What is hyperthyroidism?

The thyroid is a small gland located in the front of the neck that produces the hormones thyroxine (T4) and triiodothyronine (T3). The body requires proper thyroid hormone levels to perform various functions. Thyroid hormones stimulate the body’s metabolism by acting on virtually every cell in the body, whereby they stimulate those cells to produce proteins that the body needs to function and to increase the cells’ oxygen usage.ⁱ

The actions of these hormones on the cells in the body have many downstream effects, including regulating heart rate, changing how calories are burned and food digests, stimulating growth, maintaining healthy skin and hair, and maintaining fertility. Hyperthyroidism is a condition that occurs in the presence of an overactive thyroid gland, or one that has a higher than normal thyroid uptake.ⁱⁱ The number of people who experience symptoms from an overactive thyroid is low, particularly with regard to those who need to take thyroid hormone medication. Only between 0.2 and 1.3 percent of people in the world suffer from symptomatic hyperthyroidism.ⁱⁱⁱ

Residents of certain countries are more likely than others to experience symptomatic hyperthyroidism. Specifically, the number is higher (~3 percent) in countries without enough iodine in their diets.^iv Iodine is required to make thyroid hormone and a lack of iodine can lead to both hyper- and hypothyroidism.^v

An overactive thyroid is more common in women compared to men,^vi and patients with autoimmune diseases are more likely to experience hyperthyroidism as well. For example, studies indicate that 10 percent of patients with Graves' disease, an autoimmune condition causing hyperthyroidism, also have another autoimmune disease.^vii

A person's chance of developing hyperthyroidism is also increased if they^viii:

• Are iodine deficient
• Consume too much iodine
• Have a family member with autoimmune thyroid disease
• Smoke (2x risk)
• Take certain medications, such as amiodarone (heart medication) and lithium (psychiatric medication)

‍

Hyperthyroidism vs hypothyroidism

Hyperthyroidism and hypothyroidism both affect the thyroid gland and hormone production, though in different ways. With hyperthyroidism, the gland produces too much thyroid hormone, whereas in hypothyroidism, the gland produces too little. If a person has signs of thyroid problems, a practitioner will check for an enlarged thyroid gland, and recommend they undergo testing to evaluate their hormone levels as well as various other assessments.  

The first test used to measure thyroid hormone levels and function is called the thyroid-stimulating hormone (TSH) test, a measurement of the level of the hormone that stimulates the thyroid to produce thyroid hormone.^ix The normal value for TSH is between 0.4 and 4 mIU/L (though sometimes the upper limit of normal is 5 mIU/L in certain laboratories).^x

If the TSH is above the upper limit of normal, patients may have an underactive thyroid or primary hypothyroidism. TSH that is below the lower limit of normal is a potential indicator of an overactive thyroid or hyperthyroidism.^xi

‍

What are the symptoms of hyperthyroidism?

While testing is required for a definitive diagnosis of hyperthyroidism, people may also have symptoms that could indicate a thyroid disorder.

The symptoms of hyperthyroidism occur as organs of the body are exposed to too much thyroid hormone or from inflammation caused by TSH receptor antibodies. Hyperthyroidism can cause psychiatric and nerve symptoms such as anxiety, lethargy, and a tremor in the hand or fingers. It can also affect the heart and blood vessels, leading to heart palpitations, an abnormal heartbeat, and high blood pressure.^xii  Elevated thyroid hormone levels can also contribute to unintentional weight loss, sweating, and a feeling of being overheated. Pain or swelling in the thyroid gland (located in the neck) can be present.^xiii  Women may experience irregular menstrual cycles while men may suffer from erectile dysfunction, which could also contribute to problems with conception.^xiv‍

Other possible symptoms that can occur in either gender include the following^xv:

• Diarrhea
• Thickened red skin (with Graves’ disease only)
• Bulging eyes (with Graves' disease only)
• Insomnia

Because many of the above symptoms can be caused by other conditions, it is not uncommon for patients with hyperthyroidism to have a delay in diagnosis.^xvi

‍

What causes hyperthyroidism?

In most cases, a person cannot control whether or not they develop hyperthyroidism. The most common cause of hyperthyroidism is Graves’ disease. Graves’ disease is an autoimmune disorder, or a condition where the patient’s immune system targets its own healthy cells or tissues.^xvii

In Graves’ disease, the immune system creates an antibody to the TSH receptors in the thyroid, which subsequently stimulates the thyroid gland to grow and produce an excess of thyroid hormone, even when the normal signaling hormones from the brain are not signaling the thyroid gland to produce thyroid hormone. These TSH receptor antibodies can also cause inflammation in the thyroid (known as thyroiditis) and in other parts of the body where TSH receptors are present, leading to bulging eyes (Graves’ orbitopathy) and raised darkened skin, most commonly over the shins (infiltrative dermopathy). Medications such as amiodarone (heart medication) can also lead to thyroiditis and cause thyroid gland pain and hyperthyroidism, as well as hypothyroidism.^xviii

Another common cause of hyperthyroidism is the growth of benign (non-cancerous) masses in the thyroid (called “nodules”). These thyroid nodules can produce excess thyroid hormone, even without normal stimulation by TSH.^xix This uncontrolled production of thyroid hormone then leads to hyperthyroidism. 

Masses outside the thyroid are another, albeit much rarer, cause of hyperthyroidism. In central hyperthyroidism, a mass (typically benign) grows in the pituitary gland, i.e., the part of the brain that secretes TSH. This mass can secrete excess TSH which then over-stimulates the thyroid gland to make thyroid hormone.^xx It is also possible to have cancers of the ovary or other parts of the body that produce TSH. In these cases, the thyroid gland itself is normal, but there is an excess of the hormone that normally stimulates the thyroid gland, leading to hyperthyroidism.^xxi

Finally, it is important to note that iodine is essential to the thyroid’s ability to create thyroid hormone, and a lack of sufficient iodine intake is associated with both hypothyroidism and hyperthyroidism. For this reason, in the United States, Canada, and much of the rest of the world, salt is fortified with iodine to ensure enough iodine in people’s diets. In countries where iodine is deficient in the diet and is not supplemented, the rate of hyperthyroidism is increased.^xxii

‍

How is hyperthyroidism diagnosed?

Diagnosing hyperthyroidism and determining the cause requires testing; a person with symptoms of hyperthyroidism can have their doctor send a simple blood test to measure the level of thyroid stimulatory hormone (TSH) and determine if the levels are within normal hormone range.^xxiii In patients with hyperthyroidism, the TSH value is typically low because the thyroid is producing extra thyroid hormone, which sends a signal to the brain to reduce the amount of TSH. Normally, TSH would stimulate the thyroid to produce thyroid hormone, but when there is already too much thyroid hormone being produced, the brain makes less TSH in an attempt to decrease the amount of thyroid hormone erroneously being produced.^xxiv If the TSH value is below the normal level, thyroid hormones (free T4 and T3) are then measured. If the thyroid hormones are elevated, a diagnosis of primary hyperthyroidism is confirmed.

After the initial diagnosis, a physician will conduct further testing to determine the cause of hyperthyroidism. First, they will measure specific antibodies that may be stimulating the thyroid gland to produce too much hormone (such as the antibodies produced in Graves’ disease).^xxv Sometimes, endocrinologists may order a special test called a thyroid scan or a radioactive iodine uptake test. In these tests, patients are given a radioactive tracer that binds to iodine and is taken up in the thyroid gland as the thyroid uses the tagged iodine to produce thyroid hormones. If there are parts of the gland that are producing extra thyroid hormone, these parts will light up brighter as they take up more of the tracer. This can help identify patients who have hyperthyroidism caused by nodules in the thyroid.^xxvi In some cases, such as if a patient is pregnant, a radioactive uptake test cannot be performed. An ultrasound can then be used instead to locate any thyroid masses.

Often, doctors will order other lab work such as blood tests to measure white and red blood counts, or liver function tests. From this testing, a physician can identify the abnormal lab values that are seen in patients with hyperthyroidism.^xxvii When a physician finds nodules in the thyroid gland, a biopsy is sometimes performed to determine if the nodules are benign or cancerous.^xxviii

After determining the root cause of the condition, a physician can then determine an appropriate course of action to control the overproduction of thyroid hormone.

‍

How does hyperthyroidism impact fertility and pregnancy?

Thyroid hormone production plays a vital role in the human body, and this starts during fetal development. Maternal thyroid hormones are essential to the normal development of the growing fetus, particularly with regard to the growth and maturation of the fetal brain. Because of this, if the mother’s thyroid gland produces too much – or too little – thyroid hormone, the fetus may fail to develop normally. This can lead to spontaneous miscarriages or birth defects.^xxix Although hypothyroidism is more common and thus more likely to cause infertility or miscarriages, overt hyperthyroidism may also impact fertility and pregnancy.^xxx

Approximately 6 percent of women with hyperthyroidism experience infertility,^xxxi which is similar to patients without hyperthyroidism. However, this is reflective of the widespread diagnosis and treatment of hyperthyroidism, as treatment can reverse female infertility.^xxxii Untreated hyperthyroidism can affect fertility because it can cause abnormal hormone levels, interfering with ovulation and menstruation. Women with hyperthyroidism are 2.5 times more likely to have irregular menstrual cycles. Research shows that 60 percent of women with hyperthyroidism have infrequent or absent menstrual cycles and 5 percent have abnormally heavy menstrual bleeding.^xxxiii

In patients with Graves' disease, infertility may not necessarily be associated with menstrual abnormalities. Aside from the influence of increased thyroid hormones on the menstrual cycle, thyroid antibodies found in autoimmune hyperthyroidism (e.g., Graves’ disease) may also affect fertility directly, though it is unclear how this occurs.^xxxiv

During pregnancy, uncontrolled hyperthyroidism can lead to problems with both the mother and fetus. In very severe cases, a pregnant woman can develop heart failure or a condition called “thyroid storm,” where extremely high levels of thyroid hormone can lead to confusion, fast heart rate, and organ failure. Preeclampsia, a condition characterized by high blood pressure in pregnancy, is also associated with hyperthyroidism. With regard to fetal outcomes, miscarriage, low birth weight, and preterm birth may be more common in patients with hyperthyroidism.^xxxv

Hyperthyroidism can affect fertility in not only women but in men as well, since an overactive thyroid can cause issues with both achieving and maintaining an erection as well as with premature ejaculation.^xxxvi Fortunately, with proper treatment for high thyroid hormone levels, it is possible to successfully reverse these causes of infertility.^xxxvii

‍

Can IVF drugs cause thyroid problems?

During the course of infertility treatment, a woman may receive various medications to facilitate the process. Each medication has the possibility of side effects, often leading to concern as to whether the treatment process could lead to hyperthyroidism.

While there is some evidence that fertility treatments may lead to an increase in thyroid stimulating hormone (TSH) and asymptomatic (sub-clinical) hyperthyroidism, these effects are typically self-limiting (resolve after hormone treatment).^xxxviii Currently, it is unclear how this affects the success of IVF, particularly when compared to those who do not experience hyperthyroidism.^xxxix

‍

What treatments exist and how successful are they?

Appropriate hyperthyroidism treatment depends on the underlying cause of the condition as well as the severity. A physician conducts a thorough medical history evaluation as well as extensive testing to determine a course of action. Sometimes, medications can also be given to treat the symptoms of hyperthyroidism. For example, if the patient experiences an irregular heartbeat from the disease, a doctor may prescribe medication to regulate the heart rate (beta-blockers).

Treatment may also address the underlying cause of hyperthyroidism. The three ways of treating hyperthyroidism are anti-thyroid medications, surgery (removal of the whole thyroid gland or any overactive thyroid nodules), or treatment with radioactive iodine.^xl Each option is effective but has specific side effects that should be discussed to determine the treatment option most preferred by the patient.

One of two medications can be used to suppress the creation of excess thyroid hormone: methimazole and propylthiouracil (PTU). Both of these medications interfere with the ability of the thyroid gland to release thyroid hormone. These medications can be used indefinitely, or for a short period of time until radioactive iodine ablation or surgery to remove the thyroid can be performed. Approximately 50 percent of patients stop responding to long-term treatment with these medications and need alternate therapy in the form of surgery or radioactive ablation.^xli

The surgical approach, which is a permanent cure, involves removing either the entire thyroid gland or the part of the gland that is producing excess hormone (in the case of an overactive nodule).^xlii If the entire gland is removed, permanent hypothyroidism will result, which requires lifelong thyroid hormone supplementation.^xliii

For Graves’ disease and toxic nodular goiter, radioactive iodine may be the preferred treatment.^xliv With this treatment, iodine is tagged with radiation and then injected into the bloodstream. The thyroid takes up the iodine, after which the radiation kills some of the thyroid cells thereby leading to the involution or “death” of much of the thyroid gland. Some patients do not require thyroid supplementation after treatment, though many patients do need to take lifelong thyroid supplements to replace the normal thyroid gland that was also rendered non-functional from the treatment.^xlv

Hyperthyroid treatment options are limited in pregnancy because radioactive iodine can lead to birth defects, and surgery is often deferred until after the pregnancy when possible due to anesthesia risks. Therefore, oral medications are often the treatment of choice. The type of oral medication used depends on the trimester, due to different benefits and risks of the medications. In general, PTU is used in the first trimester and either continued throughout the pregnancy or switched to methimazole in the second trimester.

‍

What are the other hyperthyroidism risks or complications?

The most severe form of hyperthyroidism can lead to something called a “thyroid storm” in which there is a sudden and severe surge of excess thyroid hormone. This can lead to sudden fluctuations in heart rate and blood pressure, severe fever, sweating, vomiting, confusion, seizures, and liver failure. While rare, this can obviously be life-threatening.^xlvi

‍

Conclusion

Thyroid hormones at the correct levels are necessary to perform certain functions in the body. When levels are abnormal, a person may experience issues or complications which can lead to more serious consequences if left untreated. In particular, hyperthyroidism can be a cause of infertility in both men and women, though it can be treated with proper medical intervention.

‍