Introduction

What is thyrotoxicosis?

Thyrotoxicosis refers to the signs and symptoms caused by having excessive amounts of thyroid hormone acting in the body.¹ Thyrotoxicosis is a common endocrine condition affecting approximately 2% of UK women, 0.2% of men (with those aged 20 to 50 years most commonly affected) and 1 to 2 children per 10,000.^1,7

The thyroid gland is an endocrine gland found in the front of the neck and is responsible for the production and secretion of two hormones: triiodothyronine (T3) and thyroxine (T4). Thyroid hormones T3 and T4 have many functions, including regulating metabolism, heart rate, body temperature, muscle contraction and growth.^2,3 

The release of thyroid hormones is controlled by the hypothalamic-pituitary-thyroid axis, a self-regulating system which maintains homeostasis; it involves the hypothalamus, the pituitary gland and the thyroid gland working together to coordinate the release of hormones.³

The thyroid gland can be overactive and underactive, leading to hyperthyroidism and hypothyroidism, respectively. While hyperthyroidism and thyrotoxicosis seem similar, hyperthyroidism is essentially a subset of thyrotoxicosis specifically caused by the thyroid gland producing too much thyroid hormone. In contrast, thyrotoxicosis refers to the clinical manifestations caused by too much thyroid hormone and can be a result of several different conditions.^1,2,4,5

What causes thyrotoxicosis? 

Thyrotoxicosis is most commonly caused by Graves’ disease and toxic nodular goitre but can also be caused by thyroiditis, ingestion of thyroid hormone, different types of adenomas and cancers and medication containing iodine.^1,6,9 

Importance of accurate diagnosis

It is essential to determine the cause of thyrotoxicosis in order to select the right therapy/medication and treat it appropriately. Determining the cause of thyrotoxicosis involves considering the signs exhibited and the symptoms experienced, as well as diagnostic tests and imaging techniques.⁸

Clinical presentation of Thyrotoxicosis

The symptoms of thyrotoxicosis you may experience include:⁹

• Palpitations 
• Increased appetite 
• Diarrhoea 
• Heat intolerance 
• Neck swelling 
• Poor concentration 
• Muscle weakness

Signs of thyrotoxicosis that your doctor may observe include:⁹

• Weight loss
• High heart rate (tachycardia) 
• High blood pressure (hypertension)
• Goitre 
• Lid lag (slow movements of eyelids compared to the eyes)
• Tremor 
• Hair loss 

Diagnostic approach

Patient history and physical exam

During your appointment, a healthcare professional will ask questions about you, the symptoms you have experienced, the medication you take and your past and family medical histories.⁷ They will also conduct a physical exam, during which they will look out for the aforementioned signs and symptoms. The information they gather during the consultation and physical exam helps determine which tests they need to conduct to help diagnose thyrotoxicosis and its cause. 

Key blood tests for Thyrotoxicosis

Serum thyroid function tests

Serum thyroid function tests are blood tests that measure specific thyroid hormone levels within the blood. 

Thyroid-stimulating hormone

Thyroid-stimulating hormone (TSH) is produced and released from the pituitary gland. TSH stimulates the thyroid gland to produce thyroid hormones T4 and T3. Abnormal levels of TSH are an early sign of thyroid problems, so it is often the first hormone to be tested.^10,11 

The typical reference range of TSH for a healthy adult ranges from 0.4 milliunits per litre to 4.0 milliunits per litre.¹⁰ A normal level of TSH nearly always excludes the possibility of thyrotoxicosis, except in rare cases such as the presence of TSH-secreting pituitary adenomas.⁹ Low or undetectable (less than 0.01 milliunits per litre) TSH levels indicate thyrotoxicosis.⁹

If the TSH level is below the normal reference range, free T4 and free T3 levels are measured from the same blood sample.⁷

Free T4 and T3 

T4 is the main form of thyroid hormone found in the blood, and it is converted into T3 when it reaches specific organs and tissues. The term ‘free’ means the hormone is active, unbound and able to enter and affect tissues.¹²

The typical reference range of free T4 for a healthy adult ranges from 9.0 picomoles per litre to 25.0 picomoles per litre, while the typical reference range of free T3 for a healthy adult ranges from 3.5 picomoles per litre to 7.8 picomoles per litre.¹⁰

A diagnosis of overt hyperthyroidism is suspected if the TSH level is below the normal reference range and free T4 and/or free T3 levels are above the normal reference ranges.⁷ A diagnosis of subclinical hyperthyroidism is suspected if the TSH level is below the normal reference range and free T3 and free T4 levels are within the normal reference ranges.⁷

Additional blood tests 

The following blood tests may be conducted in addition to the aforementioned blood tests for specific scenarios, for example, if you are pregnant, if your doctor suspects you have Graves’ disease or to determine the particular cause of thyrotoxicosis.⁷

Thyroid antibodies

Antibodies are a type of protein that the immune system produces in response to antigens. Thyroid antibodies are made when an individual’s immune system mistakenly attacks the body’s thyroid cells and tissues, causing thyroid gland dysfunction. Graves’ disease and Hashimoto’s thyroiditis are types of autoimmune disorders that are caused as a result of thyroid antibodies.

A TSH receptor antibody (TRAb) blood test is used if you are pregnant or if your doctor suspects you have Graves’ disease. TRAbs are raised in Graves’ disease.^1,7,9

A thyroid peroxidase antibody (TPOAb) blood test may be requested if you are postpartum, and if your doctor suspects you have postpartum thyroiditis or Hashimoto’s thyroiditis. TPOAbs are raised in Hashimoto’s thyroiditis and occasionally raised in Graves’ disease.^1,7

A thyroglobulin antibody (TGAb) blood test may be requested if your doctor suspects you have Hashimoto’s thyroiditis. TGAbs are occasionally raised in Hashimoto’s thyroiditis.

Inflammatory markers 

Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are inflammatory markers that may indicate thyroiditis is the cause of thyrotoxicosis.⁷ 

Imaging tests

Thyroid ultrasound

If your doctor detects an enlarged thyroid or nodule(s) (lumps) during the physical examination, they will arrange for an ultrasound of the neck.⁷

Ultrasound uses sound waves to form an image of an organ. During a thyroid ultrasound examination, a small amount of gel is placed on the ultrasound transducer, which is then moved around the front of the neck. The ultrasound image will be analysed to see if the thyroid is enlarged, if there are any changes to the tissues and to find out more about the nodules.¹⁰

Radioactive iodine uptake and thyroid scintigraphy

Radioactive iodine uptake (RAIU) is an imaging technique that quantifies (measures) iodine metabolism in the thyroid gland. Thyroid scintigraphy detects abnormalities in the thyroid cells.¹⁴ 

The normal thyroid uptake of a radioactive iodine tracer is 3% to 16% at 6 hours and 8% to 25% at 24 hours.¹⁵ Destructive thyrotoxicosis (high levels of free T3 and T4 but low levels of TSH) is characterised by a low RAIU and scintigraphically reduced radiotracer activity. Conversely, productive thyrotoxicosis (that is, hyperthyroidism) is characterised by high RAIU and scintigraphically increased radiotracer activity, which can be localised (due to thyroid nodules) or widespread (for example, with Graves’ disease).^14,16

While thyroid scintigraphy imaging is not commonly used to diagnose thyrotoxicosis, it helps determine the cause of thyrotoxicosis if this is not established through the physical examination, medical history or laboratory tests.⁶

Advanced or confirmatory tests

Fine-needle aspiration

Fine-needle aspiration (FNA) biopsy is a procedure whereby a very small, hollow needle is inserted into the thyroid to remove cell samples to be tested. FNA can help determine if the thyroid tissue is inflamed or if nodules have become malignant.¹⁰

Summary

• Thyrotoxicosis refers to the signs and symptoms caused by having excessive amounts of thyroid hormones T3 and/or T4
• Thyrotoxicosis is primarily caused by Graves’ disease and toxic nodular goitre 
• Thyrotoxicosis can be diagnosed by considering findings of a physical examination, symptoms, past medical and family history, blood tests and imaging techniques
• Differing levels of T3, T4, and TSH can be used to distinguish between overt and subclinical hyperthyroidism, a subset of thyrotoxicosis 
• Tests for thyroid autoantibodies and inflammatory markers, in addition to radioactive iodine uptake and thyroid scintigraphy, can help determine the cause of thyrotoxicosis