Graves’ Disease

Robert James Graves 1830

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Clinical Science
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 Definition
Graves’ disease merupakan gangguan autoimun berupa
peningkatan kadar hormon tiroid yang dihasilkan kelenjar tiroid.
Kondisi ini disebabkan karena adanya thyroid timulating antibodies
(TSAb) yang dapat berikatan dan mengaktivasi reseptor TSH
(TSHr).
Aktivasi reseptor TSH oleh TSAb memicu perkembangan dan
peningkakan aktivitas sel-sel tiroid menyebabkan peningkatan
kadar hormon tiroid melebihi normal.

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 Definition
Graves’ Disease (GD) is an autoimmune disease characterized by
hyperthyroidism, ophthalmopathy,and dermopathy. The thyroidal
component is driven by antithyrotropin receptor (TSHR)
antibodies.

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 America
﹡ Incidence- 30-200 new Epidemiology
cases per 100,000 per
year
Indonesia
﹡ Prevalence- 2.5 % of ﹡ 70-80% dari kasusu
women and 0.23% of
hipertiroidisme
men
﹡ 0.5% populasi dan
﹡ GD is distributed
sebagian besar diderita
relatively equally across
oleh wanita.
races and around the
globe
﹡ Most common cause of
hyperthyroidism in
iodine sufficient areas
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 Risk Factors
﹡ Genetic
﹡ Monozygotic twins (35%) have a greater
concordance rate than dizygotic twins (3%)
﹡ Susceptibility genes (CD40, CTLA-4,
PTPN22) have been associated with GD
﹡ Increased frequency of HLA DR3 and
DQA10501 haplotypes in GD

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 Risk Factors
﹡ Gender
﹡ Female to male ratio (8-10: 1)
﹡ Age
﹡ low incidence in childhood
﹡ Pregnancy
﹡ Environmental factors associated with GD
﹡ Infection
﹡ Stress (emotional or physical)
﹡ Medications • Iodine • Amiodarone
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 Symptoms
﹡ Irritability
﹡ A fine tremor
﹡ Sensitivity to heat
﹡ Weight loss
﹡ A rapid heartbeat
﹡ goiter, which is an
enlarged thyroid that
may cause the neck to
look swollen
﹡ Fatigue
﹡ Perspiration
﹡ Brittle hair
﹡ Light menstrual periods
﹡ Frequent bowel
movements  diarrhea

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 Pathogenesis
﹡ GD is an autoimmune disease in which host susceptibility
genes and environmental factors interact to initiate cellular
and humoral immune responses against host antigens
﹡ The TSH receptor (TSHR) is an autoantigen in GD.
﹡ anti-TSHR antibodies (IgG class) stimulate the TSHR
without modulation and cause hyperthyroidism

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 Diagnosis
﹡ Clinical • Goiter • Thyrotoxicosis
﹡ Symptoms • Ophthalmopathy • Dermopathy
﹡ Biochemical • TSH, T3, T4, TSI (thyroid
stimulating immunoglobulins)
﹡ Nuclear Medicine • % Thyroidal Iodine
uptake • Diffuse pattern of thyroidal uptake
(scan)

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 Treatments
﹡ Reversible • Thionamides* (PTU,
Methimzole) • B-blockers (Propranolol) •
Corticoteroids
﹡ Definitive • Radioactive iodine therapy •
Surgery

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 Farmakologies Treatment
Dosis awal :
﹡ PTU : 300-600mg/hari (3-4 kali sehari)
﹡ Methimazole : 30–60 mg/hari (3 kali sehari)
﹡ Carbimazole : 20-60 mg/hari (3 kali sehari)
Dosis pemeliharaan :
﹡ PTU 50-300 mg/hari, Methimazole 5-30 mg/hari, Carbimazole 5-
15mg/hari
﹡ Terapi obat antitiroid sebaiknya dilanjutkan sampai 12-24 bulan
untuk memicu remisi jangka panjang. Pasien sebaiknya diawasi tiap
6-12 bulan setelah remisi.

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 Farmakologies Treatment
﹡ Iodine (larutan potassium iodine) :
﹡ – dosis : 3-10 tetes (120-400mg) oral tiap 6 jam
﹡ – tiap tetes mengandung 38 mg Iodida atau 6,3 mg Iodida
dalam larutan Lugol
﹡ – Diberikan 1 jam setelah pemberian obat anti-tiroid
﹡ – Diberikan selama 7-14 hari pre operasi
﹡ Efek samping : reaksi hipersensitivitas, ‘iodisme’ (rasa
logam, mulut dan tenggorokan terbakar, nyeri pada gigi dan
gusi, terkadang gangguan perut dan diare), ginekomastia

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 Prognostic
﹡ Remission can occur after thionamide therapy
(12-18 months). Long term remission is rare
with high % per year recurrence after
discontinuation of thionamide therapy.
﹡ Severity of hyperthyroidism, goiter size,
higher T3, higher TSI are poor prognostic
features for achieving remission

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Graves Disease in
Pregnancy

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 Graves Disease in Pregnancy
﹡ Graves’ disease:
﹡ • is uncommonly diagnosed during pregnancy
﹡ • thyrotoxicosis often improves and autoimmune
phenomenon often remit during pregnancy
﹡ • commonly relapses or develops in the post-partum period
in susceptible hosts
﹡ High maternal TSI levels after 25 weeks of gestation are
associated with increased risk of antibody transfer to fetus
and the development of transient fetal thyroidal dysfunction

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TAO
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GD Associated Manifestations Thyroid
Associated Ophthalmopathy (TAO)
﹡ 20 % of patients with GD develop clinically
obvious opthalmopathy
﹡ Symptoms • Gritty, sandy sensation, Tearing •
Retrobulbar pain and discomfort • Diplopia •
Photophobia • Blurred vision

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 Treatment
﹡ General
﹡ • Local/ protective measures
﹡ • Tinted spectacle lenses
﹡ • Artificial tears/ointment
﹡ • Nighttime eye patch/taping lids
﹡ • Prisms
﹡ • Smoking cessation*

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 Treatment
﹡ Treatment of coexistent hyperthyroidism
﹡ Immunomodulatory (most effective in active
phase)
﹡ • Steroid Therapy : PO, IV
﹡ • Radiation Therapy
﹡ Surgery (three step-reserved for stable
disease) • Orbital decompression • Muscle
surgery • Eyelid surgery

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Dermophaty

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 Therapy
﹡ • Local application of corticosteroids
﹡ • Avoid trauma/biopsy
﹡ • Does not improve with correction of
hyperthyroidism

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Acropachy

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﹡ Acropachy Triad of:
﹡ • digital clubbing
﹡ • Soft tissue swelling of hands and feet
﹡ • Peri-osteal new bone formation

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 Sources
﹡ http://www.bartsendocrinology.co.uk/resources/Graves.pdf
﹡ http://
juke.kedokteran.unila.ac.id/index.php/medula/article/viewFile/158
2/pdf
﹡ https://
www.niddk.nih.gov/health-information/endocrine-diseases/graves-
disease
﹡ http://hmpd.fk.ub.ac.id/hipertiroid-thyrotoxicosis/
﹡ https://www.scribd.com/doc/97601064/Endokrin-Graves-Disease
﹡ https://emedicine.medscape.com/article/120619-treatment

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