Graves’s disease

Dr A Sibindlana
 Outline
• Background
• Causes
• Pathophysiology
• Diagnosis
• Management
• Prognosis
 Background
• Named after Robert J. Graves in the 1830s

• Other synonyms

• Autoimmune disease characterized by

hyperthyroidism, due to circulating auto-
antibodies

• Most common cause of hyperthyroidism

 Epidemiology
• Occurs primarily in younger adults

• Peak incidence between age 20-40

• More common in Whites/Asians than blacks

• M:F ratio = 3.5 : 1

 Epidemiology
• If left untreated, can cause severe thyrotoxicosis
• Thyroid storm can occur, in patients who have
unrecognized or inadequately treated thyrotoxicosis
• Superimposed precipitating event:
 thyroid surgery
 Non-thyroid surgery
 Infection
 trauma

This is NOT epidemiology

• Mortality rate ~20% with aggressive therapy
and early recognition of syndrome
• Graves’s disease associated with:
 ophthalmopathy
 dermopathy
 acropachy
• Leads to severe weight loss, with catabolism
of bone and muscle
• Cardiac complications: rhythm disturbances
such as:
– Extrasystolic arrthymia, Atrial fibrillation, flutter

• Pyschiatric manifestations: mood and anxiety

disorders
 Causes

• Exact cause is unknown

• Involve combination of genetic and environmental factors

• Genetic predisposition to TSH receptor activating antibody

• Genes involved include those for:

TG
Thyrotropin receptor
Protein tyrosine phosphate nonreceptor type22
Cytotoxic T-lymphocyte associated Antigen-4
Environmental factors:
Infectious trigger
• Viral or bacterial infection may trigger
antibodies which cross react with human TSH
receptor ( Antigenic mimicry)
• Stress

• Smoking

• Sudden increase in iodine uptake may

precipitate Graves disease
 Pathophysiology
• Body produces antibodies to TSH receptor
• Antibodies to TG,T3 &T4 may also be produced
• Antibodies cause hyperthyroidism, they bind to
TSH-receptor and stimulate it
• TSH-receptor expressed on the follicular cells of
thyroid gland
• Result of stimulation is abnormal high
production of T3 & T4
Pathophysiology
• Causes clinical symptoms of hyperthyroidism
• Enlargement of the thyroid gland visible as
goiter
• Infiltrative exophthalmos:
Thyroid gland and extraocular muscles share a
common antigen , recognized by antibodies.
Antibodies binding to extraocular muscles cause
swelling behind the eyeball
Orange peel: infiltration of antibodies to the
skin, causing inflammatory reaction and fibrous
plaques
• 3 types of autoantibodies:
 TSIgs: Antibodies act as long-acting thyroid
stimulants.
Activating cells in a longer and slower way
than TSH
Leading to elevated production of thyroid
hormone
Thyroid growth Igs:
Abs bind directly to TSH receptor and implicated
in the growth of thyroid follicles

Thyrotropin binding-inhibiting Igs:

Abs inhibit normal union of TSH with its
receptor
• Bone loss from osteoporosis:
Caused by increased excretion of calcium and
phosphorus in the urine & stool
 Diagnosis
• Characteristic signs:
Rapid heart beat (80%)
Diffuse palpable goiter with audible bruit
(70%)
Tremor (40%)
Exophthalmos (periorbital edema 25%)
Fatigue
Weight loss
• Heat intolerance (55%)
• Tremulousness (55%)
• Palpitations
• 2 truly diagnostic signs:
 exophthalmos
 Non-pitting edema
• Biochemistry: -increased free T3 & T4
- TSH undetectable
 Management
• Antithyroid drugs
• RAI (I-131)
• Thyroidectomy: Prior to thyroidectomy, preop
treatment with antithyroid drugs to render
patient euthyroid
• Antithyroid drugs given for 6 month- 2yrs to be
effective
• Risk of recurrence is 40-50%
• Lifelong treatment with antithyroid drugs:
agranulocytosis and liver disease
• RAI: Rationale
• Contraindications:
Absolute (Pregnancy)
Relative (Ophthalmopathy)
• Disadvantage: high incidence of
hypothyroidism ( up to 80%): require thyroid
hormone supplement (pills)
• Beta blockers: Propranolol: inhibit
sympathetic nervous system until antithyroid
treatment start to take effect
 Role of Nuclear Medicine

• Diagnosis:
– Thyroid uptake
– Thyroid scintigraphy

• Treatment:
– Radioactive iodine
• You might need to mention when each
treatment option is favoured over the other.

• Also, maybe a little more on RAI in Graves’

disease
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