Thyrotoxicosis and Hyperthyroidism

Definitions

• Hyperthyroidism is release of excessive T3/T4 by the thyroid
• Thyrotoxicosis is toxicity due to excess T3/T4 from any source

Prevalence

• Prevalence of hyperthyroidism is 0.8% in Europe,and 1-3% in the USA

Causes

Graves Disease with goitre and eye signs

Clinical

• Weight loss, Heat intolerance, Increased sweating and warm skin
• Palpitations e.g. ectopics, AF, Resting tachycardia
• Anxiety and irritability, Fine tremor
• Diarrhoea and increased bowel frequency
• Proximal myopathy
• Grave's disease - eye disease, thyroid acropachy (rare, resembles clubbing) and eye disease (smokers) and pretibial myxoedema (thyroid dermopathy)

Investigations

• Raised Free T3 and Free T4 and Low TSH (All have Low TSH except the rare TSH-secreting pituitary adenoma.
• Mildly raised Calcium and Alkaline phosphatase
• Bone mineral density - Osteoporosis after many years
• Hypokalaemia Periodic paralysis (especially S.E. Asian)
• ECG shows AF - with risk of stroke ++
• Thyroid USS with doppler: provides information on thyroid size, echogenicity, presence/absence of nodules, and vascularization.
• Thyroid radioactive iodine uptake test: Graves disease would show diffusely increased uptake. However, RAI uptake would be normal or high with an asymmetrical and irregular pattern in a toxic multinodular goitre, and a localised and focal pattern in toxic adenoma, with suppressed uptake in the remaining thyroid tissue.
• TSH-receptor antibodies (TRAb; ie, thyroid-stimulating immunoglobulins, or thyroid-stimulating antibodies
• Antithyroid peroxidase (TPO) or antithyroglobulin antibodies may be increased in autoimmune thyroid disease and may be asociated with later hypothyroidism

Management

• If there are no contraindications a beta blocker such as Propranolol is started first for symptoms control. Propranolol has the added advantage of inhibiting T4 ? T3
• Carbimazole would be a very reasonable first agent to start once the biochemistry confirms the diagnosis. Other agents include propylthiouracil. In the US Methimazole would be the drug of choice. However, in the US, many patients first-line treatment would be radioactive iodine and beta-blockade for symptom control.
• There are 2 different schools of thought for medical treatment. One is to simply titrate those dose of carbimazole to try to render the patient euthyroid. The other is to give a higher dose of carbimazole to reduce and block endogenous T3/T4 production and simply to replace it with Thyroxine. This seems to have less rates of relapse when the carbimazole is stopped. Carbimazole is used for about 18 months. However, once euthyroid the patient can be referred for RAI
• The risk of agranulocytosis with carbimazole and propylthiouracil is 1/200 and CSM advice is clear and specific that written advice should be given and any patient with a fever or sore throat or other sign of infection needs an urgent check FBC.

Radioactive iodine

• Radioactive iodine is very effective and can be used in those of childbearing agent with certain precautions.
• However Pregnancy must be excluded before dosing and contraceptive advice is given.
• The patient should also not even be around children for some time after the RAI has been given.
• There are theoretical risks of malignancy if infant thyroid is exposed to radioactive iodine.
• There is a possibility of the patient become hypothyroid and needing long term Thyroxine.
• In those with Grave's disease RAI can worsen eye disease especially in smokers

Surgical

• Total thyroidectomy is recommended since the frequency of successful outcomes are significantly higher than with subtotal thyroidectomy in patients with large obstructing glands or glands containing nodules that are identified as malignant or equivocal on fine-needle aspiration.Before surgery, patients should be euthyroid or else are at risk of thyroid storm precipitated by surgery, and thyroid symptoms. There may be the removal of parathyroid glands with hypocalcaemia.

Pregnancy: Get specialist advice

• Pregnant women with severe hyperthyroidism, which is difficult to control with antithyroid drugs, can be treated with thyroidectomy during the second trimester in specialist centres.
• 1st Trimester: Propylthiouracil
• 2nd Trimester: Methimazole (Williams, 26th ed)

References

• NICE Hyperthyroidism Last revised in February 2020
• HyperthyroidismSimone De Leo#, Sun Y Lee#, and Lewis E Braverman