Himawan Sanusi

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

TRAPPING ORGANIFICATION
I I PEROXIDASE
OXIDIZED
H2O2 IODIDE MIT DIT T3
TGB TGB
COUPLING STORAGE
Tyrosine?
Tyr Tyr
DIT DIT T4
Iodinase
AA TGB TGB TGB
Tyrosine

MIT MIT DIT

DEIODINATION DIT

RELEASE TGB
PROTEOLYSIS
T3 T T3 --
Protease
3T TGB
T4
4 T4 --
TGB
CAPILLARY FOLLICULAR CELL
COLLOID Cryer PE. Diagnostic endocrinology 1976:35
 HYPOTHALAMUS
Basic elements in regulation TRH
of thyroid function

T3

PORTAL SYSTEM
I

ANTERIOR
PITUITARY
T4
+
“FREE” T3 _ TSH
T4 T3

TISSUE

I +
THYROID
T4
 Usually Complain thyroid
disease
• Thyroid enlargement which
may be diffuse or nodular
• Symptom of thyroid hormone
deficiency or Hypothyroidism
• Symptoms of thyroid hormone
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
THYROID DISEASES
HYPERTHYROIDISM
HYPOTHYROIDISM
THYROIDITIS
THYROID NODUL
THYROID DYSFUNCTION PREVALENCE

• Hypothyroidism 2%
• Sublinical hypothyroidism 5-7 %
• Hyperthyroidism 0,2 %
• Subclinical hyperthyroidism 0,1-6,0%
 Hyperthyrodism

Is a set of disorders that involeve excess

synthesis and secretion of thyroid
hormone by the thyroid gland which
leads to the hyper-metabolic condition
Diagnosis of hyperthyrodism
• Thyroid function tests :
– FT4 / FT3
– TSH
Diagnosis hyperthyroidism
according to lab results
• Primary hyperthyroidism
– FT4 high, TSH low, TRH low
• Secondary hyperthyroidism
– FT4 high, TSH high, TRH low
• Tertiary hyperthyroidism
– FT4 high, TSH high, TRH high
• Subclinical hyperthyroidism
– FT4 and FT3 normal, but TSH low
• T3 thyrotoxicosis
– FT4 normal, FT3 high,, TSH low
 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
 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
autoimmune disease of unknown cause
• There 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 Antagonist
TSHR-Ab Antibody Antibody

TSHR

CELL CELL
STIMULATION BLOCKADE
Davies TR. Graves’ disease in Werner & Ingbar’s : The thyroid ; 2000 ;520
 Clinical features Graves’ 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
Stellwag’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, atrophy n.
opticus
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
 Laboratorium
• Thyroid function tests : FT4 &
TSHs  repeated regularly to
ensure euthyroidism (3 monthly)
• Serum TSH-receptor antibodies ,
anti TPO (75% positif)
Atypical fashion Graves’ Disease
• Periodic paralysis thyrotoxicosis
• Thyroid heart disease
• Apethetic hyperthyrodism
Atypical fashion Graves’ Disease
• Thyrotoxic periodic paralysis:
• usually Asian males,
• sudden attack flacid paralysis (after large
ingestion of carbohydrate)
• hypokalemia,
• usualy subsides spontaneously.
• Prevention: K+ supplement & Beta
blockers
Atypical fashion Graves’ Disease
Thyrocardiac disease :
• Primarily with symptoms of heart
involvement : refractory AF insensitif
digoxin with high output heart failure,
• Left ventricle hypertrophy (ECG)
• Cardiomegaly (Chest X ray)
• 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, preparation
before others treatment of GD
Propylthiouracil,
Imidazol (carbimazol and methimazole)

Act by inhibiting TPO-mediated iodination of

thyroglobulin to form T4 and T3 within the
thyroid gland
Duration treatment 6m-15 months
Relaps 50-60%.
PTU inhibits the conversion T4T3,
effect more quickly compare to
imidazole (1st line for thyroid storm)
Imidazole - longer duration, single
dose
Therapy 3-6 months  tappering dose
and sometimes combination
levothyroxin 0.1 mg/d for 12-24
months
 Anti thyroid drugs therapy

Side effects : Allergic reaction (rash),

agranulocytosis, jaundice (imidazol) ,
liver failure (PTU)

• Special consideration :
– 1st semester pregranancy : PTU
– 2nd and 3th semester pregnancy : imidazol
 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)
Complications of surgical treatment :
Hypothyroidism , recurrent laryngeal
nerve injury, hypoparathyroidism
Treatment of Graves’ disease
• Radioactive
iodine ablation
therapy
USA  NaI 131I 
euthyroid over 6-12
weeks (prepared
with antithyroid
drugs)
Complication :
hypothyroidism
Treatment of Graves’ disease
• Other medical measures:
Beta-adrenergic blocking agents
Propranolol 10-40 mg every 6
hours, or bisoprolol 2,5-5 mg daily
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 threatening.
Thyroid crisis (thyroid storm)
Etiology
After thyroid surgery or RAI131 ablation in
patients who has been inadequatlely
prepared,
Parturition with uncontrolled thyrotoxicosis
Stressfull illness (infection, stroke, acute
myocardial infarction)
• Thyrotoxic crisis (thyroid “storm”)

Clinical manifestation:
Fever, Sweating, flushing, tachycardia
/ AF, heart failure, agitation, delirium,
coma, jaundice, nausea, vomiting and
diarrhea.

50% death………….
 Treatment of Thyrotoxic crisis
(“thyroid storm”)
• Prophylthiourasil (PTU): 4 x 300 mg or
• Imidazol 6 x 20 mg.
• Yodium : Sodium yodida IV 1 mg/12 jam,
atau lugols’ solution 5% 3 x10 drops /day
• Propranolol (Inderal): IV 1-5 mg/6 hour, or
tab 4 x 60-80 mg/day
• Corticosteroid: Dexamethason 2 mg/6 hour
• Antibiotic (only if infection)
 Hyperthyroidism in pregnancy
• 1st trimester : PTU
• 2nd and 3rd trimester : metimazol or
carbimazole
• Check FT4 regularly…..once/month
• 2 weeks before parturition…stop anti
thyroid