Hyperthyroidism (Thyrotoxicosis)

Epidemiology:

• Common. Affects ~2-5% of all females at some time
• Women 5x more than men
• Nearly all cases (>90%) are caused by intrinsic thyroid disease; a pituitary cause is extremely rare

Common causes of hyperthyroidism:

• Grave’s disease
• Solitary toxic nodule/adenoma
• Toxic multinodular goitre
• Thyrotoxicosis factitia (secret T₄ consumption)
• Exogenous iodine
• Drugs (e.g. amiodarone)
• Metastatic differentiated thyroid carcinoma
• TSH-secreting tumours (e.g. pituitary)
• HCG-producing tumours
• Hyperfunctioning ovarian teratoma (struma ovarii)

Uncommon causes of hyperthyroidism:

Acute thyroiditis:

• Viral (De Quervain’s thyroiditis)
• Autoimmune
• Post-irradiation

Symptoms of hyperthyroidism:

• Weight loss (despite increased appetite)
• Restlessness
• Tremor
• Palpitations
• Heat intolerance
• Diarrhoea
• Muscle weakness
• Oligomenorrhoea
• Loss of libido

Signs of hyperthyroidism:

• Tachycardia
• AF
• Warm, vasodilated peripheries
• Pretibial myxoedema
• Exophthalmus
• Lid lag
• Goitre
• Proximal myopathy

Grave’s disease:

• Most common cause of thyrotoxicosis and is due to an autoimmune process
• Serum IgG antibodies bind to the thyroid TSH receptor and stimulate thyroid hormone production (i.e. behaving like TSH)
• Yersinia enterocolitco and Escherichia coli contain TSH-binding sites. It is believed that infection by these organisms may invoke some form of ‘molecular mimicry’ in a genetically susceptible individual and lead to the formation of autoantibodies
• Is also associated with other autoimmune diseases, such as:
• Pernicious anaemia
• Myasthenia gravis

• Natural history is one of fluctuation with many patients showing a pattern of alternating relapse and remission.
• ~40% of patients have a single episode
• Many patients eventually become hypothyroid

Toxic solitary nodule/adenoma (Plummer’s disease):

• Responsible for ~5% of cases of hyperthyroidism
• Does NOT usually remit after a course of antithyroid drugs

Toxic multinodular goitre:

• Commonly occurs in older women
• Again, usually does not respond to antithyroid drugs

De Quervain’s thyroiditis:

This is transient hyperthyroidism from an acute inflammatory process (presumed to be viral in origin)

Clinical features:

• Thyrotoxicosis
• Fever
• Malaise
• Pain in the neck
• Tachycardia
• Local thyroid tenderness

On investigation:

• Initial hyperthyroidism
• Raised ESR
• Thyroid uptake scans show suppression of uptake in the acute phase, although hypothyroidism (usually transient) may then follow after a few weeks)

Treatment of the acute phase is:

• Aspirin
• Short-term prednisolone (in severely symptomatic cases)

Investigating hyperthyroidism:

Serum TSH:

• Is suppressed in thyrotoxicosis (< 0.1mU/L)
• There are, however, rare instances of TSH hypersecretion leading to thyrotoxicosis

Most physicians also like to measure serum T₃ and T₄ levels. They will be elevated.

TSH receptor antibodies:

• Not measured routinely but are commonly present
• TSI 80% positive
• TBII 60-90% in Grave’s disease

Treatment:

There are 3 main options:

• Antithyroid drugs
• Surgery
• Radioiodine

Most patients (90%) with thyrotoxicosis have a diffuse goitre.

Those with large single or multinodular goitres are unlikely to remit after a course of antithyroid drugs. Severe biochemical hyperthyroidism is, also, less likely to respond.

Antithyroid drugs:

• Most commonly used antithyroid drug in the UK is carbimazole.
• Occasionally, propylthiouracil is also used
• The main action of these drugs is to inhibit the formation of thyroid hormones. They are also, to a lesser extent, immunosuppressants
• Although thyroid hormone synthesis is reduced very quickly, the long half-life of T₄ (~7 days) means that clinical benefit is not apparent for 10-20 days
• As many of the manifestations of hyperthyroidism are mediated via the SymNS, Β-blockers may be used to provide rapid, partial symptomatic control
• Β-blockers should not be used on their own to treat hyperthyroidism, except when the condition is self-limiting, as in subacute thyroiditis
• Approximately 50% of patients will relapse after withdrawal of the antithyroid medication

Antithyroid drugs – toxicity:

The major side-effect is agranulocytosis:

• Occurs in 1 in 1000 patients
• Usually within 3 months of treatment
• Patients should be warned to seek medical attention if they develop an unexplained fever or sore throat

If toxicity occurs with carbimazole, propylthiouracil may be used and vice-versa. Side-effects are only very rarely repeated with the other drug

Surgery – subtotal thyroidectomy:

• Should only be performed in patients who have already be rendered euthyroid
• Conventional practice is to stop the antithyroid drug 10-14 days before the operation and give potassium iodide (60mg TID), which reduces the vascularity of the gland

Particular indications for surgery include:

• Patient choice
• A large goitre, which is unlikely to respond to antithyroid medication

Indications for either surgery OR radioiodine include:

• Persistent drug side-effects
• Poor compliance with drug therapy
• Recurrent hyperthyroidism after drugs

Possible complications of the operation:

Early postoperative bleeding causing tracheal compression and asphyxia:

• Is a rare emergency
• Requires immediate removal of all clips/sutures to allow escape of the blood/haematoma

Laryngeal nerve palsy:

• Occurs in 1% of cases
• Vocal chord movement should be checked preoperatively
• Mild hoarseness is more common and thyroidectomy is best avoided in professional singers!

Transient hypocalcaemia:

• Occurs in up to 10% of cases
• Fewer than 1% of cases have permanent hypoparathyroidism

Recurrent hyperthyroidism:

• Occurs in 1-3% within one year, then 1% per year

Hypothyroidism:

• Occurs in ~10% of patients within one year, and the percentage increase over time
• It is likeliest if microsomal antibodies are positive

Radioactive iodine:

• ¹³¹I in an empirical dose (usually 200-500MBq) accumulates in the thyroid and destroys the gland by local radiation
• Takes several months to be fully effective
• Patients must be rendered euthyroid before treatment, although they must stop treatment at least 4 days before radioiodine, and not recommence until 3 days after radioiodine

Contraindicated in:

• Children
• Pregnancy
• Whilst breast-feeding

Early discomfort in the neck and immediate worsening of hyperthyroidism are sometimes seen:

• If this occurs, the patient should NOT receive carbimazole for 2-3 days after radioiodine, as it will prevent radioiodine uptake by the gland
• They should receive propranolol until carbimazole can be restarted as necessary
• Euthyroidism usually returns in 2-3 months

Apart from the immediate problems, as outlined above, a major complication is the progressive incidence of subsequent hypothyroidism affecting the majority of subjects over the following 20 years