Thyrotoxicosis or hyperthyroidism

Hyperthyroidism, or thyrotoxicosis, refers to thyroid overactivity of any cause. Diagnosis is often clinical, but antibody testing may help identify the cause.

Base investigations - all patients

Full blood count

Useful indicator of general health and underlying disease. 

Normocytic normochromic anaemia and eosinophilia may be seen with glucocorticoid deficiency.

Serum B12

B12 deficiency may indicate associated pernicious anaemia or coeliac disease.

Urea and electrolytes

Hypokalaemia may occur in association with thyrotoxicosis with hypokalaemic periodic paralysis, which is more common in people of Chinese ethnic origin.

Hyperkalaemia and hyponatraemia may occur in glucocorticoid deficiency.

Liver function test

Liver function should be tested at baseline before starting medical treatments.

Bone profile

Hypercalcaemia may occur with thyrotoxicosis and glucocorticoid deficiency.

9am cortisol

Addison's disease may be associated with auto-immune thyrotoxicosis. A 9am cortisol can be a useful screen, although a synacthen test is required to formally exclude this condition. Serum cortisol levels below 250nmol/l demand thorough assessment, levels above 590nmol/l exclude glucocorticoid deficiency.

Ensure patients have stopped sex steroid therapy, for example HRT or the combined oral contraceptive pill for six weeks prior to test.

Thyroid stimulating hormone

A low TSH confirms a clinical suspicion of hyperthyroidism.

TSH levels within the normal range imply normal thyroid function, except in those with potential pituitary disease, in whom a normal TSH may be seen with hypothyroidism.

Ideal treatment of thyroid disease is reflected by control of symptoms and a serum TSH in the middle of the reference range approximately 1mU/L.

Free thyroxine

TSH and free thyroxine should be tested together in all patients suspected of having thyroid dysfunction.

Elevated thyroxine implies hyperthyroidism of any cause. The level of this elevation is a useful indicator of disease severity.

Elevated thyroxine combined with suppressed TSH confirms the cause to be primary hyperthyroidism.

Electrocardiogram

ECG should be performed in all patients at baseline to document and confirm any arrhythmias or other changes.

Thyroid auto-antibody screen

There are multiple different tests available for thyroid auto-antibodies, with varying levels of sensitivity.

Thyroid peroxidise (TPO) antibodies are commonly used as an initial screen and may be positive in patients with any auto-immune thyroid condition. Higher titres occur in patients with Hashimoto’s thyroiditis and hypothyroidism.

TSH receptor stimulating antibodies occur specifically in Graves' disease, and may be particularly helpful in the assessment of pregnant patients.

Free liothyronine

Free liothyronine levels are not usually necessary for the assessment and treatment of thyrotoxicosis, though they may be useful if the TSH is suppressed and thyroxine level normal. The pattern of an elevated liothyronine, suppressed TSH, and normal thyroxine is known as 'T3 toxicosis', and is often seen with nodular thyroid disease.

Further investigations - selected cases only

HbA1c and fasting glucose

Patients with auto-immune thyroid dysfunction are at increased risk of developing diabetes mellitus.

Falling insulin requirements, hypoglycaemia or new weight loss may all be early signs of thyrotoxicosis or of Addison's disease in patients with established diabetes.

Thyroid ultrasound scan

Ultrasound scan may be helpful where the aetiology of hyperthyroidism is unclear, and nodular disease is suspected. This is not required in thyrotoxicosis with positive antibodies or eye signs as the diagnosis of Graves' disease is apparent.

Ultrasound scan is essential in the assessment of palpable thyroid nodules and to guide how, and whether, to perform fine needle aspiration.

Ultrasound scan with colour doppler flow may be useful in patients with thyrotoxicosis, who are taking amiodarone therapy to determine whether the gland is inflamed and so determine the best treatment approach (steroids or anti-thyroid drugs).

Bone densitometry

Bone mineral density should be assessed where there is clinical suspicion of osteoporosis, for example in some older patients with biochemical thyrotoxicosis.

Vitamin D levels

Patients with coeliac disease may well have low serum vitamin D levels.

In patients with known or suspected osteoporosis, serum vitamin D levels will guide whether routine calcium and vitamin D supplementation is enough, or whether specific high dose vitamin D replacement is required.

Thyroid radionucleide uptake scan

This is useful in patients with acute thyrotoxicosis to help distinguish between Graves' disease, in which case the whole gland will have increased uptake, or viral or other forms of thyroiditis, in which case the gland will not take up iodine.

Coeliac auto-antibody screen

Tissue transglutaminase and anti gliadin antibodies should be checked if there is clinical suspicion of coeliac disease.

Short synacthen test

A short synacthen test must be performed if there is clinical or biochemical suspicion of Addison’s disease.

Ultrasound guided fine needle aspiration

Fine needle aspiration should be performed on any suspicious nodules. Ultrasound scanning improves the safety and efficacy of this procedure.