第08章 甲状腺功能亢进症

nullHyperthyroidism (THYROTOXICOSIS)Hyperthyroidism (THYROTOXICOSIS)Lecturer: LIAO ERYUANnullHyperthyroidism is only a diagnosis of excessive TH status, never means a concrete disease . It is wrong to say “Graves disease (GD)” as “hyperthyroidism ” in brief.Regardless of the pathogenesis, Hyperthyroidism is characterized byRegardless of the pathogenesis, Hyperthyroidism is characterized bynullA. Thyroidal origin 1. Graves disease (GD) 2. Multiple nodular thyrotoxicosis 3. Plummer disease (toxic thyroid adenoma) 4. Hyperfunctional thyroid nodule 5. MEN with hyperthyroidism 6. Thyroid carcinomas 7. Neonatal hyperthyroidism 8. Genetic toxic thyroid hyperplasia/goiter 9. Iodine-induced hyperthyroidism Pathogenesis of HyperthyroidismnullB. Pituitary origin 1. Pituitary TSHoma 2. TH insensitivity syndrome 3. Para-carcinoma syndrome 4. HCG-related hyperthyroidism 5. Ovarian goiter with hyperthyroidism 6. Iatrogenic hyperthyroidismnullC. Transient hyperthyroidism 1. Subacute de Quervian thyroiditis subacute lymphocytic thyroiditis traumatic thyroiditis radioactive thyroiditis 2. Chronic chronic lymphocytic thyroiditisnullTRHTSHT3,T4INormal FeedbackITSHR-AbT3,T4Graves’ DiseaseT3TSHTRHnullPathogenesis Histopathology Clinical presentation Laboratory and special exams Diagnosis and differential diagnosis TreatmentGRAVES DISEASE (GD)nullGraves disease diffuse toxic goiter Basedow disease Subclinical hyperthyroidism normal TH decreased TSH no symptoms or signs nullA. Abnormalities of immune system 1. TSH-R-Ab + TSH-R →mimic TSH →hyperfunction/goiter. 2. functioning Ig → Th hypersensitivity + IL-1, IL-2 → TSH-R-Ab (TRAb)Pathogenesisnull stimulating IgG hyperfunction(TSAb) 3. TRAb inhibitory IgG hypofunction/antagonist of TSHR and TSAb (TF1Ab, TGBAb) growth-stimulating IgG (TGI)nullB. Other factors genetic factors infective factors stress (physical or emotional)nullThyroid-associated ophthalmo- pathy (TAO) unknown GAG accumulation, T cell infiltration, edema, fibrosis and sight loss.nullA. Thyroid goiter: symmetrical, diffuse, lobular follicles: hyperplastic with scant colloid, papillary projections, vascularity: increased infiltration: lymphocytes/plasma cellsII Histopathology Overactivity of the thyroid gland nullThe thyroid follicles are lined by cuboidal follicular epithelium nullUnder high power microscope, the tall columnar epithelium is lined by hyperplastic infoldingsnullB. Eyes orbital contents↑, with mucoprotein, GAG (glycosaminoglycan), and lymphocytes. C. Skin (dermopathy) 1. hyaluronic acid, chondroitin sulfates↑ 2. featured by separated collagen fibers, with plaque formation, 3. lymphatic drainage decreasednullA. General considerations incidence 0.5% male: female ≈ 1: 4~6 common in 30~40yrs family onset constitutionClinical PresentationnullB. Hypermetabolic states nervousness (99%) irritability (90%) palpitation (88%) tachycardia (82%) insomnia (60%) fatigue (70%) heat intolerance (70%) weight loss (75%) voracious appetite (65%) menstruation changes (50%)nullC. Thyroid consistency: soft, firm, rubbery enlargement: symmetrical surface: smooth thrill with audible bruit nullD. Eyes a. non-infiltrative orbitopathy fissure widened, sclera exposed, lid retraction, lid tremor, lid lay, globe lay. Typical manifestations of the eyes and thyroid Typical manifestations of the eyes and thyroid Staring gaze is one of the early signs of TAOnullToxic goiter is the important feature of GD inflammation and hypertrophy of the tissues around the eyes causing swelling nullb. infiltrative orbitopathy: excessive tearing exophthalmos (asymmetrical) eyelids unclosed blurred vision double vision visual acuity decreased corneas ulcerated and infected sight lossnullc. Classification of Graves orbitopathy: NOSPECS (American Thyroid Association) Class Definition 0 No physical signs or symptoms 1 Only signs, no symptoms (signs limited to upper lid retraction, stare, lid lag, and proptosis to 22mm) 2 Soft tissue involvement (symptom and sign) 3 Proptosis>22mm 4 Extraocular muscle involvement 5 Corneal involvement 6 Sight loss (optic nerve involvement)nullE. Others tremor of hands and tongue muscle wasting rapid reflex response liver function wbc↓ and anemia, vitiligo/hair loss pretibial myxedema null Early feature of pretibial myxedema: thickening of the skin over the lower legsnullF. Complications a. cardiopathy/heart failure arrhythmia, heart enlargement and failure, disappeared after treatment b. Thyrotoxic crisis exaggerated abruptly precipitating factors: infection, trauma, surgery, radiation, DKA, parturition Additional pictures: arrhythmias, pulmonary edema, abdominal pain, apathy, coma, shocknullc. hypokalemic periodic paralysis more common in Asia abruptly paralysis with hypokalemia precipitated by carbohydrate or vigorous exercise some companied by myasthenia gravis. nullA. Serum TH and TSH a. FT3 and FT4 b. TT3 and TT4 c. rT3 d. TSH B. TSH receptor antibodies Laboratory and Special ExamsnullC. TRH stimulation test euthyroid Graves ophthalmopathy GD medication D. 131I uptake and T3 suppression test E. pathological examsnullA. Functional diagnosis suspected when weight loss diarrhea slight fever tachycardia atrial fibrillation fatigue dysmenorrhea difficult in control of DM, TB, heart failure, CHD, liver diseaseDiagnosis and Differential DiagnosisnullB. Types FT3 /FT4 ↑, uTSH↓: hyperthyroidism Only FT3 ↑, uTSH↓: T3 hyperthyroidism Only FT4 ↑, uTSH↓: T4 hyperthyroidism Only uTSH↓: subclinical hyperthyroidismC. Pathogenic diagnosis TRAb, TgAb, TPOAb, HCG, 131I uptakenullA. General management sedatives for restlessness/insomnia. B. Management a. medical methylthiouracil (MTU) propylthiouracil (PTU) 300~600mg/d methimazole (MM) carbimazole (CMZ) 30~60mg/d Treatmentnullb. dosage and course 1st stage (6 wks) full dosage to control symptoms 2nd stage (4~8wks) dosage decrease gradually 1/6 dosage/wk 3rd stage (>1yr) PTU 50mg/MM 5mg, Qd nullc. “block-replace” regimens TH added to prevention of hypothyroidism. T4 50µg, Qd. not recommended in general d. drug withdrawal goiter subsides minimal dosage to maintain effects TSH return to normal TSAb negative normal response to TRHnulle. drug side-effects agranulocytosis (<1%, within 2 mos) WBC / wk-monullC. Radioiodine (131I) a. more commonly used than before b. contraindications pregnant young people (<20yrs) severe exophthalmos thyrotoxic crisis failed to uptake I nullC. Complications hypothyroidism radiation thyroiditis thyrotoxic crisis exaggarated proptosis (smokers, >40 yrs, male)nullD. Surgery indications failed to medication huge thyroid tumor suspected retrosternal goiter contraindications severe proptosis severe systemic diseases early and late pregnancy thyrotoxicosis not controllednullE. Treatment decision-making a. firstly treated with medications for all patients b. after controlled, decided by age run course severity/complications thyroid states doctor’s experience patient’s willings nullF. Special concerns a. minimal iodide supplement b. treat severe proptosis with caution, including TH supplement and prednisone c. thyroid crisis treated with NaI, PTU, DXM, and propranololnull d. PTU for pregnant cases, never makes TSH <0.5mU/L e. treated with digoxin may be dangerous in some cases