Graves Disease
- Most common cause of endogenous hyperthyroidism
- It is characterised by a triad of clinical findings;
- Hyperthyroidism due to a hyperfunctional diffuse enlargement of the thyroid
- Infiltrative ophthalmopathy with resultant exophthalmos
- Localised infiltrative dermopathy called pretibibial myxedema which is present in a minority of patients
- Peak incidence between age 20-40 F>M 7:1
- Affects around 1% of the population
- Genetic associations – linked with HLA-B8 and HLA-DR3. It is also associated with polymorphisms in CTLA-4.
Pathogenesis
- Autoimmune associated with autoantibodies, particularly those recognising the TSH receptor
- Different types of autoantibodies include;
- Thyroid stimulating immunoglobulin (TSI) – TSI is specific for
Graves disease - Thyroid growth stimulating immunoglobulin (TGI) – also directed against the TSH receptor. TGI is implicated in the proliferation of thyroid follicular epithelium
- TSH-binding inhibitor immunoglobulins (TBII) – block the binding of TSH to its receptor. These antibodies may be stimulating or inhibitory. Often both forms exist which may explain why
Graves patients can spontaneously develop periods of hypothyroidism
- Thyroid stimulating immunoglobulin (TSI) – TSI is specific for
- In
Graves ophthalmopathy the volume of the retro-orbital connective tissues and extraocular muscles increases due to; - Infiltration of the retro-orbital space my mononuclear cells predominantly T cells
- Inflammatory oedema and swelling of the extra-occular muscles
- Accumulation of extracellular matrix components especially hydrophilic GAGs
- Increased numbers of adipocytes
- May be due to orbital preadipocytes expressing the TSH receptor
- There is an increased susceptibility to develop other autoimmune diseases
Morphology
- Gland is normally symmetrically enlarged because of diffuse hypertrophy and hyperplasia
- Gland is smooth and soft and the capsule is intact
- Histologically the dominant feature is too many cells
- Lymphoid aggregates and germinal centres are common
Clinical course
- Diffuse enlargement is present in all cases of
Graves disease and may be accompanied by a bruit due to increased blood flow through the hyperactive gland - Sympathetic over activity produces a wide starring gaze and lid lag
- Exophthalmos is common and there may be weakness of the extraoccular muscles. It may persist despite treatment, resulting in corneal injury
- There nay be scaly thickening and induration of the skin of the shins. The skin might also be hyperpigmented
- Lab findings include elevated T3 and T4 and a depressed TSH
- Radioactive iodine uptake is increased
- Treatment is via;
- b-blockers
- Thionamides such as propylthiouracil
- Radioiodine ablation
- Surgical intervention
- b-blockers