H Y P ER TH Y R O ID

Oleh:
Dr. W. Sri Wardani, Sp.PD

SMF Ilmu Penyakit Dalam

RSUD Sanjiwani, Gianyar
November 2014
Topic outlines

Introduction
Forms of thyrotoxicosis
Diffuse toxic goiter
Other forms of thyrotoxicosis
Toxic adenoma
Toxic multinodular goiter
Amiodaron induced thyrotoxicosis
Subacute and silent thyroiditis
Thyrotoxicosis factitia
Rare form of thyrotoxicosis
Summary
PLASMA FOLLICULAR CELL COLLOID

Dietary Iodide Iodide

Iodide Traping Peroxidase

Iodine
+Tyrosil
Residues

Iodine
+ MIT + DIT
Tyrosil
Residues
T4 + T3
Deiodo- Thyroglobulin

Tyrosinase
MIT + DIT
Thyroglobulin

T4 T3
T4 + T3 T4 + T3
Protease MIT DIT
SIN TESA & SEK R ESI H O R M O N
TIR O ID .
Tahap traping
Tahap Oksidasi (Organifikasi).
Tahap Coupling.
Tahap Penimbunan.
Tahap Deyodinisasi.
Tahap Proteolisis
Tahap Pelepasan Hormon Tiroid.
Pengaturan Fisiologis Hormon Tiroid Melalui
Hypothalamic-Pituitary-Tiroid Axis
 FUNGSI HORMON TIROID

Kalorigenik
Metabolisme Protein
Metabolisme Karbohidrat
Metabolisme Lemak
Metabolisme Vitamin
Interaksi Dengan Sistem Saraf Simpatis
TH Y R O TO X IC O S IS
D efi
nition

Thyrotoxicosis:
Clinical syndrome that results when tissues
are exposed to high level of thyroid hormones
Hyperthyroidism:
Thyrotoxicosis is due to hyperactivity of
the thyroid gland
Conditions associated w ith thyrotoxicosis

1.Diffuse toxic goiter (Graves

disease )
2.Toxic adenoma (Plummers
disease)
3.Toxic multinodular goiter
4.Amiodaron induced thyrotoxicosis
5.Subacute thyroiditis andsilent
thyroiditis
6.Thyrotoxicosis factitia
7.Rare forms of thyrotoxicosis
1.D iff
use toxic goiter (G raves
disease)

The most common form

of thyrotoxicosis
Female : male = 5 : 1
Peak incidence in the 20 40
y
The syndrome consist of :
Thyrotoxicosis
Goiter
Ophthalmopathy (exophthalmos)
Dermopathy (pretibial mixedeme)
Acropachy
Etiology

Autoimmune disease of unknown

cause
Circulating thyroid antibody
Familial predisposition
Monozygotic > dizygotic twins
Environmental triggers: stress,
tobacco,infection, iodine exposure
Postpartum
Pathogenesis

Antigen sensitize T lymphocytes and stimulate

B lymphocytes to synthesize antibody (thyroid

stimulating antibody= TSab/TSI)
TSab/TSI directed against the TSH receptor in

the thyroid cell membrane

Pathogenesis

Some factors that may incite the immune response

of graves disease :
Pregnancy; particulary postpartum period
Iodine excess
Interferon alfa
viral and bacterial infection
Psychological stress

The symptoms : due to thyroid hormone-mediated

increase in membrane-bound adrenergic receptors
Proposed pathogenesis of Gravesdisease. Ginsberg,J. CMAJ 168:575-585.2003
ClinicalFeatures

A. Simptoms
Palpitations
Nervousness
Easy fatigability
Hyperkinesia
Diarrhea
Excessive sweating
Intolerance to heat
Preference for cold
ClinicalFeatures

A. Signs
Younger patient:
Weight loss without loss of appatite
Thyroid enlargement
Thyrotoxic eye sign
Mild tachycardia
Muscle weakness and loss of muscle mass
Children:
Rapid growth with accelerated bone maturation
Over age 60:
Cardiovascular and miopathic manifestation
predominate
ClinicalFeatures

A. Signs
Younger patient:
Weight loss without loss of appatite
Thyroid enlargement
Thyrotoxic eye sign
Mild tachycardia
Muscle weakness and loss of muscle mass
Children:
Rapid growth with accelerated bone maturation
Over age 60:
Predominant: Cardiovascular and miopathic
manifestation
W ayne index
Symptoms of recent onset score
and/or increased severity
Dyspneu on effort +1
Palpitations +2
Tiredness +2
Preference for heat -5
Preference for cold +5
Excessive sweating +3
Nervousness +2
Appetite
Increased +3
Decreased -3
Weight
Increased -3
decreased +3
 W ayne index
Signs Present Absent
Palpable thyroid +3 -3
Bruit over thyroid +2 -2
Exophthalmos +2
Lid retraction +2 -
Lid lag +1 -
Hyperkinesia +4 -2
Hand
Hot +2 -2
moist +1 -1
Casual pulse rate
> 80x/min - -3
> 90 x/min +3 -
Atrial fibrilation +4 -

Total score : > 19 = toxic

11-19 = equivocal
< 11 = euthyroid
Laboratory test

FT4
TSH
T3
RAIU
TSab
123I or Technetium scan

CT and MRI scan

g. Laboratory tests useful in DD of hyperthyroidism

FT4 and TSH

FT4, TSH FT4, TSH FT4 N, TSH

Hyperthyroidism
No eye signs TSH secreting
Uni-or pituitary tumor
No eye signs Multinodular GRTH T3
Eye signs No goiter or goiter PRTH
Goiter small goiter
Toxic adenoma High Low Normal
or toxic
123I (UcI) uptake
multinodular Early Graves Euthyroid sickSubclinical
goiter disease Syndrome Hyperthyroidism
Graves
High Toxic nodular Drugs: usually due to:
disease Low goiter dopamin Levothyroxine,
corticosteroidMild gravesds
Graves Spontaneously resolving hyperthyroidism: Toxic multinodular
disease -Subacute thyroiditis goiter
-Silent thyroiditis
Chorio carcinoma
Graves disease or toxic nodular goiter in iodine loaded patient
Levothyroxin treatment, rare struma ovarii
O ther presentations

Muscle atrophy
Thyrotoxic periodic paralysis
Thyrocardiac disease
Apathetic thyrotoxicosis
 Com plications
Thyrotoxic crisis (thyroid storm)
Hypermetabolism and excessive adrenergic
response
Fever : 38-410C, flushing and sweating
Cardiac symptoms: tachycardia, atrial fibrillation, highpulse
pressure, occasionally heart failure
CNS symptoms: agitation, restlessness, delirium, coma
Gastrointestinal symptoms: nausea, vomiting, diarrhea,
jaundice
Fatal outcome: heart failure and shock
Pathogenesis:
Sudden release of T4 and T3
Adrenergic binding sites for catecholamine increase
Treatm ent

Antithyroid drug therapy

Radioactive iodine therapy
Surgical treatment
Other medical measures
Antithyroid drug therapy
(PTU and m etim azole)

Mechanism:
Inhibiting TPO-mediated iodination of
thyroglobulin to form T4 and T3
Blocks peripheral T4 to T3 conversion : PTU
Immunosuppresive effects
Dosage:
PTU: 100 mg every 8 hr initially (4-8
weeks) 50- 200 mg once or twice daily
Metimazole: 10-20 mg for 1-2 months
5-10mg
Antithyroid drug therapy
Duration of therapy:
Usually : 12-24 months
Sustain remissions related to:
Thyroid gland return to normal size
The disease controlled with a relative small dose of antithyroid
drugs
TSabs are no longer detectable in serum
Reaction to antithyroid drugs:
Allergic reaction:
minor reaction : rash 5% of patient
major reaction : agranulocytosis: 0.5%
Cholestatic jaundice with metimazole
Hepatocellular toxicity and vasculitis with PTU
Acute arthritis
Radioactive iodine therapy

Indication:
Age over 21 y
Without underlying heart disease
Elderly and other medical problem : underlying heart
ds, severe thyrotoxicosis, large gland (>100g) prior
achieve to euthiroid state.
Dosage:
Dose = 80-200Ci x gm thyroid tissue
gm thyroid fractional 24 hr
tissue radioiodine uptake
Given orally as a single capsule
Become euthyroid over a period of 2-6 months
Radioactive iodine therapy

Contraindications:
Severe Graves eye disease

Complications:
hypothyroidism
exacerbations hyperthyroidism in severe underlying
hyperthyroid, cigarrete smoking
Surgical treatm ent

Indications:
Very large thyroid gland

Multinodular goiter

Allergic or noncompliant with antithyroid drugs

Refuse radioactive iodine

Pregnant women with severe Gravesdisease who are

allergic to antithyroid drugs

Surgical treatm ent

Preparations:
Antithyroid drugs untill euthyroid
Given saturated solution of potassium iodida: 5
drops twice daily starting 2 weeks before
operation
Methods
Total thyroidectomy
Partial thyroidectomy

Complications:
hypoparathyroidism
Laryngeal reccurent nerve injury
O ther m edicalm easures

Beta adrenergic blocking agents:

Propranolol: 10-40 mg every 6 hr
Long acting beta blockers: nadolol, atenolol,
metoprolol
Adequate nutrition and rest
Oral cholecystographyc dyes: 1 gm daily
inhibit thyroid hormone syntesis, and release as well as
seroconversion
Sodium ipodate
Iopanoic acid
Cholestiramin 4 gm orally 3 times daily
Treatm ent com plications

Thyrotoxic crisis
ophthalmopathy
Thyrotoxic and pregnancy
Course and prognosis

Remission and exacerbation

Euthyroid for long period
25% lifetime hypothyroidism
2.O ther form s ofthyrotoxicosis

A. Toxic adenoma (Plummers

disease)
B. Toxic multinodular goiter
C. Amiodaron induced thyrotoxicosis
D. Subacute thyroiditis andsilent
thyroiditis
E. Thyrotoxicosis factitia
F. Rare forms of thyrotoxicosis
A.Toxic adenom a

A functioning adenoma
Slowly increase in size
Older individual (usually >40 y)
Symptoms:
Thyrotoxicosis
Goiter
Ophthalmopathy (Never present)
Physical examination:
Definite nodule on one side
Very little thyroid tissue
A.Toxic adenom a
Laboratory:
Supressed TSH
Elevation in serum T3
Borderline elevation of FT4
Scan: hot nodule, with diminished or
absent function of contralateral lobe
Benign folicular adenoma, almost never
maligna
A.Toxic adenom a

Treatment:
Radioactive iodine: generally
effective and attractive
Surgery :
Very large nodule
Obstructive symptoms
Antithyroid drugs prior to
radioiodine or surgery
B.TOXIC M ULTINO D ULAR G O ITER

Older patient with longstanding

euthyroid
Symptoms:
Tachycardia, heart failure, or arrythmia
Sometimes weight loss, nervousness,
weakness, tremors and sweats
Physical examination:
Multinodular goiter: small or quite large and
may extend substernally
B.TOXIC M ULTIN O D ULAR G O ITER
Laboratory test:
Supressed TSH

Elevation in serum T3 level

Less stricking elevation of serum T4

Radioiodine Scan: multiple functioning
nodule, occasionally an irregular, patchy
distribution
B.TOXIC M ULTIN O D ULAR G O ITER

Treatment:
Difficult : often elderly, with other
comorbidities
Control of the hyperthyroid with
antithyroid drugs followed by
radioiodine
Surgery :
Very large nodule
Good surgical candidates
Antithyroid drugs used to normalize
thyroid function
C.Am iodarone Induced
Thyrotoxicosis
Amiodarone : an antiarrhythmic drug that
contains 37.3% iodine
In US: 2% of patient treated with amiodarone
amiodarone induced thyrotoxicosis
Thyrotxicosis is due to:
Excess iodine
thyroiditis
Treatment:
Methimazole : 40-60 mg/d
Beta adrenergic blockade
Potasium perchlorate
Prednisone therapy
D .SUBACUTE AND SILENT TH YRO ID ITIS
Acute release of T4 and T3 into
circulation
Symptoms:
Mild to severe thyrotoxicosis
Symptoms spontaneusly over a period of
weeks or months
Laboratory test:
RAIU : supressed
E.TH YRO TOXICO SIS FACTITIA

Ingests excessive amounts of T4 or

thyroid hormone preparation
Usually a women for weight control
Symptoms:
Thyrotoxicosis
Goiter : absent
Eye sign : absent
Laboratory test:
TSH : suppressed
Serum FT4 and T3 levels are elevated
Thyroglobulin: low
RAIU : nil
E.TH YRO TOXICO SIS FACTITIA
Management:
Stop thyroid hormone
Careful discussion
psychotherapy
F.Rare Form s of Thyrotoxicosis
1) Struma ovarii:
Teratoma ovarii
Symptoms
Mild : weight loss and tachycardia
No goiter and no eye signs
Laboratory test:
FT4 and T3 : mildly elevated
serum TSH : suppressed
RAIU : low
Total body scan : uptake of radioiodine in
the pelvis
Treatment:
Removal of the teratoma
F.Rare Form s of Thyrotoxicosis

2) Thyroid carcinoma
Follicular carcinoma of thyroid
Metastatic thyroid cancer
Symptoms : a few case of metastatic thyroid cancer
Weakness, weight loss, palpitations
thyroid nodule
No ophthalmopathy
Laboratory test:
Follicular carcinoma : concentrate radioactive iodine, but
rarely convert iodine into active hormone
Total body scan : area of uptake usually distant from the
thyroid (eg, bone or lung)
Treatment:
Radioactive iodine
F.Rare Form s of Thyrotoxicosis
3) Hydatidiform Mole and Choriocarcinoma
Produce high levels of chorionic
gonadotropin which has intrinsic TSH like
activity

Induce:
Thyroid hyperplasia
Increased radioiodine uptake
Suppressed TSH
Mild elevation of serum T4 and T3 levels
Rarely associated with overt thyrotoxicosis
Treatment:
Removal of the mole or treatment of the tumor
F.Rare Form s of Thyrotoxicosis
4) Hamburger thyrotoxicosis
An epidemic thyrotoxicosis in midwestern
United states
Hamburger made from neck trim the strap
muscle from the neck of slaughtered cattle
(contained beef thyroid tissue)

Treatment:
Prohibited the use of this material for human
consumption
F.Rare Form s of Thyrotoxicosis
5) Syndrome of Inappropriate of TSH Secretion
Laboratory test:
Elevated serum FT4
Elevated or inappropriately normal
serum imunoreactive TSH levels

Conditions are associated with this unusual

lab. value:
TSH secreting pituitary adenoma
Nonneoplastic pituitary hypersecretion of TSH
F.Rare Form s of Thyrotoxicosis

5) Syndrome of Inappropriate of TSH Secretion

) Symptoms and signs:
TSH secreting pituitary adenoma
Mild thyrotoxicosis and goiter
No eye signs
May have a concurrent pituitary hormonal deficiency
Lab:
FT4 and T3 and TSH
Increased of TSH is not suppressible with high dose of
thyroid hormones
Visual field examination:
Bitemporal defect
CT /MRI:
Sella usually reveal a pituitary tumor
 F.Rare Form s of Thyrotoxicosis

5) Syndrome of Inappropriate of TSH Secretion

)Symptoms and sign:

Visual field examination:
Bitemporal defect
CT /MRI:
Sella usually reveal a pituitary tumor
) Management:
Control of thyrotoxicosis with antithyroid drugs
removal of the pituitary tumor
Radiation therapy
Sum m ary
Thyrotoxicosis is a Clinical syndrome that results when
tissues are exposed to high level of thyroid hormones but
Hyperthyroidism is Thyrotoxicosis due to hyperactivity of the
thyroid gland

The most common cause of thyrotoxicosis is Graves disease

Symptoms and signs of thyrotoxicosis associated with excess

thyroid hormone in various organs

Thera are four modalities therapy of thyrotoxicosis according

to the indication