Download 2015 Thyriod hormones

Thyroid hormones and
antithyroid drugs
Shi-Hong Zhang (张世红)
[email protected]
Thyroid gland
Front view
Biosynthesis of thyroid hormones
1. Uptake of iodide
2. Oxidation of iodide (peroxidase) and iodination and
coupling of tyrosine
3. Formation of thyroxine (T4) and triiodothyronine (T3)
from iodotyrosine (peroxidase)
4. Secretion of thyroid hormones (proteolytic enzymes)
5. Regulation by thyroid stimulating hormone (TSH), T4,
T3
三碘甲状腺原氨酸
四碘甲状腺原氨酸
甲状腺素的生理及药理作用
1．维持生长发育
2．促进代谢和产热
3．提高交感神经系统的敏感性
Hypothyroidism
Hypothyroidism After treatment
cretinism (呆小症)
simple goiter
(单纯性甲状
腺肿) 瘿
Hyperthyroidism
颤抖
甲状腺肿大，突眼，情绪激动
腱反射亢进
心慌，心脏肥大
多食、腹泻、消瘦
Therapeutic drugs on thyroid
dysfunction
• Hypothyroidism: iodine and iodides (small
doses); thyroid hormone
甲状腺素的临床应用
1 甲状腺功能低下：呆小病；黏液性水肿（甲状腺功能减退）；
不典型及亚临床型甲状腺功能减退；甲状腺切除术后
2 单纯性甲状腺肿
3 T3抑制试验（服用T3后摄碘率下降50%者为单纯性甲状腺肿，
<50%者为甲亢）
Therapeutic drugs on thyroid
dysfunction
• Hypothyroidism:
– thyroid hormones
– iodine and iodides (小剂量)
• Hyperthyroidism:
– antithyroid drugs:
thiourea derivatives 硫脲类
iodine and iodides 碘和碘化物 （大剂量）
 receptor antagonists
Radioiodines 放射性碘:
131I
(硫代酰胺；硫脲类)
Antithyroid drugs
Thiourea
derivatives
丙硫氧嘧啶
PTU
甲巯咪唑，他
巴唑 MMI
硫脲类
卡比马唑，甲亢平
Antithyroid drugs
Thiourea derivatives
1. Pharmacological effects
(1) Inhibit the formation of thyroid hormones by interfering
with iodination: competing peroxidation, then the
iodination and coupling
Symptom relieving: 2-3 weeks
Basic metabolic rate returning: 1-2 months
(2) Inhibit peripheral deiodination of T4: T4  T3 
(propylthiouracil 丙硫氧嘧啶), rapid remission of
hyperthyroidism due to T3 upregulation.
Antithyroid drugs
Thiourea derivatives
1. Pharmacological effects
(3) Inhibit glucose metabolism by downregulating β receptor
(4) Immunosuppression: TSI↓
Thiourea derivatives
2. Clinical uses
(1) Non-operative therapy of hyperthyroidism: long duration (12y)
(2) Preoperative therapy of hyperthyroidism: combined with
large dose of iodide
(3) Thyrotoxic crisis: propylthiouracil, combined with large dose
of iodide,
3. Adverse effects
(1)Hypersensitivity
(2)Agranulocytosis (0.2% or more)
(3) GI reactions
(4) Goitrogenic action (goiter): TSH↑
Antithyroid drugs
Iodine and iodides
1. Pharmacological effects
(1) Small doses: simple goiter
(2) Large doses for short term use: inhibit the
synthesis and release of thyroid hormone
(proteolysis ) by inhibiting peroxidase and
GSH reductase.
After iodide use, the thyroid vascularity is reduced,
and the gland becomes much firmer, the cells
become smaller.
Antithyroid drugs
2. Clinical uses
(1) Simple goiter (small doses)
(2) Preoperative therapy of hyperthyroidism:
combined with thiourea derivatives
(3) Thyrotoxic crisis: combined with
thiourea derivatives (propylthiouracil)
Lugol’s solution 卢戈氏液: 5% iodine and
10% potassium iodide
Antithyroid drugs
3. Adverse effects
(1) Acute effects: hypersensitivity, angioedema,
swelling of the larynx
(2) Chronic intoxication (iodism)
(3) Thyroid dysfunction: exacerbation of
hyperthyroidism, goiter
Antithyroid drugs
Radioiodines
• 131I, 125I, 123I
• Destroying thyroid tissue: βray
• Careful use for hyperthyroidism and
differentiated thyroid carcinoma
• Radioactive iodine uptake test
21
Antithyroid drugs
 receptor antagonists
1. Pharmacological effects
(1) Heart: 1 block
(2) CNS: relieving anxiety
(3) Presynaptic 2 receptor: NE release 
(4) Decrease T3: inhibit deiodination of T4
2. Clinical uses
Adjuvant therapeutic drug
Case report
• A 47-year-old woman consulted her physician
because of heart palpitations, tremulousness,
weight loss and heat tolerance. Examination:
heart rate 110, BP 150/70, diffusely enlarged
thyroid glands, wide-eyed stare, lid lag, FT4 40
pmol/L (normal: 10-31), FT3 10.6 pmol/L(normal:
4-10), TSH undetectable (2-10 mU/L), TSI (甲状
腺刺激性免疫球蛋白)↑. The diagnosis was
Graves’s disease.
Case report
Continued
• She was started on treatment with propranolol, 40 mg tid,
propylthiouracil (丙硫氧嘧啶) 200 mg bid. She became
euthyroid (甲状腺功能正常) in 6 weeks, and the
propranolol dose was gradually reduced and finally
discontinued. She continued receiving a maintenance
dose of propylthiouracil (50 mg bid) for 1 year, after
which the drug was discontinued.
Case report
Continued
• The symptoms of hyperthyroidism recurred 3 years
later, and treatment with propranolol and
propylthiouracil was reinitiated. However, she
developed severe rash over her whole body.
Therefore, the treatment was changed with oral
Na131I for definitive control of her hyperthyroidism.
Case report
Continued
• Three months later, the patient complained of lethargy,
tiredness, a feeling of coldness at room temperature,
puffiness (肿胀) around the eyes, and constipation.
Laboratory testes showed lowered level of T4 and T3,
but elevated level of TSH, confirming the diagnosis of
hypothyroidism. She was started on levothyroxine 0.1
mg daily, and 6 weeks later, her complaints disappeared.
She has remained well on this therapy.