Subclinical Hypothyroidism

What is Subclinical Hypothyroidism?

Subclinical hypothyroidism is a condition that typically shows normal levels of a hormone called thyroxine (T4) but high levels of thyroid stimulating hormone (TSH). Even small changes in T4 levels can cause big changes in TSH levels. While TSH levels might differ quite a lot among people, an individual’s TSH level usually remains relatively constant because each person has an individual set point within their hormonal balance.

There’s usually a clear relationship between TSH and T4. However, for some people, this relationship can be more complex which might explain why some have normal T4 levels but high TSH levels, while others have low T4 levels. Various research studies estimate that 3% to 10% of people have subclinical hypothyroidism, this percentage can increase to 18% to 20% among older adults. It is also more commonly seen in women and older adults.

Several research studies have shown that having subclinical hypothyroidism (specifically with a TSH level equal to or above 10 mIU/L) can increase the risk of having dangerous events related to heart diseases, such as a heart attack or a stroke. Because of this increased risk, it’s important for physicians to be aware of these patients.

Given the more widespread use of sensitive tests that can identify thyroid function, we predict more people will be diagnosed with this disorder in the future. Levothyroxine, a medication used to treat hypothyroidism, is the second most commonly prescribed medication in the US. This increased use is likely due to the increased recognition and treatment – or trials with levothyroxine replacement therapy – of individuals with subclinical hypothyroidism. In fact, a study from the UK showed more people were getting treated for hypothyroidism from 2005-2014, increasing from 2.3% to 3.5% of the total population.

What Causes Subclinical Hypothyroidism?

Subclinical hypothyroidism and hypothyroidism have the same origins. Around the world, the leading cause of hypothyroidism is a lack of iodine in a person’s diet. However, in the United States, the main cause is Hashimoto thyroiditis, which is an autoimmune disease that affects the thyroid.

Other causes of hypothyroidism can be surgeries or medical treatments that affect the thyroid, conditions that impact the central nervous system, or certain medications. The medications that can cause hypothyroidism include lithium, amiodarone, checkpoint inhibitors, and tyrosine kinase inhibitors.

Moreover, people with obesity also tend to have higher levels of TSH, a hormone associated with hypothyroidism. As people lose weight, these levels usually decrease.

Risk Factors and Frequency for Subclinical Hypothyroidism

Subclinical hypothyroidism is a condition that’s not always obvious but can be quite common, affecting anywhere from 3% to 15% of people, depending on the group being studied. It tends to be more common in women, older people, and those with type 2 diabetes. A study known as the Whickham survey found that 8% of women and 3% of men have this condition. Every year, between 2% and 6% of people with subclinical hypothyroidism may go on to develop overt hypothyroidism, a more serious form of the disease. This rate is higher (3% to 8%) for people who have high TSH levels and show TPO antibodies. The chance of developing overt hypothyroidism is greater for women, for those with high TSH levels, and for those with TPO antibodies.

However, there’s also a good chance of the condition resolving on its own. In one study of individuals aged 65 and older, 46% had their subclinical hypothyroidism resolve without treatment over the course of 4 years. Another study with participants 55 years and older showed a similar pattern, with 52% seeing their TSH levels normalize on their own after about 32 months. Having a TSH level below 7 and no TPO antibodies seemed to increase the chances of this automatic resolution.

Signs and Symptoms of Subclinical Hypothyroidism

Subclinical hypothyroidism is a condition that usually doesn’t show any symptoms. However, when symptoms do appear, they can be quite diverse and impact many bodily systems. The decision to treat with thyroid replacement therapy is often made based on the severity of these symptoms. Here are some of the signs and symptoms linked with hypothyroidism:

On the skin: Dry skin, hair loss, thinning eyebrows, facial puffiness.
On breathing: Sleep apnea, changes in voice.
On digestion: Constipation, difficulty swallowing, loss of appetite, gallstones.
On the heart: High diastolic blood pressure, slow heart rate, pericardial effusions (fluid around the heart), decreased cardiac output, and dyslipidemia. These occur only in cases of severe and prolonged low blood pressure.
On the nervous system: Decreased attention span, memory problems, entrapment neuropathies with carpal tunnel syndrome being the most frequent.
On the muscles and skeleton: Muscular weakness, cramps, stiffness, fatigue.
On reproductive health: Irregular menstrual periods, heavy menstrual bleeding, decreased sex drive.
On metabolism: Weight gain, intolerance to cold, low sodium levels in the blood.

Testing for Subclinical Hypothyroidism

The key indicator of subclinical hypothyroidism, a condition where your thyroid is not producing enough thyroid hormone, is seen in a lab test. This test might show a high level of TSH (thyroid-stimulating hormone) but a normal T4 (thyroxine) level. However, an illness unrelated to the thyroid or certain medicines can also cause a high TSH level. So these factors need to be checked and ruled out before a diagnosis of subclinical hypothyroidism can be made.

For patients with a TSH level below 10 mIU/L and a normal T4 level, the thyroid lab test should be repeated in about 3 to 6 months before starting treatment. This is because almost half of these patients may see their thyroid levels return to normal on their own.

Your doctor might also check for TPO (thyroid peroxidase) antibodies in your blood. If these are present, it might mean that your hypothyroidism is due to an autoimmune disease. Importantly, the presence of these antibodies doubles the risk of subclinical hypothyroidism progressing to full-blown hypothyroidism. Over time, the levels of TPO antibodies decrease and there’s usually no need to test for them again.

An ultrasound scan might show changes in the structure of the thyroid gland in patients with an autoimmune thyroid disease. However, such a scan is usually not used to confirm a diagnosis of hypothyroidism.

Since subclinical hypothyroidism could be linked to heart disease, heart failure, and declining mental abilities, it’s important to check patients for the risk of these conditions and any other illnesses they might have.

Treatment Options for Subclinical Hypothyroidism

Deciding whether to start treatment with levothyroxine, a type of thyroid medication, in patients with subclinical hypothyroidism (mild underactivity of the thyroid) can be difficult. Especially when dealing with older patients, we need to consider several factors, such as, the patient’s age, how much their thyroid-stimulating hormone (TSH) levels are elevated, if there are any heart disease-related risks, symptoms, and the presence of specific antibodies. An initial approach could be to monitor the patient, as some individuals with this condition will naturally return to normal TSH levels. Hence, conducting a repeat check of TSH levels is important before starting any treatment.

Certain guidelines, like the ones from American Thyroid Association (ATA) and the American Association of Clinical Endocrinology (AACE), suggest starting levothyroxine treatment specifically when:
– TSH levels are higher than 10 mIU/L,
– The patient shows symptoms of hypothyroidism,
– The patient has positive TPO antibodies (which suggest an increased risk of developing hypothyroidism),
– The patient is of reproductive age.

Guidelines recommend treatment for younger patients, i.e., 70 years or below, especially when TSH levels are higher than 10 mIU/L and no history of heart diseases is reported. The dose of levothyroxine does not have to be a full dose; it can be graduated based on the patient’s TSH levels and symptoms. Those with a history of heart diseases who aren’t currently symptomatic can start with the lowest levothyroxine dose to see how well they tolerate it.

Moreover, for individuals aged 70 or above, the decision to initiate levothyroxine treatment needs to be evaluated individually, considering the patients’ symptoms and history of heart disease.

Treatment guidelines do not apply to future mothers, as even slight thyroid dysfunctions should be treated due to associated risks to the pregnancy and the baby’s health.

However, the value of treating subclinical hypothyroidism in older adults is controversial. For example, a research study called TRUST found no noticeable differences in hypothyroid symptoms or tiredness in patients aged 65 or older treated with levothyroxine compared to those who received a placebo.

Similarly, other studies from 2017 found no improvement in patients’ symptoms, mood, or quality of life after treating with levothyroxine. However, medication did improve some heart disease-related factors. Regrettably, other studies showed an increased risk of death associated with levothyroxine treatment in older individuals with certain health conditions.

So, while some research alludes to a connection between mild thyroid underactivity and an increased risk of heart disease and death in the elderly, no long term studies have confirmed the benefits of levothyroxine in treating these issues. Therefore, treatment decisions shouldn’t be based solely on these factors.

Various factors not related to the thyroid gland can temporarily increase the levels of the thyroid-stimulating hormone (TSH), which can lead to a false diagnosis of a condition called subclinical hypothyroidism. It’s crucial to distinguish between these non-thyroid causes of elevated TSH and actual subclinical hypothyroidism. Here are some of these factors:

Getting older, which can cause TSH concentration to increase
Illnesses not related to the thyroid
Interference in lab results
Adrenal insufficiency, a condition where the adrenal glands do not produce enough hormones
Chronic kidney failure

Certain medications like amiodarone, lithium, tyrosine kinase inhibitors, checkpoint inhibitors, metoclopramide, amphetamine, ritonavir, and St Johns wort can also affect TSH levels.

What to expect with Subclinical Hypothyroidism

About half of patients with mild thyroid dysfunction can expect their thyroid function to return to normal within one to two years. However, about 25% of these patients may develop overt hypothyroidism, a more severe form of the disease. A diagnosis of subclinical hypothyroidism is associated with an increased risk of cardiovascular problems, heart failure, and a decline in kidney function.

Possible Complications When Diagnosed with Subclinical Hypothyroidism

Hypothyroidism, or low thyroid function, can increase the risk of heart diseases by escalating vascular resistance and reducing the amount of blood your heart pumps. The hormone, triiodothyronine (T3), normally relaxes the blood vessels to lower vascular resistance. But in hypothyroidism, the lacking T3 leads to increased vascular resistance. Thyroid hormones also directly influence the heart rate and cardiac contractility. So, low thyroid hormone equals slower heart rate and reduced cardiac output.

Various studies have been conducted on the relation between hypothyroidism and heart problems. A study followed 55,000 patients and discovered that a certain level of TSH (a hormone indicating your thyroid function) corresponds to an increased chance of heart diseases and cardiovascular mortality. However, in older individuals (85 or above), high TSH levels were associated with reduced death rate. Another study involving 2730 older individuals (between ages 70-79) showed a higher risk of heart failure with a certain level of TSH.

Another aspect of hypothyroidism is its effect on blood pressure, cholesterol, triglyceride, LDL-cholesterol, lipoprotein(a), homocysteine, and carotid intima-media thickness – all potentially heart disease indicators. A study conducted on 54 women with subclinical hypothyroidism (where complications aren’t very apparent) showed increased measures of these substances, which normalized after the women were treated with levothyroxine, a common treatment for hypothyroidism.

Hypothyroidism also affects your physical capacity. For instance, lack of thyroid hormones can reduce muscle strength and exercise performance. This was evident in a study where women treated with levothyroid showcased better exercise performance after six months.

The condition is also associated with mental health problems and cognitive decline. For example, triiodothyronine plays an essential role in neuron development and function. Studies have shown conflicting results about this, but some have found increased cognitive decline risk in young individuals (under 75) with subclinical hypothyroidism. Others found no relation at all. There is also evidence that young people (under 60) with subclinical hypothyroidism may face depression, but this doesn’t seem to affect older individuals.

Lastly, hypothyroidism can affect kidney function. Studies have shown that 18% of patients with kidney disease, not on dialysis, have subclinical hypothyroidism. This condition was linked to a steady decline in the kidney filtration rate over two years. Furthermore, a study found the reduced kidney filtration rate and increased cystatin-C (a marker of kidney function) levels associated with subclinical hypothyroidism, which normalized after the patients received hypothyroidism treatment.

Preventing Subclinical Hypothyroidism

Patients should be educated about the symptoms of an underactive thyroid, also known as hypothyroidism. They should also be informed about what the test results could mean when the level of thyroid stimulating hormone, or TSH, is less than or more than 10 mIU/L.

For patients who have slightly high levels of TSH (above 70 mIU/L), it’s important to explain that a minor increase in these levels can be related to growing older. These patients should also understand that studies have not shown significant improvement in symptoms with treatment.

Because this condition can also raise the risk of heart disease and other health issues, recommendations for healthy lifestyle changes should be encouraged. This will help manage the condition and reduce potential risks.

Frequently asked questions

Subclinical hypothyroidism is a condition characterized by normal levels of thyroxine (T4) but high levels of thyroid stimulating hormone (TSH). It is more commonly seen in women and older adults, and it can increase the risk of heart diseases.

Subclinical hypothyroidism affects anywhere from 3% to 15% of people, depending on the group being studied.

Some signs and symptoms of subclinical hypothyroidism include: - On the skin: dry skin, hair loss, thinning eyebrows, facial puffiness. - On breathing: sleep apnea, changes in voice. - On digestion: constipation, difficulty swallowing, loss of appetite, gallstones. - On the heart: high diastolic blood pressure, slow heart rate, pericardial effusions (fluid around the heart), decreased cardiac output, and dyslipidemia (only in severe and prolonged cases). - On the nervous system: decreased attention span, memory problems, entrapment neuropathies (such as carpal tunnel syndrome). - On the muscles and skeleton: muscular weakness, cramps, stiffness, fatigue. - On reproductive health: irregular menstrual periods, heavy menstrual bleeding, decreased sex drive. - On metabolism: weight gain, intolerance to cold, low sodium levels in the blood. It's important to note that not all individuals with subclinical hypothyroidism will experience symptoms, and the decision to treat with thyroid replacement therapy is often based on the severity of these symptoms.

Subclinical hypothyroidism can be caused by various factors, including iodine deficiency, Hashimoto thyroiditis (an autoimmune disease), surgeries or medical treatments affecting the thyroid, conditions impacting the central nervous system, certain medications, and obesity.

The doctor needs to rule out the following conditions when diagnosing Subclinical Hypothyroidism: - Illnesses not related to the thyroid - Interference in lab results - Adrenal insufficiency - Chronic kidney failure - Certain medications like amiodarone, lithium, tyrosine kinase inhibitors, checkpoint inhibitors, metoclopramide, amphetamine, ritonavir, and St Johns wort.

The types of tests that are needed for subclinical hypothyroidism include: - Thyroid-stimulating hormone (TSH) test: This test measures the level of TSH in the blood. A high TSH level is a key indicator of subclinical hypothyroidism. - Thyroxine (T4) test: This test measures the level of T4 in the blood. A normal T4 level, along with a high TSH level, is characteristic of subclinical hypothyroidism. - Thyroid peroxidase (TPO) antibodies test: This test checks for the presence of TPO antibodies in the blood. The presence of these antibodies suggests an autoimmune cause of hypothyroidism and increases the risk of subclinical hypothyroidism progressing to full-blown hypothyroidism. - Ultrasound scan: An ultrasound scan of the thyroid gland can show changes in its structure, particularly in patients with an autoimmune thyroid disease. However, this scan is not typically used to confirm a diagnosis of hypothyroidism. It is also important for the doctor to assess the patient for any other illnesses or risk factors, such as heart disease, heart failure, and declining mental abilities, as subclinical hypothyroidism may be linked to these conditions. The decision to start treatment with levothyroxine, a type of thyroid medication, should take into account various factors, including the patient's age, TSH levels, presence of specific antibodies, symptoms, and any heart disease-related risks.

The treatment of subclinical hypothyroidism depends on various factors. Guidelines from the American Thyroid Association (ATA) and the American Association of Clinical Endocrinology (AACE) suggest starting levothyroxine treatment in certain cases. These include when TSH levels are higher than 10 mIU/L, when the patient shows symptoms of hypothyroidism, when the patient has positive TPO antibodies (indicating an increased risk of developing hypothyroidism), and when the patient is of reproductive age. For younger patients, especially those below 70 years old without a history of heart disease, treatment is recommended if TSH levels are higher than 10 mIU/L. The dose of levothyroxine can be adjusted based on TSH levels and symptoms. However, the value of treating subclinical hypothyroidism in older adults is controversial, as studies have shown mixed results and no long-term studies have confirmed the benefits of levothyroxine in treating these issues. Treatment decisions should not be based solely on these factors.

When treating Subclinical Hypothyroidism, there can be potential side effects, including: - No noticeable improvement in hypothyroid symptoms or tiredness in older adults aged 65 or older. - No improvement in patients' symptoms, mood, or quality of life after treatment with levothyroxine. - Increased risk of death associated with levothyroxine treatment in older individuals with certain health conditions. - Potential impact on heart disease-related factors, although the long-term benefits of levothyroxine treatment in this regard are not confirmed. - Potential impact on blood pressure, cholesterol, triglyceride, LDL-cholesterol, lipoprotein(a), homocysteine, and carotid intima-media thickness, which are all indicators of heart disease. - Potential reduction in muscle strength and exercise performance due to the lack of thyroid hormones. - Potential association with mental health problems and cognitive decline, although the evidence is conflicting. - Potential impact on kidney function, with subclinical hypothyroidism being linked to a decline in kidney filtration rate and increased cystatin-C levels. Treatment for hypothyroidism can help normalize these kidney function markers.

The prognosis for subclinical hypothyroidism can vary. Some individuals may see their TSH levels normalize on their own without treatment, especially if their TSH level is below 7 and they have no TPO antibodies. However, about 25% of patients with mild thyroid dysfunction may develop overt hypothyroidism, a more severe form of the disease. Additionally, a diagnosis of subclinical hypothyroidism is associated with an increased risk of cardiovascular problems, heart failure, and a decline in kidney function.

An endocrinologist.

Hormones and Body Chemistry