36-1 - Hyperthyroidism Department of endocrinology and...

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Unformatted text preview: Hyperthyroidism Department of endocrinology and metabolism Renji Hospital Hyperthyroidism Hyperthyroidism Definition: A clinical syndrome is brought about by thyroid hormone overproduction of various causes. CNS input hypothalamus TRH pituitary TSH thyroid T4,T3-TBG------------ FT4,FT3 ↑ FT4 Target tissue FT3 Target cell receptor Classification of hyperthyroidism Greaves’ desease TSI ↑ Adenoma tumor Resistance to T3,T4 TSH analog↑ HCG↑ Abnormal thyroid stimulator ↑ pituitary TSH↑ THYROID FT3,FT4 Classification of hyperthyroidism Diffuse toxic goiter Subacute thyroiditis Chronic thyroiditis transient thyrotoxicosis Disorder of storage Thyroid destruction Hyperfunction adenoma Iod-Basedow’s disease Toxic multinodular goiter Excess iodide Carcinoma Toxic adenoma(Plummer’s disease) THYROID Extrathyroid source of hormone FT3, FT4 Graves' disease Graves' Thyroid hormone overproduction AutoImmune (TSI - TSH-R Ab) mediated Graves' disease Graves' Featured as: • Hyperthyroidism • Autoimmune mediated Diffuse goiter Exophthalmos Pretibial myexedema Etiology And Pathogenesis - autoimmune disease HLA-DR3 HLA-DR3 genetic factors Infection mental factors Environmental risk factor defect in immunoregulation with failure of “suppressor ” T lymocytphes function. allowing “helper” T lymocytphes to stimulate B lymphocytes to produce TSH receptor antibodies(TRAb) Thyroid­stimulating antibody (TSAb) Thyroid­ stimulating blocking antibody (TSBAb) Graves' disease Graves' Thyroid manifestations of Graves' disease Thyroid • diffuse toxic goiter Extrathyroidal manifestations of Graves' disease Be immunologically mediated activation of Be fibroblasts in the extraocular muscles and skin, with accumulation of glycosaminoglycans, leading to the trapping of water and edema. Later, fibrosis becomes prominent prominent • Ophthalmopathy Ophthalmopathy • Dermopathy The fibroblast activation is caused by cytokines derived from locally infiltrating T cells and macrophages. cells Clinical Manifestations Clinical Hyperthyroidism ­ common to any cause of thyrotoxicosis Autoimmune mediated ­ specific for Graves' disease Diffuse goiter Exophthalmos Pretibial myexedema Clinical Manifestations Clinical The clinical presentation depends on the severity of thyrotoxicosis, the duration of the disease, individual susceptibility to excess thyroid hormone, and the age of the patient. Symptoms of hypermetabolism • unexplained weight loss, despite an enhanced unexplained appetite appetite • sweating and heat intolerance, particularly during warm weather, during Symptoms of sympathetic hyperactivity • hyperactivity, nervousness, and irritability • Insomnia and impaired concentration • Fine tremor • hyperreflexia, muscle wasting, and proximal hyperreflexia, myopathy without fasciculation. Gastrointestinal : • Gastrointestinal transit time is decreased, leading to Gastrointestinal increased stool frequency, often with diarrhea and occasionally mild steatorrhea. Sex: • Women frequently experience oligomenorrhea or Women amenorrhea; in men there may be impaired sexual function and, rarely, gynecomastia. bone: • osteopenia in long-standing thyrotoxicosis cardiovascular manifestation palpitations (sinus tachycardia, supraventricular palpitations tachycardia, Atrial fibrillation ) tachycardia, a bounding pulse, widened pulse pressure, and bounding an aortic systolic murmur (due to high cardiac output ) worsening of angina or heart failure in the elderly worsening or those with preexisting heart disease. Diffuse goiter Thyroid is usually diffusely enlarged to two Thyroid to three times its normal size. There may be a thrill or bruit due to the There increased vascularity of the gland and the hyperdynamic circulation. hyperdynamic Exophthalmos a staring appearance -Lid retraction, is the result staring of sympathetic overactivity. a sensation of grittiness, eye discomfort, and sensation excess tearing. proptosis some cases of euthyroid ophthalmopathy. the enlarged extraocular muscles typical of the the disease disease compression of the optic nerve at the apex of the compression orbit, leading to papilledema, peripheral field defects, and, if left untreated, permanent loss of vision. vision. NO SPECS scheme NO 0 = No signs or symptoms 1 = Only signs (lid retraction or lag), no nly symptoms symptoms 2 = Soft tissue involvement (periorbital edema) 3 = Proptosis (> 22 mm) 4 = Extraocular muscle involvement (diplopia) 5 = Corneal involvement 6 = Sight loss Special Clinical Manifestations Special Thyroid storm Infiltrating exophthalmos Hyperthyroid heart disease Periodic paralysis Atypical Hyperthyroidism T3 .T4 type hyperthyroidism Subclinical hyperthyroidism Pregnancy hyperthyroidism Pretibial myexedema Thyrotoxic crisis Thyrotoxic be precipitated by • acute illness (e.g., stroke, infection, trauma, diabetic ketoacidosis) diabetic • surgery (especially on the thyroid) surgery • overdoses of thyroid hprmone overdoses • radioiodine treatment of a patient with partially treated or untreated hyperthyroidism. Thyrotoxic crisis Thyrotoxic Manifestation: • • • • • • Fever(>39C) Fever(>39C) Increased heart rate,Af,AF, Weight loss sweating vomiting, diarrhea, and jaundice delirium, seizures, coma, delirium, hypokalemic periodic paralysis hypokalemic this disorder is particularly common in Asian males with thyrotoxicosis. Hypokalemia was recovered after patasium supplement or rest Released after hyperthyroidism well control Thyroid dermopathy Thyroid the anterior and lateral aspects of the the lower leg (pretibial myxedema) lower noninflamed, indurated plaque with a deep pink or purple color and an "orangedeep skin" appearance. Nodular involvement can occur, and the condition can rarely extend over the whole lower leg and foot, mimicking elephantiasis. Hyperthyroid heart disease Featured as: • heart enlargement • arrhythmias • Heart failure Other causes excluded Be recovered after hyperthyroidism well control in a pulsatile manner spontaneous CNS input rhythms Diurnal rhythms its highest levels occur at night. hypothalamus TRH pituitary TSH THYROID T4,T3-TBG------------ FT4,FT3 FT4 FT3 Target cell receptor Target tissue Thyroid 5 nmol <5 nmol Type I/II deiodinase rT3 45 nmol T4 25 nmol TETRAC 35 nmol T3 Protein bound T3T4 TBG 99.96% T4 >T3 TPBA Measure the level of hormone Measure the level of hormone total vs. free Basal level(rhythms) Stimulation test Inhibitory test step1: Biochemically confirmed thyrotoxicosis hypothalamus TRH stimulated test TRH ③ pituitary TSH T3 inhibitory test ④ illness, medications genetic factors estrogens, androgens, the nephrotic syndrome ① THYROID set-point" in this axis , a sensitive and specific marker T4,T3------------ FT4,FT3 ② TBG FT4 Target cell FT3 receptor Target tissue TSH Na+ /I− symporter I - I - TPO H2O2 I 0 Tg-I Tg TPO T4T3-Tg coupling Tg DIT,MIT-Tg I- Tyr DI Tg T4 T3 I- Step: Etiological diagnosis TRAb ① TPOAb,TGAb TSH Na+ /I− symporter I - I - TPO H2O2 I 0 Tg-I ③ T4T3-Tg TPO Tg DIT,MIT-Tg Tyr DI ② thyroid scan Tg Tg coupling II uptake ① ④ FNA biopsies T4 T3 I- Graves' disease is characterized by an enlarged gland and increased tracer uptake that is distributed homogeneously. Toxic adenomas appear as focal areas of increased uptake, with suppressed tracer uptake in the remainder of the gland. In toxic multinodular goiter, the gland is enlarged often with distorted architecture and there are multiple areas of relatively increased or decreased tracer uptake. Subacute thyroiditis is associated with very low uptake because of follicular cell damage and TSH suppression. Thyrotoxicosis factitia, caused by self-administration of thyroid hormone, is also associated with low uptake. Diagnosis of Graves' disease Diagnosis function diagnosis: function • • • • manifestations of hyperthyroidism diffuse goiter on palpation Ophthalmopathy biochemically confirmed thyrotoxicosis Etiological diagnosis : • positive TRAb, (TGAb, TPOAb,possible) antibodies • often a personal or family history of autoimmune often disorders. Differential Diagnosis Simple goiter Neurosis pheochromocytoma TREATMENT TREATMENT Reducing thyroid hormone synthesis ---Reducing antithyroid drugs antithyroid Reducing the amount of thyroid tissue---Reducing radioiodine (131I) treatment or subtotal radioiodine I) thyroidectomy. thyroidectomy. antithyroid drugs antithyroid propylthiouracil, methimazole. propylthiouracil, iinhibit the function of TPO, reducing oxidation nhibit reducing and organification of iodide. also reduce thyroid antibody levels by also mechanisms that remain unclear, and they appear to enhance rates of remission. Propylthiouracil inhibits deiodination of T4 → T3. Propylthiouracil However, this effect is of minor benefit, except in the most severe thyrotoxicosis, and is offset by the much shorter half-life of this drug (90 min) compared to methimazole (6 h). compared The initial dose : The • methimazole 10 to 20 mg q8h or q12 h, but once-daily methimazole dosing is possible after euthyroidism is restored. • Propylthiouracil 100 to 200 mg q6h or q8 h, and Propylthiouracil divided doses are usually given throughout the course. titration regimen: dose be gradually reduced as titration thyrotoxicosis improves. • The usual daily maintenance doses : methimazole 2.5 to 10 mg methimazole propylthiouracil 50 to 100 mg block-replace regimen: high doses combined block-replace with levothyroxine supplementation to avoid drug-induced hypothyroidism. drug-induced Maximum remission rates are achieved by 18 to Maximum 24 months Thyroid function tests and clinical Thyroid manifestations are reviewed 3 to 4 weeks after starting treatment, and the dose is titrated based on free T4 levels. All patients should be followed closely for All relapse during the first year after treatment and at least annually thereafter. and side effects side common :rash, urticaria, fever, and common arthralgia (1 to 5% of patients). hepatitis, an SLE-like syndrome SLE agranulocytosis (e.g., sore throat, fever, agranulocytosis mouth ulcers) (< 1%). mouth 1%). monitor blood counts, as the onset of agranulocytosis is idiosyncratic and abrupt. abrupt. Other regimen Propranolol (20 to 40 mg every 6 h) or longer acting beta blockers, such as atenolol, may be useful to control adrenergic symptoms, especially in the early stages before antithyroid drugs take effect. complex iodide Radioiodine Radioiodine causes progressive destruction of thyroid cells be used as initial treatment or for relapses after be a trial of antithyroid drugs. The risk of thyrotoxic crisis can be avoided by The pretreatment with antithyroid drugs for at least a month before treatment. Antithyroid drugs must be stopped 3 to 5 days Antithyroid before radioiodine administration to achieve optimum iodine uptake. optimum dose based on clinical features, such as the dose severity of thyrotoxicosis, the size of the goiter (increases the dose needed), and the level of radioiodine uptake (decreases the dose needed). needed). 131I dosage generally ranges between 185 MBq (5 mCi) to 555 MBq (15 mCi). Many authorities favor an approach aimed at thyroid ablation (as opposed to euthyroidism), given that levothyroxine replacement is straightforward. straightforward. Pregnancy and breast feeding are Pregnancy absolute contraindications to radioiodine treatment, but patients can conceive safely 6 to 12 months after treatment. Surgery Careful control of thyrotoxicosis with antithyroid drugs antithyroid followed by potassium iodide (3 drops SSKI orally tid) to avoid thyrotoxic crisis and to reduce the vascularity of the gland. Management of Thyrotoxic crisis Thyrotoxic Prevention Treatment principles: intensive monitoring and supportive care identification and treatment of the precipitating cause identification measures that reduce thyroid hormone synthesis. measures • iinhibitory action on T4 → T3 conversion: Large doses of nhibitory propylthiouracil (600-mg loading dose and 200 to 300 mg every 6 h) should be given orally or by nasogastric tube or per rectum h) • One hour after the first dose of propylthiouracil, stable iodide is given to block thyroid hormone synthesis :potassium iodide (5 drops SSKI every 6 h), may be given orally. • Propranolol should also be given to reduce tachycardia and other adrenergic manifestations (40 to 60 mg orally every 4 h; or 2 mg intravenously every 4 h). • glucocorticoids (e.g., dexamethasone, 2 mg every 6 h), glucocorticoids antibiotics if infection is present, cooling, and intravenous fluids. antibiotics Ophthalmopathy Ophthalmopathy mild or moderate :requires no active treatment mild Discomfort can be relieved with artificial tears Discomfort (e.g., 1% methylcellulose) and the use of dark glasses with side frames. glasses Periorbital edema responds to a more upright sleeping position. sleeping Corneal exposure during sleep can be avoided by taping the eyelids shut. Minor degrees of diplopia improve with prisms fitted to spectacles. Severe ophthalmopathy • high-dose glucocorticoids + cyclosporine high-dose (sometimes)→be tapered by 5 mg every 1 to 2 weeks, (sometimes) be • Pulse therapy: intravenous methylprednisolone followed by an oral regimen • External beam radiotherapy of the orbits • Octreotide • LT4:adjust hypothalamus­pituitary­thyroid axis Graves' disease in pregnancy Graves' absolute contraindications to radioiodine treatment Propylthiouracil is usually used because of relatively low Propylthiouracil transplacental transfer and its ability to block T4 → T3 conversion. The lowest effective dose of propylthiouracil should be The given, as blocking doses of these drugs produce fetal hypothyroidism. Breast feeding is safe with low doses of antithyroid Breast drugs. drugs. Subtotal thyroidectomy is an option during pregnancy (4th-6th) (4th-6th) Radioactive iodine therapy Simple method for the treatment of thyrotoxicosis, no increased prevalence of thyroid carcinoma, leukemia or transmissible genetic damage. 1.complication • Hypothyroidism • Radiation throiditis • Exacerbation of hyperthyroidism 2.indication 3. Forbidden Cases ...
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This note was uploaded on 12/24/2011 for the course STEP 1 taught by Professor Dr.aslam during the Fall '11 term at Montgomery College.

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