Download Graves` disease

THE THYROID GLAND
Thyroid
cartilago
Pyramidal
lobe
Left lobe
Isthmus
Right lobe
Internal
jugular vein
External
carored
arteri
THYROID GLAND HISTOLOGY
http://arbl.cvmbs.colostate.edu/hbooks/pathphys/endocrine/thyroid/anatomy.html
Thyroid hormone synthesis, storage and release
ORGANIFICATION
TRAPPING
I
I
PEROXIDASE
OXIDIZED
IODIDE
H2O2
MIT DIT T3
TGB
Tyr
Tyrosine?
Tyr
Iodinase
AA
TGB
Tyrosine
T4
CAPILLARY
COLLOID
TGB
PROTEOLYSIS
T
3T
4
STORAGE
DIT DIT T4
MIT
DIT
DEIODINATION
T3
COUPLING
TGB
RELEASE
TGB
Protease
FOLLICULAR CELL
Cryer PE. Diagnostic endocrinology 1976:35
MIT
DIT
TGB
T3 -TGB
T4 -TGB
HYPOTHALAMUS
Basic elements in
regulation of thyroid
function
TRH
T3
PORTAL SYSTEM
I
ANTERIOR
PITUITARY
“FREE”
T4
T4
T3 _
+
TSH
T3
TISSUE
+
I
THYROID
T4
Usually Complain thyroid
disease
• Thyroid enlargement which
may be diffuse or nodular
• Symptom of thyroid deficiency
or Hypothyroidism
• Symptoms of thyroid hormon
excess, or Hyperthyroidism
Usually Complain thyroid
disease
Complications of a Spesific form
hyperthyroidism : Graves’ disease
which may present which prominence
of the eyes or exophthalmos and
thickening of the skin over the lower
legs (rare) or thyroid dermopathy
Physical Examination
• Inspection : Good light coming
from behind the examiner, The
patient is instructed to swallow a
sip of water, Observe the gland as
it
moves up and down.
Enlargement and nodularity can
often be noted.
Physical Examination
• Palpate the gland from
behind the patient with the
middle threes fingers on
each lobe while the patients
swallows. Nodules can be
measured in a similar way.
Physical Examination
• On physical examination the normal
thyroid gland about 2cm in vertical
dimension and about 1cm in horizontal
dimention above the isthmus
• Enlarged thyroid gland is called Goiter
• The generalized enlargement is termed
diffuse goiter, irreguler or lumpy
enlargement is called nodular goiter
THYROID DISEASES
HYPERTHYROIDISM
HYPOTHYROIDISM
THYROIDITIS
THYROID NODUL
THYROID DYSFUNCTION
• Hypothyroidism
• Sublinical hypothyroidism
• Hyperthyroidism
• Subclinical hyperthyroidism
PREVALENCE
2%
5-7 %
0,2 %
0,1-6,0%
Hyperthyroidism & Thyrotoxicosis
• Thyrotoxicosis is the clinical syndrome
that results when tissues are exposed to
high levels of circulating thyroid hormone.
• Thyroxicosis is due to hyperactivity of the
thyroid gland or hyperthyroidism
• Occasionally, thyrotoxicosis may be due to
other causes such us excessive ingestion
of the thyroid hormone or excessive
thyroid hormon from ectopis site
Conditions associated with thyrotoxicosis
•
•
•
•
•
Diffuse toxic goiter (Graves’ disease)
Toxic adenoma (Plummer’s disease)
Toxic multinodular goiter
Subacute thyroiditis
Hyperthyroid phase of Hashimoto’s
thyroiditis
• Thyrotoxicosis factitia
• Rare: Ovarian struma, metastatic thyroid
carcinoma, hydatiform mole
GRAVES’ DISEASE (DIFFUSE
TOXIC GOITER)
• GD is the most common form of
thyrotoxicosis, may occur at any age, more
commonly in females than in males (5X)
• The syndrome consist one or more of the
following features:
1. THYROTOXICOSIS
2. GOITER
3.OPHTHALMOPATHY(Exophthalmos)
4. DERMOPATHY (Pretibial myxedema)
ETIOLOGY & PATHOGENESIS
• GD is currently viewed as an
autoimmun disease of unknown cause
• Ther is a strong familial predisposition
in that about 15%. 50% GD have
circulating thyroid autoantibodies
• Peak incidence 20-40-year
• T-lymphocytes sensitized to antigen
within thyroid gland and stimulate B
lymphocyte  antibodies
Autoimmune thyroiditis
Agonist
Antibody
TSHR-Ab
Antagonist
Antibody
TSHR
CELL
STIMULATION
CELL
BLOCKADE
Davies TR. Graves’ disease in Werner & Ingbar’s : The thyroid ; 2000 ;520
Clinical features
Graves’s disease
• Symptoms: in younger patients: palpitation,
nervousness, easy fatigability, hyperkinesia,
diarhhea, excessive sweating, intolerance to
heat, weight loss, without loss appetite
• Signs: Thyroid enlargement, exophthalmos,
tachycardia, muscle weakness, tremor
Older patients cardiovascular & myopatic
predominate
clinical
manifestation

palpitatation, dyspnea on exersice, tremor,
nervousness, weight loss
Ophtamopathy Graves disease
• Infitratif  sympathetic overstimulation
Lid retraction (Dalrymphe’s sign)
Van Graves sign late palpebra sup
Stellwat’s sign the wink eyes late
Jefroy’s sign  fold of forehead not see
Mobius’sign  convergention of the eyes late
• Infiltratif  autoimmune
Exophthalmus, oculopathy congestif: cheimosis,
conjunctivitis, periorbital edema
Ulcerasi Cornea , neuritis optica, atrophi n
opticus
DISEASE SEVERITY
Thyroid eye disease can be divided into
MILD disease
MODERATE disease
SEVERE disease
MILD DISEASE
•
•
•
•
•
Usually young patient
Dry eyes---->lubricants
Lid retraction
Lid malposition-entropion
Mild proptosis
MODERATE DISEASE

Thyroid myopathy

asymmetric involvement

tends to involve vertical
muscles in Asians
LID RETRACTION
HERTEL EXOPHTHALMOMETER
EXOPHTHALMOS : >18 MM
Computerised Axial
Tomography
Thyroid Dermopathy
• Thickening of the skin,over the
lower tibia due to accumulation
glycosaminglicans , rare (2-3%)
• TSH-R Ab high titer
• Osteopathy in the metacarpal
bones
Non Pitting oedema
Suspected hyperthyroidism
TSH &FT4
Normal
FT4 &TSH
Low TSH
& Normal
FT4
Low TSH &
high FT4
Normal / high
TSH & high
FT4
Measure FT3
Hyperthyroidism
excluded
TSH- secreting
pituitary adenoma.
Normal FT3
Subclinical hyperthyroidism
Evolving Graves’ disease
Or toxic nodular goiter
Excess thyroxine replacement
Non thyroidal illness
High FT3
Hyperthyroidism
Thyroid hormoneresistance syndrome
T3 Hyperthyroidism
Repeat tests in 2-3 months: annual
follow-up if no progression
Laboratoy tests useful in DD of hyperthyroidism
Graves’disease
Toxic nodular goiter
Thyroiditis
Gestational Hyperthyroidism
Factitious or iatrogenic hyperthyroidism
Thyroid Carcinoma
Struma Ovarii
Tumor secreting Chorionic gonadotropin
Familial nonautoimmun hyperthyroidism
Atypical fashion Graves’
Disease
• Thyrotoxic periodic paralysis:
usually Asian males, sudden attack flacid
paralysis, hypokalemia, usualy subsides
spontaneously. Prevention: K+
supplement & Betablockers
• Thyrocardiac disease:
primarily with symptoms of heart
involvement: refrsctory AF insensitif
digoxin or high output heart failure, no
evidence underlying heart disease (50%).
Treatment of thyrotoxicosis  cure
Atypical fashion Graves’ Disease
• Apethetic hyperthyroidism:
Older patients: weight loss,
small goiter, slow AF, severe
depression with none clinical
features
Treatment modalities
• Anti-thyroid
• Surgery
• I131 radioactive
Treatment of Graves’ Disease
1. Antithyroid drug therapy:
Young pts, small glands, mild disease
Propylthiouracil, methimazole (6m-15 mo),
relaps 50-60%.
PTU inhibits the conversion T4T3, effect
more quickly compare to methimazole
Methimazole - longer duration, single dose
Therapy 3-6 months  tapering dose and
combination levothyroxin 0.1 mg/d 12-24
months
Allergic reaction (rash), agranulocytosis,
jaundice, liver failure
Treatment of Graves’ diseae
• Surgical treatment
Subtotal thyroidectomy  treatment of
choice for very large glands, or
multinodular goiter, prepared wth anti
thyroid drug (about 6 months)
Complication :
Hypothyroidism,recurent laryngeal
nerve injury
Treatment of Graves’ disease
• Radioactive
iodine therapy
USA  NaI 131I 
euthyroid over 612 weeks
Complication:
hypothyroidism
Treatment of Graves’ disease
• Other medical measures:
Beta-adrenergic blocking agents
Propranolol 10-40 mg every 6
hours, multivitamin supplements,
phenobarbital as sedative + to
lower T4 levels
Cholestyramine, 4 gr orally 3X
daily lower T4
Complication of Graves’
Disease
Thyrotoxic crisis (thyroid storm)
Acute exacerbation symptoms thyrotoxicosis.
May be mild & febrile until life threatning.
Etiology : after thyroid surgery in patients
who has been inadequatlely prepared, RAI131,
parturition
in
adequately
controlled
thyrotoxicosis or stressfull illnes.
• Thyrotoxic crisis(thyroid
“storm”):
Clinical manifestation:
Fever, Sweating, flushing, tachycardia
/ AF, heart failure, agitation, delirium,
coma, jaundice, nausea, vomiting and
diarrhea.
75% death………….
Treatment of Thyrotoxic crisis
(“thyroid storm”)
• Prophiltriourasil (PTU): 4 x 300 mg atau
• Neomercazole 6 x 20 mg.
• Yodium : Sodium yodida IV 1 mg/12 jam,
atau lugol 5% 3x10 tts /hr
• Propranolol (Inderal): IV 1-5 mg/6jam, atau
tab 4x60-80 mg/hr via sonde lambung
• Kortikosteroid: Dexamethason 2 mg/6 jam
• Antibiotik dianjurkan jika infeksi sebagai
pencetus.