From the Guidelines
Graves' disease is an autoimmune disorder that causes hyperthyroidism due to abnormal stimulation of the thyroid gland, resulting in excessive production of thyroid hormones, which can lead to increased heart rate, tremor, and nervousness, as seen in patients with thyrotoxicosis or symptomatic hyperthyroidism 1. The condition occurs when antibodies called thyroid-stimulating immunoglobulins (TSIs) bind to thyroid-stimulating hormone (TSH) receptors on the thyroid gland, mimicking TSH and causing excessive production of thyroid hormones.
- Key features of the disease include:
- Excessive production of thyroid hormones
- Increased heart rate and tremor
- Nervousness and other symptoms of hyperthyroidism
- Potential for reduced systemic vascular resistance associated with the hormonal disease
- Inhibition of the peripheral conversion of T4 to the more biologically active hormone, T3, by beta-blockers like propranolol 1 This overproduction leads to the classic symptoms of hyperthyroidism including weight loss, rapid heartbeat, anxiety, heat intolerance, and tremors.
- The disease also has unique features including:
- Exophthalmos (bulging eyes)
- Pretibial myxedema (skin thickening) The underlying pathophysiology involves a breakdown in immune tolerance, with genetic factors playing a significant role, and environmental triggers like stress, infection, or pregnancy can precipitate disease onset in genetically susceptible individuals.
- The thyroid gland typically becomes enlarged (goiter) due to hyperplasia of follicular cells, and blood tests typically show elevated free T3 and T4 levels with suppressed TSH levels, and the presence of TSI antibodies confirms the diagnosis 1. Treatment options include anti-thyroid medications, radioactive iodine therapy, or thyroidectomy, with the goal of reducing thyroid hormone production and managing symptoms, and beta-blockers like propranolol may be used to treat the increased heart rate and tremor associated with the disease 1.
From the Research
Pathophysiology of Graves' Disease
- Graves' disease is an autoimmune disease that primarily affects the thyroid gland, causing hyperthyroidism due to autoantibodies to the thyroid-stimulating hormone receptor (TSHR) that act as agonists and induce excessive thyroid hormone secretion 2.
- The pathophysiology of Graves' disease involves the synergism of insulin-like growth factor 1 receptor (IGF1R) with TSHR autoantibodies, causing retro-orbital tissue expansion and inflammation, leading to Graves' orbitopathy (GO) and pretibial myxoedema 2.
- The aetiology of Graves' disease remains unknown, but evidence indicates a strong genetic component combined with random potential environmental insults in an immunologically susceptible individual 2.
Hyperthyroidism in Graves' Disease
- Hyperthyroidism is an excessive concentration of thyroid hormones in tissues caused by increased synthesis of thyroid hormones, excessive release of preformed thyroid hormones, or an endogenous or exogenous extrathyroidal source 3.
- The most common causes of an excessive production of thyroid hormones are Graves' disease, toxic multinodular goiter, and toxic adenoma 3.
- Hyperthyroidism caused by overproduction of thyroid hormones can be treated with antithyroid medications, radioactive iodine ablation of the thyroid gland, or surgical thyroidectomy 3, 4.
Treatment and Management
- The treatment of Graves' disease has not changed substantially for many years and remains a choice between antithyroid drugs, radioiodine, or surgery 2, 4.
- Antithyroid drug use can cause drug-induced embryopathy in pregnancy, radioiodine therapy can exacerbate GO, and surgery can result in hypoparathyroidism or laryngeal nerve damage 2, 4.
- Pretreatment with antithyroid drugs before radioactive iodine therapy does not interfere with the final outcome, and similar cure rates and time required to achieve hypothyroidism after radioiodine were observed when patients were pretreated with methimazole compared to non-pretreated patients 5, 6.