therefore, by definition 1.00, with a normal range of approximately 0.83 to 1.16. Some laboratories call the THBI the thyroid hormone-binding ratio (THBR).
The free T4 index is calculated by "correcting" the total T4 by the T3 uptake or THBI:
Free T4 index = total T4 x T3 uptake, or free T4 index = total T4 x THBI
If the index is calculated by using the T3-uptake, the result is a unitless number with a normal range distinct for the laboratory. If the index is calculated using the THBI, the index should have approximately the same normal range as the total T4 values for the laboratory.
T3 攝取旨在區分 TBG 過多和缺乏與甲狀腺功能亢進和甲狀腺功能減退：
-甲狀腺功能亢進 – 血清總 T4 高、T3 攝取或 THBI 高、游離 T4 指數高
-TBG 過量 – 血清總 T4 高、T3 攝取或 THBI 低、游離 T4 指數正常 -
甲狀腺功能減退– 血清總T4 低、T3低 -攝取或 THBI，低游離 T4 指數
-TBG 缺乏 – 血清總 T4 低，高 T3 攝取或 THBI，游離 T4 指數正常
然而，該指數可能無法完全糾正結合蛋白異常的極端情況。
•平衡透析——只有少數參考實驗室可以通過平衡透析測量游離T4。經典技術測量平衡狀態下游離 T4 在透析膜上的分佈，以估計未結合的分數。該方法對於日常使用來說過於繁瑣且昂貴。
The T3-uptake was designed to distinguish TBG excess and deficiency from hyperthyroidism and hypothyroidism:
-Hyperthyroidism – High serum total T4, high T3-uptake or THBI, high free T4 index
-TBG excess – High serum total T4, low T3-uptake or THBI, normal free T4 index
-Hypothyroidism – Low serum total T4, low T3-uptake or THBI, low free T4 index
-TBG deficiency – Low serum total T4, high T3-uptake or THBI, normal free T4 index
However, the index may not fully correct at the extremes of binding protein abnormalities.
•Equilibrium dialysis – Measurement of free T4 by equilibrium dialysis is available only in a few reference laboratories. The classic technique measures the distribution of free T4 at equilibrium across a dialysis membrane to estimate the unbound fraction. The method is too tedious and expensive for routine use.
反向 T3 — 反向 T3 (rT3) 是甲狀腺素的無活性代謝物。它被替代性健康從業者廣泛測量，以證明使用 T3 療法和補充劑的合理性，這些補充劑被認為可以增強 T4 向 T3 的轉化。對於傳統醫生來說，它在評估罕見疾病（例如消耗性甲狀腺功能減退症、MCT8 或 SBP2 突變）或可能區分危重住院患者的中樞性甲狀腺功能減退症和非甲狀腺疾病方面的效用極其有限[21 ]。
Reverse T3 — Reverse T3 (rT3) is an inactive metabolite of thyroxine. It is widely measured by alternative health practitioners to justify the use of T3 therapy and supplements thought to enhance the conversion of T4 to T3. It has extremely limited utility for conventional medical practitioners for assessing rare conditions such as consumptive hypothyroidism, MCT8 or SBP2 mutations, or possibly distinguishing central hypothyroidism from nonthyroidal illness in critically ill hospitalized patients [21].
甲狀腺功能測試的臨床應用
甲狀腺功能測試在各種臨床環境中用於評估甲狀腺功能障礙、評估左旋甲狀腺素治療的充分性以及監測甲狀腺功能亢進症的治療（表 2）。假設穩態條件且不存在垂體或下丘腦疾病，最好通過測量血清 TSH 來評估甲狀腺功能。然而，血清 TSH 和甲狀腺激素水平的測量對於可能有甲狀腺功能障礙症狀的患者仍然很重要，因為血清 TSH 正常並不能明確排除 TSH 分泌腫瘤導致中樞性甲狀腺功能減退或中樞性甲狀腺功能亢進的可能性。
“篩查”是指對有患甲狀腺疾病風險且目前未知患有甲狀腺疾病的無症狀患者進行甲狀腺功能測試的測量。關於對明顯無症狀患者進行篩查或病例發現的成本效益存在一些爭議。該主題已在別處詳細討論。
CLINICAL USE OF THYROID FUNCTION TESTS
Thyroid function tests are used in a variety of clinical settings to evaluate thyroid dysfunction, assess the adequacy of levothyroxine therapy, and monitor the treatment of hyperthyroidism (table 2). Assuming steady-state conditions and the absence of pituitary or hypothalamic disease, thyroid function is best assessed by measuring serum TSH. However, measurement of serum TSH and thyroid hormone levels remains important in patients with symptoms of possible thyroid dysfunction since a normal serum TSH does not unequivocally exclude the possibility of central hypothyroidism or central hyperthyroidism from a TSH secreting tumor.
"Screening" refers to the measurement of thyroid function tests in asymptomatic patients at risk of having thyroid disease who are presently not known to have thyroid disease. There is some debate over the cost effectiveness of screening or case finding in apparently asymptomatic patients. This topic is reviewed in detail elsewhere.
評估甲狀腺功能障礙
●門診環境 – 在門診環境中進行評估時，許多實驗室使用以下策略來限制不必要的實驗室檢測： •血清 TSH 正常 – 不進行進一步檢測•血清TSH 高– 添加游離T4 以確定程度甲狀腺功能減退症的症狀
Evaluating for thyroid dysfunction
●Outpatient setting – When evaluation is performed in the outpatient setting, many laboratories use the following strategies to limit unnecessary laboratory testing:
•血清 TSH 低 – 添加游離 T4 和 T3 以確定甲狀腺功能亢進的程度
當用於評估個體患者可能的甲狀腺功能障礙時，我們對此策略進行了兩項修改：
•Serum TSH normal – No further testing performed
•Serum TSH high – Free T4 added to determine the degree of hypothyroidism
•Serum TSH low – Free T4 and T3 added to determine the degree of hyperthyroidism
•如果患者儘管TSH 結果正常但仍出現甲狀腺功能亢進或甲狀腺功能減退症狀，我們會測量血清游離T4。
We make two amendments to this strategy when used to assess possible thyroid dysfunction in an individual patient:
•如果垂體或下丘腦有甲狀腺功能障礙，我們會測量血清TSH 和游離T4懷疑患有疾病（例如年輕女性閉經和疲勞）。
•We measure both serum TSH and free T4 if pituitary or hypothalamic disease is suspected (eg, a young woman with amenorrhea and fatigue).
•如果患者儘管TSH 結果正常但仍出現甲狀腺功能亢進或甲狀腺功能減退症狀，我們會測量血清游離T4。
•We measure serum free T4 if the patient has symptoms of hyper- or hypothyroidism despite a normal TSH result.
然而，一些專家建議出於評估目的，對所有患者同時測量血清TSH 和游離T4，因為在繼發性或中樞性甲狀腺功能減退症或TSH 介導的甲狀腺功能亢進症患者中僅測量TSH 可能會出現錯誤。這種方法增加了相當大的篩查成本，並且可能會發現少數未被懷疑的垂體疾病病例。例如，在一項針對 4843 名社區居民的研究中，測量 TSH 僅會漏掉 3.8% 游離 T4 異常的患者，而這些患者中 85% 的游離 T4 濃度僅有最低限度的高或低 [24 ]。
Serum TSH assays are both more sensitive and specific than serum free T4 measurements for outpatients if a single test is utilized [22,23]. However, some experts recommend that both serum TSH and free T4 be measured in all patients for evaluation purposes since errors may be made when only TSH is measured in patients with secondary or central hypothyroidism or TSH-mediated hyperthyroidism. This approach adds considerable cost to screening and is likely to pick up few cases of unsuspected pituitary disease. As an example, in a study of 4843 community-dwelling individuals, measuring a TSH only would have missed 3.8 percent of patients with an abnormal free T4, and 85 percent of these patients had only minimally high or low free T4 concentrations [24].
●住院環境——在住院環境中評估甲狀腺功能是一個更困難的問題，除非強烈懷疑甲狀腺疾病，否則不建議這樣做，因為在嚴重的非甲狀腺疾病中，甲狀腺激素、結合蛋白和TSH濃度會發生變化（參見“甲狀腺疾病” ）在非甲狀腺疾病中發揮作用”）。這些變化可能包括[ 25 ]：
●Inpatient setting – Evaluating thyroid function in the inpatient setting is a more difficult problem, and it is not recommended unless thyroid disease is strongly suspected, since changes in thyroid hormones, binding proteins, and TSH concentrations occur in severe nonthyroidal illness ). These changes may include [25]:
所有三種結合蛋白濃度均低
• 游離脂肪酸濃度高，可取代結合蛋白中的甲狀腺激素
• 獲得性中樞性甲狀腺功能減退症
• 患者可能正在接受影響甲狀腺功能的藥物（表 1）
雖然有人主張血清 TSH 或游離 T4 對住院患者更有用，但大多數專家建議血清 TSH 和游離 T4 或總 T4 對於評估住院患者的甲狀腺功能都是必要的 [26-28 ]。
監測左旋甲狀腺素治療 — 評估甲狀腺功能的更常見原因之一是評估左旋甲狀腺素治療的充分性。
•Low concentrations of all three binding proteins
•High concentrations of free fatty acids that displace thyroid hormones from binding proteins
•Acquired central hypothyroidism
•The patient may be receiving medications that affect thyroid function (table 1)
While there are advocates for either serum TSH or free T4 being more useful in inpatients, most experts suggest that both serum TSH and free T4 or total T4 are necessary to assess thyroid function in hospitalized patients [26-28].
Monitoring levothyroxine therapy — One of the more common reasons for assessing thyroid function is to assess the adequacy of levothyroxine therapy.
原發性甲狀腺功能減退症——正在服用左旋甲狀腺素的原發性甲狀腺功能減退症患者可以僅通過評估血清 TSH 來監測替代治療。一般來說，無血清 T4 測量對於評估左旋甲狀腺素劑量的適當性非常不敏感。左旋甲狀腺素劑量比最佳劑量高出 40% 可能會導致血清 TSH 濃度低於正常水平，但血清游離 T4 濃度通常仍保持在正常範圍內 [ 29 ]。然而，當 TSH 非常高或非常低時，游離 T4 測量可用於確定適當的劑量增加或減少。
●Primary hypothyroidism – Patients with primary hypothyroidism who are taking levothyroxine replacement therapy can be monitored by assessing the serum TSH only. In general, serum free T4 measurements are very insensitive for assessing the appropriateness of the levothyroxine dose. Doses of levothyroxine that are 40 percent higher than optimal may result in subnormal serum TSH concentrations, yet serum free T4 concentrations frequently remain within the normal range [29]. Nevertheless, free T4 measurements can be useful to determine appropriate dose increases or decreases when TSH is very high or low, respectively.
（T3，Cytomel）通常不推薦用於治療甲狀腺功能減退症。然而，對於接受左旋甲狀腺素單藥治療但出現持續性甲狀腺功能減退症狀的患者，有時會添加 T3。在這種情況下，我們不會定期監測 T3 水平。目前的含T3製劑，由於其胃腸道吸收快，且循環半衰期相對較短（約1天），因此全天T3濃度波動較大。
Liothyronine (T3, Cytomel) is generally not recommended for treating hypothyroidism. However, in patients with persistent hypothyroid symptoms on levothyroxine monotherapy, T3 is sometimes added. In this setting, we do not routinely monitor T3 levels. With the currently available T3-containing preparations, there are wide fluctuations in T3 concentrations throughout the day due to its rapid gastrointestinal absorption and its relatively short half-life in the circulation (approximately one day).
●繼發性甲狀腺功能減退症——應使用血清游離T4值來滴定甲狀腺激素劑量的一種情況是，由於垂體或下丘腦疾病而導致TSH釋放缺失或受損的繼發性甲狀腺功能減退症患者。在這種情況下，游離 T4 水平應維持在正常範圍的 50% 以上。(參見“中樞性甲狀腺功能減退症”，關於‘治療’一節)
●Secondary hypothyroidism – The one setting in which the serum free T4 value should be used to titrate the thyroid hormone dose is in patients with secondary hypothyroidism due to pituitary or hypothalamic disease who have absent or impaired TSH release. In this situation, the free T4 level should be maintained in the upper 50 percent of the normal range.
●甲狀腺癌——對於服用左旋甲狀腺素抑制TSH分泌以預防甲狀腺癌復發的
患者來說，監測的目標和要求是不同的。
●Thyroid cancer – The goal and requirement for monitoring are different in patients taking levothyroxine for suppression of TSH secretion to prevent recurrence of thyroid cancer.
●甲狀腺結節和甲狀腺腫——很少使用左旋甲狀腺素輕度抑制TSH來防止甲狀腺腫組織的生長或再生。
●Thyroid nodules and goiter – Rarely, mild suppression of TSH with levothyroxine is used to prevent growth or regrowth of goitrous tissue.
甲狀腺功能亢進症治療的監測 — 在使用抗甲狀腺藥物、放射性碘或手術治療甲狀腺功能亢進症的早期過程中，血清 TSH 可能會持續數週，很少持續數月。因此，治療的初始監測應包括定期臨床評估、血清游離 T4 的測量以及經常測量的總 T3 水平。在許多類型的甲狀腺功能亢進症中，血清 T3 濃度可能不成比例地高於血清 T4 濃度。此外，抗甲狀腺藥物治療可使血清游離 T4 水平恢復正常，而血清 T3 水平可能持續升高。一旦穩態條件得到保證，血清 TSH 的測量只能用於評估治療效果。
Monitoring treatment of hyperthyroidism — During the early treatment of hyperthyroidism with antithyroid drugs, radioiodine, or surgery, serum TSH may remain subnormal for several weeks and rarely for several months. Initial monitoring of therapy, therefore, should consist of periodic clinical assessment, measurements of serum free T4, and often measurements of total T3 levels. Serum T3 concentrations may be disproportionately higher than serum T4 concentrations in many types of hyperthyroidism. Also, serum free T4 levels may normalize with antithyroid drug therapy, while serum T3 levels may remain persistently elevated. Once steady-state conditions are assured, measurement of serum TSH only can be used to assess the efficacy of therapy.
