Disorders of the Thyroid

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

PEROXIDASE

OXIDIZED IODIDE

H2O2

MIT DIT T3
TGB

Tyr

Tyrosine?

Tyr

Iodinase

AA
TGB
Tyrosine

T3
T4
CAPILLARY
COLLOID

COUPLING

TGB

TGB

PROTEOLYSIS

T
3T
4

STORAGE

DIT DIT T4

MIT
DIT

DEIODINATION
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

T3

T4
T3 _

+
TSH

TISSUE

I
T4

THYROID

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

PREVALENCE

Hypothyroidism
2%
Sublinical hypothyroidism
5-7 %
Hyperthyroidism
0,2 %
Subclinical hyperthyroidism
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 (Plummers disease)
Toxic multinodular goiter
Subacute thyroiditis
Hyperthyroid phase of Hashimotos
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

CELL

STIMULATION

BLOCKADE

Davies TR. Graves disease in Werner & Ingbars : The thyroid ;

2000 ;520

Clinical features
Gravess 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 (Dalrymphes sign)
Van Graves sign late palpebra sup
Stellwats sign the wink eyes late
Jefroys sign fold of forehead not see
Mobiussign 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

Gravesdisease
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 T4T3, 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, RAI 131,
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.

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