What is subclinical thyroid disease?

Subclinical thyroid disease is often referred to as borderline thyroid disease. This can indicate either mild thyroid failure (subclinical hypothyroidism) or mild thyroid overactivity (subclinical hyperthyroidism).

How is it detected?

Many patients with subclinical thyroid disease will have no symptoms. Doctors will not routinely screen for it in healthy people without symptoms. Often, it is only picked up as a result of blood screening for other conditions or because there is a family history of thyroid disorders. Typically, blood tests will detect either raised or low levels of Thyroid Stimulating Hormone (TSH) levels, with normal levels of thyroid hormone thyroxine (T4).

Does it require treatment?

Generally, doctors will adopt a ‘wait and see’ approach in patients with subclinical thyroid disease to avoid unnecessary treatment. This is because blood TSH levels restore themselves to normal in around half of patients over time. There is also little current clinical evidence to suggest treatment offers any long-term benefit for patients with subclinical thyroid disease. However, where it is clear there may be underlying thyroid disease, or that you may benefit, then doctors may offer treatment.

Content overview

Subclinical hypothyroidism (borderline underactive thyroid)

What are the symptoms

How is it monitored?

In what circumstances is subclinical hypothyroidism treated?

Causes

Subclinical hypothyroidism in older people

Subclinical hypothyroidism in people with increased body weight

Subclinical hypothyroidism and pregnancy

Subclinical hyperthyroidism (borderline overactive thyroid)

What are the symptoms?

How is it monitored?

In what circumstances is subclinical hyperthyroidism treated?

Causes

Subclinical hyperthyroidism and pregnancy

Other reasons for abnormal thyroid function results

Subclinical hypothyroidism (borderline underactive thyroid)

Subclinical hypothyroidism is also known as mild hypothyroidism or borderline hypothyroidism. It is typically defined by a slightly raised TSH level that is higher than the laboratory reference ranges and less than 10 mU/l with normal levels of T4. It is a common condition and it occurs more frequently in women and as we age. If you have subclinical hypothyroidism you will sometimes have no obvious symptoms and the diagnosis is only picked up as a result of blood tests for an unrelated condition, or because you have a family history of thyroid disorders. It may be tested for if you have non-specific symptoms. If you have subclinical hypothyroidism you will usually be tested for thyroid peroxidase antibodies (TPOAb) to establish whether the underlying cause is autoimmune hypothyroidism (Hashimoto’s thyroiditis).

What are the symptoms?

Most people will have subclinical hypothyroidism detected for unrelated symptoms. Even when some people may have symptoms of an underactive thyroid it is difficult to be certain if the symptoms are related to the thyroid. This is because the symptoms of an underactive thyroid are vague and could be related to many other conditions. For example, fatigue or weight gain could more likely be due to lifestyle or other common conditions than thyroid disease. The most common symptoms of an underactive thyroid are:

• Fatigue and tiredness
• Increased awareness of the cold
• Dry and coarse skin
• Dry and thinning hair
• Hoarse or croaky voice
• Slight weight gain
• Constipation
• Muscle weakness, cramps and aches
• Pins and needles in the fingers and hands (carpal tunnel syndrome)
• Heavier and longer periods
• Fertility problems
• Low libido
• Puffy face and bags under the eyes
• Slow speech, movements and thoughts
• Low mood or depression
• Memory problems
• Difficulty in concentration
•  Slow heartbeat
• Slightly raised blood pressure
• Raised cholesterol
• Slow growth (in children)

How is it monitored?

Subclinical hypothyroidism can be an indicator that you may go on to develop (full) hypothyroidism, especially if the TSH level is quite raised or if TPOAb are positive.

Your doctor will usually monitor your thyroid function annually in any of the following circumstances:

·         You have positive antibodies

·         You have had previous thyroid surgery or radioactive iodine treatment

·         You have come off a trial of levothyroxine treatment for subclinical hypothyroidism

Where there is no suggestion of thyroid disease, doctors will normally measure your thyroid function every two to three years.

In what circumstances is subclinical hypothyroidism treated?

When deciding whether to treat patients with subclinical hypothyroidism, doctors will take into consideration factors that may suggest underlying thyroid disease. This can include symptoms of hypothyroidism, previous thyroid surgery or radioiodine treatment or raised thyroid antibodies.

If you are an adult under 65 with symptoms of hypothyroidism, and your TSH is raised on two separate occasions at least three months apart (but lower than 10 mU/l), your doctor may consider a six-month trial of levothyroxine to see whether it improves symptoms.

Your doctor will re-measure TSH within 12 weeks of starting the dose. If TSH levels remain raised, they may then increase the dose. If symptoms persist despite the TSH coming back into the reference range, your doctor may consider stopping your levothyroxine trial and assessing for other possible reasons for the symptoms whilst continuing to monitor you for subclinical hypothyroidism.

Causes

Subclinical hypothyroidism can be caused by autoimmune thyroid disease (diagnosed by the presence of TPOAb) and this means that you have a higher risk of developing full hypothyroidism in the future.

Other causes include:

• Radioactive iodine treatment and surgery to remove your thyroid for hyperthyroidism or for thyroid cancer
• Too high doses of antithyroid drugs given to treat hyperthyroidism 
• Certain medicines including lithium (used for certain mental health conditions), amiodarone (used for certain heart problems), immune checkpoint inhibitors such as pembrolizumab and nivolumab (used to treat certain cancers).
• Some health foods containing iodine taken in excess e.g. kelp
• Radiation for head and neck cancers
• Older age (more details below)
• Increased body weight (more details below)

Subclinical hypothyroidism in older people

The recommendations for people over 65 with subclinical hypothyroidism are different. This is because there is less likely to be an improvement in your symptoms with treatment. There is also greater potential for harm from suppressing your TSH (such as strain on your heart or increased risk of brittle bones). There is currently a debate about whether the standard TSH reference range is suitable for older people. This is because it has been found that TSH levels naturally increase with age (typically 70+ years of age) and are not always associated with poor health.

Your doctor will continue to monitor your TSH levels annually if there are signs of underlying thyroid disease. Where there is no suggestion of thyroid disease, tests will normally be done every two to three years.

Subclinical hypothyroidism in people with increased body weight

The relationship between thyroid function and body weight is complex. While it is known that underactive thyroid leads to a slight weight gain (typically 3-4 kg) it is also becoming clear that weight gain can also lead to a slightly raised blood TSH level with normal T4 (indicating subclinical hypothyroidism). Several trials of treatment with levothyroxine in subclinical hypothyroidism have shown no benefit in reducing body weight. However, weight reduction by other means (such as diet and exercise, weight-reducing drugs or after weight loss surgery) have shown that blood TSH levels either normalise or reduce. Therefore, treatment of subclinical hypothyroidism in people with increased body weight is not recommended purely as a means to reduce weight.

Subclinical hypothyroidism and pregnancy

If you are trying for a baby, or are pregnant, you would normally be treated with levothyroxine if your TSH is greater than the pregnancy-specific reference range, or greater than 4 mU/L if there are no pregnancy ranges available locally.

If your thyroid peroxidase antibodies are raised then the current American Thyroid Association (ATA) guidelines recommend treatment if your TSH is greater than 2.5 mU/l. However, the benefit of treatment in this context is less clear.

Subclinical hyperthyroidism (borderline overactive thyroid)

Subclinical hyperthyroidism is also known as mild hyperthyroidism or borderline hyperthyroidism. It is defined by a TSH level that is slightly lower than the laboratory reference ranges with normal levels of T4 and the active thyroid hormone triiodothyronine (T3). Most patients with subclinical hyperthyroidism have no obvious symptoms.

What are the symptoms?

Where symptoms are present, they will usually be mild and may include:

• Weight loss
•  Sweating and heat intolerance
  
• Shakiness
• Feeling anxious
• Mood swings and irritability

How is it monitored?

Subclinical hyperthyroidism can be an indicator that you may go on to develop (full) hyperthyroidism. This is more likely if the TSH level is very low or if TSH receptor antibody (TRAb) levels are positive.

If you are an adult with untreated subclinical hyperthyroidism your doctor will usually measure your TSH every few months. They may also measure your T4 and T3 levels. In children and young people they may measure this more frequently.

If your TSH level stabilises i.e. you have two similar readings within reference range three to six months apart, your doctor may consider stopping monitoring your thyroid function.

In what circumstances is subclinical hyperthyroidism treated?

In many cases, hormone levels will restore themselves to normal levels without intervention over time. Your doctor will usually consider referring you to a specialist if:

·         You have two TSH readings lower than 0.1mU/l at least three months apart and

·         There is evidence of thyroid disease such as positive antibodies or a goitre (swelling in the neck)

Causes

Subclinical hyperthyroidism can be caused by the presence of another thyroid antibody (TRAb). Where these are raised, it can indicate underlying autoimmune thyroid disease (Graves’) and could indicate you may go on to develop full hyperthyroidism. In people with subclinical hyperthyroidism due to Graves’ disease a third of affected people will normalise thyroid function over time, a third will remain in the subclinical hyperthyroid state and a third will progress to full hyperthyroidism.

Toxic nodular goitre (either in the form of multiple nodules or a single overactive nodule) can also be a cause in hyperthyroidism.

In many cases, subclinical hyperthyroidism is temporary and will get better without treatment. For example, inflammation of the thyroid gland, known as thyroiditis, can cause subclinical hyperthyroidism in its initial phases. This may resolve itself in most people but may progress to symptoms of hypothyroidism in some.

Too high doses of levothyroxine to treat hypothyroidism, or certain other drugs including lithium, amiodarone, interferons, interleukin-2 and immune checkpoint inhibitors, can also cause higher levels of thyroid hormone.

Subclinical hyperthyroidism and pregnancy

Blood TSH and thyroid hormone levels change during pregnancy with TSH levels being lower and T4 levels being slightly higher. This is why reference ranges for thyroid function tests are different during pregnancy. Subclinical hyperthyroidism is defined as TSH levels that are lower and T4 and T3 levels that are within the pregnancy reference ranges. Treatment is generally not required for subclinical hyperthyroidism in pregnancy. However, if subclinical hyperthyroidism is thought to be due to Graves’ disease then the doctors may monitor thyroid function more closely during and just after the pregnancy.

Other reasons for abnormal thyroid function results

A low TSH with a low FT4 may result from a failure of the pituitary gland. This is called secondary hypothyroidism caused by hypopituitarism. A pituitary tumour is the most common cause of this. These tumours are almost always benign (not cancer).

A variety of abnormal thyroid function results can also be due to a response to any  signficicant illness that does not involve your thyroid. This is known as euthyroid sick syndrome or non-thyroidal illness. Usually this does not need to be treated as thyroid function should normalise as you recover from your other illness.

Biotin can sometimes result in false thyroid function levels giving a reading which suggests an overactive thyroid (hyperthyroidism). If you are taking biotin supplements the American Thyroid Association advises avoiding these for two days before having blood tests in order to minimise the risk of a false reading. It is also advisable to let your doctor know you have been taking these, or any other supplements, when going for your blood test.

Further information

BTF patient guides

Hypopituitarism  - You and Your Hormones

NICE guideline on thyroid disease: assessment and management