Hyperthyroidism Department of endocrinology and metabolism Renji Hospital
A clinical syndrome is brought about by thyroid hormone overproduction of various causes.
T 4 ,T 3 -TBG------------ FT 4 ,FT 3 receptor TSH CNS input TRH thyroid hypothalamus pituitary Target tissue Target cell FT 4 FT 3
TSH THYROID pituitary Classification of hyperthyroidism
Abnormal thyroid stimulator
FT3,FT4 Adenoma Resistance to T3,T4
TSI TSH analog HCG tumor
THYROID Classification of hyperthyroidism
Diffuse toxic goiter
Toxic multinodular goiter
Toxic adenoma(Plummer’s disease)
FT3, FT4 Extrathyroid source of hormone transient thyrotoxicosis Disorder of storage Thyroid destruction Iod-Basedow’s disease Excess iodide
Thyroid hormone overproduction
AutoImmune ( TSI - TSH-R Ab ) mediated
HLA-DR3 genetic factors Infection 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)
Thyroid-stimulating antibody (TSAb)
Thyroid- stimulating blocking antibody (TSBAb)
Etiology And Pathogenesis - autoimmune disease mental factors
Thyroid manifestations of Graves' disease
diffuse toxic goiter
Extrathyroidal manifestations of Graves' disease
Be immunologically mediated activation of fibroblasts in the extraocular muscles and skin, with accumulation of glycosaminoglycans, leading to the trapping of water and edema. Later, fibrosis becomes prominent
The fibroblast activation is caused by cytokines derived from locally infiltrating T cells and macrophages.
- common to any cause of thyrotoxicosis
- specific for Graves' disease
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 appetite
sweating and heat intolerance, particularly during warm weather ,
Symptoms of sympathetic hyperactivity
hyperactivity, nervousness, and irritability
Insomnia and impaired concentration
hyperreflexia, muscle wasting, and proximal myopathy without fasciculation.
Gastrointestinal transit time is decreased, leading to increased stool frequency, often with diarrhea and occasionally mild steatorrhea.
Women frequently experience oligomenorrhea or amenorrhea; in men there may be impaired sexual function and, rarely, gynecomastia.
radioiodine treatment of a patient with partially treated or untreated hyperthyroidism.
Increased heart rate,Af,AF,
vomiting, diarrhea, and jaundice
delirium, seizures, coma,
hypokalemic periodic paralysis
this disorder is particularly common in Asian males with thyrotoxicosis.
Hypokalemia was recovered after patasium supplement or rest
Released after hyperthyroidism well control
the anterior and lateral aspects of the lower leg ( pretibial myxedema )
noninflamed, indurated plaque with a deep pink or purple color and an "orange-skin" appearance.
Nodular involvement can occur, and the condition can rarely extend over the whole lower leg and foot, mimicking elephantiasis.
Hyperthyroid heart disease
Other causes excluded
Be recovered after hyperthyroidism well control
T 4 ,T 3 -TBG------------ FT 4 ,FT 3 receptor TSH CNS input TRH THYROID hypothalamus pituitary Target tissue Target cell spontaneous rhythms Diurnal rhythms its highest levels occur at night. in a pulsatile manner FT 4 FT 3
T 4 rT 3 T 3 45 nmol 35 nmol 25 nmol TETRAC Thyroid 5 nmol <5 nmol Protein bound T 3 T 4 99.96% TBG TPBA T 4 >T 3 Type I/II deiodinase
Measure the level of hormone
total vs. free
Basal level(rhythms) Stimulation test Inhibitory test
T 4 ,T 3 ------------ FT 4 ,FT 3 receptor TSH TRH THYROID hypothalamus pituitary Target tissue Target cell T3 inhibitory test set-point" in this axis , a sensitive and specific marker step1: Biochemically confirmed thyrotoxicosis FT 4 FT 3 TRH stimulated test TBG illness, medications genetic factors estrogens, androgens, the nephrotic syndrome ① ② ③ ④
I - I - TPO I 0 Tg I - I - T 4 T 3- Tg DIT,MIT-Tg T 4 T 3 Tg H 2 O 2 Tyr DI Na /I symporter Tg Tg-I TPO coupling TSH
I - I - TPO I 0 Tg I - I - T 4 T 3- Tg DIT,MIT-Tg T 4 T 3 Tg H 2 O 2 Tyr DI Na /I symporter Tg Tg-I TPO coupling TSH TPOAb,TGAb I uptake thyroid scan Step: Etiological diagnosis TRAb ① ① ② ③ ④ FNA biopsies
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
manifestations of hyperthyroidism
diffuse goiter on palpation
biochemically confirmed thyrotoxicosis
Etiological diagnosis :
positive TRAb, (TGAb, TPOAb,possible) antibodies
often a personal or family history of autoimmune disorders.
Reducing the amount of thyroid tissue---- radioiodine ( 131 I) treatment or subtotal thyroidectomy.
inhibit the function of TPO , reducing oxidation and organification of iodide.
also reduce thyroid antibody levels by mechanisms that remain unclear, and they appear to enhance rates of remission.
Propylthiouracil inhibits deiodination of T4 T3. 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).
The initial dose :
methimazole 10 to 20 mg q8h or q12 h, but once-daily dosing is possible after euthyroidism is restored.
Propylthiouracil 100 to 200 mg q6h or q8 h, and divided doses are usually given throughout the course.
titration regimen: dose be gradually reduced as thyrotoxicosis improves.
The usual daily maintenance doses :
methimazole 2.5 to 10 mg
propylthiouracil 50 to 100 mg
block-replace regimen: high doses combined with levothyroxine supplementation to avoid drug-induced hypothyroidism.
Maximum remission rates are achieved by 18 to 24 months
Thyroid function tests and clinical 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 relapse during the first year after treatment and at least annually thereafter.
common :rash, urticaria, fever, and arthralgia (1 to 5% of patients).