HYPERTHYROIDISM

Dr. dr. Shahrul Rahman, Sp.PD, FINASIM

Departemen Ilmu Penyakit Dalam

Fakultas Kedokteran
Universitas Muhammadiyah Sumatera Utara
 Thyroid Disease Spectrum
Overt Hypothyroidism
TSH >4.0 IU/mL, Free T4 Low

Mild Thyroid Failure

TSH >4.0 IU/mL, Free T4 Normal

Euthyroid
TSH 0.4-4.0 IU/mL, Free T4 Normal

Thyrotoxicosis
TSH <0.4 IU/mL, Free T3/T4 Normal or Elevated

0 5 10
TSH, IU/mL
Braverman LE, et al. Werner & Ingbar’s The Thyroid. A Fundamental and Clinical Text. 8th ed. 2000.
Canaris GJ, et al. Arch Intern Med. 2000;160:526-534.
Vanderpump MP, et al. Clin Endocrinol (Oxf). 1995;43:55-68.
 Typical Thyroid Hormone Levels
in Thyroid Disease

TSH T4 T3
Hypothyroidism High Low Low
Hyperthyroidism Low High High
Subclinical Hypothyroidsm High normal normal
Subclinical Hyperthyroidsm Low normal normal
Thyrotoxicosis and Hyperthyroidism
Definitions
• Thyrotoxicosis
–The clinical syndrome of hypermetabolism that
results when the serum concentrations of free
T4, T3, or both are increased
• Hyperthyroidism
–Sustained increases in thyroid hormone
biosynthesis and secretion by the thyroid gland
• The 2 terms are not synonymous

Braverman LE, et al. Werner & Ingbar’s The Thyroid. A

Fundamental and Clinical Text. 8th ed. 2000.
• Thyroid Storm Rare complication of
hyperthyroidism where manifestations of
thyrotoxicosis become life threatening. Also may be
termed Thyrotoxic Crisis.

• Apathetic Thyrotoxicosis Rare form usually

occurring in the elderly. Often presents as single
organ failure (CHF). Patient may develop thyroid
storm without the typical manifestations.
 Hyperthyroidism Etiology

• Graves’ disease
• Multinodular goiter
• Autonomous nodule
• Exogenous thyroid hormone
• Transient—subacute thyroiditis,
postpartum thyroiditis
• Drugs—amiodarone
Causes of Thyrotoxicosis
 Causes of Thyrotoxicosis
Divided by Degree of Radioiodine Uptake

High I123 Uptake Low I123 Uptake

Graves’ disease Subacute thyroiditis
123
I I123
Toxic nodular goiter Hashitoxicosis
TSH-mediated thyrotoxicosis Drug-induced
Pituitary tumor Iodide
Pituitary resistance to Thyroid hormone
thyroid hormone Struma ovarii
HCG-mediated thyrotoxicosis Factitious
Hydatidiform mole
Choriocarcinoma
Other HCG-secreting tumors
Thyroid carcinoma (very rare)
 Common Signs and Symptoms
of Thyrotoxicosis
Symptoms Signs
 Nervousness  Hyperactivity
 Fatigue  Tachycardia
 Weakness  Systolic hypertension
 Increased perspiration  Warm, moist, or smooth skin
 Heat intolerance  Stare and eyelid retraction
 Tremor  Tremor
 Hyperactivity  Hyperreflexia
 Palpitations  Muscle weakness
 Appetite/weight changes
 Menstrual disturbances
Braverman LE, et al. Werner & Ingbar’s The Thyroid. A
Fundamental and Clinical Text. 8th ed. 2000.
 SYSTEMIC EFFECTS
RESPIRATORY

• Dyspnea, panting, hyperventilation

• respiratory muscle weakness
• increased tissue carbon dioxide levels
• +/- congestive heart failure
 SYSTEMIC EFFECTS
CARDIOVASCULAR

• Thyrotoxic cardiomyopathy
– Hypermetabolic state
– Systemic hypertension
– Direct T3 and T4 action on heart
muscle
• LV hypertrophy, IVS hypertrophy,
RA and aortic dilation, enhanced
contractility
 Signs and Symptoms of
Hyperthyroidism
Hoarseness/
Nervousness/Tremor Deepening of Voice

Mental Disturbances/ Persistent Dry or Sore Throat

Irritability
Difficulty Swallowing
Difficulty Sleeping
Bulging Eyes/Unblinking Stare/ Palpitations/
Vision Changes Tachycardia

Enlarged Thyroid (Goiter) Impaired Fertility

Weight Loss or Gain
Menstrual Irregularities/
Light Period Heat Intolerance
Increased Sweating
Frequent Bowel Movements
Sudden Paralysis
Warm, Moist Palms

Family History of
First-Trimester Miscarriage/
Thyroid Disease
Excessive Vomiting in Pregnancy
or Diabetes
Signs and Symptoms of
Hyperthyroidism
1. Graves’ Disease (Toxic Diffuse Goiter)

• The most common cause of hyperthyroidism

– Accounts for 60% to 90% of cases
– Incidence in the United States estimated at 0.02% to
0.4% of the population
– Affects more females than males, especially in the
reproductive age range
• Graves disease is an autoimmune disorder
possibly related to a defect in immune tolerance
- Pertama kali dikenal oleh Coindet (1821) sbg akibat
pemberian yodium.
- KMD oleh Parry (1825) dan Robert Graves (1835),dan
tahun 1840 Von Basedow melaporkan sindroma yg sama
dan dikenal sbg Morbus Basedowi
- Penyakit multisistem yg ditandai dengan gondok
difusa,tiroktoksikosis,ofthalmopathi, dan kadang-kadang
dermatopati infiltratif
 Graves Disease
• Autoimmune disorder
– Production of TSH receptor autoantibodies
– Stimulate thyroid hormone overproduction
• Characterized by the presence of B- and T-
lymphocytes in thyroid tissue
– TSH receptor activation
– Thyroglobulin and thyroid peroxidase antibodies
– Sodium/iodide cotransporter (NIS) activity enhanced
(increased RAI)
– Autoantigens
Abbott Laboratories Diagnostics Division Web site. Available at: et al. Werner & Ingbar’s The
Thyroid. A Fundamental and Clinical Text. 8th ed. 2000.
 Graves' Disease
Goiter
Hyperthyroidism
Exophthalmos
Localized myxedema
Thyroid acropachy
Thyroid stimulating immunoglobulins
 Clinical Characteristics of Goiter
in Graves’ Disease
Diffuse increase in thyroid gland size
Soft to slightly firm
Non-nodular
Bruit and/or thrill
Mobile
Non-tender
Without prominent adenopathy
Graves’ Disease - Localized Myxedema

Margins sharply
demarcated
Nodularity

Thickened skin
Margins sharply
demarcated
 Graves’ Ophthalmopathy

• Class one: spasm of upper

lids with thyrotoxicosis
• Class two: periorbital edema
and chemosis
• Class three: proptosis
• Class four: extraocular
muscle involvement
• Class five: corneal
involvement
• Class six: loss of vision due
to optic nerve involvement
 Tanda-tanda mata pada tirotoksikosis :
Joffroy’s sign : kening tidak berkerut bila pasien
disuruh mengikuti gerakan tangan
pemeriksa dari bawah ke atas
Von Graefe : penutupan palpebra lambat bila pasien
disuruh mengikuti gerakan tangan
pemeriksa dari atas ke bawah
Mobius : kedua bola mata tidak bisa
konvergensi bila pasien disuruh
menatap jari tangan pemeriksa
Stellwag : mata jarang berkedip bila pasien
menatap kedepan
Dalrymple : retraksi kelopak mata atas
Rosenbach : tremor bola mata bila mata ditutup
 DIAGNOSTICS

• Endocrine Testing
– Total T4: 5-10% will be normal
– Total T3: 30% will be normal
– Free T4: false negative with NTI and
shipping
– fT4 better
– T3 supression
– TRH stimulation and TSH response
 INDEKS WAYNE
Gejala :
Sesak kalau bekerja………..+3 Keringat banyak……………….+3
Palpitasi……………………….+2 Selera makan bertambah…...+3
Lelah (tiredness )…………...+2 Selera makan berkurang……...-3
Suka suasana panas……….. -5 Berat badan menurun….……..+3
Suka suasana sejuk…………+5 Berat badan meningkat….…….-3
Suka panas/dingin…………....0 Cemas (nervousness)………...+2
Kelainan klinis : Ada Tak ada
Kelenjar tiroid teraba +3 -3
Bruit di atas tiroid +2 -2
Exoptalmus +2 0
Retraksi kelopak mata +2 0
Lid lag +1 0
Gerakan berlebih +4 -2
Tremor halus jari-jari +1 0
Tangan (telapak) panas +2 -2
Tangan (telapak) lembab +1 -1
Tanda :
Ada kacau serambi ………………………..+4
Teratur kurang dari 80x/menit …………………………-3
Teratur 80-90xd/menit ………………………… 0
Teratur > 90x/menit …………………………+3

Penilaian :
Skor  +19 ( tirotoksikosis )
Skor +11 smp +18 (kemungkinan tirotoksikosis)
Skor  +10 ( eutiroid )
 INDEKS NEW CASTLE

Umur mulai dikenai 15-24 th 0

25-34 th +4
35-44 th +8
45-54 th +12
55 th dst +16
Pencetus psikologis Dijumpai -5
Tak dijumpai 0
Sering memeriksakan diri Ada -3
Tak pernah 0
Kecemasan hebat Ada -3
Tak ada 0
Selera makan bertambah Ya +5
Tidak 0
Gondok ( goiter ) Ada +3
Tak ada 0
Bising pembuluh tiroid Ada +18
Tak ada 0
Exoptalmus Dijumpai +9
Tak dijumpai 0
Retraksi kelopak mata Dijumpai +2
Tak dijumpai 0
Hiperkinesia Dijumpai +4
Tak dijumpai 0
Tremor halus jari-jari tangan Dijumpai +7
Tak dijumpai 0
Frek denyut nadi radialis >90x/mnt +16
80-90x/mnt +8
< 80x/mnt 0

Penilaian : Skor > 40 (hipertiroid)

Skor +24 smp +39 (meragukan)
Skor -11 smp +23 (eutiroid )
 2. Toxic Multinodular Goiter

• More common in places with lower iodine

intake
– Accounts for less than 5% of thyrotoxicosis cases
in iodine-sufficient areas
• Evolution from sporadic diffuse goiter to toxic
multinodular goiter is gradual
• Thyrotropin receptor mutations and TSH
mutations have been found in some patients
with toxic multinodular goiters
• Th/ Surgery or 131I is recommended treatment
Braverman LE, et al. Werner & Ingbar’s The Thyroid. A
Fundamental and Clinical Text. 8th ed. 2000.
 Toxic Multinodular Goiter

• MNG is an enlarged thyroid gland containing

multiple nodules
– The thyroid gland becomes more nodular with
increasing age
– In MNG, nodules typically vary in size
– Most MNGs are asymptomatic
• MNG may be toxic or nontoxic
– Toxic MNG occurs when multiple sites of autonomous
nodule hyperfunction develop, resulting in
thyrotoxicosis
– Toxic MNG is more common in the elderly
 3. Toxic Adenoma

• Autonomously functioning thyroid

nodule hypersecreting T3 and T4
resulting in thyrotoxicosis (Plummer’s
disease)
• Almost never malignant
• Manage with antithyroid drugs followed
by either I-131 or surgery
 Laboratory Testing in Thyroid
Disease
• TSH:
– Pituitary hormone which stimulates thyroid
– May rise transiently in recovery from other illness
• Free T4:
– direct measure of thyroxine activity
– May be transiently suppressed in severe acute
illness
• Free T3: suspect hyperthyroid but normal FT4
• Thyroid peroxidase/thyroperoxidase antibody:
– Anti-TPO
– High levels in Hashimoto’s (95%) & Graves
– TSH receptor stimulating Ab measures activity in
Graves-use in pregnancy
 Scans/Ultrasound

• Radioiodine uptake (RAIU)

• Thyroid Scan
• Ultrasound
• Fine needle Aspiration
Treatment of Hyperthyroidism
1. Antithyroid drugs

2. Surgical resection

3. Radioactive iodine therapy

Braverman LE, et al. Werner & Ingbar’s The Thyroid. A

Fundamental and Clinical Text. 8th ed. 2000.
 1. Antithyroid Drug Therapy
• Acute hyperthyroid symptoms
• Goal of therapy:
– Inhibit peripheral conversion of T4 to T3
– Inhibit synthesis and release of T4 and T3
from thyroid gland
• Propylthiouracil (PTU)
• Methimazole
 Antithyroid Drug Therapy
• A. PTU:
– Inhibits peripheral conversion of T4 to T3
– Inhibits thyroid hormone synthesis and
release from thyroid gland
• B. Methimazole [generic]:
– Inhibits thyroid hormone synthesis and
release from thyroid gland
PTU:
- As immunosuppressive : ↓ TSHR-Ab (Stim)
concentration
- Inhibits peripheral conversion of T4 to T3
- Inhibits thyroid hormone synthesis and release
from thyroid gland

Methimazol :
Inhibits thyroid hormone synthesis and release
from thyroid gland
 Side Effects of PTU

- Allergy ( rash )  5%  antihistamine

- Agranulositosis 0,5% ( nasopharingitis,
fever, leucopenia, ↑ granulocyte ) 
* stop antithyroid drugs
* antibiotic
* shift to other antithyroid therapy
- Cholestatic jaundice
- Angioneurotic oedema
- Hepatocelluler toxicity
- Acute artralgia
 Choice of Antithyroid Drugs
Started with large divided dose → when patient
become clinically euthyroid → maintenance
therapy with lower single morning dose.

• MMI : 5 & 10 mg
/tablet
• Need < tablet MMI • PTU : 50 mg /tablet
• Initial dose : 20-40 • Need > tablet PTU
mg/day • Initial dose : 100/day
• Almost patients : • Devided dose
– Once daily
– Small dose
• C. Beta-blocker therapy:
– Ameliorates tachycardia, sweating,
tremor, nervousness, HT, AF
– ↓ T3 concentration in serum
– Propanolol:
* starting dose 10-40 mg PO q6h
* can be give 20-80 mg every 6-8
hours
– Caution in patients with :
* CHF
* bronchospasm
 Total Block Therapy

• Methimazole untill euthyroid ( 3-6 months ) 

then added levothyroxine 0,1 mg/day  than
continue methimazole 10 mg/day + levothyroxine
0,1 mg/day 12-24 months  then stop
methimazole at that time or if the size of the
gland is return to normal

• Aim : to prevent the development of hypothyroid

• But incidence of relaps is about the same as after

treatment with methimazole alone.
 Sustain Remission

May be predicted in about 80 % of treated

patient in the following circumstance :
• if the thyroid gland returns to normal size
• if the disease can be controlled with a
relative low dose of antithyroid drugs
• if THSR-Ab ( stim) is no longer detectable
in serum
 2. Subtotal Thyroidectomy

• Surgical complications:
– Vocal cord paralysis (1%)
– Hypothyroidism (up to 43% after 10 years)
– Hypoparathyroidism
– Recurrence of hyperthyroidism (10-15%)
 3. Radioactive Iodine 131[I]

Ablation
• Treatment of choice in patients > 21
years old with Graves’ Disease
• Treatment of choice in patients < 21
years old without remission after
antithyroid drug therapy
• Treatment of choice in patients with
toxic multinodular goiter or toxic thyroid
adenoma
 Radioactive Iodine Ablation (cont’)

• Single dose of 131[I] orally

• 80% euthyroid after single dose
• > 50% of patients will develop
hypothyroidism
– Assay TSH every 3 months after therapy
 Radioactive Iodine Ablation (Cont’)

• Levothyroxine therapy when patient

becomes hypothyroid
• Life-long Levothyroxine therapy
• RIA contraindicated in pregnancy,
lactation, iodine allergy
– Screen pre-menopausal women for
pregnancy prior to treatment
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