Hyperthyroidism is a state in which the body is producing too much thyroid hormone. The main hyperthyroid conditions are:

- Graves' disease

- Toxic thyroid nodule

- Thyroid storm

- Toxic nodular struma (Plummer's disease)

- Hashitoxicosis: "transient" hyperthyroidism that can occur in Hashimoto's thyroiditis

Certain medications can have the unintended side effect of affecting thyroid function. While some medications can lead to significant hypothyroidism or hyperthyroidism and those at risk will need to be carefully monitored, some medications may affect thyroid hormone lab tests without causing any symptoms or clinical changes, and may not require treatment. The following medications have been linked to various forms of thyroid disease:

- Amiodarone (more commonly can lead to hypothyroidism, but can be associated with some types of hyperthyroidism)

- Lithium salts (hypothyroidism)

- Some types of interferon and IL-2 (thyroiditis)

- Glucocorticoids, dopamine agonists, and somatostatin analogs (block TSH, which can lead to hypothyroidism)

There are several causes of hyperthyroidism. Most often, the entire gland is overproducing thyroid hormone. Less commonly, a single nodule is responsible for the excess hormone secretion, called a "hot" nodule. Thyroiditis (inflammation of the thyroid) can also cause hyperthyroidism. Functional thyroid tissue producing an excess of thyroid hormone occurs in a number of clinical conditions.

The major causes in humans are:

- Graves' disease. An autoimmune disease (usually, the most common etiology with 50-80% worldwide, although this varies substantially with location- i.e., 47% in Switzerland (Horst et al., 1987) to 90% in the USA (Hamburger et al. 1981)). Thought to be due to varying levels of iodine in the diet. It is eight times more common in females than males and often occurs in young females, around 20 – 40 years of age.

- Toxic thyroid adenoma (the most common etiology in Switzerland, 53%, thought to be atypical due to a low level of dietary iodine in this country)

- Toxic multinodular goiter

High blood levels of thyroid hormones (most accurately termed hyperthyroxinemia) can occur for a number of other reasons:

- Inflammation of the thyroid is called thyroiditis. There are several different kinds of thyroiditis including Hashimoto's thyroiditis (Hypothyroidism immune-mediated), and subacute thyroiditis (de Quervain's). These may be "initially" associated with secretion of excess thyroid hormone but usually progress to gland dysfunction and, thus, to hormone deficiency and hypothyroidism.

- Oral consumption of excess thyroid hormone tablets is possible (surreptitious use of thyroid hormone), as is the rare event of consumption of ground beef contaminated with thyroid tissue, and thus thyroid hormone (termed "hamburger hyperthyroidism").

- Amiodarone, an antiarrhythmic drug, is structurally similar to thyroxine and may cause either under- or overactivity of the thyroid.

- Postpartum thyroiditis (PPT) occurs in about 7% of women during the year after they give birth. PPT typically has several phases, the first of which is hyperthyroidism. This form of hyperthyroidism usually corrects itself within weeks or months without the need for treatment.

- A struma ovarii is a rare form of monodermal teratoma that contains mostly thyroid tissue, which leads to hyperthyroidism.

- Excess iodine consumption notably from algae such as kelp.

Thyrotoxicosis can also occur after taking too much thyroid hormone in the form of supplements, such as levothyroxine (a phenomenon known as exogenous thyrotoxicosis, alimentary thyrotoxicosis, or occult factitial thyrotoxicosis).

Hypersecretion of thyroid stimulating hormone (TSH), which in turn is almost always caused by a pituitary adenoma, accounts for much less than 1 percent of hyperthyroidism cases.

Worldwide about one billion people are estimated to be iodine deficient; however, it is unknown how often this results in hypothyroidism. In large population-based studies in Western countries with sufficient dietary iodine, 0.3–0.4% of the population have overt hypothyroidism. A larger proportion, 4.3–8.5%, have subclinical hypothyroidism. Of people with subclinical hypothyroidism, 80% have a TSH level below the 10 mIU/l mark regarded as the threshold for treatment. Children with subclinical hypothyroidism often return to normal thyroid function, and a small proportion develops overt hypothyroidism (as predicted by evolving antibody and TSH levels, the presence of celiac disease, and the presence of a goiter).

Women are more likely to develop hypothyroidism than men. In population-based studies, women were seven times more likely than men to have TSH levels above 10 mU/l. 2–4% of people with subclinical hypothyroidism will progress to overt hypothyroidism each year. The risk is higher in those with antibodies against thyroid peroxidase. Subclinical hypothyroidism is estimated to affect approximately 2% of children; in adults, subclinical hypothyroidism is more common in the elderly, and in Caucasians. There is a much higher rate of thyroid disorders, the most common of which is hypothyroidism, in individuals with Down syndrome and Turner syndrome.

Very severe hypothyroidism and myxedema coma are rare, with it estimated to occur in 0.22 per million people a year. The majority of cases occur in women over 60 years of age, although it may happen in all age groups.

Most hypothyroidism is primary in nature. Central/secondary hypothyroidism affects 1:20,000 to 1:80,000 of the population, or about one out of every thousand people with hypothyroidism.

Thyroid storm presents with extreme symptoms of hyperthyroidism. It is treated aggressively with resuscitation measures along with a combination of the above modalities including: an intravenous beta blockers such as propranolol, followed by a thioamide such as methimazole, an iodinated radiocontrast agent or an iodine solution if the radiocontrast agent is not available, and an intravenous steroid such as hydrocortisone.

Hypothyroidism is diagnosed by noting a high TSH associated with a subnormal T4 concentration. Subclinical hypothyroidism (SCH) is present when the TSH is high but the T4 level is in the normal range but usually low normal. SCH is the commonest form of hypothyroidism in pregnancy and is usually due to progressive thyroid destruction due to autoimmune thyroid disease.

Several studies, mostly retrospective, have shown an association between overt hypothyroidism and adverse fetal and obstetric outcomes (e.g. Glinoer 1991). Maternal complications such as miscarriages, anaemia in pregnancy, pre-eclampsia, abruptio placenta and postpartum haemorrhage can occur in pregnant women with overt hypothyroidism. Also, the offspring of these mothers can have complications such as premature birth, low birth weight and increased neonatal respiratory distress. Similar complications have been reported in mothers with subclinical hypothyroidism. A three-fold risk of placental abruption and a two-fold risk of pre-term delivery were reported in mothers with subclinical hypothyroidism. Another study showed a higher prevalence of subclinical hypothyroidism in women with pre-term delivery (before 32 weeks) compared to matched controls delivering at term. An association with adverse obstetrics outcome has also been demonstrated in pregnant women with thyroid autoimmunity independent of thyroid function. Treatment of hypothyroidism reduces the risks of these adverse obstetric and fetal outcomes; a retrospective study of 150 pregnancies showed that treatment of hypothyroidism led to reduced rates of abortion and premature delivery. Also, a prospective intervention trial study showed that treatment of euthyroid antibody positive pregnant women led to fewer rates of miscarriage than non treated controls.

It has long been known that cretinism (i.e. gross reduction in IQ) occurs in areas of severe iodine deficiency due to the fact that the mother is unable to make T4 for transport to the fetus particularly in the first trimester. This neurointellectual impairment (on a more modest scale) has now been shown in an iodine sufficient area (USA) where a study showed that the IQ scores of 7-9 year old children, born to mothers with undiagnosed and untreated hypothyroidism in pregnancy, were seven points lower than those of children of matched control women with normal thyroid function in pregnancy. Another study showed that persistent hypothyroxinaemia at 12 weeks gestation was associated with an 8-10 point deficit in mental and motor function scores in infant offspring compared to children of mothers with normal thyroid function. Even maternal thyroid peroxidase antibodies were shown to be associated with impaired intellectual development in the offspring of mothers with normal thyroid function. Interestingly, it has been shown that it is only the maternal FT4 levels that are associated with child IQ and brain morphological outcomes, as opposed to maternal TSH levels.

Normal hormone changes during pregnancy cause thyroid hormone levels to increase. The thyroid may enlarge slightly in healthy women during pregnancy, but not enough to be felt. These changes do not affect the pregnancy or unborn baby. Yet, untreated thyroid problems can threaten pregnancy and the growing baby. Symptoms of normal pregnancy, like fatigue, can make it easy to overlook thyroid problems in pregnancy.

Thyroid hormone is vital during pregnancy. The unborn baby's brain and nervous system need thyroid hormone to develop. During the first trimester, the baby depends on the mother's supply of thyroid hormone. At 10 to 12 weeks of pregnancy, the baby's thyroid begins to work on its own. But the baby still depends on the mother for iodine, which the thyroid uses to make thyroid hormone. Pregnant women need about 250 micrograms (mcg) of iodine a day. Some women might not get all the iodine they need through the foods they eat or prenatal vitamins. Using iodized salt — salt that has had iodine added to it over plain table salt is recommended. Prenatal vitamins that contain iodine are also recommended.

Some women develop thyroid problems in the first year after giving birth. This is called postpartum thyroiditis. It often begins with symptoms of an overactive thyroid, which last 2 to 4 months. Mild symptoms might be overlooked. Affected women then develop symptoms of an underactive thyroid, which can last up to a year. An underactive thyroid needs to be treated. In most cases, thyroid function returns to normal as the thyroid heals.

Screening for hypothyroidism is performed in the newborn period in many countries, generally using TSH. This has led to the early identification of many cases and thus the prevention of developmental delay. It is the most widely used newborn screening test worldwide. While TSH-based screening will identify the most common causes, the addition of T testing is required to pick up the rarer central causes of neonatal hypothyroidism. If T determination is included in the screening done at birth, this will identify cases of congenital hypothyroidism of central origin in 1:16,000 to 1:160,000 children. Considering that these children usually have other pituitary hormone deficiencies, early identification of these cases may prevent complications.

In adults, widespread screening of the general population is a matter of debate. Some organizations (such as the United States Preventive Services Task Force) state that evidence is insufficient to support routine screening, while others (such as the American Thyroid Association) recommend either intermittent testing above a certain age in both sexes or only in women. Targeted screening may be appropriate in a number of situations where hypothyroidism is common: other autoimmune diseases, a strong family history of thyroid disease, those who have received radioiodine or other radiation therapy to the neck, those who have previously undergone thyroid surgery, those with an abnormal thyroid examination, those with psychiatric disorders, people taking amiodarone or lithium, and those with a number of health conditions (such as certain heart and skin conditions). Yearly thyroid function tests are recommended in people with Down syndrome, as they are at higher risk of thyroid disease.

Women being treated for Hashimoto's disease can become pregnant. It is recommended that thyroid function be well-controlled before getting pregnant.

Untreated or poorly treated underactive thyroid can lead to problems for the mother, such as:

- Preeclampsia

- Anemia

- Miscarriage

- Placental abruption

- High cholesterol

- Postpartum bleeding

It also can cause serious problems for the baby, such as:

- Preterm birth

- Low birth weight

- Stillbirth

- Birth defects

- Thyroid problems

Pregnant women who are positive for Hashimoto's thyroiditis may have decreased thyroid function or the gland may fail entirely. If a woman is TPOAb-positive, clinicians can inform her of the risks for themselves and their infants if they go untreated. "Thyroid peroxidase antibodies (TPOAb) are detected in 10% of pregnant women," which presents risks to those pregnancies. Women who have low thyroid function that has not been stabilized are at greater risk of having an infant with: low birth weight, neonatal respiratory distress, hydrocephalus, hypospadias, miscarriage, and preterm delivery. The embryo transplantion rate and successful pregnancy outcomes are improved when Hashimoto's is treated. Recommendations are to only treat pregnant women who are TPOAb-positive throughout the entirety of their pregnancies and to screen all pregnant women for thyroid levels. Close cooperation between the endocrinologist and obstetrician benefits the woman and the infant. The Endocrine Society recommends screening in pregnant women who are considered high-risk for thyroid autoimmune disease.

Thyroid peroxides antibodies testing is recommended for women who have ever been pregnant regardless of pregnancy outcome. "...[P]revious pregnancy plays a major role in development of autoimmune overt hypothyroidism in premenopausal women, and the number of previous pregnancies should be taken into account when evaluating the risk of hypothyroidism in a young women ["sic"]."

Sequence of events:

1. Iodine deficiency leading to decreased T4 production.

2. Induction of thyroid cell hyperplasia due to low levels of T4. This accounts for the multinodular goitre appearance.

3. Increased replication predisposes to a risk of mutation in the TSH receptor.

4. If the mutated TSH receptor is constitutively active, it would then become 'toxic' and produces excess T3/T4 leading to hyperthyroidism.

A genetic predisposition for Graves' disease is seen, with some people more prone to develop TSH receptor activating antibodies due to a genetic cause. Human leukocyte antigen DR (especially DR3) appears to play a role. To date, no clear genetic defect has been found to point to a single gene cause.

Genes believed to be involved include those for thyroglobulin, thyrotropin receptor, protein tyrosine phosphatase nonreceptor type 22, and cytotoxic T-lymphocyte–associated antigen 4, among others.

The exact cause is unclear; however, it is believed to involve a combination of genetic and environmental factors. While a theoretical mechanism occurs by which stress could cause an aggravation of the autoimmune response that leads to Graves' disease, more robust clinical data are needed for a firm conclusion.

Hypothyroidism is common in pregnancy with an estimated prevalence of 2-3% and 0.3-0.5% for subclinical and overt hypothyroidism respectively. Endemic iodine deficiency accounts for most hypothyroidism in pregnant women worldwide while chronic autoimmune thyroiditis is the most common cause of hypothyroidism in iodine sufficient parts of the world. The presentation of hypothyroidism in pregnancy is not always classical and may sometimes be difficult to distinguish from the symptoms of normal pregnancy. A high index of suspicion is therefore required especially in women at risk of thyroid disease e.g. women with a personal or family history of thyroid disease, goitre, or co-existing primary autoimmune disorder like type 1 diabetes.

The transition from hyperthyroidism to thyroid storm is typically triggered by a non-thyroidal insult including, but not limited to fever, sepsis, dehydration, myocardial infarction, and psychiatric diseases. Individuals are at higher risk of thyroid storm if their hyperthyroidism is incompletely treated or if their anti-thyroid drugs are discontinued. Many of these individuals have underlying primary causes of hyperthyroidism (Graves disease, toxic multi-nodular goiter, solitary toxic adenoma). However, thyroid storm can occur in individuals with unrecognized thyrotoxicosis experiencing non-thyroid surgery, labor, infection, or exposure to certain medications and radiocontrast dyes.

Thyroid hormone resistance syndrome is rare, incidence is variously quoted as 1 in 50,000 or 1 in 40,000 live births. More than 1000 individuals have been identified with thyroid hormone resistance, of which 85% had thyroid hormone beta receptor mutation.

According to newer theories, thyroid storm results from allostatic failure in a situation were thyrotoxicosis hampers the development of non-thyroidal illness syndrome, which would help to save energy in critical illness and other situations of high metabolic demand.

Usually, in critical illness (e.g. sepsis, myocardial infarction and other causes of shock) thyroid function is tuned down to result in low-T3 syndrome and, occasionally, also low TSH concentrations, low-T4 syndrome and impaired plasma protein binding of thyroid hormones. This endocrine pattern is referred to as "euthyroid sick syndrome" (ESS), "non-thyroidal illness syndrome" (NTIS) or "thyroid allostasis in critical illness, tumours, uraemia and starvation" (TACITUS). Although NTIS is associated with significantly worse prognosis, it is also assumed to represent a beneficial adaptation (type 1 allostasis). In cases, where critical illness is accompanied by thyrotoxicosis, this comorbidity prevents the down-regulation of thyroid function. Therefore, the consumption of energy, oxygen and glutathione remains high, which leads to further increased mortality.

These new theories imply that thyroid storm results from an interaction of thyrotoxicosis with the specific response of the organism to an oversupply of thyroid hormones.

Toxic multinodular goiter (also known as toxic nodular goiter, or Plummer's disease) is a multinodular goiter associated with hyperthyroidism.

It is a common cause of hyperthyroidism in which there is excess production of thyroid hormones from functionally autonomous thyroid nodules, which do not require stimulation from thyroid stimulating hormone (TSH).

Toxic multinodular goiter is the second most common cause of hyperthyroidism (after Graves' disease) in the developed world, whereas iodine deficiency is the most common cause of hypothyroidism in developing-world countries where the population is iodine-deficient. (Decreased iodine leads to decreased thyroid hormone.) However, iodine deficiency can cause goitre (thyroid enlargement); within a goitre, nodules can develop. Risk factors for toxic multinodular goiter include individuals over 60 years of age and being female.

Worldwide, the most common cause for goitre is iodine deficiency, usually seen in countries that do not use iodized salt. Selenium deficiency is also considered a contributing factor. In countries that use iodized salt, Hashimoto's thyroiditis is the most common cause. Goitre can also result from cyanide poisoning; this is particularly common in tropical countries where people eat the cyanide-rich cassava root as the staple food.

- Sarcoidosis

- Amyloidosis

- Hydatidiform mole

- Cysts

- Acromegaly

- Pendred syndrome

Goitre is more common among women, but this includes the many types of goitre caused by autoimmune problems, and not only those caused by simple lack of iodine.

The strong genetic component is borne out in studies on monozygotic twins, with a concordance of 38-55%, with an even higher concordance of circulating thyroid antibodies not in relation to clinical presentation (up to 80% in monozygotic twins). Neither result was seen to a similar degree in dizygotic twins, offering strong favour for high genetic aetiology.

Hashimoto's thyroiditis is associated with "CTLA-4" ("Cytotoxic T-lymphocyte Antigen-4") gene polymorphisms. CTLA-4 downregulates., i.e. transmits an inhibitory signal to T cells so reduced functioning is associated with increased T-lymphocyte activity. A family history of thyroid disorders is common, with the "HLA-DR5" gene most strongly implicated conferring a relative risk of 3 in the UK.

Having other autoimmune diseases is a risk factor to develop Hashimoto’s thyroiditis, and the opposite is also true. Autoimmune diseases most commonly associated to Hashimoto’s thyroiditis include celiac disease, type 1 diabetes, vitiligo, and alopecia.

Preventable environmental factors, including high iodine intake, selenium deficiency, as well as infectious diseases and certain drugs, have been implicated in the development of autoimmune thyroid disease in genetically predisposed individuals.

The genes implicated vary in different ethnic groups and the incidence is increased in people with chromosomal disorders, including Turner, Down, and Klinefelter syndromes usually associated with autoantibodies against thyroglobulin and thyroperoxidase. Progressive depletion of these cells as the cytotoxic immune response leads to higher degrees of primary hypothyroidism, presenting with a poverty of T3/T4 levels, and compensatory elevations of TSH.

Outcomes are typically good when treated. Most can expect to live relatively normal lives. Someone with the disease should be observant of symptoms of an "Addison's crisis" while the body is strained, as in rigorous exercise or being sick, the latter often needing emergency treatment with intravenous injections to treat the crisis.

Individuals with Addison's disease have more than a doubled mortality rate. Furthermore, individuals with Addison's disease and diabetes mellitus have an almost 4 time increase in mortality compared to individuals with only diabetes.

The frequency rate of Addison's disease in the human population is sometimes estimated at roughly one in 100,000. Some put the number closer to 40–144 cases per million population (1/25,000–1/7,000). Addison's can affect persons of any age, sex, or ethnicity, but it typically presents in adults between 30 and 50 years of age. Research has shown no significant predispositions based on ethnicity.

Thyroid cancers are thought to be related to a number of environmental and genetic predisposing factors, but significant uncertainty remains regarding their causes.

Environmental exposure to ionizing radiation from both natural background sources and artificial sources is suspected to play a significant role, and there are significant increased rates of thyroid cancer in those exposed to mantlefield radiation for lymphoma, and those exposed to iodine-131 following the Chernobyl, Fukushima, Kyshtym, and Windscale nuclear disasters. Thyroiditis and other thyroid diseases also predispose to thyroid cancer.

Genetic causes include multiple endocrine neoplasia type 2 which markedly increases rates, particularly of the rarer medullary form of the disease.

80% of patients with pituitary antibodies also have antibodies to thyroid gland or its hormones. Likewise, 20% of autoimmune thyroid patients also have pituitary antibodies. It follows that a subset of thyroid patients may have a disease related to autoimmune hypophysitis. Recent research has focused on a defect at the CTLA-4 gene which, coupled with other factors, may result in autoimmunity primarily focusing on certain endocrine glands including the pituitary and thyroid.