What is hypothyroidism?
Hypothyroidism is a condition in which the thyroid gland doesn’t produce enough thyroid hormones (1).
The thyroid gland is shaped like a butterfly and located on the neck, right below the Adam’s apple.
There are four main hormones involved in thyroid function:
1. Thyrotropin-releasing hormone (TRH)
TRH is produced by the hypothalamus and stimulates the release of TSH from the pituitary gland (2).
2. Thyroid-stimulating hormone (TSH)
TSH stimulates the thyroid gland to produce thyroid hormones (T3 and T4) (3).
The pituitary gland releases less TSH when T3 and T4 levels are high (as in hyperthyroidism) and more TSH when T3 and T4 levels are low (as in hypothyroidism (3).
3. Thyroxine (T4) and triiodothyronine (T3)
There are several different types of thyroid hormone (T1 through T4), but T3 is the main active form.
Here’s how they are made (4).
The thyroid gland contains cells called thyrocytes that produce a clear gooey liquid called thyroglobulin.
Thyroglobulin stores materials like tyrosine and iodide, which are used in thyroid hormone production.
Next, iodine attaches to tyrosine to create thyroid hormone:
- Tyrosine + 1 iodine molecule = T1 thyroid hormone
- Tyrosine + 2 iodine molecules = T2 thyroid hormone
- T1 + T2 = T3 (the main active thyroid hormone!)
- T2 + T2 = T4 (a 300% less active form of thyroid hormone that can be converted to T3 elsewhere in the body)
The main hormones produced by the thyroid gland are T4 (80%) and T3 (20%), which affect nearly every organ system in the body (5).
They play important roles in energy metabolism, brain development, heart function, and bone health (5).
Although thyroid receptors can bind to both T3 and T4, they have a much higher affinity for T3, so T4 is considered inactive (5).
However, after being released from the thyroid gland, T4 can be converted to T3 in various tissues throughout the body via deiodination (the removal of an iodine molecule) (6).
Only 20% of T3 hormone is made directly by the thyroid gland. 25% is made from T4 in the liver and kidneys, and 55% is made from T4 in the pituitary, central nervous system, and skeletal muscle (7).
What factors could prevent someone from converting T4 to T3 properly?
- Chemotherapy (8)
- Deficiency in growth hormone (9)
- Diabetes (10, 11)
- Excessive alcohol intake (12)
- Excessive iodine intake (13)
- Fasting (14)
- Heavy metals (especially lead and cadmium) (15)
- Kidney & liver diseases (since that is where a lot of the conversion happens) (16, 17)
- Nutrient deficiencies (especially selenium) (15)
- PCBs (15)
- Pesticides (15)
- Some chemicals in personal care products (15)
What are the different types of hypothyroidism?
Hypothyroidism can be categorized as primary or secondary based on which hormone gland is the root cause of dysfunction.
- Primary hypothyroidism occurs when the thyroid gland is unable to produce enough thyroid hormone, resulting in thyroid hormone deficiency (1). This accounts for more than 99% of all hypothyroidism cases (18).
- Secondary hypothyroidism (also known as central hypothyroidism) occurs when either the pituitary gland doesn’t produce enough TSH or when the hypothalamus doesn’t produce enough TRH (1, 19). More than half of these cases are caused by pituitary adenomas (benign tumors) (20).
- Sometimes secondary hypothyroidism is used to refer to hypothyroidism caused by pituitary dysfunction, while the term tertiary hypothyroidism is used to refer to hypothyroidism caused by hypothalamic dysfunction (19).
Based on the severity of disease, hypothyroidism can be further categorized as subclinical or overt.
- Subclinical hypothyroidism occurs when TSH is elevated but free T4 is normal (21). Despite being labeled “subclinical,” some patients with this condition experience symptoms (22). Approximately 2-6% of cases will progress to overt hypothyroidism per year (23).
- Overt hypothyroidism is defined by elevated TSH and low free T4 levels (1). These patients typically present with symptoms and require treatment.
How common is hypothyroidism?
The prevalence of hypothyroidism in the United States is approximately 3.7% (0.3% overt and 3.4% subclinical) (24).
Hypothyroidism is 10 times more likely to occur in women compared to men, and the risk increases with age (25).
What are the signs and symptoms?
Signs and symptoms of hypothyroidism include the following:
- Anxiety (26)
- Brittle nails (27, 28)
- Cold intolerance (19)
- Constipation (19, 21)
- Depression (26)
- Dry, coarse skin (19, 29)
- Elevated LDL cholesterol (30, 31)
- Erectile dysfunction (32)
- Fatigue (21)
- Goiter (33)
- Hair loss (19, 34)
- High blood pressure (35)
- High cholesterol (36, 37)
- Hoarse voice (38)
- Loss of libido (39, 40)
- Muscle weakness (41, 42)
- Menstrual irregularities (43, 44)
- Muscle cramps (41)
- Poor memory (45)
- Slow heart rate (46)
- Swollen or puffy face (47)
- Weight gain (48)
For more details, see The Ultimate Hypothyroidism Symptom Checklist.
What is the potential harm from missing a hypothyroid diagnosis?
According to one study, white women in the US with subclinical hypothyroidism (TSH >4 and normal free T4) had a 70% increased risk of heart disease and more than double the risk of heart attack (49).
The link was even stronger in women with Hashimoto’s.
Hashimoto’s more than triples the risk of miscarriage (50).
What causes hypothyroidism?
The following factors have been linked to the development of hypothyroidism:
1. Nutrient imbalances
Globally, iodine deficiency is the most common cause of hypothyroidism (1).
On the other hand, excess iodine intake also increases the risk of developing hypothyroidism (53).
In the United States, Hashimoto’s thyroiditis is the most common cause of hypothyroidism (1).
Hashimoto’s (also known as autoimmune thyroiditis) is a condition in which the immune system attacks the thyroid gland (61).
Eventually, the thyroid becomes so damaged that it can’t produce enough thyroid hormones (61).
3. Exposure to radiation
Hypothyroidism is a common adverse effect in patients who receive radiation therapy for head and neck cancer (62).
It is well known that high-dose radiation damages the thyroid gland, but it’s unclear whether low-dose radiation has similar effects (63).
4. Drug interactions
Certain drugs can induce hypothyroidism by inhibiting the production of thyroid hormones or TSH, or by increasing the risk for autoimmune thyroiditis (64).
Some of these include amiodarone, interferon, lithium, and tyrosine kinase inhibitors (64).
- rs3184504 (SH2B3 gene)
- rs4704397 (PDE8B gene)
There is also a genetic condition called congenital hypothyroidism, in which the thyroid gland isn’t functioning properly, and the thyroid gland is often absent, smaller than normal, or abnormally located (67).
This may be due to the changes in the immune system during pregnancy (fetal cells entering the mother’s circulation, potentially setting the stage for an immune response or autoimmunity) (70).
Most women fully recover within one year, but some develop permanent hypothyroidism (69).
More research is needed (73).
8. Heavy metal toxicity?
More research is needed to determine whether mercury exposure is a direct cause of thyroid dysfunction.
9. Gut dysbiosis?
Preliminary research shows a link between altered gut microbiota and hypothyroidism.
It has been reported that more than 50% of patients with hypothyroidism have small intestinal bacterial overgrowth (SIBO) (79).
Some have hypothesized that gut bacteria influence thyroid function by contributing to thyroid hormone synthesis and altering the processing of certain minerals (iodine, selenium, iron, zinc) (80, 81).
The following conditions are associated with hypothyroidism:
1. Myxedema coma
When severe hypothyroidism is left untreated for a long period of time, low thyroid hormone levels eventually lead to hypothermia and suppressed heart functioning (82).
The body compensates by decreasing blood volume, restricting blood flow to the extremities, and increasing blood pressure in an attempt to maintain a normal core body temperature (83).
Myxedema coma (also called myxedema crisis), occurs when a precipitating event (trauma, stroke, infection, etc.) disrupts this homeostasis, and organs begin to fail due to inadequate blood supply (83).
2. Celiac disease
In fact, it is recommended that everyone with Hashimoto’s be screened for Celiac disease (85).
In females, low thyroid hormone levels can lead to low estrogen and testosterone levels, as well as menstrual disturbances (such as irregular periods) (87).
One study found that 24% of infertile women had hypothyroidism, and 77% of these women were able to conceive within 6 weeks to 1 year of starting levothyroxine treatment (91).
Evidence suggests that patients with PCOS are at least three times more likely to be diagnosed with autoimmune thyroiditis (Hashimoto’s) than healthy participants (95).
More research is needed to determine the mechanism underlying this association.
A 2017 meta-analysis found that subclinical hypothyroidism (with AND without thyroid autoimmunity) was a risk factor for miscarriage before 20 weeks of pregnancy (96).
6. Heart failure
Because thyroid hormone receptors are present in the cardiac muscle and throughout blood vessels, it is thought that alterations in thyroid hormone levels can significantly alter cardiac function (101).
7. Autoimmune diseases
Polyautoimmunity occurs when a patient is diagnosed with two or more autoimmune diseases (106).
Some scientists have hypothesized that patients with polyautoimmunity have a dysregulated immune system that predisposes them to autoimmune diseases (106).
8. Type 2 diabetes
Type 2 diabetes is associated with a nearly two-fold increase in the risk of subclinical hypothyroidism (107).
It is thought that genetic factors leading to insulin resistance may play a role in the relationship between hypothyroidism and type 2 diabetes, but more research is needed (108).
10. Depression and anxiety
The link between hypothyroidism and psychiatric disorders, such as depression and anxiety, is controversial.
More research is needed to fully understand the relationship between thyroid function and mental health (117).
11. Obstructive sleep apnea
A 2016 meta-analysis found a high prevalence of hypothyroidism in patients with obstructive sleep apnea (OSA), although obesity might have been a confounder (118).
Hypothyroidism is known to cause mucus deposits throughout the body, and some experts believe these deposits may build up in the pharynx, increasing the risk for OSA (119).
12. Carpal tunnel syndrome
Some evidence suggests that carpal tunnel syndrome, a condition that causes pain and numbness in the hand, is more common in patients with hypothyroidism (120).
The proposed mechanism is that hypothyroidism causes mucus deposits to form on the median nerve, eventually compressing the nerve and leading to symptoms (121).
Hypothyroidism can cause hypochlorhydria or achlorhydria (low or no stomach acid) because thyroid hormone is necessary for the production of hydrochloric acid (122).
Who should be checked for hypothyroidism?
The following people may want to be screened for hypothyroidism due to increased risk:
- Patients with autoimmune diseases, including type 1 diabetes, pernicious anemia, and celiac disease (85, 123, 124, 125).
- Patients with a family history of thyroid problems or autoimmune disorders (126).
- Patients with a prior history of thyroid surgery or dysfunction (21).
- Patients diagnosed with depression, anxiety, or other mood disorders (127).
- Patients on lithium or amiodarone (anti-arrhythmia drug) (128, 129, 130).
What labs are used to diagnose hypothyroidism?
A doctor may look at the following labs when diagnosing hypothyroidism:
In primary hypothyroidism, TSH levels are elevated because the body is struggling to produce enough thyroid hormones (3).
In conventional medicine, TSH is used to screen for thyroid dysfunction and is often the only test used to diagnose hypothyroidism (131).
The most recent guidelines state that the normal range for serum TSH in adults is 0.4-4.0 mIU/L, and overt hypothyroidism is defined by TSH>10 mIU/L (132).
2. T3 and T4
In hypothyroidism, T3 and T4 levels are low because the thyroid isn’t producing enough thyroid hormones (3).
Both T3 and T4 can be measured as either “free” (the amount of unbound hormones) or “total” (both bound and unbound hormones).
Free hormone measurements are generally more helpful to measure, because only free hormones are available to be used by the body (136).
3. Reverse T3
When T4 is metabolized, it naturally forms some 3,3´5´-triiodothyronine (also known as reverse T3 or rT3), which is inactive (137).
Reverse T3 is often elevated in critically ill or malnourished patients despite the absence of any HPA axis dysfunction (known as nonthyroidal illness or euthyroid sick syndrome) (138).
In conventional medicine, reverse T3 isn’t tested because it is not considered to be helpful in diagnosing hypothyroidism (139).
Most functional medicine practitioners test reverse T3 levels because they believe that elevated levels may point to a problem in the conversion of T4 (where too much rT3 is being made, relative to active T3) (139).
The idea is that reverse T3 competes with T3 at binding sites on T3 receptors and that high levels can cause symptoms of hypothyroidism because reverse T3 is preventing active T3 from exerting its effects on tissues (139).
However, some experts are critical of this theory because the affinity of T3 for the T3 receptor is 100 times higher than the affinity of rT3 (140).
4. Thyroid antibodies
In autoimmune thyroiditis (Hashimoto’s), the immune system produces antibodies that attack the thyroid gland (61).
The most common thyroid antibodies are anti-thyroid peroxidase (TPOAb) and anti-thyroglobulin (TgAb) (141).
TPO antibodies tend to precede the development of thyroid dysfunction and are present in 90-95% of patients with Hashimoto’s (141).
An older study found that the risk of developing overt hypothyroidism nearly doubled (from 2.6% to 4.3%) in individuals with TPO antibodies (142).
Unless TPO antibodies are also present, Tg antibodies are not significantly associated with thyroid disease (144).
What are the normal ranges for these labs?
More research is needed to establish universally standardized values.
- TSH: 0.4-4.0 uIU/mL
- Free T4: 0.8-1.9 ng/dL
- Free T3: 1.8-4.2 pg/mL
- Reverse T3: 14.9-26.1 ng/dL
- Anti-TG antibody titer: </=40 IU/mL
- Anti-TPO antibody titer: </=34 IU/mL
Biotin can interfere with these lab results, so any supplements containing biotin should be avoided for a few days before the blood draw (146).
It may cause falsely low TSH, thyroglobulin, and thyroid antibody results, while free T3 and T4 may be falsely elevated.
Which companies offer these lab tests?
- Vibrant America (TSH, Total T3, Total T4, Free T3, Free T4 Reverse T3, TPOAb, TgAb)
- Genova Diagnostics Comprehensive Thyroid Assessment (TSH, Free T3, Free T4, Reverse T3, TPOAb, TgAb)
- DHA Laboratory (TSH, Total T3, Total T4, Free T3, Free T4, Reverse T3, TPOAb, TgAb, T3 uptake)
- Ulta Lab Tests ULTA Thyroid Panel (TSH, Free T3, Free T4, Total T4, Reverse T3, TPOAb, TgAb, T3 uptake, Free T4 Index)
- Paloma Complete Thyroid Test (TSH, Free T3, Free T4, TPOAb, Reverse T3 and Vitamin D optional add-ons)
What do doctors typically do to treat hypothyroidism?
Overt hypothyroidism (TSH>10 mIU/L) is usually treated with levothyroxine (Synthroid), a synthetic version of thyroxine (T4), which is taken orally once a day (147).
Alternatively, there is a natural medication, known as desiccated thyroid extract (DTE), which is made from the thyroid glands of pigs and contains both T4 and T3 (21).
When someone first starts their meds, they will usually go in for blood work every 6-8 weeks to adjust the dosage until they find the right one (152).
Once they are stable, they will still need at least annual check-ups.
The goal is to help the patient feel better and to get TSH, T4, and T3 into normal ranges.
Subclinical hypothyroidism (TSH 4.5-10 mIU/L) is not treated by most conventional doctors and remains a controversial topic (21).
More research is needed, but limited evidence suggests there are no clinically significant benefits from treating subclinical hypothyroidism with thyroid medication, except in pregnant women with TSH>2.5 mIU/L (153, 154). (However, potential root causes should still be analyzed and addressed.)
What are the dietary recommendations for hypothyroidism?
The following diets may be helpful for people with hypothyroidism:
1. Consume enough carbohydrates.
Carbohydrates are important for thyroid hormone production, and there is evidence that low carbohydrate diets reduce serum T3 levels (155).
A 2017 study found that 17% of patients treated with a ketogenic diet for epilepsy developed hypothyroidism within 6 months (156).
More research is needed to determine the ideal carbohydrate intake for thyroid health.
2. Eliminate gluten?
Because Hashimoto’s has been linked with celiac disease, it is thought that a gluten-free diet might be beneficial for these patients (157).
A 2019 study found that a gluten-free diet significantly reduced thyroid antibodies and increased vitamin D levels in participants with Hashimoto’s (157).
Currently, there is no evidence that a gluten-free diet provides any benefit to patients whose hypothyroidism is not caused by Hashimoto’s.
3. Avoid goitrogens?
It is often recommended that patients with hypothyroidism avoid foods high in goitrogens, but current evidence suggests this is probably only necessary for people with iodine deficiency (160).
Still, consuming excessive amounts of these foods should probably be avoided, especially if iodine intake is inadequate.
See our note on goitrogens for more information on this topic.
A recent study looked at the effects of the Autoimmune Protocol (AIP), a modified Paleo elimination diet, on thyroid function and quality of life in women with Hashimoto’s (164).
After 10 weeks, health-related quality of life was significantly increased, and symptoms scores were significantly decreased.
However, there were no changes in markers of thyroid function (TSH, T3, T4, thyroid antibodies).
Which nutrients could be beneficial for hypothyroidism?
The following nutrients are important for proper thyroid function:
However, excess iodine intake (via supplementation, iodized salt, or drinking water) can actually cause hypothyroidism as well (53).
It’s unclear how this occurs, but research in animals has shown a reduction in thyroid hormones following large doses of iodine (167).
Selenium is important for efficient thyroid hormone production and conversion of T4 to T3 (168).
The thyroid gland also expresses large numbers of selenoproteins (selenium-containing proteins), such as glutathione peroxidase, which act as antioxidants and protect the thyroid from damage (168, 169, 170).
A recent study found that selenium supplementation (83 mcg/day for 4 months) normalized TSH levels in patients with subclinical hypothyroidism due to Hashimoto’s (171).
Iron is required by thyroid peroxidase (TPO), the enzyme responsible for incorporating iodine with thyroglobulin to produce thyroid hormones (168).
One study found that iron supplementation in combination with levothyroxine reduced TSH levels in patients with iron deficiency anemia and subclinical hypothyroidism compared to iron or levothyroxine alone (174).
The thyroid gland needs magnesium in order to utilize iodine and convert inactive T4 to active T3 (178).
Low serum magnesium levels have been linked with an increased risk of hypothyroidism and higher levels of thyroid antibodies (55).
A 2007 study found that exercising to the point of exhaustion resulted in a reduction in thyroid hormones, but participants who received magnesium sulfate supplementation (10 mg/kg body weight per day) maintained stable thyroid hormone levels (179).
However, more research is needed to evaluate whether magnesium supplementation might be beneficial for hypothyroidism.
Zinc is required for the synthesis of TRH and TSH, and also plays a role in converting T4 into T3 (180).
A 2015 trial found that zinc supplementation (30 mg zinc gluconate/day) resulted in significantly increased free T3 levels compared to placebo in participants with hypothyroidism (181).
More research is needed to confirm these effects.
6. Vitamin A
A 2012 trial in healthy women found that vitamin A supplementation (25,000 IU/day of retinyl palmitate) for 4 months caused a reduction in serum TSH levels and an increase in T3 levels (182).
This suggests that vitamin A might ameliorate some of the negative effects of iodine deficiency (183).
7. Vitamin D
In one study, TPOAb levels were decreased by 20% after patients with vitamin D deficiency received vitamin D3 supplements (1200-4000 IU/day) for 4 months (185).
Another trial showed a significant decrease in TSH in individuals with hypothyroidism who received 50,000 IU vitamin D weekly for 12 weeks (188).
Vitamin D’s role in immune health may be responsible for these effects (189).
8. Vitamin B12
Scientists believe that the link between vitamin B12 deficiency and Hashimoto’s is related to the presence of other autoimmune disorders such as atrophic gastritis or pernicious anemia (58).
Still, it’s unclear why non-autoimmune hypothyroidism is associated with low vitamin B12 levels and whether supplementation could improve thyroid hormone levels.
In order for the thyroid to produce enough thyroid hormones, there must be an adequate supply of the amino acid tyrosine (191).
Foods high in tyrosine include meat, fish, eggs, dairy, cheese, whole grains, and legumes (192).
A 2007 study found that tyrosine supplementation (12 g/day for 3 months) reduced TSH levels by about 30% in healthy subjects living in Antarctica (193).
Further research is needed to determine whether tyrosine supplementation might be beneficial for those with hypothyroidism.
Do any other supplements help?
The following supplements may be helpful for hypothyroidism:
Inositol is a sugar found naturally in food (especially grains and legumes) that can also be produced by the body (194).
In thyroid cells, myo-inositol (a form of inositol) regulates the generation of hydrogen peroxide, which is required for thyroid hormone synthesis (195).
Several studies in patients with Hashimoto’s have shown that supplementation with myo-inositol (600 mg/day) and selenium (16-83 mcg/day) for 6 months results in decreased TSH and thyroid antibodies, as well as increased free T4 levels (196, 197, 198).
More research is needed to confirm these results.
One recent study found that supplementation with ashwagandha root extract (600 mg/day) decreased TSH while increasing T3 and T4 in patients with subclinical hypothyroidism (199).
More studies are needed to determine the mechanism responsible for this effect, but researchers believe ashwagandha may play a role in regulating the HPA axis (199).
3. Supplements under evaluation
A recent study found that probiotic supplementation (VSL#3) for 2 months had no effect on markers of thyroid function (TSH, free T3, free T4) (200).
However, the treatment group required fewer levothyroxine dose adjustments, suggesting that probiotics may prevent hormonal fluctuations.
What other lifestyle changes are recommended?
1. Avoid intense exercise?
More research in individuals with hypothyroidism is needed.
Erica is a registered dietitian nutritionist and lover of science and learning. She has a never-ending passion for education, and gladly spends her time writing & growing this blog! When she’s not at the computer, she can be found in the kitchen with her family, rocking out to good music and cooking up a storm.