LANGKAH- LANGKAH

MENGHADAPI KELAINAN TIROID

Patients with thyroid disease will usually complain of

1. thyroid enlargement, diffuse or nodular;

2. symptoms of thyroid deficiency ( hypothyroidism)
3. symptoms of thyroid hormone excess
(hyperthyroidism) or
4. complications of a specific form of
hyperthyroidism e.g Graves’ disease
* prominence of the eyes (exophthalmos) and,
* thyroid dermopathy
Hyperthyroidism & thyrotoxicosis

Thyrotoxicosis = clinical syndrome that results when

tissues are exposed to high levels of

circulating thyroid hormone

due to hyperactivity of the thyroid gland,

hyperthyroidism
Clinical Features of Thyrotoxicosis
A. Symptoms
* palpitations,
* nervousness,
* easy fatigability,
* hyperkinesia,
* diarrhea,
* excessive sweating,
* intolerance to heat,
* preference for cold.
* marked weight loss without loss
of appetite
* emosional instability
* kind of insomnia
B. Signs
* Thyroid enlargement,
• Thyrotoxic eye signs
(exophthalmos in
Graves’ disease)
• Tachycardia
• Skin : smooth, moist
and warm
• Fine tremor of the fingers
* Muscle weakness and
* Loss of muscle mass ( myopathy)
* Atrial fibrillation insensitive to digoxin
Pemeriksaan “fine tremor”
 INDEKS WAYNE
Gejala yang baru terjadi + - Tanda-tanda + -
Dan bertambah berat
Sesak pada kerja +1 - Tiroid teraba +3 -3
Berdebar-debar +2 - Bising pembuluh +2 -2
Lekas lelah +3 - Eksopthalmus +2 -
Lebih suka hawa panas -5 - Retraksi palpebra +2 -
Lebih suka dingin +5 - Kelambatan palpebra +1 -
Berkeringat banyak +3 - Hiperkinesis +4 -2
Gugup +2 - Tremor jari +1 -
Nafsu makan bertambah +3 - Tangan panas +2 -1
Nafsu makan berkurang -3 - Tangan lembab +1 -1
Berat badan bertambah -3 - Denyut nadi sewaktu
< 80 / menit -3 -
80-90 / menit - -
> 90 / menit +3 -
Fibrilasi atrium +4 -
Jumlah
Nilai :  19 : toksik, 11 – 19 : Equivocal, < 11 : non toksik
Laboratory Findings

High TT4/FT4 + suppressed TSH (< 0,1 uU/L)

 Hyperthyroidism

Hyperthyroidism+ Exophthalmos Graves’ Disease

Normal TT4/FT4 + low TSH (< 0,1 uU/L)

Subclinical hyperthyroidism

Normal TT4/FT4 + high TSH ( > 5 uU/L)

Subclinical hypothyroidism
 Struma dengan gambaran klinis
yang mencurigakan
T4 (fT4)

Normal atau tinggi

“borderline”

T3 (fT3) Tirotoksikosis

normal tinggi

RAIU
TSHs

normal rendah
tinggi rendah

eutiroid Tiroiditis
Tirotoksikosis Tirotoksikosis T3 Hipertiroid Tirotoksikosis
subklinis - isme iatrogenik
Radioactive iodine uptake (RAIU)

Thyrotoxicosis + high RAIU  hyperthyroidism

Thyrotoxicosis with a very low thyroidal RAIU occurs in

(1) in subacute thyroiditis;

(2) during the active phase of Hashimoto’s thyroiditis,;

(3) in thyrotoxicosis factitia

Conditions associated with thyrotoxicosis

1. Diffuse toxic goiter (Graves’ disease)

2. Toxic adenoma (Plummer’s disease)
3. Toxic multinodular goiter
4. Subacute thyroiditis
5. Hyperthyroid phase of Hashimoto’s thyroiditis
6. Thyrotoxicosis factitia
Graves’ Disease
Graves’ Disease
(Diffuse Toxic Goiter)

Females > males  (5) : (1)

Between 20-40 years of age.
Consists of one or more of the following features :
(1) thyrotoxicosis,
(2) diffuse goiter,
(3) ophthalmopathy (exophthalmos), and
(4) dermopathy (pretibial myxedema).
Etiology
An autoimmune disease of unknown cause
Strong familial predisposition

Pathogenesis
T lymphocytes sensitized to antigens within the thyroid gland
stimulate B lymphocytes to synthesize antibodies to these
antigents :
against the TSH receptor cell membrane

stimulate the thyroid cell

increased growth and function

(TSH-R Ab [stim]).
Pathogenesis of exophthalmos

Involve cytotoxic lymphocytes (killer cells)

and cytotoxic antibodies

Sensitized to a common antigen found in

orbital fibroblasts,
orbital muscle,
thyroid tissue
Treatment of Graves’ Disease
Management has been largely directed toward controlling
the hyperthyroidism.

1. Blocking of hormone synthesis by antithyroid drug

therapy,
2. Partial ablation of the thyroid gland by surgery, and
3. Destruction of thyroid cells by radioactive iodine
therapy.
Choice of Therapy

Choice of therapy will vary with

* the nature and severity of the illness
* prevailing customs.
In the opinion of many authors :
1. Treatment with antithyroid drugs
2. Surgery or
3. RAI
A. Antithyroid Drug Therapy

The drugs :propylthiouracil or methimazole

Started with large divided doses:
 when the patient becomes clinically euthyroid,
 maintenance therapy with a lower dose.

Propylthiouracil (PTU) also inhibits the conversion of T4 to T3,

Methimazole  longer duration of action

Could be given as a single daily dose
Duration of therapy
Can range from 6 months to 20 years or more.
Remission may be predicted in the following
circumstances:

1. if the thyroid gland returns to normal size;

2. if the disease can be controlled with
a relatively small dose of antithyroid drugs;
3. if TSH-R Ab [stim] is no longer detectable in the
serum; and
4. if the thyroid gland becomes normally
suppressible following the administration of
iodothyronine.
Reaction to antithyroid drugs

Allergic reactions
Agranulocytosis  Cessation of all antithyroid
drug therapy.
Shift to an alternative
therapy  radioactive iodine.
B.Surgical Treatment

Subtotal thyroidectomy  treatment of choice for very large

glands or multinodular goiters.

The patient should be euthyroid

Starting 2 weeks before the day or operation,

 saturated solution KJ is given to hypervascularity

Complication to surgical therapy

Hypothyroidism
Hypoparathyroidism
Recurrent laryngeal nerve injury

in about 1% of cases.
C. Radioactive Iodine Therapy

Following the administration of radioactive iodine,

the gland will shrink and

the patient will become euthyroid

over a period of 6-12 weeks.
The major compication of radioactive iodine
therapy

hypothyroidism
Complications
Thyrotoxic crisis (“thyroid storm”) is

- the acute exacerbation of all of the symptoms of

thyrotoxicosis,
- often presenting as a syndrome that may be of
life- threatening severity,
- has the mortality rate of 50%.
THYROTOXIC CRISIS
(“THYROID STORM”)
Thyrotoxic crisis is a rare, life-threatening
syndrome characterized by exaggerated clinical
manifestations of thyrotoxicosis.
The mechanism by which acute illness or injury
precipitates thyrotoxic crisis is poorly understood,
and it is likely that several factors are important

Prompt diagnosis and vigorous therapy are

required to avoid a fatal outcome; the mortality
rates of hospitalized patients have ranged from
10% to 75 %
 EVENTS ASSOCIATED WITH
THE ONSET OF THYROTOXIC CRISIS

Infection
Other acute medical illness
Acute emotional stress
Acute psychosis
Nonthyroid surgery
Parturition
Trauma
Thyrotoxicosis factitia
After radioiodine therapy
Post thyroidectomy
After high-dose iodine administration
lodinated radiographic contrast agent administration
Discontinuation of antithyroid drug therapy
Vigorous palpation of thyroid gland
*Post molar evacuation in molar pregnancy + thyrotoxicosis
Clinical manifestations of thyroid crisis

√ Marked hypermetabolism
√ Excessive adrenergic response
√ Fever ranges from 38 to 41OC
+ sweating.
√ Marked tachycardia,
+ atrial fibrillation
+ high pulse pressure
occasionally with heart failure.
CNS symptoms : marked agitation,
restlessness,
delirium, and coma

Gastrointestinal symptoms:
nausea,
vomiting
diarrhea, and jaundice

A fatal outcome will be associated with heart failure

and shock.
Pathogenesis

Binding sites for catecholamines increases,

in heart and nerve tissues

Sensitivity to circulating catecholamines.

 DIAGNOSTIC CRITERIA FOR THYROTOXIC CRISIS
Points
Points
Thermoregulatory dysfunction
Temperature (°F): 99-99.9 5
100-100.9 10
101-101.9 15
102-102.9 20
103-103.9 25
>104 30
Central nervous system effects
Absent 0
Mild agitation 10
Delirium, psychosis, lethargy
20
Seizure or coma 30
Gastrointestinal dysfunction
Absent 0
Diarrhea, nausea, vomiting, or abdominal pain 10
Unexplained jaundice 20
Cardiovascular dysfunction
Tachycardia (beats/min): 90-109 5
110-119 10
120-129 15
130-139 20
>140 25
Congestive heart failure: Absent 0
Mild (edema) 5
Moderate (bibasilar rales) 10
Severe (pulmonary edema) 15
Atrial fibrillation: Absent 0
Present 10
History of precipitating event (surgery, infection, etc.)
Absent 0
Present 10
The diagnosis of thyrotoxic storm is: unlikely, <25; im­pending, 25-44; likely, 45-60; highly likely, >60.
Adapted from Burch HB, Wartofsky L. Life-threatening thyrotoxico-sis: thyroid storm. Endocrinol Metab Clin North Am 1993;22:263, with permission
TREATMENT tight control ICU
   
Treatment of thyrotoxic crisis is given toward :
 
1. Decrease T4 & T3 synthesis and secretion
2. Systemic disturbances such as fever,
hypovolemia etc
3. The tissue effects of high serum T4 and T3
4. Underlying precipitating illness or injury
 
Decrease T4 & T3 synthesis and secretion

   
Decrease T4 & T3 synthesis : Decrease T4 & T3 secretion :
 
 
  
PTU (200mg-250mg)/4 hours   
or Inorganic iodide / Lugol’s Sol
Methimazole/ Carbimazole
20 mg /4 hrs 8 drops / 6 hrs
One hour after anti thyroid drug
Systemic Disturbances
Fever promptly give antipyretic
 
Acetaminophen ! Salicylate X
 
Fluid loss (by fever and diaphoresis, or )diarrhea
 
 
Nacl 0,9% + Dextrose 5% or 10%
   
Congestive heart failure
 
 
Furosemide or HCT with digoxin
 High doses of glucorticosteroid
-          

* empirical postulated risk of adrenal

insufficiency

   * inhibit conversion of T4 T3

Hydrocortisone 200-300 mg initially

Followed by 100 mg / 8 hrs
The Tissue Effects of High Serum T4 and T3
 
 

Blunt
 
the increased sympathetic activity
Propranolol preferred -adrenergic antagonist :
 Blunt the increased sympathetic activity
  Inhibit conversion of T4 T3
 Improvement of agitation, tremor, fever

Orally 60 mg –80 mg / 6 hrs

or
I.V 1-3 mg / several hrs
Underlying precipitating illness or injury
 

If infection or trauma is obvious

Treat properly
 PROGNOSIS
 
Most patients treated as
described improve considerably
 

in 12 - 24 hours

Improvement : decreased temperature, heart rate,

sweating, agitation
 
 Pathogenesis ?

Thyrotoxicosis
“untreated” Thyrotoxic crisis

Precipitating Severe clinical thyrotoxisosis

factors + temperature
No-prompt treatment

Death
Conditions associated with thyrotoxicosis
1. Diffuse toxic goiter (Graves’ disease)
2. Toxic adenoma (Plummer’s disease)
3. Toxic multinodular goiter

4. Subacute thyroiditis
5. Hyperthyroid phase of Hashimoto’s thyroiditis
6. Thyrotoxicosis factitia
• Subacute thyroiditis
• Hyperthyroid phase of Hashimoto’s thyroiditis
•

• - Hyperthyroid phase of

• Hashimoto’s thyroiditis
- Subacute Thyroiditis
HYPOTHYROIDISM

-Primary
-Secondary ( drug’s side effect)
Symptoms and Signs :

The reverse of Hyperthyroidism

GRAVES’ DISEASE IN PREGNANCY
 Thyroid and Pregnancy
Effect on fetal development

< 11 Weeks the fetal thyroid does not concentrate I

TSH system begin to function  at about 11 weeks.

Thyroid hormone secretion, (-)   brain development

 skeletal maturation

cretinism

(mental retardation and

dwarfism)
 Normal pregnancy

 Oestrogen  hGG  I Renal I Loss to

clearance Feto-placental
complex
 TBG  TSA

 TT4 TSH  Availability of iodine

(Normal - fT4) fT4
(high normal)  TSH
Goiter
Normal fT4
Thyrotoxicosis and Pregnancy
Thyrotoxicosis during pregnancy  a special problem :
RAI  crosses the placenta freely

may injure the fetal thyroid.

contraindicated

Prophylthiouracil ( better than Methimazole)

Subtotal thyroidectomy can be performed
safely during the mid trimester.
Graves’ Disease in Pregnancy

•  TSH-R Ab (Stim) Graves’ disease

• In Pregnancy Immunosupression
of all system

Immunosupression of
auto immune diseases
Successful implantation
of fetal allograft
Immunosupression of
Graves’ disease

 TSH-R Ab (Stim) GD gradual improvement

Hyperthyroidism in pregnancy
Diagnosis
Based on clinical
picture difficult
(Tachycardia,Goiter,TT4)

Laboratory findings High fT4 and

very low TSH
(< 0.10 mU/L)
 INDEKS WAYNE
Gejala yang baru terjadi + - Tanda-tanda + -
Dan bertambah berat
Sesak pada kerja +1 - Tiroid teraba +3 -3
Berdebar-debar +2 - Bising pembuluh +2 -2
Lekas lelah +3 - Eksopthalmus +2 -
Lebih suka hawa panas -5 - Retraksi palpebra +2 -
Lebih suka dingin +5 - Kelambatan palpebra +1 -
Berkeringat banyak +3 - Hiperkinesis +4 -2
Gugup +2 - Tremor jari +1 -
Nafsu makan bertambah +3 - Tangan panas +2 -1
Nafsu makan berkurang -3 - Tangan lembab +1 -1
Berat badan bertambah -3 - Denyut nadi sewaktu
< 80 / menit -3 -
80-90 / menit - -
> 90 / menit +3 -
Fibrilasi atrium +4 -
Jumlah
Nilai :  19 : toksik, 11 – 19 : Equivocal, < 11 : non toksik
EFFECT OF UNTREATED HYPERTHYROIDISM
IN PREGNANCY
Fetus :
• Low birth weight
• Increased neonatal mortality
• Fetal thyrotoxicosis
Mother :
• Affect myocardial function
• Thyroid storm during labor

Hyperthyroidism in pregnancy
should be treated
 AFTER LABOR

PLACENTA – RELATED
 IMMUNOSUPRESSION

 TSH – R Ab (Stim)

RECURRENCE OF THYROTOKXICOSIS
(POST PARTUM HYPERTHYROIDISM)
 PRINCIPLE OF MANAGEMENT

TO CONTROL THE HYPERTHYROIDISM WITHOUT

DISTURBING FETAL
THYROID FUNCTION
CONDITIONS TO BE CONSIDERED
 RAI is absolutely contra indication
(may injures fetal thyroid)

 Antithyroid drugs (esp PTU) should be given

in the 1st trimester

 Sub total thyroidectomy – if needed – should

be performed in mid trimester

 ATD could be given through the pregnancy

Treatment
Exclusively treated with thionamide
antithyroid drug (ATD)
Propythiouracyl
preferred to metimazole

dosage maintained
at a minimum
tight control

discontinue as soon
as possible
Treatment
Prognosis of Control of

ς
mother & fetus hyperthyroidism

• Early diagnosis Proper treatment

• Treatment after mid
2nd trimester Good fetal outcome

Poorer fetal outcome

Maternal fT4 level high normal range

Optimal for fetal thyroid function

at delivery
VASKOVA, 1998
• Regular ATD 74,3%
Completely healthy

5% low birth weight

12,8% pre-term

• Treatment after the 1st trimester

or non-regular treatment

Some hyperthyroidism
Some malformation
Babies of mothers with Graves’ disease
How cute !!
TERIMA KASIH
Non-toxic Goiter
 Struma tanpa gambaran klinis

TSHs

tinggi normal Rendah

(<0,1 μLU/ml)

Hipotiroid Eutiroid Hipertiroidi

T4 (fT4) T4, T3 (fT4, fT3)

normal rendah Normal atau tinggi

“borderline”

Hipotiroidisme Hipotiroidisme Hipertiroidisme hipertiroidisme

subklinis subklinis
 Nodul Tiroid non Toksik

Sidik Tiroid

Panas Hangat Dingin

Observasi 1- tiroksin USG

(4- 8 minggu )
Kista Padat Campuran

Sidik Tiroid FNA *) FNA FNA

Ulangan

Panas Dingin

Stop T/ FNA
Keterangan : *) dapat dilakukan sekaligus terapi aspirasi
TERIMA KASIH
THE THYROID GLAND
 Effects of TSH on
the Thyroid cell

Changes in thyroid cell morphology

Cell growth
Iodine metabolism
Stimulation of glucose uptake,
and oxygen consumption,
 TSH

The serum level is

about 0.5-5 mU/L;
It is increased in hypothyroidism
Decreased in primary hyperthyroidism
 Effect of Iodide Deficiency
on Hormone Biosynthesis

Low iodine diet  intrathyroidal iodine content

Synthesis of thyroid hormone

Serum TSH.

Struma
 Effect of Iodide Deficiency on Hormone Biosynthesis

A diet very low in iodine reduces intrathyroidal iodine content –

increases the intrathyroidal ratio of MIT to TIT-

increases the ratio of T3 to T4 ---

decreases the secreation of T4,-

increases serum TSH.

Struma
 Thyroid hormone transport

Bound to carrier proteins.

0,04% of T4 and 0.4% of T3 are “free,”

responsible for hormonal activity

The Action of thyroid hormones
1. The thyroid hormone receptor
Free thyroid hormones bind to a specific receptor in the cell nucleus.

Within the cell , T4 - T3  biological effect

2. Physiologic Effects of Thyroid Hormones

-- on tissue growth, brain maturation,

-- increased heat production and oxygen consumption,
-- increased beta adrenergic receptors.
Effects on Oxygen Consumption,
 Heat Production,

* increased basal metabolic rate

( sensitivity to heat in hyperthyroidism
and hypothyroidism.)

Cardiovascular Effects
improving cardiac muscle contractility.
Anatomy :
 The throid is in the superficial anterior neck
 Is bilobed, with a connecting isthmus.
 The shape Is often described as that of the H of the
Honda car symbol.
 Neoplastic or hyperplastic growth may extend inferiorly
(retrosternal),
 The adjacent anatomy of the laryngeal nerves and
parathyroid glands is an important surgical
consideration.
 In adults it wheighs approximately 10-20 gram.
 The thyroid gland has a rich blood suppy
 Sympathetic Effects

number of beta adrenergic receptors

in heart muscle,
skeletal muscle,
adipose tissue

myocardial alpha adrenergic receptors.

Amplify catecholamine action at a posttreceptor

site
 Gastrointestinal Effects

Thyroid hormones stimulate gut motility

increased motility and diarrhea in hyperthyroidism.

Slowed bowel transit and constipation in

hypothyroidism.
Skeletal Effects

Thyroid hormones  increase bone turnover

increasing bone resorption

Neuromuscular Effects

increase synthesis of many structural proteins,

Hyperthyroidism   protein turnover and loss

of muscle tissue  myopathy.

 speed of muscle contraction and relaxation

hyperreflexia  hyperthyroidism
Effects on Lipid & Carbohydrate Metabolism

Hyperthyroidism   hepatic gluconeogenesis

and glycogenolysis
 intestinal glucose absorption
 hyperthyroidism will
exacerbatin underlying
diabetes mellitus.
  Cholesterol synthesis and  degradation

cholesterol levels decline

Endocrine Effects

Ovulation may be impaired in

both hyperthyroidism and hypothyroidism

infertility  corrected by restoration of the

euthyroid state.
TERIMA KASIH
On physical examination
Histology