Graves' disease

An auto-immune condition characterised by thyrotoxicosis and ophthalmopathy, associated with auto-antibodies stimulating the TSH receptor. Diagnosis is often clinical, but the presence of antibodies may help confirm the cause of thyrotoxicosis.

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 Grave's thyrotoxicosis with hypokalaemic periodic paralysis. This is more common in people of Chinese ethnic origin.

Hyperkalaemia and hyponatraemia may occur in Addison's disease which may be associated with auto-immune thyrotoxicosis.

Liver function test

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

Bone profile

Useful indicator of general health and underlying disease.

Hypercalcaemia may occur with thyrotoxicosis and glucocorticoid deficiency.

9am cortisol

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

A synacthen test is required to formally exclude Addison’s, however, a 9am cortisol can be a useful screen. Levels below 250nmol/l demand thorough assessment, levels above 590nmol/l exclude glucocorticoid deficiency.

Thyroid stimulating hormone

A low thyroid stimulating hormone (TSH) confirms hyperthyroidism in suspected Graves' disease.

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. Elevated thyroxine with suppressed TSH confirms this to be due to 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 antibodies are commonly used as an initial screen and may be positive in patients with any autoimmune thyroid condition, with higher titres occurring 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 Graves' 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 or hypoglycaemia in established diabetes, may be an early sign of thyrotoxicosis.

Thyroid ultrasound scan

Ultrasound scan is not usually required in the assessment of Graves' disease, though may be helpful where the aetiology of thyroid dysfunction is unclear, for example between nodular goitre and Graves' disease, or if a nodule is palpated within the gland.

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

This must be performed if there is clinical or biochemical suspicion of Addison’s disease.

MRI orbits

The activity of Graves' ophthalmopathy can be difficult to assess. If in doubt, MRI scanning can confirm disease activity or quiescence and is also useful to asses disease severity.