Thyroid Disorders Lecture Notes

Thyroid Gland

• The thyroid is a butterfly-shaped gland located in the neck, just below the thyroid cartilage (Adam's apple) (甲狀腺是一個蝴蝶狀腺體，位於頸部，就在甲狀腺軟骨（喉結）下方).

• It comprises follicles which include (它由毛囊組成，其中包括):

  • An outer layer of follicle cells surrounding a lumen containing gelatinous colloid (圍繞著含有凝膠狀膠體的管腔的卵泡細胞外層).

  • Thyroglobulin (甲狀腺球蛋白).

  • Associated parafollicular cells (C cells) (相關的濾泡旁細胞（C 細胞）).

• The follicles produce and secrete thyroid hormones: thyroxine (T4) and triiodothyronine (T3) (卵泡產生和分泌甲狀腺激素：甲狀腺素 （T4） 和三碘甲狀腺原氨酸 （T3）).

• The parafollicular cells produce calcitonin (濾泡旁細胞產生降鈣素).

Hormone Production and Secretion

• The hypothalamus produces thyrotropin-releasing hormone (TRH), which signals the anterior pituitary to produce thyroid-stimulating hormone (TSH) (下丘腦產生促甲狀腺激素釋放激素 （TRH），向垂體前葉發出信號以產生促甲狀腺激素 （TSH))

• Released TSH binds to its receptor on thyroid follicle cells, stimulating the production and release of thyroid hormones: T3 (tri-iodo-thyronine) and T4 (tetra-iodo-thyronine), which are iodinated amine hormones (釋放的 TSH 與其在甲狀腺濾泡細胞上的受體結合，刺激甲狀腺激素的產生和釋放：T3（三碘甲狀腺原氨酸）和 T4（四碘甲狀腺原氨酸），它們是碘胺激素).

• The thyroid gland produces calcitonin, a peptide hormone, in response to increased blood calcium levels (甲狀腺產生降鈣素，一種肽激素，以響應血鈣水準升高).

Thyroid Hormone Production Process

• Tyrosine-rich thyroglobulin is synthesized and released into the lumen (富含酪氨酸的甲狀腺球蛋白被合成並釋放到管腔中).

• Iodide is actively taken up from the blood and transported into the lumen (碘從血液中被主動吸收並輸送到管腔中).

• The enzyme thyroid peroxidase converts iodide to free iodine (甲狀腺過氧化物酶將碘轉化為遊離碘).

• Oxidized iodine atoms iodinate tyrosine in thyroglobulin, adding one or two iodines per tyrosine (氧化的碘原子使甲狀腺球蛋白中的酪氨酸碘化，每個酪氨酸添加 1 或 2 個碘).

• Mono- or di-iodotyrosines couple together to form thyroxine (T4) or triiodothyronine (T3) (單碘酪氨酸或二碘酪氨酸偶聯在一起形成甲狀腺素 （T4） 或三碘甲狀腺原氨酸 （T3)).

• The follicular cells take up this iodinated thyroglobulin, and lysosomal enzymes break it down, allowing T4 and T3 to diffuse into the bloodstream (濾泡細胞吸收這種碘化甲狀腺球蛋白，溶酶體酶將其分解，使 T4 和 T3 擴散到血液中).

Activities of T4 and T3

• Approximately 90% of the thyroid hormone secreted by the thyroid gland is T4, a less potent "prohormone", while 10% is the more potent T3 (甲狀腺分泌的甲狀腺激素中約有 90% 是 T4，這是一種效力較弱的“激素原”，而 10% 是效力較強的 T3).

• Both T3 and T4 circulate in a bound, inactive form, binding to thyroxine-binding globulin or albumin, which improves solubility and prevents urinary excretion (T3 和 T4 都以結合的、無活性的形式迴圈，與甲狀腺素結合球蛋白或白蛋白結合，從而提高溶解度並防止尿液排泄).

• T3 and T4 must dissociate from their transport proteins to exert their biological effects (T3 和 T4 必須從它們的轉運蛋白上解離才能發揮其生物學效應).

• T4 must be activated to T3 in peripheral target tissues (especially the liver and kidneys) through the removal of one iodine (T4 必須通過去除一個碘在外周靶組織（尤其是肝臟和腎臟）中被啟動為 T3).

• T3 and T4 act via the intracellular thyroid hormone receptor, a hormone-responsive transcription factor (T3 和 T4 通過細胞內甲狀腺激素受體（一種激素反應性轉錄因數）起作用).

Dysregulation of Hypo-pituitary-thyroid Axis

• Iodine deficiency impairs thyroid hormone production, leading to hypothyroidism (碘缺乏會損害甲狀腺激素的產生，導致甲狀腺功能減退).

• The negative feedback mechanism is suppressed due to thyroid hormone deficiency (由於甲狀腺激素缺乏，負反饋機制受到抑制).

• TRH and TSH levels increase, prompting the thyroid gland to produce more thyroid hormone (TRH 和 TSH 水準升高，促使甲狀腺產生更多的甲狀腺激素).

• The thyroid gland swells, leading to a condition called goitre (甲狀腺腫脹，導致一種稱為甲狀腺腫的疾病).

Disorders of the Thyroid Gland

• Dysfunction can result in the overproduction or underproduction of thyroid hormone (功能障礙可導致甲狀腺激素產生過多或不足).

• Enlargement of the thyroid gland (goitre) can occur in both hypothyroidism and hyperthyroidism, but it is not always present (甲狀腺腫大（甲狀腺腫）可發生在甲狀腺功能減退症和甲狀腺功能亢進症中，但並不總是存在).

• Autoimmune destruction (Hashimoto’s thyroiditis), antibodies (Grave’s disease), dietary iodine deficiency, inflammation, pituitary tumors, and inherited disorders can all affect thyroid hormone production (自身免疫性破壞（橋本氏甲狀腺炎）、抗體（格雷夫氏病）、膳食碘缺乏、炎症、垂體瘤和遺傳性疾病都會影響甲狀腺激素的產生).

Hypothyroidism

• The thyroid gland does not produce enough thyroid hormones (甲狀腺不能產生足夠的甲狀腺激素).

• Symptoms develop gradually and may be overlooked (癥狀逐漸發展，可能被忽視).

  • Symptoms in adults include (成人的癥狀包括):

    • Tiredness (疲勞)

    • Sensitivity to cold (對寒冷敏感)

    • Weight gain (體重增加)

    • Slow movements and thoughts (動作和思維緩慢)

    • Slow heart rate (心率緩慢)

    • Muscle aches and weakness (肌肉酸痛和無力)

    • Dry, thickened skin (皮膚乾燥、增厚)

    • Brittle hair and nails (頭髮和指甲變脆)

    • Loss of sex drive (喪失

    • Depression (抑鬱症)

    • Confusion and memory loss (意識模糊和記憶喪失)

    • Irregular or heavy periods (月經不調或月經量大)

    • Growth and mental retardation in children (兒童生長髮育遲緩)

Treatment of Hypothyroidism

• Hormone replacement with levothyroxine (identical to endogenous T4) (用左旋甲狀腺素替代激素（與內源性 T4 相同)).

  • Long half-life means the dose is not often critical (半衰期長意味著劑量通常不重要).

• T3 (liothyronine) can also be given as it is faster-acting but has a shorter half-life than T4 (也可以給予 T3（碘塞羅寧），因為它起效更快，但半衰期比 T4 短).

• If a dietary iodine deficiency underlies hypothyroidism, iodine supplements are administered (如果膳食碘缺乏是甲狀腺功能減退症的基礎，則給予碘補充劑).

Hyperthyroidism

• Occurs when the thyroid gland produces too much thyroid hormone (當甲狀腺產生過多的甲狀腺激素時發生).

• Common, particularly in women, where 2% of women have hyperthyroidism (甲狀腺功能亢進症). (常見，尤其是在女性中，其中2%)

• Symptoms in adults include (成人的癥狀包括):

  • Sensitivity to heat (熱敏感)

  • Weight loss (減肥)

  • Anxiety (焦慮)

  • Rapid heart rate (心率加快)

  • Atrial fibrillation (心房顫動)

  • Bulging eyes (眼睛凸出)

  • Hair loss (脫髮)

  • Longer period cycles (更長的週期)

  • Hand tremor (手震顫)

  • Thirst (口渴)

  • Hunger (饑餓)

Treatment of Hyperthyroidism

• Inhibitors of thyroid synthesis, e.g., carbimazole and propylthiouracil, inhibit thyroid peroxidase and prevent the iodination of thyroglobulin (甲狀腺合成抑製劑，例如卡比馬唑和丙硫氧嘧啶，可抑制甲狀腺過氧化物酶並阻止甲狀腺球蛋白的碘化).

  • Long-term use can lead to thyroid hypertrophy and goitre (長期使用可導致甲狀腺肥大和甲狀腺腫大).

• Surgical resection of the thyroid (甲狀腺手術切除).

• Thyroid ablation with radioactive iodine (放射性碘甲狀腺消融術).

Hashimoto's Disease

• Hashimoto's thyroiditis can cause the thyroid gland to not produce enough thyroid hormone (橋本氏甲狀腺炎會導致甲狀腺不能產生足夠的甲狀腺激素).

• It is an autoimmune disease (這是一種自身免疫性疾病).

• The body produces antibodies that attack the cells in the thyroid (身體產生抗體，攻擊甲狀腺中的細胞).

• Symptoms may include (症狀可能包括):

  • Enlarged thyroid gland (goiter) (甲狀腺腫大（甲狀腺腫）)

  • Tiredness (疲勞)

  • Weight gain (體重增加)

  • Muscle weakness (肌無力)

Grave's Disease

• Graves' disease is an autoimmune condition causing the thyroid gland to produce too much thyroid hormone—hyperthyroidism (格雷夫斯病是一種自身免疫性疾病，導致甲狀腺產生過多的甲狀腺激素——甲狀腺功能亢進症).

• It is the most common cause of an overactive thyroid, accounting for about 4 out of 5 cases (它是甲狀腺功能亢進症的最常見原因，約佔 4/5 的病例).

• Symptoms can affect multiple systems (癥狀可能影響多個系統).

• More common in women and people over 30 (更常見於女性和 30 歲以上的人群).

• The immune system produces thyroid-stimulating antibodies (TRAb) that stimulate the thyroid gland, leading to excess hormone production (免疫系統產生刺激甲狀腺的促甲狀腺抗體 （TRAb），刺激甲狀腺，導致激素分泌過多).

• TRAb mimics thyroid-stimulating hormone (TSH), causing the thyroid to continue producing thyroid hormones, despite the pituitary trying to switch off the thyroid by stopping the production of TSH (TRAb 類似於促甲狀腺激素 （TSH），導致甲狀腺繼續產生甲狀腺激素，儘管垂體試圖通過停止 TSH 的產生來關閉甲狀腺).

• The condition often runs in families and affects young to middle-aged women (這種疾病通常在家族中遺傳，影響中青年女性).

• Smoking increases the risk (吸煙會增加風險).

• Diagnosis is confirmed through a blood test that detects anti-thyroid antibodies (通過檢測抗甲狀腺抗體的血液檢查來確診).

• Treatment focuses on reducing thyroid hormone levels and relieving symptoms (治療的重點