The basics - Hyperthyroidism

There are a number of causes for excess secretion of thyroid hormones.

Goitre is fuelled by either iodine deficiency or by dietary goitrogens
Goitre is fuelled by either iodine deficiency or by dietary goitrogens

Hyperthyroidism is defined as the excess secretion of thyroid hormones (T4 and T3) due to thyroid overactivity.

Thyrotoxicosis is the term used for the resulting clinical state, whether due to thyroid overactivity or otherwise. It is caused by a number of clinical conditions, the most important of which are discussed here.

T4 and T3 are normally produced in response to the anterior pituitary released TSH. A raised T4 and T3 with a low TSH is typical of hyperthyroidism.

Variants of this include subclinical hyperthyroidism (TSH low, T4 and T3 normal) and T3-toxicosis (TSH low, T4 normal, T3 high). A raised T4 with a raised TSH implies secondary hyperthyroidism.

Prevalence
The prevalence of overt hyperthyroidism in the UK is 1.9 per cent in women and 0.16 per cent in men. Subclinical disease is slightly more common, at 2 per cent in adults and 3 per cent in patients over 80.

The rate of progression from subclinical disease to overt disease is low, with a rate of 1.5 per cent per year in women and a negligible rate in men.

Presentation
Left untreated, hyperthyroidism can present with a wide range of signs and symptoms from sympathetic activation (tremor, sweating, heat intolerance and so on), and cardiovascular symptoms (tachycardia, AF, dyspnoea) to oligomenorrhoea and eye symptoms in Graves' disease.

In pregnant women, hyperthyroidism can lead to increased risk of miscarriage, eclampsia, premature labour, low birthweight and neonatal thyrotoxicosis. Rarely, when combined with stress (for example in childbirth, surgery or diabetic ketoacidosis) a thyrotoxic storm can be precipitated. This is a medical emergency, with a mortality of 20-30 per cent.

Symptoms include hyperpyrexia, tachycardia, abdominal symptoms and confusion.

Graves' disease
The most common cause (50-60 per cent of cases) of hyperthyroidism is Graves' disease. Graves' is an autoimmune condition where antibodies are directed against the TSH receptor mimicking the effects of TSH, stimulating growth and causing the classic triad of hyperthyroidism, diffuse goitre and eye symptoms (in 25-50 per cent of patients).

Spontaneous remission can occur but only in approximately 10 per cent of patients with Graves' disease and may not be sustained.

Toxic multinodular goitre
The second most common cause in the UK is toxic multinodular goitre, which is usually a progression from long-standing diffuse goitre. Goitre is fuelled either by subtle defects in hormone synthesis or by iodine deficiency and secondary TSH stimulation directly by dietary goitrogens.

Goitrogens are found in vegetables of the Brassica family (such as broccoli, cabbage and kale) and other plants such as cassava and maize.

Rapidly growing tissue undergoes infarction and scarring giving rise to the multinodular appearance. The nodules then become autonomous due to a TSH receptor mutation and hence become toxic or excessively hormone secreting.

Thyroid adenoma
Around 5 per cent of cases are due to thyroid adenomas, which show up as a single toxic thyroid nodule.

In most cases thyroid adenomas present as a painless lump in the thyroid and usually patients are euthyroid. Toxic adenomas are the exception.

Thyroiditis
Thyroiditis, the fourth main cause, can be triggered by a variety of causes. It can occur postpartum, secondary to possible viral infection (de Quervain's), post radio-iodine treatment and infarction of an adenoma.

Usually it is subacute or transient in nature and self-resolving. Patients with persisting disease will require specialist management.

Other causes
Other causes of hyperthyroidism occur after exposure to excess iodine, drugs such as amiodarone, lithium and interferon.

Amiodarone-induced hyperthyroidism is mediated either through its high iodine content (type-1) or a direct toxic effect on the thyroid (type-2).

Rare causes of hyper- thyroidism include metastatic thyroid cancer, ovarian teratomas and thyroid hormone resistance syndrome. Pituitary adenomas and pregnancy through the direct thyroid-stimulating effect of human chorionic gonadotrophin can cause secondary hyperthyroidism.

Patients taking too much replacement thyroxine can also cause iatrogenic hyperthyroidism.

Subclinical disease
Subclinical hypothyroidism has a low rate of progression to frank disease but the risk is increased in the presence of multinodular goitre or a functioning solitary nodule, especially when exposed to high iodine concentrations.

Patients should have TFTs monitored six- to 12-monthly.

Persistent subclinical disease in the presence of a goitre should be referred.

Screening
Routine screening is not recommended. Instead, a targeted approach is recommended with testing for TSH and FT4 (FT3 when the TSH is low) in cases of goitre, menstrual problems, subfertility, AF, osteoporosis, and both type-1 (annually) and type-2 diabetes (on presentation).

Positive TPO-Ab titre is a risk factor for thyroid dysfunction in patients starting amiodarone or lithium or patients with type-1 diabetes. A positive result is suggestive of Graves' disease.

Where a swelling is present an ultrasound of the gland and a combination of thyroid radio isotope scans, fine needle biopsy and CT or MRI may be required to rule out malignancy.

Screening is also recommended in women with a goitre who are considering pregnancy and in those with a positive family or personal history of thyroid disease.

Regular checkups are recommended for patients who have undergone treatment for hyperthyroidism (especially those who have had a partial thyroidectomy) looking for recurrence, untreated subclinical hyper-thyroidism and drugs associated with thyroid disease.

Treatment
The aim of curative treatment is to restore normal thyroid function. The chief options are antithyroid drugs, radioactive iodine therapy and surgery.

Patients who are severely unwell should be admitted immediately, while those with less severe symptoms can be started on beta-blockers or diltiazem where contraindicated, until they see a specialist.

Initiation of carbimazole or propylthiouracil can be made with specialist advice.

Ophthalmopathy due to Graves' disease should be referred to secondary care. Red flags indicative of optic nerve compression due to Graves' include unexplained deterioration in vision, change in quality of colour vision in one or both eyes and papilloedema.

All pregnant women with pre-existing or newly diagnosed disease should be referred for specialist management.

  • Dr Hashmi is a former GP in London working as a consultant in family medicine in Jeddah, Saudi Arabia

References

1. Clinical Knowledge Summaries. Hyperthyroidism. Available at www.cks.nhs.uk/hyperthyroidism

2. Lloyd RV (Ed). Endocrine Pathology: Differential Diagnosis and Molecular Advances. Totowa, NJ, Humana Press, 2003.

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