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