Graves' disease

Any patient with a solitary nodule, a dominant nodule within the gland, with palpable lymph nodes or with any other suspicious features, requires urgent ultrasound guided aspiration.

Patients with suspected eye disease require evaluation by an endocrinologist or ophthalmologist experienced in Graves' ophthalmopathy. Patients should be reassured that treatment is available and is highly effective, and a detailed patient information sheet is available. Simple lubricants, avoidance of smoky environments, and avoidance of bright sunlight and strong winds by wearing sunglasses should be advised in all patients.

Patients with incomplete lid closure require taping at night to protect from corneal abrasion, and require rapid specialist ophthalmological assessment.

Patients with asymmetry, periorbital oedema and abnormalities of external ocular movements also require rapid assessment for consideration of steroid or other medical therapy.

Patients with reduced acuity require urgent assessment for the consideration of medical or surgical decompression. Radiotherapy may also be considered in the acute phase.

In stable disease, prism spectacles for diplopia, orbital muscle surgery, and reconstructive and corrective orbital and lid surgery are all also available and highly effective.

Smoking increases the risk and severity of ophthalmopathy.

It is standard practise to use propylthiouracil rather than carbimazole in patients who may be or are planning pregnancy.

Patients with uncontrolled thyrotoxicosis should be advised to avoid pregnancy until biochemical control is achieved due to the risk of miscarriage. Treatment during pregnancy requires close monitoring typically every six weeks.

Radioactive iodine is contraindicated in pregnant or breast feeding individuals. Women should be advised to avoid conception for six months and men should avoid fathering children for four months following radioactive iodine treatment.

Any patient with severe clinical or biochemical thyrotoxicosis requires immediate medical treatment, before long term decisions are taken, in line with national guidelines. However, the options of medical treatment, radioactive iodine and surgery should all be introduced at this stage.

All patients must receive verbal and written safety warnings regarding drug therapy.

Usual treatment starts with high dose carbimazole, for example 40-60mg daily, though lower doses may be appropriate in those with milder disease. Propyl thiouracil may be substituted in patients intolerant of carbimazole, using an approximate dose equivalence of 50mg propyl thiouracil for 5mg carbimazole.

Patients with tachycardia or other severe symptoms are also usually treated with beta blockade, for example propranolol 120-240mg daily in divided doses.

All patients should receive instructions as to the timing of dose reduction and firm arrangements made for serial monitoring. Typical monitoring intervals are every six weeks initially. There should be rapid dose reduction through 20mg, 15mg, 10mg to a maintenance therapy of 5mg, according to the early fall in T4 levels.

Once on maintenance doses, monitoring of TSH only is necessary, aiming for a detectable, normal TSH with complete resolution of symptoms. This is typically repeated every three months until the end of the treatment course.

Typical treatment course for Graves' thyrotoxicosis is 18 months. Monitoring is typically required every six weeks initially, and three monthly once patients are on a stable maintenance dose. 

All patients with auto-immune hyperthyroidism should be warned of a 50% chance of disease recurrence after their initial treatment course. Male patients, older patients, those with high antibody titres, those with previous episodes and those with severe biochemical disease are at the highest risk of future recurrence.

Dose titration may be inappropriate in certain circumstances, in which case high dose carbimazole is continued, with thyroxine added once the serum thyroxine falls to within the normal range.

Thyroxine dose should then be adjusted according to symptoms and aiming for a normal serum TSH level.

It is usual to start medical treatment at presentation particularly in those with severe biochemical disease in order to allow them to make an informed decision regarding long term management. Written information about radioactive iodine and other treatments should also be given to the patient to consider before making a decision.

Radioactive iodine is highly effective at rendering patients euthyroid, usually after one treatment, and offers the advantage of preventing future recurrence. It is therefore particularly suitable for patients with relapsed Graves' disease, or those at high risk of recurrence for example male patients, those with severe biochemical disease, or those with high antibody titres.

Patients must be warned about standard radioactive iodine precautions. Patients should also be warned that transient thyroid swelling may occur, that repeat applications may be necessary, that long term monitoring is required, and that hypothyroidism requiring thyroxine replacement therapy is likely to ensue.

Radioactive iodine is absolutely contraindicated in pregnancy. Women should also be advised to avoid conception for six months, and men should avoid fathering children for four months following radioactive iodine treatment.

Radioactive iodine should be discussed with an experienced ophthalmologist in the case of severe eye disease. Mild to moderate eye disease does not preclude the use of radioactive iodine, but it is standard practise to render the patient euthyroid medically and wait for the eye disease to become quiescent first, and then to protect the eyes with glucocorticoid therapy to reduce the risk of exacerbation.

Typical doses would be prednisolone 30mg starting on the day of the treatment, continuing for 14 days, then reducing by 5mg every 14 days thereafter. This should be prescribed with bone protection, for example alendronate, calcium and vitamin D.

Thyroid function should be assessed at least every three months for the first year after radioactive iodine, and then annually thereafter for emerging hypothyroidism or for recurrent thyrotoxicosis.

Subsequent hypothyroidism should be treated conventionally.

Subsequent recurrence of hyperthyroidism should be treated with repeat application of radioactive iodine.

Annual monitoring of serum TSH levels is usually all that is required after treatment for Graves' disease. Patients should also be warned to report any symptoms suggestive of thyroid dysfuntion before this routine monitoring. Patients are also at increased risk of developing auto-immune conditions, however, routine surveillance is not usually required if all other baseline investigations were normal.

Surgery is no longer considered a first line treatment for Graves' disease as most patients prefer either a course of medical treatment or a one off treatment with radioactive iodine. However, in patients intolerant or unresponsive to medical treatments, and who decline or are unsuitable for radioactive iodine, surgery can provide an alternative highly effective treatment.

Generally, it is a straight forward and effective procedure, with a very low risk of complications such as hypoparathyroidism or recurrent laryngeal nerve damage. However, all patients must be warned that surgery does not offer a guaranteed cure of their thyrotoxicosis, that relapse is possible, and that subsequent hypothyroidism may ensue.