The thyroid gland is a small butterfly-shaped gland located at the front base area of your neck (Figure 1) that is responsible for producing thyroid hormones (THs) which play an important role in regulating metabolism, helping the body to stay warm and keeping the brain, heart, muscles and other organs to maintain proper function [1-3]. The two main hormones produced by the thyroid gland are thyroxine (T4) and triiodothyronine (T3) which get released into the blood and taken up by all tissues of the body [4].

 

Common Symptoms of the Thyroid Diseases [5-8]: 

• Fatigue

• Enlarged thyroid gland

• Trouble sleeping

• Dry skin

• Hair loss

• Irregular menstrual periods

• Muscle pain and weakness

• Depression

• Irregular bowel movements

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Figure 1. Visual representation of the thyroid gland and its location in the front base of the neck area.

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1. Thyroid Hormone Regulation

Thyroid function is regulated by the hypothalamus and the pituitary gland, both located in the forebrain, and by the thyroid gland, as shown in Figure 2 below [2].

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Figure 2. The hypothalamus, pituitary gland, and thyroid gland hormone regulation. 

Image source: Shutterstock [713995831]

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Regulation of the thyroid hormones occurs by the hypothalamus and pituitary gland, which are continuously sensing the level of thyroid hormone circulating in the bloodstream [9]. When the hypothalamus detects a low level of TH, regulation occurs upon the hypothalamus release of TRH (thyrotropin-releasing hormone) which in turn activates the pituitary gland to produce TSH (thyroid-stimulating hormone) [9]. TSH in the bloodstream then activates the thyroid gland to produce T4 and a small amount of T3 [9]. T4 can get converted to T3 once it reaches a target tissue since different tissues require different T3 levels for optimal function [9]. Once the concentration of T4 and T3 hormones reach their normal levels in the blood (which can vary from one individual to another; see Table 1 for typical ranges for TSH, T3 and T4 in Canada), there is a feedback signaling event at the location of the pituitary gland and hypothalamus gland to decrease production of TSH and TRH, respectively [9].

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Table 1. Thyroid Hormone Levels Ranges Measured in Canada 

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*Source: LifeLabs Canada; guideline for normal ranges of thyroid hormones in blood.

 

2.  Diseases of the Thyroid Gland

According to the American Thyroid Association (ATA), women are 5 to 8 times more likely to have thyroid problems than men, with 1 in 8 women developing a thyroid disorder during their lifetime [3].

 

Thyroid disease is caused when the thyroid gland is not able to make the right amount of hormones to regulate metabolic function in the body. Some thyroid conditions can also cause thyroiditis, or inflammation of the thyroid gland. Low production of thyroid hormones is known as hypothyroidism (i.e., underactive thyroid) and can occur with Hashimoto’s disease, which is an auto-immune thyroiditis condition. Overproduction of thyroid hormones is known as hyperthyroidism (i.e., overactive thyroid) and can be caused by several conditions including Grave’s disease, painless or transient thyroiditis, toxic adenoma, and toxic multinodular goiter [7]. General summary shown in Figure 3.

 

Adequate Iodine levels, a trace element commonly found in iodized salt, dairy foods, grain products, and seafoods, are also required for the production of thyroid hormones [3, 10-12]. Severe iodine deficiency can lead to hypothyroidism and/or the development of an enlarged or bulging thyroid gland at the base of the neck, called a goiter [8,10,11,13]. In contrast, too much exposure to iodine can lead to hyperthyroidism [8-11]. This is especially true with elderly individuals who have thyroid nodules [8-11].

 

The standard of care for diagnosing thyroid disease involves a blood biochemistry test of the following thyroid hormones, as an indirect measure of thyroid function in the body [4,6,7,9,14]: 

• Thyroid stimulating hormone (TSH)

• Thyroxine (T4)

• Triiodothyronine (T3) levels

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Figure 3. General summary of thyroid diseases based on hormone levels found during blood biochemistry tests. Dotted line represents thyroid under-stimulation in the direction of the arrow and the dark blue line represents thyroid over-stimulation in the direction of the arrow. Image source: American Thyroid Association, 2019.

 

 

For individuals with suspected autoimmune thyroid disorders such as Hashimoto’s disease or Grave’s disease, a physician may also order a specific blood test to detect the presence of one or more thyroid autoantibodies (antibodies produced by an individual’s immune system to directly attack one or more its own proteins), for the following thyroid antigens [4]: 

 

• Thyroid PerOxidase (TPOAb, also known as ‘Anti-TPO Test) –  test is done to confirm Hashimoto’s or Grave’s disease.

• Thyroglobulin (TgAb) – test is done to confirm Hashimoto’s or Grave’s diseases.

• TSH receptor (TRAb) – test is done to confirm Grave’s disease.

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Thyroid Nodules and Thyroid Cancer

It is also important to note that 65% of the general population have one or more thyroid nodules, which are lumps or growths on the thyroid that may be either solid or fluid filled [15]. In most cases, about 90% of thyroid nodules are benign with 95% of them not causing any symptoms [15]. In other cases, thyroid nodules may be malignant and can lead to thyroid cancer or may cause symptoms such as difficulty breathing, fullness in the neck, or a choking sensation [15,16]. Thyroid nodules may also progress to chronic conditions such as Hashimoto’s disease [15].

 

Depending on their location within the thyroid gland, thyroid nodules can be palpable and detected with a physical exam by a trained physician [15]. Typically, the thyroid nodule is diagnosed through an ultrasound image of the thyroid gland. In cases where thyroid cancer is suspected, a fine needle aspiration biopsy (FNAB) is used as the standard diagnostic test [15,16]. 

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If malignant thyroid cancer is diagnosed, treatment options include thyroidectomy which involves the total removal of the thyroid if the tumour is larger than 1 cm; if the tumour is smaller, a thyroid lobectomy is used to remove one of the two thyroid lobes, leaving the other intact. Depending on the stage and type of thyroid cancer, treatment with radioactive iodine therapy or molecular therapy with tyrosine kinase inhibitors may also be indicated therapies [16].

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Thyroid Disease and Women’s Hormonal Health

There is inconclusive research regarding the association between thyroid diseases, more specifically autoimmune thyroiditis, and the development of endometriosis. Some studies found that the prevalence of a thyroid disease is higher in women who have endometriosis, while other studies have shown that there is no correlation [17,19]. 

 

Regarding polycystic ovary syndrome (PCOS), there is an increased risk of individuals with PCOS developing hypothyroidism or thyroid autoimmunity but the mechanism by which it may happen is not yet understood [20,21]. 

 

Diagnosing thyroid disease in postmenopausal women is a challenge since the common symptoms (for example, fatigue, dry skin/hair, hair loss) are often similar to perimenopause/menopause symptoms [22,23]. Older individuals are also at a higher risk of developing thyroid cancer [22].

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To learn more about endometriosis, PCOS, menopause and other hormonal health related topics, visit our Knowledge Center. 

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2.1 Hypothyroidism   

Hypothyroidism affects between 4% and 10% of the world’s population [14,24]. Although it is not a curable disease, hypothyroidism can be managed with a synthetic thyroxine pharmaceutical treatment, which is often taken daily for the rest of an individual's life [13]. Disease management also requires periodic blood work monitoring to ensure that thyroid hormone levels are within the normal range for the individual, otherwise there is a risk of hypothyroidism developing into hyperthyroidism if the dosage of thyroxine is not correct [13]. Individuals with hypothyroidism are also at an increased risk of cardiovascular changes such as ventricular arrhythmias (abnormal heartbeat), bradycardia (slow heart rate), systemic hypertension (high blood pressure) and decreased pulse pressure [10]. 

 

There are four types of hypothyroidism [10]: 

• Primary hypothyroidism (thyroid gland does not produce enough T4 and T3) – this condition is most often diagnosed and according to the ATA, about 2% of Americans have hypothyroidism [6,10]. 

• Secondary hypothyroidism (the pituitary gland does not produce enough TSH).

• Tertiary hypothyroidism (not enough TRH, thyrotropin-releasing hormone).

• Peripheral hypothyroidism, also called extrathyroidal hypothyroidism.

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What causes hypothyroidism?

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There is increased risk of developing hypothyroidism if an individual has another autoimmune disorder such as type 1 diabetes, rheumatoid arthritis, multiple sclerosis, celiac disease, Addison’s disease, pernicious anemia, or vitiligo [13]. There is also increased risk of developing hypothyroidism if there is family history of an autoimmune disease [13].

 

A diet low in iodine can cause hypothyroidism since the body will not have the adequate levels of iodine to make the thyroid hormones T4 and T3 [6,8,10,25]. 

 

Hypothyroidism can also be caused by damage or destruction of the thyroid gland due to thyroidectomy and radioactive iodine therapy for thyroid cancer. It can also arise as a result of radiation for head and neck cancer [10]. 

 

Congenital hypothyroidism is insufficient thyroid hormone production detected at birth due to an underdeveloped thyroid gland (thyroid dysgenesis) [6,26,27].

 

Medications can affect thyroid function such as those that interrupt hormone signaling between the hypothalamus and pituitary gland (ex. Glucocorticoids and dopamine, bromocriptine, growth hormone), those that affect thyroid hormone synthesis and secretion (ex. iodine, perchlorate, lithium, cytokines), those that alter thyroid hormone metabolism (ex. Rifampicin, tyrosine kinase inhibitors, phenytoin) [10,28]. 

 

Women with hypothyroidism have decreased fertility; if they become pregnant, they are at higher risks of miscarriage, gestational hypertension, anemia, abruptio placenta, and postpartum hemorrhage [29]. In addition, maternal hypothyroidism can lead to preterm birth, low birth weight, and respiratory distress on the neonate [28,29].

 

Symptoms [5,6]

• Fatigue

• Weight gain

• Enlarged thyroid gland (possible goiter) - classically found in Hashimoto’s, which is inflamed thyroiditis

• Trouble sleeping

• Poor concentration

• Dry skin

• Hair loss

• Irregular and heavy menstrual periods

• Muscle pain and weakness

• Depression

• Constipation

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Diagnosis and Treatment

Diagnosis of hypothyroidism involves biochemical testing ordered by your doctor along with a physical examination and/or an ultrasound of the thyroid gland to determine the cause of thyroid dysfunction [4–7,10,14,25,27,30]. Blood work would indicate elevated TSH with below normal T4 [3,9,31]. 

 

The standard of care for hypothyroidism involves pharmaceutical drug therapy with levothyroxine, a thyroid replacement hormone which is the synthetic version of thyroxine (T4) [4–7,10,14,25,27,30]. It is sold under the brand names Synthroid®, Levoxyl®, Levothyroid®, and Unithyroid® [13]. 

 

Combination therapy of triiodothyronine (T3) and levothyroxine is also an option, but it is reserved as an experimental therapy when the symptoms of hypothyroidism persist despite taking levothyroxine [14].

 

In some cases, thyroid surgery may be recommended by a doctor if the thyroid is causing issues such as difficulty breathing or swallowing due to the visible enlargement of the thyroid gland, or there is risk of cancer [10,11,13].

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2.2 Hashimoto’s disease

Hashimoto’s disease is also known as chronic autoimmune thyroiditis [4,10,32]. It is determined by the presence of lymphocytes and thyroid antibodies (autoantibodies developed by a person’s immune system that mistakenly attacks the thyroid cells and tissues) in the thyroid gland, and commonly with the visible presentation of a goiter (Figure 4). It is commonly diagnosed in female individuals [10]. Symptoms of Hashimoto’s disease overlap with those for hypothyroidism.

 

Hashimoto’s disease is the main cause of hypothyroidism in pregnant individuals as a result of the increased metabolic need [10].

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Figure 4. Visual representation of Hashimoto’s disease as seen by the enlarged goiter in the neck area. Image Source: Cleveland Clinic, 2023. 

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Diagnosis & Treatment

Diagnosis for Hashimoto’s disease is the same as for hypothyroidism. An Anti-TPO test is commonly done to measure the presence of anti-thyroid peroxidase (anti-TPO) antibodies which are usually increased in people who have Hashimoto’s [10,13]. Blood testing would reveal elevated TSH levels but normal T4 levels [3,9,10,13,31]. In some cases, TPO antibodies may be elevated with thyroid function tests coming back within the normal range, in which case individuals do not require treatment [13]. Otherwise, treatment for Hashimoto’s is the same as for hypothyroidism – lifelong treatment with levothyroxine.

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2.3 Hyperthyroidism

The prevalence of hyperthyroidism worldwide is between 0.2% and 1.3% in the general population living in iodine-sufficient areas such as Europe and the USA [11]. Hyperthyroidism is caused by the overproduction of thyroid hormones as a result of an overactive thyroid gland or due to the presence of nodules (solid or fluid filled lumps) on the thyroid.

 

In cases where the thyroid is not overactive, hyperthyroidism can be caused by [33]:

• Thyroiditis – a condition where the thyroid gland leaks stored thyroid hormone, caused by an immune system issue or an infection.

• High dose of thyroid hormone therapy – due to artificial exposure of excess thyroid hormone.

 

Symptoms [7]

• Trouble sleeping

• Irregular menstrual periods or pausing of menstrual cycle

• Weight loss, despite having increased appetite

• Enlarged thyroid gland

• Incomplete closure of eyes when sleeping

• Vision problems or eye irritation

• Muscle pain and weakness

• Feeling sensitive to heat

• Anxiety

• Irregular bowel movements

 

Diagnosis and Treatments

In addition to biochemical tests, a radioactive iodine uptake test accompanied by a thyroid gland ultrasound is commonly done to assess for abnormalities that cause thyroid dysfunction (e.g., enlarged thyroid) [7,31]. Blood work would indicate decreased TSH levels and increased T4 levels [3,9,31]. 

 

Treatments for hyperthyroidism include [11,31,33]:

 

A) Drug Therapies

• Antithyroid therapy (e.g., methimazole – the gold standard for hyperthyroidism, propylthiouracil).

• Beta blockers (e.g., atenolol, propranolol).

• Cholestyramine – decreases reabsorption of TH in the gut and helps remove TH from the body.

• Glucocorticoids (e.g., prednisone, hydrocortisone).

• Nonsteroidal anti-inflammatory drugs (NSAIDs) – for pain management.

 

B) Radioactive iodine therapy

 

C) Supersaturated potassium iodide – used with antithyroid therapy to protect the thyroid from absorbing the radioactive iodide.

 

D) Thyroid surgery to remove part (lobectomy) or all (total thyroidectomy) of the thyroid gland in the cases of thyroid cancer or other medical conditions that may compromise the patient’s general health [7,11,16,31].

 

2.4 Grave’s disease

Grave’s disease is an autoimmune condition caused by your immune system attacking the thyroid gland resulting in the overproduction of hormones. This condition is also known as diffuse toxic goiter (enlarged thyroid gland) [7]. In iodine-sufficient parts of the world, Grave’s disease accounts for 70 to 80% of cases of hyperthyroidism [11]. 

 

Symptoms

The symptoms of Grave’s disease overlap with those of hyperthyroidism, and can also include:  

• Bulging eyes (one or both) called Grave’s eye disease (GED) or thyroid eye disease (TED) [3,9]

• Clubbing of fingers and toes

• Swelling of hands and feet

• Reddening and thickening of the skin

 

Diagnosis & Treatments

Same as for hyperthyroidism, the tests ordered by your doctor will determine the cause of thyroid dysfunction [4,7,9]. An additional test for thyrotropin receptor antibodies (TRAbs) will further confirm Grave’s disease. Blood testing would indicate decreased TSH levels but elevated T4 levels [3,9,31].

 

Common treatments for Grave’s Disease include [4,7]: 

• Drug options – methimazole (not recommended for pregnant women in the first trimester) or propylthiouracil.

• Radioactive iodine ablation of the thyroid gland.

• Thyroidectomy surgery to remove all or almost all of the thyroid gland.

 

Always consult with your doctor if you think you may be experiencing symptoms of thyroid disease to determine the right diagnosis and treatment options for you.​

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References

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