THYROTOXICOSIS

(HYPERTHYROIDISM)

HEMI SINORITA
THYROTOXICOSIS:
a condition caused by excessive thyroid
hormon whether the excess result from
overproduction by thyroid gland, originates
outside the thyroid or or is due to loss/leakage of
storage from thyroid gland.

HYPERTHYROIDISM:
a condition caused by excessive thyroid
hormon whether the excess result from
overproduction by thyroid hyperfunction
The thyroid hormone regulation cycle involves
the hypothalamus, pituitary, and thyroid glands
 Classification of Thyrotoxicosis

A. Associated with thyroid

hyperfunction
(hyperthyroidism)
1. Excess production of TSH
2. Abnormal thyroid
stimulator
a. Graves’ disease
b. Trophoblastic tumor
3. Intrinsic thyroid autonomy
a. Hyperfunctioning
adenoma
b. Toxic multinoduler
goiter
 …Classification
B. Not associated with thyroid
hyperfunction
1. Disorder of hormone
storage
a. Subacute thyroiditis
b. Chronic thyroiditis with
transient thyrotoxicosis
2. Extrathyroid source of
hormon
a. Thyrotoxicosis factitia
b. Hamburger toxicosis
c. Ectopic thyroid tissue
(1) Struma ovarii
(2) Functioning follicular ca.
 Graves' Disease
(Diffuse Toxic Goiter)

► Parry’sdisease or Basedow’s disease

► The most common form of hyperthyroidism
accounting for 60-70% of all cases. It occurs in
up to 3% of the population.
 A disorder with 3 major manifestations :

1. Hyperthyroidism
with diffuse
goiter
2. Opthalmopathy
3. Dermopathy

Acropachy
PREVALENCE …GRAVES’ DISEASE
- Can occur at any age,
common in the 3rd & 4th
decades
- Women : men ratio = 7 : 1
- Genetic factor: increased
frequency of
 HLA-B8 and DRw3 –
Caucasian
 HLA-Bw36 – Japanese
 HLA-Bw46 – Chinese

Related autoimmune
thyroid disease
 Graves’ disease
 Hashimoto’s disease
 Primary myxedema
► Graves' disease is an autoimmune disorder of unknown cause, characterized by
circulating antibodies against various thyroid antigens. The most important
antibody is the TSH receptor antibody (TSH-R Ab) which is directed against the
TSH receptor on the thyroid follicular cell membrane.
► The basic defect in Graves’ disease is an HLA-related organ specific
defect in suppressor T-lymphocyte function. Precipitating factors from
the environment (e.g.. stress, infection, drugs, trauma) may cause
further dysfunction in suppressor T-lymphocyte which together with
the genetic abnormality result in the activation of thyroid directed
helper T-lymphocytes. The activated helper T-lymphocytes become
sensitized to thyroid antigens and stimulate specific B-lymphocytes to
produce TSH-R Ab. Antibodies against other thyroid antigens
such as thyroid peroxidase (TPO) and thyroglobulin (TG) are
also present in patients with Graves' disease.
Disruption of homeostatic
mechanism that control hormone … PATHOGENESIS GRAVES’ DISEASE
secretion results from the presence
of thyroid stimulating
immunoglobulin (TSI) of the IgG
class that are elaborated by
lymphocytes
There are 3 types of autoantibodies
to the TSH receptor:
1.TSI, Thyroid stimulating
immunoglobulins: these antibodies
(mainly IgG) act as LATS (Long
Acting Thyroid Stimulants)
2. TGI, Thyroid growth
immunoglobulins: these antibodies
bind directly to the TSH receptor and
have been implicated in the growth
of thyroid follicles.
3. TBII, Thyrotrophin Binding-
Inhibiting Immunoglobulins: these
antibodies inhibit the normal union of
TSH with its receptor
OPhtalmopathy: Fibroblast from
orbital tissue contain material that
reacts with antibodies to the TSH
receptor.
Cytokines & growth factors released
by T cell may lead production of an
inflammatory reaction with
proliferation of fibroblasts
glycosaminoglycan
production→initiating edema &
retroorbital fat.
 BINDING TO TSH RECEPTOR MAY CAUSE :

1. Stimulation
2. No action
3. Even antagonize

the response may be

hyper, eu or
hypothyroidism
 Manifestation
Symptoms Signs
- Nervousness - Hyperactivity
- Fatigue - Tachycardia/arrythmia
- Weakness - Systolic hypertension
- Increased perspiration - Warm, moist, smooth skin
- Heat intolerance - Stare and eyelid retraction
- Hyperactivity - Tremor
- Tremor - Hyperreflexia
- Increase apetite - Muscle weakness
- Palpitation
- Weight loss
- Menstrual disturbance
 …GRAVES’ DISEASE
OCULAR SIGNS & SYMPTOMS

- Wide palpebral aperture

(Dalrymple’s sign)
- Lid lag (von Graefe’s sign)
- Staring or frigthened expressions
- Infrequent blinking (Stellwag’s sign)
- Absence of farehead wringkling on
upward (Joffroy’s sign)
- Inability to keep converged (Mobius’
sign)
- Diplopia
- Swelling of orbital contents and
puffiness of the lids
- Chemosis, corneal
injection/ulceration
- Exophthalmus
- Decreased visual acuity, retinal
edema/hemorrhages, optic nerve
damage
 …GRAVES’ DISEASE
CARDIAC MANIFESTATION
- Tachycardia
- Atrial fibrillation
- LVH and strain on ECG
- Premature atrial/ventricular contractions
- Congestive heart failure
- Angina with/without coronary artery disease
- Myocardial infarction
- Resistance to some drug effects (digoxin)
- Residual cardiomegaly
Systolic BP ↑ Diastolic BP ↓
Pulse pressure 50-80 mmHg
 GASTROINTESTINAL

- The appetite is usually increased (weight loss).

- Increased frequency of normal bowel movement.
- Occasionally diarrhea occurs.

MUSCLES
- Myasthenia
→muscular weakness and atrophy.
- Hypokalemic – periodic paralysis
 Particularly in young men
 Frequent in Asia
 Occur after a meal/exercise

NEURAL AND MENTAL

- Nervousness, irritability, restless.

- Impossible to remain still for an instant.
- The tendon reflexes tend to be brisk and reflex relaxation time is
shortened.
- Mental: hypomania, euphoria, hallucination and psychosis.
 SKELETON

- Decalcification → osteoporosis.
- Ca absorption is reduced.
- Fecal & urinary Ca excretion is augmented.

REPRODUCTIVE SYSTEM

- Menstruation is decreased in volume.

- Menstrual cycle may be either shortened, prolonged or
amenorrhea.
- Fertility is depressed but pregnancy nonetheless can develop.
SKIN

- Hot, moist (dripping wet), erythematous.

- Plummer’s nails:
the free margin of the nail leaves the nail bed.
- Hair tends to be fine, soft and straight. Alopecia is rare.
- Dermatopathy(thickening of the skin)
 CARBOHYDRATE
- Absorption of carbohydrate is accelerated.
- Oral glucose load 30-60 minute blood glucose
> 200 mg/dl, 2 h post load is normal.
- Insulin resistance is present.

LIPID
Synthesis and degradation are increased but
degradation > synthesis
→ serum cholesterol level is depressed
 Malnutrition & weight loss
 Hypermetabolism
DIAGNOSIS

► Signs and symptoms

► Laboratory :
 Increased value of FT3,
FT4
 Decreased value of TSH
 Increased value of
RAIU (hyperfunction)
TREATMENT

► Anti Thyroid Drug

► Radioactive Iodine
► Surgical Therapy
Table 3
Treatment of Hyperthyroidism
Treatment Mechanism of action Indications
Beta blockers Inhibit adrenergic Prompt control of symptoms;
treatment of choice for
effects thyroiditis; first-line therapy
before surgery, radioactive
iodine, and antithyroid drugs;
short-term therapy in
pregnancy
Iodides Block the conversion of T4 to T3 and Rapid decrease in thyroid hormone
inhibit hormone release levels; preoperatively when
other medications are
ineffective or contraindicated;
during preg-nancy when
antithyroid drugs are not
tolerated; with antithyroid drugs
to treat amiodarone-
(Cordarone-) induced
hyperthyroidism
Antithyroid drugs (methimazole Interferes with the organification of Long-term treatment of Graves'
[Tapazole] iodine; PTU can block disease (preferred first-line
peripheral conversion of T4 to treatment in Europe, Japan,
and PTU) T3 in large doses and Australia); PTU is
treatment of choice in patients
who are pregnant and those
with severe Graves' disease;
preferred treatment by many
endocrinologists for children
and for adults who refuse
radioactive iodine;
pretreatment of older and
cardiac patients before
radioactive iodine or surgery;
both medications considered
safe for use while
breastfeeding
Radioactive iodine Concentrates in the thyroid gland and High cure rates with single-dose
destroys thyroid tissue treatment (80 percent);
treatment of choice for Graves'
disease in the United States,
multinodular goiter, toxic
nodules in patients older than
40 years, and relapses from
antithyroid drugs
Contraindications and complications
Use with caution in older patients and
in patients with pre-existing
heart disease, chronic
obstructive pulmonary disease,
or asthma
Paradoxical increases in hormone
release with prolonged use;
common side effects of
sialadenitis, conjunctivitis, or
acneform rash; interferes with
the response to radioactive
iodine; prolongs the time to
achieve euthyroidism with
antithyroid drugs
High relapse rate; relapse more likely
in smokers, patients with large
goiters, and patients with
positive thyroid-stimulating
antibody levels at end of
therapy; major side effects
include polyarthritis (1 to 2
percent), agranulocytosis (0.1
to 0.5 percent); PTU can cause
elevated liver enzymes (30
percent), and immunoallergic
hepatitis (0.1 to 0.2 percent);
methimazole can cause rare
cholestasis and rare congenital
abnormalities; minor side
effects (less than 5 percent)
include rash, fever,
gastrointestinal effects, and
arthralgia
Delayed control of symptoms;
posttreatment hypothyroidism
in majority of patients with
Graves' disease regardless of
dosage (82 percent after 25
years); contraindicated in
patients who are pregnant or
breastfeeding; can cause
transient neck soreness,
 Anti Thyroid Drug
1. Thionamides :
 Propylthiouracil (PTU)
 Methimazalev (MMI) &
Carbimazole
2. Inorganic Iodide
3. Potassium Perchlorate
4. Lithium Carbonate
-adrenergic Antagonist Drugs
PTU & MMI
Action
1. Intrathyroidal
a.
Inhibition of iodine oxidation & organification
b.
Inhibition of iodotyrosine coupling
c.
Possible alteration of structure of thyroglobulin
d.
Possible inhibition of thyroglobulin
biosynthesis
2. Extrathyroidal : inhibition of conversion of T4 to
T3 (only by PTU)
3. On the immune system
PTU & MMI
► Long-term treatment of Graves' disease
(preferred 1st-line treatment in Europe,
Japan, & Australia)
► PTU is treatment of choice in patients who
are pregnant and those with severe Graves'
disease;
► Preferred treatment by many
endocrinologists for children and for adults
who refuse radioactive iodine
► Pretreatment of older and cardiac patients
before radioactive iodine or surgery
► Both medications considered safe for use
while breastfeeding
P T U & M M I…
Side effects
- High relapse rate; relapse more likely in
smokers, patients with large goiters, and
patients with positive thyroid-stimulating
antibody levels at end of therapy
- Rash, urticaria
- Transient granulocytopenia
- Agranulocytosis (0,2 – 0,5%)
- Very rare : * hepatitis/cholestatic
* aplastic anemia
Inorganic Iodide
• To decrease T3 & T4 synthesis
Inhibiting iodide transport, oxidation and
organification (Wolff-Chaikoff effect)
• To block the release of T3 & T4 from thyroid
• Rapid decrease in thyroid hormone levels
• Preoperatively when other medications are
ineffective or contraindicated
• During pregnancy when antithyroid drugs are
not tolerated
• With antithyroid drugs to treat amiodarone-
(Cordarone-) induced hyperthyroidism
BETA ADRENERGIC ANTAGONIST

Many of the manifestation of thyrotoxicosis

mimic a hyper adrenergic state
Blockade of adrenergic receptor relief from
some symptoms of thyrotoxicosis
Possible: inhibit conversion of T4 to T3
Treatment of choice for thyroiditis
First-line therapy before surgery, radioactive
iodine, and antithyroid drugs
Short-term therapy in pregnancy
 Radioactive iodine

► High cure rates with single-dose treatment

(80 percent)
► Treatment of choice for Graves' disease in
the United States, multinodular goiter, toxic
nodules in patients older than 40 years, and
relapses from antithyroid drugs
► Contraindicated in patients who are
pregnant or breastfeeding
 Side effects

► Delayed control of symptoms

► Posttreatment hypothyroidism in majority of
patients with Graves' disease regardless of
dosage
 Surgery (subtotal thyroidectomy)

► Treatment of choice for patients who are pregnant

and children who have had major adverse
reactions to antithyroid drugs, toxic nodules in
patients younger than 40 years, and large goiters
with compressive symptoms
► Can be used for patients who are noncompliant,
refuse radioactive iodine, or fail antithyroid drugs,
and in patients with severe disease who could not
tolerate recurrence; may be done for cosmetic
reasons
 Side effects

► Risk of hypothyroidism (25 percent) or

hyperthyroid relapse (8 percent)
► Temporary or permanent hypoparathyroidism or
laryngeal paralysis (less than 1 percent)
► Higher morbidity and cost than radioactive iodine
► Requires patient to be euthyroid preoperatively
with antithyroid drugs or iodides to avoid
thyrotoxic crisis
Toxic Nodular Goiter

- A proportion of patients with non

toxic nodular thyroid glands develop
thyrotoxicosis
- Directly correlates to the goiter’s
duration;
- Thyrotoxicosis develops insidiously
- Diagnosis by scintifigraphy
hyperfunctioning / toxic nodular
will concentrate the radionuclide;
- Treatment:
thyroidectomy or I radioctive
Thyroid with toxic nodule before (A) and after (B)
treatment with 131I
 SUBACUTE THYROIDITIS
► Subacute thyroiditis is an acute inflammatory disease of the
thyroid probably caused by a virus.

► Symptoms include fever and thyroid tenderness, neck pain

characteristically shifts from side to side and may settle in one
area, frequently radiating to the jaw and ears

► Symptoms of hyperthyroidism are common early in the disease

because of hormone release from the disrupted follicles

► Diagnosis is clinical and with thyroid function tests.

► Treatment is with high doses of NSAIDs or with
corticosteroids.

► Subacute thyroiditis is self-limited, generally subsiding in a few

months; occasionally, it recurs and may result in permanent
hypothyroidism when follicular destruction is extensive.
► If hypothyroidism persists, thyroid hormone replacement
therapy may be required.
► Radioactive iodine uptake scan
showing normal condition in a 30-year-
old woman with postpartum thyroiditis
(subacute lymphocytic thyroiditis).

Radioactive iodine uptake scan showing

hyperthyroid (increased uptake) condition
in a 52-year-old woman with Graves'
disease.

Radioactive iodine uptake scan showing

hypothyroid (decreased uptake) condition,
or thyroiditis, in a 42-year-old woman with
subacute granulomatous thyroiditis.
terima kasih
Table 3
Treatment of Hyperthyroidism
Treatment Mechanism of action Indications
Beta blockers Inhibit adrenergic Prompt control of symptoms;
treatment of choice for
effects thyroiditis; first-line therapy
before surgery, radioactive
iodine, and antithyroid drugs;
short-term therapy in
pregnancy
Iodides Block the conversion of T4 to T3 and Rapid decrease in thyroid hormone
inhibit hormone release levels; preoperatively when
other medications are
ineffective or contraindicated;
during preg-nancy when
antithyroid drugs are not
tolerated; with antithyroid drugs
to treat amiodarone-
(Cordarone-) induced
hyperthyroidism
Antithyroid drugs (methimazole Interferes with the organification of Long-term treatment of Graves'
[Tapazole] iodine; PTU can block disease (preferred first-line
peripheral conversion of T4 to treatment in Europe, Japan,
and PTU) T3 in large doses and Australia); PTU is
treatment of choice in patients
who are pregnant and those
with severe Graves' disease;
preferred treatment by many
endocrinologists for children
and for adults who refuse
radioactive iodine;
pretreatment of older and
cardiac patients before
radioactive iodine or surgery;
both medications considered
safe for use while
breastfeeding
Radioactive iodine Concentrates in the thyroid gland and High cure rates with single-dose
destroys thyroid tissue treatment (80 percent);
treatment of choice for Graves'
disease in the United States,
multinodular goiter, toxic
nodules in patients older than
40 years, and relapses from
antithyroid drugs
Contraindications and complications
Use with caution in older patients and
in patients with pre-existing
heart disease, chronic
obstructive pulmonary disease,
or asthma
Paradoxical increases in hormone
release with prolonged use;
common side effects of
sialadenitis, conjunctivitis, or
acneform rash; interferes with
the response to radioactive
iodine; prolongs the time to
achieve euthyroidism with
antithyroid drugs
High relapse rate; relapse more likely
in smokers, patients with large
goiters, and patients with
positive thyroid-stimulating
antibody levels at end of
therapy; major side effects
include polyarthritis (1 to 2
percent), agranulocytosis (0.1
to 0.5 percent); PTU can cause
elevated liver enzymes (30
percent), and immunoallergic
hepatitis (0.1 to 0.2 percent);
methimazole can cause rare
cholestasis and rare congenital
abnormalities; minor side
effects (less than 5 percent)
include rash, fever,
gastrointestinal effects, and
arthralgia
Delayed control of symptoms;
posttreatment hypothyroidism
in majority of patients with
Graves' disease regardless of
dosage (82 percent after 25
years); contraindicated in
patients who are pregnant or
breastfeeding; can cause
transient neck soreness,