Recognize and Treat Hashimoto’s Thyroiditis
Hashimoto’s thyroiditis is the most common cause of hypothyroidism. It is an autoimmune disease in which the body attacks and destroys the thyroid gland. Read on to find out more about its symptoms, causes, and available treatments.
What Is Hashimoto’s Thyroiditis?
Hashimoto’s thyroiditis (also known simply as Hashimoto’s, chronic lymphocytic thyroiditis, or autoimmune thyroiditis) is a progressive autoimmune disease in which the body attacks and destroys the thyroid gland.
Hashimoto’s is characterized by inflammation of the thyroid gland and high levels of antibodies against thyroid enzymes. Eventually, the damage and inflammation progress to hypothyroidism, where the thyroid gland can no longer make enough thyroid hormones thyroxine (T4) and triiodothyronine (T3) [R].
Johns Hopkins Hospital reports Hashimoto’s thyroiditis accounted for 6% of all thyroidectomies from 1942 to 2012 [R].
Additionally, Hashimoto’s is:
- Four to ten times more prevalent in females than males [R]
- Most common in whites
- Most frequent between 45 to 55 years of age [R, R, R]
- More common in women using Hepatitis C treatment (interferon-α) [R, R]
- Hepatitis C virus is likely a triggering factor for all ages [R]
Hashimoto’s Thyroiditis Symptoms
Symptoms of Hashimoto’s thyroiditis are not specific to the disease and may be confused with other autoimmune disorders. The most commonly observed symptoms include [R]:
- Cold intolerance
- Depressive mood
- Dry skin
- Puffy eyes
- Weight gain
- Slowed heart rate
- Joint and muscle pain
- Goiter (enlarged thyroid gland)
*Many patients with autoimmune thyroid diseases also have celiac disease. Therefore, it may be prudent to get tested for celiac disease if some of the symptoms cannot be attributed to Hashimoto’s thyroiditis [R].
There are two forms of Hashimoto’s:
- Atrophic (associated with HLA-DR3), where autoantibodies break down the thyroid gland until it is no longer functional. where
- Goitrous (associated with HLA-DR5), the thyroid gland becomes inflamed and swollen [R].
Primary Tests for Diagnosis of Hashimoto’s
Diagnosis of Hashimoto’s thyroiditis is defined primarily by:
1) High Levels of TSH and Low Levels of Thyroid Hormones
Thyroid-stimulating hormone (TSH) is a hormone made by the pituitary gland that causes the thyroid gland to make T4. It is the most commonly tested hormone to screen for hypothyroidism before other tests are done [R, R].
Generally, the higher the TSH is, the lower the thyroid function [R].
Thyroid hormones are also tested. The normal ranges for thyroid hormones are:
- Total T3 (tT3): 4.2 to 9.1 pmol/L
- Total T4 (tT4): 10.0 to 27.2 pmol/L
- Free or unbound T4 (fT4): 0.9 to 1.7 ng/dL
- Free or unbound T3 (fT3): 2.5 to 4.3 pg/mL
2) The Presence of Thyroid Hormone Antibodies
Antibodies against four different thyroid compounds can be found:
- Thyroxine (T4): Least active form of thyroid hormone
- Triiodothyronine (T3): Most active form of thyroid hormone
- Thyroglobulin: A protein that transports T4 and T3 in the blood
- Thyroperoxidase: An enzyme that helps produce T4 and T3
Individuals without thyroid diseases are not expected to have detectable levels of thyroid autoantibodies, although there are some exceptions.
- Anti-thyroxine positive at >8.0% in blood [R, R]
- Anti-triiodothyronine positive at >8.0% in blood [R, R]]
- Anti-thyroglobulin or anti-TG at 5 – 40 IU/mL
- Anti-thyroperoxidase or anti-TPO at 0 – 35 IU/mL
*The study that defined these ranges considered anti-TPO <35 and anti-TG <40 as “negative.”
3) Ultrasound or Needle Biopsy of the Thyroid Gland
Secondary Tests for the Diagnosis of Hashimoto’s
1) Physical examination of the thyroid gland for inflammation (goiter). A physician will examine the front of the neck to feel for evidence of swelling or goiter.
2) Urinary iodide concentration/excretion (UIC/UIE) measurements [R, R]. Children with autoimmune thyroiditis between the ages of 6 to 12 have high (>300 μg/L) levels of UIC/UIE compared to healthy children and are at higher risk of progressing to clinical hypothyroidism [R].
5 Stages of Hashimoto’s Thyroiditis Progression
Stage One: Thyroid function is normal and there are no thyroid antibodies present. However, for those who have a genetic predisposition, there may be evidence of immune activation (abnormal cell types found in serologic tests).
Stage Two: Thyroid antibodies are detected in the blood, with increasing concentration over time. Higher levels of TSH, which can lead to thyroid inflammation in predisposed people, become apparent.
Stage Three: This is subclinical thyroid dysfunction. Thyroid antibody levels continue to increase until overt Hashimoto’s thyroiditis develops.
Stage Four: This is overt Hashimoto’s thyroiditis with diagnosable hypothyroidism. At this stage, patients are at the highest risk of developing clinical hypothyroidism (non-functioning thyroid gland).
Stage Five: Complete hypothyroidism as a result of Hashimoto’s thyroiditis progression and other factors (lifestyle, genetics, etc.) [R].
Genetic Causes of Hashimoto’s Thyroiditis
Genes account for 70% of the risk of developing Hashimoto’s disease, while the environment accounts for the remaining 30% [R].
If you have a sibling with Hashimoto’s, you have twice the risk of developing the disease compared to healthy people. If one of your parents has Hashimoto’s, then you may have triple the risk of developing the disease [R].
Genes that are commonly found in Hashimoto’s patients include:
1) ZFAT (cell survival gene) is a gene that prevents cell death (apoptosis).
Reduced production of ZFAT has been associated with cell death in connective tissue and problems with cell development [R].
Having a T variant for Ex9b-SNP10 at intron 9 is associated with increased risk for autoimmune thyroiditis [R].
2) PDE8B is a gene that functions primarily in the thyroid.
A SNP (rs4704397) of PDE8B has been associated with hypothyroidism. PDE8B gene mutations may lead to higher TSH levels [R].
3) PTPN22 encodes a protein that prevents the activation of immune cells called T-cells (involved in H inhibitor of T-cell activation
4) The Thyroglobulin (Tg) gene is involved in the synthesis of thyroid hormones T4 and T3.
SNPs of the Tg gene at exon-33 may predispose people to autoimmune thyroid diseases, although the exact mechanisms are unknown. The D8S272 marker is indirectly linked to susceptibility to autoimmune thyroid diseases [R].
The 1623 A/G SNP of the Tg gene promoter (rs180195) is positively associated with Hashimoto’s thyroiditis. Individuals with Hashimoto’s are more likely to have the A/G variants [R].
5) The Vitamin D receptor gene (the “sunshine gene”) is critical for Vitamin D absorption.
Mutations in the vitamin D receptor gene can cause vitamin D deficiency (<30 ng/mL) [R].
Vitamin D deficiency is positively correlated with increased thyroid antibodies, a common feature of autoimmune thyroid diseases [R].
Environmental Risk Factors for Hashimoto’s Thyroiditis
There is no known single environmental cause of Hashimoto’s, but several have been associated with the development of autoimmune thyroiditis.
1) Postpartum Hormonal Fluctuation Increases the Risk of Developing Hashimoto’s
Thyroid antibody concentration decreases during pregnancy to prevent rejection of the fetus. Following birth, there is a rebound in thyroid antibodies. This fluctuation of thyroid hormones puts a mother at risk of developing postpartum thyroiditis (observed in 3-8% of all pregnancies), a common forerunner of other permanent autoimmune hypothyroidisms [R, R].
2) High Iodine Levels Negatively Impact Thyroid Health
The development of autoimmune thyroiditis is positively associated with excessive iodine exposure. Increased iodination of thyroglobulin (a protein involved in thyroid hormone production) may lead to autoimmune thyroiditis symptoms in susceptible individuals [R, R].
Deterioration of the thyroid gland likely follows excess iodine levels [R].
3) Selenium Deficiency Promotes Inflammation and Disease
Selenoproteins are essential to thyroid function. Selenium deficiency prevents selenoproteins from removing excess hydrogen peroxide in the thyroid gland, thus resulting in inflammation and an increased risk of thyroid disease [R].
4) Radiation Exposure Increases Risk of Developing Hashimoto’s
Prevalence of thyroid antibodies increased after the Chernobyl accident where children were exposed to radiation [R].
Significant radioactive fallout can likely increase the risk of developing autoimmune diseases like Hashimoto’s.
5) Pollutants Increase Inflammation and Influence the Autoimmune Process
Toxic substances, including tobacco smoke, solvents, and certain metals, may increase the risk of Hashimoto’s [R].
6) Drug Use May Cause Hashimoto’s in Genetically Predisposed Individuals
Certain drugs used to treat viral infection (interferon-α) or cancers (ipilimumab, pembrolizumab, and nivolumab) have been positively associated with autoimmune disorders, including Hashimoto’s [R, R].
7) Sleep Apnea May Increase the Risk of Developing Hashimoto’s Thyroiditis
Important facts about sleep apnea [R]:
- Characterized by pauses in breathing during sleep
- Causes fatigue and lethargy upon waking
- Hashimoto’s thyroiditis is prevalent in people with obstructive sleep apnea (OSA), especially among women
- People with both OSA and Hashimoto’s have elevated levels (1,000 IU/mL) of thyroid antibodies compared to people with Hashimoto’s alone (400 IU/mL)
- Positively associated with low-grade inflammation (inflammatory cytokines), which may accelerate the development of autoimmune symptoms seen in Hashimoto’s thyroiditis
The importance of the circadian rhythm:
- TSH follows a circadian rhythm, peaking at the beginning of sleep, while the lowest concentration occurs at midday [R, R].
- The circadian rhythm of TSH secretion is retained despite abnormal thyroid function in Hashimoto’s patients [R].
- Abnormalities in sleep cycle due to sleep apnea, combined with TSH rhythm, could result in excessive levels of inflammation and increase the risk for autoimmune diseases.
8) Mercury Fillings and Mercury Allergy May Raise Thyroid Antibody Levels
Inflammation from high antibody levels (anti-thyroid peroxidase and anti-thyroglobulin) worsens Hashimoto’s symptoms. Removal of mercury-containing dental amalgams decreased thyroid antibodies in 27 people with mercury allergies [R].
Hashimoto’s Thyroiditis Treatment
1) Hormone Replacement
Synthetic thyroid hormone replacement is used to restore thyroid hormone levels in the body. The most common synthetic version is levothyroxine (L-T4) [R].
Taking L-T4 on an empty stomach before bedtime results in higher thyroid hormone concentrations and lower TSH levels, but for some people, L-T4 is best taken in the morning on an empty stomach [R, R].
A significant minority (12%) of patients taking levothyroxine still report lingering symptoms after treatment, possibly due to impaired conversion of T4 into its active form, T3 [R].
One study (DB-RT) of 59 hypothyroid women found that after 12 weeks, a combination of synthetic T4 and T3 was more effective at improving quality of life, anxiety, and depression than taking T4 alone [R].
Desiccated thyroid is a supplement made from the thyroid glands of pigs and cows that is often taken to treat hypothyroidism.
A study (DB-RT) in 70 hypothyroid patients found that desiccated thyroid for 16 weeks resulted in an average weight loss of 3 lbs, whereas patients taking levothyroxine experienced no weight loss. In addition, desiccated thyroid was preferred by nearly half of the patients (34) compared to only 13 who preferred levothyroxine [R].
2) Vitamin D Supplementation May Decrease Risk of Hypothyroidism
Vitamin D deficiency is common in Hashimoto’s thyroiditis patients, and it may be a factor involved in the progression to complete hypothyroidism. Anti-thyroxine levels decreased in Hashimoto’s patients after vitamin D (D3, cholecalciferol) replacement treatment for 2 months [R, R].
However, it is important to note that in cases of women with postpartum thyroiditis, spontaneous decreases in autoantibodies may occur [R]
Additionally, one study reported low levels of vitamin D in women with significant amounts of antithyroid antibodies but did not find the same negative correlation in men [R].
Therefore, some males may not benefit as much from vitamin D supplementation to treat Hashimoto’s symptoms.
3) Iron Supplementation May Restore Thyroid Hormone Levels
Iron deficiency prevents proper thyroid function. Special iron-containing proteins (thyroid peroxidases) help produce thyroid hormones, but when iron levels are low, hormone production is too. Iron supplementation treatment may be especially relevant to anemic women with Hashimoto’s thyroiditis. Thyroid hormone concentrations can be restored in anemic women with impaired thyroids after iron supplementation [R].
4) Selenium Supplementation May Help Balance Antibody Levels
Selenium supplementation (50 to 100 μg/day) may help control autoantibody levels, thus lowering the intensity of hypothyroidism symptoms common to Hashimoto’s thyroiditis [R, R]. However, effectiveness is not equal for all individuals.
6) Stem-Cell Therapy May Prevent Activation of T-Cells Involved in Autoimmunity
Stem cells have been used to correct imbalances of antithyroid autoantibodies in female Hashimoto’s patients. In a cell study, stem cells were able to prevent the activation of T-cells involved in the destruction of the thyroid gland seen in Hashimoto’s [R].
7) Low-Level Laser Therapy May Improve Thyroid Function
8) Vitamin B12 Supplementation May Improve Symptoms
9) Melatonin Improves Symptoms of Fatigue and Sleep Apnea
Melatonin is a hormone secreted by the pineal gland that controls our cycles of sleep and wakefulness.
People suffering from the effects of fatigue or obstructive sleep apnea (OSA) as a result of impaired thyroid function may find melatonin to be an effective tool for restoring sleep cycles. Consecutive days of bright light exposure at midday increases levels of nocturnal melatonin release, which should help restore abnormalities in circadian rhythm [R].
Too much melatonin can be an issue, however. Compared with healthy individuals, melatonin secretion at midnight is higher in most people with autoimmune diseases. Consequently, higher levels of melatonin lead to inflammatory responses (increase in inflammatory cytokines) that often have adverse effects in those with autoimmune diseases [R].
High levels of melatonin have inhibitory effects on cell development and thyroid hormone synthesis [R].
Normal melatonin levels are important for achieving better sleep and lowering the intensity of autoimmune thyroiditis symptoms.
Finally, a study on the antioxidant-like effects of melatonin in porcine thyroid tissue showed that melatonin may be effective in protecting against harmful DNA destruction associated with thyroid cancer initiation (Fe + H2O2-induced fat breakdown) [R].
Diet Changes That Improve Hashimoto’s Thyroiditis
Diet is a critical component of thyroid health. The following are examples of diet changes that may improve thyroid function.
1) Low-Carbohydrate Diets May Lower Autoantibody Levels
Maintaining a low-carbohydrate diet decreases levels of antithyroid molecules and other autoantibodies (antimicrosomal, anti-thyroid peroxidase) [R].
However, it is important to note that there is no unanimous conclusion on the effectiveness of gluten-free diets for people with autoimmune diseases. A year-long study on newly diagnosed celiac disease patients found that the thyroid gland continued to atrophy despite a change to a gluten-free diet [R].
Therefore, gluten-free diets may not work for everyone to prevent the development of autoimmune diseases specifically affecting the thyroid gland.
2) Low-Goitrogen Diet May Prevent Decrease in Thyroid Hormones
Goitrogens are substances that reduce thyroid hormone production by limiting thyroid gland iodine uptake. Cruciferous vegetables (broccoli, cabbage, cauliflower) contain goitrogens and, at high levels of consumption, have been associated with increased risk of thyroid cancer in women with low iodine intake [R, R].
Goitrogens also cause thyroid inflammation, so a low-goitrogen diet may prove useful to people suffering from the goitrous variety of Hashimoto’s [R].
Interested in Learning More?
Check out the podcast with Dr. Izabella Wentz to learn more about her personal experience with Hashimoto’s thyroiditis, as well as her insight into treating autoimmune diseases.