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Chapter: Medicine and surgery: Endocrine system

Graves’ disease (primary thyrotoxicosis) - Thyroid axis

Graves’ disease is an autoimmune thyroid disease.

Graves’ disease (primary thyrotoxicosis)




Graves’ disease is an autoimmune thyroid disease.




Any. Peak 20–40 years.




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Graves’ disease results from production of an autoanti-body that binds to the TSH receptor and causes contin-uous gland stimulation.


·        Fifteen per cent of patients have a close relative with Graves’, and 50% of relatives have circulating thyroid autoantibodies.


·        Associated with HLA-B8 and DR3 in Caucasians, and with HLA-B17 in Blacks.


·        Environmental ‘triggers’ suggested: Pregnancy, iodide excess, infection.




Breakdown of self-tolerance results in the formation of stimulating autoantibody acting at the TSH receptor. This causes a generalised, uncontrolled stimulation of the thyroid gland initially causing hyperthyroidism. After many years the gland becomes non-functional and the patient becomes hypothyroid.


The thyroid antigen shares epitopes with antigens on the orbital muscles, so that cytotoxic T-cells attack these tissues causing them to swell. Other complications of Graves’ disease may also be due to similar epitopes being present in other tissues, e.g. skin and nail beds. These complications do not resolve on treatment to reduce the overactivity of the thyroid.


Some symptoms of Graves’ disease relate to apparent catecholamine (noradrenaline and adrenaline) excess, for example tachycardia, tremor and sweating. Thyroid hormones induce cardiac catecholamine receptors.

The autoantibody can cross the placenta, causing neonatal hyperthyroidism.


Clinical features


Hyperthyroidism produces palpitations, nervousness, fatigue, diarrhoea, sweatiness, tremor and intolerance of heat. Weight loss with increased or normal appetite and hyperactivity are common. There is often muscle weakness, which can be severe.


The patient may have noticed the neck swelling, which is usually soft, diffusely and symmetrically enlarged. Proptosis (exophthalmos) with lid retraction, stare and lid lag are prominent features, and in its most severe form it may cause sight loss due to damage to the optic nerve. Involvement of the orbital muscles may also cause diplopia.


Less common symptoms and signs include atrial fibrillation and heart failure, depression (see also Fig. 11.7). Thyroid dermopathy (also called pretibial myxoedema) is a thickening or ‘orangepeel appearance’ of the skin, most often affecting the lower leg. Onycholysis (weak-ening, thinning and broken nails) may occur. Thyroid acropachy (osteopathy), which is a form of clubbing, is rare and may be complicated by hypercalcaemia.




The thyroid epithelial cells are increased in number and size with large nuclei. The colloid in the centre of the follicle shows scalloped edges, which although an artefact of processing does seem to indicate increased removal of colloid for production of thyroxine. Focal lymphocyte infiltration may also be seen.




Thyroid function tests generally show high free triiodothyronine (T3) and usually thyroxine (T4), with a low thyroid-stimulating hormone (TSH). The diagnosis is made by a combination of clinical features and detection of thyroid autoantibodies.




Antithyroid drugs (usually carbimazole) are given to suppress the gland. Graves’ disease commonly enters remission after 12–18 months, so a trial of withdrawal is appropriate. Patients who are severely symptomatic with hyperthyroidism also benefit from β-blockers. Relapse is common (50%); treatment options include a second course of antithyroid drugs, radioiodine therapy or surgery. Subtotal thyroidectomy results in normalisation of thyroid function in 70%. Recurrence can be treated by further surgery. The patient must be made euthyroid before surgery with antithyroid drugs and β-blockers.




Thirty to fifty per cent of patients used to undergo spontaneous remission without treatment. Recurrence after treatment may be more likely in those with HLA association. Approximately 20% become hypothyroid with all types of treatment.

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