HARSINEN 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

ORGANIFICATION

TRAPPING

PEROXIDASE
H2O2

OXIDIZED
IODIDE

MIT DIT T3
TGB

Tyr

Tyrosine?

Tyr

Iodinase

AA
TGB
Tyrosine

RELEASE

T3

T4

T4

STORAGE

DIT DIT T4
TGB

MIT
DIT

PROTEOLYSIS

T3

CAPILLARY

COUPLING

TGB

DEIODINATION

TGB

Protease

FOLLICULAR CELL

MIT

DIT

TGB

T3 --TGB
T4 --TGB
COLLOID

Cryer PE. Diagnostic endocrinology 1976:35

HYPOTHALAMUS
Basic elements in regulation
of thyroid function

TRH

T3
PORTAL SYSTEM

I
ANTERIOR
PITUITARY

FREE

T4

T4

T3 _

+
TSH

T3

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

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
The normal thyroid gland about 2cm in vertical
dimension and about 1cm in horizontal
dimention above the isthmus
Enlarged thyroid gland is called Goiter=Struma
The generalized enlargement is termed diffuse
goiter, irreguler or lumpy enlargement is called
nodular goiter

Diffuse goiter
Simple diffus goiter
Hyperthyroidism
Hashimoto thyroiditis

Nodular goiter
1. Thyroid nodul
2. Thyroid cyst
3. Adenomatosa goiter
4. Subacut /chronis thyroiditis
5. Plummer thyroiditis

THYROID DISEASES
HYPERTHYROIDISM
HYPOTHYROIDISM
THYROIDITIS
THYROID NODUL

THYROID DYSFUNCTION

PREVALENCE

Hypothyroidism
2%
Sublinical hypothyroidism
Hyperthyroidism
%
Subclinical hypothyroidism

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.
Hyperthyroidism : Thyroxicosis is due to
hyperactivity of the thyroid gland
Occasionally, thyrotoxicosis may be due to
other causes such us excessive ingestion of
the thyroid hormone or excessive thyroid
hormon from ectopic site

Conditions asscosiated 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,

ETIOLOGY & PATHOGENESIS

Graves Disease (GD) is currently viewed as
an autoimmun 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

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)

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

Non 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 nervus opticus

LID
RETRACTION

Thyroid Dermopathy
Thickening of the skin, over the
lower tibia due to accumulation
glycosamin glicans , rare (2-3%)
TSH-R Ab high titer
Osteopathy in the metacarpal
bones

NON PITTING OEDEMA

VITILIGO

Suspected hyperthyroidism
TSH &FT4
Low TSH
& Normal
FT4

Normal
FT4 &TSH
Hyperthyroidism
excluded

Low TSH &

high FT4

Normal /
high TSH &
high FT4

Measure FT3

Normal FT3
Subclinical hyperthyroidism
Evolving Graves disease
Or toxic nodular goiter
Excess thyroxine replacement
Non thyroidal illness

TSH- secreting
pituitary adenoma.

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

Apethetic hyperthyroidism:
Older patients:
weight loss, small goiter, AF,
severe depression with none
clinical features

Atypical fashion Graves

Disease
Thyrotoxic periodic paralysis:

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

Treatment of Graves
Disease
1. Antithyroid drug therapy:
Young pts, small glands, mild disease
Propylthiouracil (PTU), methimazole (6m-15 y), relaps
50-60%.
PTU inhibits the conversion T4T3, effect more quickly
compare methimazole
Methimazole : longer duration of action,
Single dose
Therapy 3-6 months tapering dose and
combination levothyroxin 0.1 mg/d 12-24 months
Allergic reaction (rash, agranulocytosis)

Treatment of Graves
diseae
Surgical treatment
Surgical 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
Complementer therapy:
Zikir, Yoga, semedi, reiki,

Complication of Graves
Disease
Thyrotoxic crisis (thyroid storm)
Acute exacerbation symptoms thyrotoxicosis.
May be mild & febrile until life threatening.
Etiology : after thyroid surgery in patients
who has been inadequatlely prepared,
RAI131, parturition in adequately controlled
thyrotoxicosis or stressfull illnes.

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

Treatment:
Supportive therapy
Propranolol 1-2 mg IV,
PTU 250 mg every 6 hours.
Hydrocortison
Sol lugol
Antibiotic
Sedative

HYPOTHYROIDISM

HYPOTHYROIDISM
Etiology
Primary:Hashimoto thyroiditis, Radio
active iodine therapy for Graves disease,
Subtotal thyroidectomy, Excesive iodide
intake, subacute thyyroiditis, Iodide
deficiency

Secondary :
Hypopituitarism due to pituitary adenoma

Tertiary :
Hypothalamic disfunction (rare)

HYPOTIROIDISM
Clinical finding
Incidence : Various causes depending
geographic & enviromental factors
Hashimoto thyroiditis the most common
cause of hyperthyroidism
Newborn infants (Cretinism)
Fatigue, coldness, weight gain, constipation,
menstrual irregularities, muscle cramps

HYPOTIROIDISM
Physical findings:
Cool,rough, dry skin, puffy face and hands,
ahoarse voice, slow reflexes
Cardiovascular sign: bradycardia, diminished CO,
low voltage QRS, cardiac enlargement
Pulmonary function: Respiratory failure
Intestinal paralysis slowed , chronic constipation,
ileus
Renal function. Decresed GFR, renal impairement
Anemia, Severe muscle cramp, parestesias,
muscle weaknes
CNS symptoms: fatigue, inability to concentrate

Complication
1. Myxedema coma end stage of untreated
hypothyroidism, Cause Radiotherapy in
Graves Disease
2. Myxedema & Heart disease CAD
3. Hypothyroidism Neuropsychiatric disease
depression, confuse, paranoid, manic

Treatment Hypothyroidism
Levothyroxine (T4)
not liothyronine (T3) because rapid
absorption, short half life, transient effect.
Dosis T4, 1X in the morning to avoid insomnia
0.05 mg-0.2 mg/d
Mixedema coma ICU, intubation &
mechanical ventilation, Treat infection,
heart failure, IV drips with caution, l
levothyroxin IV

EXAMPLES OF THYROID DISEASES

1 Hypothyroidism

Hyperthyroidism
www.hsc.missouri.edu/~daveg/thyroid/thy_dis.html

Complication
Myxedema coma end stage of
untreated hypothyroidism, Cause
Radiotherapy in Graves Disease
Myxedema & Heart disease CAD
Hypothyroidism Neuropsychiatric
disease depression, confuse,
paranoid, manic

Definition
Thyroiditis : heterogenous group of
inflamatory disorders the thyroid gland
Etiologies range from autoimmune to
infectious origins
Clinical course Acute, subacute, or
chronic. Can be euthyroid, transient
phase thyrotoxicosis and / or
hypothyroidism. Painless or painfull

Classification of thyroiditis
I.

Autoimmune thyroiditis
Chronic autoimune thyroiditis
Hashimotos thyroiditis
Atrophic thyroiditis
Focal thyroiditis
Juvenile thyroiditis

Silent thyroiditis / Postpartum thyroiditis

Subacute thyroiditis
III. Acute suppurative thyroiditis
IV. Riedels thyroiditis
II.

Hashimotos thyroiditis
(Chronic thyroiditis)
Hakaru Hashimoto (1912)
4 patients chronic
disorder of the thyroid
diffuse lymphocytic
infiltration, fibrosis,
parenchymal atrophy, and
eosinophilic change in
some acinar cells
autoimmune or chronic
lymphocytic thyroiditis
Dr Hakaru Hashimoto

Hashimotos thyroiditis
Hashimoto thyroiditis
is the most common
cause of hypothyroidism
& goiter
in

the United States

Statosky J et al. Am Acad of Family physicians 2000;61:1054

Hashimotos
thyroiditis

Etiology & pathogenesis

HT is immunologic disorder which

lymphocytes become sensitized to thyroidal
antigens and autoantibodies are performed.
Thyroid antibodies in HT are:
1. Thyroglobulin antibody (Tg Ab)
2. Thyroid peroxidase antibody
(TPO Ab) = Microsomal antibody)
3. TSH Receptor blocking antibody
(TSH-R Ab block)

Clinical Manifestation
Hashimotos Thyroiditis
Symptom & Signs
HT usually presents with
goiter , euthyroid or mild
hypothyroidism.
Sex distribution : F/M 4:1
Painless & patients may be
anware of the goiter

Laboratory findings
T4 N/ low, TSH will be elevated.
RAIU may be high, normal or
low
Tg Ab & TPO Ab positif
Fine needle aspiration biopsy
large infiltration lymphocytes
Hurttle cells

Diagnostic procedures
Test of thyroid autoimmunity:
TPOAb 95% + in Hashimoto
thyroiditis & 90% Atrophic thyroiditis
TgAb less frequently +
Diagnostic specificity of thyroid
antibody tests is not absolute.
Test for thyroid function TSH, fT4
RAIU: normal, low or high.
USG:diffusely reduced echogenecity.
FNAB not necessary,excep. rapidly
enlarging goiter

Diagnosis of Hashimotos thyroiditis

Diffuse goiter
Anti microsomal (or TPO) antibody
Anti-thyroglobulin antibody

Positive

Negative

Hashimotos
thyroiditis

US Biopsy

Positive

Negative

Other diseases*

Sign symptom of
hypothyroidism

*Simple goiter,
adenomatous goiter etc

Treatment Hashimotos
thyroiditis

Treatment
Goiter small & asymptomatic not
require therapy
Levo-thyroxine is given over
hypothyroidism to supress TSH &
decreased serum thyroid antibody.
Levo-thyroxine in euthyroid, still
controversial

Treatment
Corticosteroids : regression pain,
reduction in size of the goiter, thyroid
antibody, not recommended in benign
disease.

Surgery indicated pain, cosmetic,

or pressure symptoms after
levothyroxine and corticosteroid
therapy.

Riedels thyroiditis
Rare 1,06/100.000, middle age or elderly
women
Etiology unknown (autoimmune
process or primary fibrotic disorder)
Characterized fibrosis replaces
normal thyroid parenchyma,1/3
cases multifocal fibrosclerosis

Riedels thyroiditis
Thyroid fibrosis (stony hard,woody),
painless, progressive anterior neck mass,
Generalized fibrosing (1/3 patients), pressure
symptoms laryngeal nerve paralysis or
hypoparathyroidism (rare)
Usually euthyroidism, hypothyroidism (30%)
Laboratorium : non spesific
USG/CT-Scan inconclusive
Difinitive diagnosis open Biopsy

Riedels thyroiditis
Treatment:
Corticosteroids medical treatment of choice
Tamoxipen, methotrexate inhibitor fibroblast
proliferation ( early stages)
Levothyroxine hypothyroidism
Surgical care diagnosis, relieving tracheal
compression
Mortality asphyxia (6-10%), extrathyroidal
fibrotic lesions may complicate the prognosis

Subacute thyroiditis
Cause unknown ( viral infection
(?) preceded URT infection,
coincidence viral disease (mumps,
measles, Echo virus, adeno virus,
epst. Barr virus, influenza)
Women : Men (3-5:1)
Onset: 20-60 yr
Summer

Subacute thyroiditis
Palpation thyroid: enlarged, asymetrical,
nodul, firm, tender & painful.
Thyrotoxicosis during inflamatory phase
euthyroidism hypothyroidism
euthyroidism (4th phases)
Laboratorium: ESR increase, leukocyt N/
increase, fT4,,TSH, RAIU
Recovery 4-6 months, spontaneous

remitting

Treatment Subacute
thyroiditis
Symptomatic: Acetaminophen 4X 0,5g, NSAID or
glucocorticoid (prednison 3 X 20 mg (7-10 days)
Betablockers symptoms of thyrotoxicosis
L-thyroxine 0.1-0.15 mg /daily hypothyroid
phase. Long-term L-thyroxine permanent
hypothyroidism (10%)
Antibioticsno value

Thyroidectomy rarely

Clinical Differentiating of the Subtype Thyroiditis

NECK PAIN
N0

YES

PRESENTING SYMPTOMS

RAIU
INCREASED

MICROBIAL
INFLAMMATORY
THYROIDITIS

HYPERTHYROIDISM

DECREASED

SUBACUTE
GRANULOMATOUS
THYROIDITIS

RAIU

GRAVES DISEASE

HYPOTHYROIDISM
CHRONIC
LYMPHOCYTIC
THYROIDITIS

SUBACUT
LYMPHOCYTIC
THYROIDITIS

Statosky J et al. Am Acad of Family physicians 2000;61:1054

Acute suppurative
thyroiditis
Rare, serious, bacterial inflamatory
disease, children, 20-40 yr, sex ratio
1:1
Etiologi: Infectious: Staph. aureus,
strep.pyogenes, strep. pneumonia,
esch.coli, pseudomonas aeruginosa
Infection by hematogenous, direct
trauma

Thyroid nodules &

Thyroid cancer

Thyroid nodules - prevalence

Thyroid nodules common, increase with
age
30-60% of thyroids have nodules at autopsy
Palpation: 5-20% (>1cm)
USG: 15-50% ( > 2mm)

Thyroid nodule
One in 12 to 15 young women has a
thyroid nodule.
One in 40 young men has a thyroid
nodule.
More than 95% of all thyroid nodules are
benign (
The incidence of thyroid nodules
increases with age.

Three Questions about

Thyroid Nodules
Is the nodule one of the few that are
cancerous?
Is the nodule causing trouble by pressing
on other structures in the neck?
Is the nodule making too much thyroid
hormone?

Diagnostic approach
Fine Needle Aspiration (FNA)
10-20% risk of suspicious cytology, therefore thyroid
surgery
95% of histology will be benign, and surgery
unnecessary

Isotop Scann(CT)
Used for evaluation 80% of nodules are cold
small cold nodules may be missed
hot nodules may be malignant

Ultrasonography (USG)

Is the nodule one of the few that are cancerous?

Is the nodule causing trouble by pressing on
other structures in the neck?
Is the nodule making too much thyroid
hormone?

Diagnostic approach
ultrasound
Identifies solid v. cystic nodules
Identifies MNG
May aid FNA
Does not exclude malignancy

Diagnostic approach - other tests

Calcitonin
very high results diagnostic for MTC
risk of borderline false positives
not for routine use

Thyroglobulin
not helpful for exclusion of carcinoma:
overlap with benign disease
best for follow-up after thyroidectomy

Thyroid nodules & Thyroid

cancer

In 95% of cases , thyroid cancer

presents as a nodule or lump in the
thyroid nodul thyroid.
Thyroid nodule extremely
common, particularly
women.Prevelance in USA 4% in
adult population. F:M ratio 4:1.
Thyroid cancer rare. Incidence
0.004% per year

Benign thyroid adenoma

Etiology :
Focal thyroiditis
Multinodular goiter
Post
surgical remnant hyperplasia
Benign adenoma: Follicular
Rare: Teratoma,
lipoma, hemangioma

Diffrentiation benign & Malignant

lesions
History : Family history of goiter suggests
benign disease, endemic goiter
Physical characteristics:
Benign: older age, woman, soft nodule, multi
nodular goiter.
Malignant: Children, young, male, solitary,
firm nodule, vocal cord paralysis, firm lymph
nodes, distant metastasis

Treatment
Thyroidectomi
Jodium 131Radioactive
Thyroxine supression

KASUS
Seorang wanita 25 tahun datang dengan
keluhan berdebar-debar, cepat lelah, sukar
berdiri dari duduk. Fisis nadi 120/menit pulsus
seler, tensi 160/80 struma difus, tremor, acral
panas.
1. Diagnosis. .
2. Untuk diagnosis pemeriksaan apa yg perlu?
3. Bila diagnosis benar maka pemeriksaan fisis
pemeriksaan laboratorium apa lagi........

4. Bila diagnosis tegak penyakit Graves

maka pemeriksaan ..
5. Pengobatan penyakit Graves antara lain
obat tablet.. Berapa lama
diberikan.
6. Selain obat apa saja cara teapi lainnya
7. Komplikasi apa saja biusa terjadi
8. Apa yang perlu difollowup pd pasien
ini..
9. Kematian thyrotoxicosis akibat Apa saja..
10. Kenapa kambuh sesudah remissi

Kasus 2
Seorang laki2 umur 49 tahun dengan
benjolan di leher kanan sebesar bola
pimpong. Keluhan tidak ada.
1. langkah apa saja yang saudara ingin
lakukan pada pasien ini?
2. bila diagnosis saudara ternyata
karsinoma anaplastik tiroid apa
langkah2nya.

 3. bila hasil diagnosis karsinoma papilare

apakah langkah saudara..
4. bila hasilnya hanya suatu adenoma tiroid
folikulare apakah tindakan saudara.
5. Bagaimanaq mebedakan karsinoma dengan
adenoma
6. bila pada pemeriksaan TSHs meningkat
sedang FT4 menurun maka diagnosius.
7. pemeriksaan imunologis apa yang diperlukan

 8.Pengobatan untuk pasien ini

9. apa sdr setuyju untuk oiperasi pasien
ini
10. kalau hasil usg ternyata kista tiroid
maka pengobatan apa yang saudara
pilih?