Thyroid disease is a medical condition that affects the function of the
thyroid gland
The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans it is in the neck and consists of two connected lobe (anatomy), lobes. The lower two thirds of the lobes are connected by a thin band of Connective tissue, tissue cal ...
. The thyroid gland is located at the front of the neck and produces
thyroid hormones
File:Thyroid_system.svg, upright=1.5, The thyroid system of the thyroid hormones T3 and T4
rect 376 268 820 433 Thyroid-stimulating hormone
rect 411 200 849 266 Thyrotropin-releasing hormone
rect 297 168 502 200 Hypothalamus
rect 66 216 386 25 ...
that travel through the blood to help regulate many other organs, meaning that it is an
endocrine organ
The endocrine system is a messenger system comprising feedback loops of the hormones released by internal glands of an organism directly into the circulatory system, regulating distant target organs. In vertebrates, the hypothalamus is the neur ...
. These hormones normally act in the body to regulate energy use, infant development, and childhood development.
There are five general types of thyroid disease, each with their own symptoms. A person may have one or several different types at the same time. The five groups are:
#
Hypothyroidism
Hypothyroidism (also called ''underactive thyroid'', ''low thyroid'' or ''hypothyreosis'') is a disorder of the endocrine system in which the thyroid gland does not produce enough thyroid hormone. It can cause a number of symptoms, such as po ...
(low function) caused by not having enough free thyroid hormones
#
Hyperthyroidism
Hyperthyroidism is the condition that occurs due to excessive production of thyroid hormones by the thyroid gland. Thyrotoxicosis is the condition that occurs due to excessive thyroid hormone of any cause and therefore includes hyperthyroidism ...
(high function) caused by having too many free thyroid hormones
# Structural abnormalities, most commonly a
goiter
A goitre, or goiter, is a swelling in the neck resulting from an enlarged thyroid gland. A goitre can be associated with a thyroid that is not functioning properly.
Worldwide, over 90% of goitre cases are caused by iodine deficiency. The term is ...
(enlargement of the thyroid gland)
#
Tumors
A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
which can be benign (not cancerous) or cancerous
# Abnormal thyroid function tests without any clinical symptoms (subclinical hypothyroidism or subclinical hyperthyroidism).
In some types, such as subacute thyroiditis or postpartum thyroiditis, symptoms may go away after a few months and laboratory tests may return to normal.
However most types of thyroid disease do not resolve on their own. Common hypothyroid symptoms include fatigue, low energy, weight gain, inability to tolerate the cold, slow heart rate, dry skin and constipation. Common hyperthyroid symptoms include irritability, anxiety, weight loss, fast heartbeat, inability to tolerate the heat, diarrhea, and enlargement of the thyroid. Structural abnormalities may not produce symptoms, however some people may have hyperthyroid or hypothyroid symptoms related to the structural abnormality or notice swelling of the neck.
Rarely goiters can cause compression of the airway, compression of the vessels in the neck, or difficulty swallowing.
Tumors, often called thyroid nodules, can also have many different symptoms ranging from hyperthyroidism to hypothyroidism to swelling in the neck and compression of the structures in the neck.
Diagnosis starts with a history and physical examination. Screening for thyroid disease in patients without symptoms is a debated topic although commonly practiced in the United States. If dysfunction of the thyroid is suspected, laboratory tests can help support or rule out thyroid disease. Initial blood tests often include
thyroid-stimulating hormone
Thyroid-stimulating hormone (also known as thyrotropin, thyrotropic hormone, or abbreviated TSH) is a pituitary hormone that stimulates the thyroid gland to produce thyroxine (T4), and then triiodothyronine (T3) which stimulates the metabolism of ...
(TSH) and free
thyroxine
File:Thyroid_system.svg, upright=1.5, The thyroid system of the thyroid hormones T3 and T4
rect 376 268 820 433 Thyroid-stimulating hormone
rect 411 200 849 266 Thyrotropin-releasing hormone
rect 297 168 502 200 Hypothalamus
rect 66 216 386 25 ...
(T4).
Total and free
triiodothyronine
Triiodothyronine, also known as T3, is a thyroid hormone. It affects almost every physiological process in the body, including growth and development, metabolism, body temperature, and heart rate.
Production of T3 and its prohormone thyroxine ( ...
(T3) levels are less commonly used.
If autoimmune disease of the thyroid is suspected, blood tests looking for
Anti-thyroid autoantibodies Antithyroid autoantibodies (or simply antithyroid antibodies) are autoantibodies targeted against one or more components on the thyroid. The most clinically relevant anti-thyroid autoantibodies are anti-thyroid peroxidase antibodies (anti-TPO antibo ...
can also be obtained. Procedures such as ultrasound, biopsy and a radioiodine scanning and uptake study may also be used to help with the diagnosis, particularly if a nodule is suspected.
Thyroid diseases are highly prevalent worldwide,
[Atasayar, Semra, Guler Demir, Sevil. Determination of the problems experienced by patients post-thyroidectomy. Clinical Nursing Research. 2019;28(5):615-635. doi:10.1177/1054773817729074.] and treatment varies based on the disorder.
Levothyroxine
Levothyroxine, also known as -thyroxine, is a manufactured form of the thyroid hormone thyroxine (T4). It is used to treat hypothyroidism, thyroid hormone deficiency (hypothyroidism), including a severe form known as myxedema coma. It may also ...
is the mainstay of treatment for people with hypothyroidism,
while people with hyperthyroidism caused by Graves' disease can be managed with iodine therapy, antithyroid medication, or surgical removal of the thyroid gland.
Thyroid surgery may also be performed to remove a thyroid nodule or to reduce the size of a goiter if it obstructs nearby structures or for cosmetic reasons.
Signs and symptoms
Symptoms of the condition vary with type: hypo- vs. hyperthyroidism, which are further described below.
Possible symptoms of
hypothyroidism
Hypothyroidism (also called ''underactive thyroid'', ''low thyroid'' or ''hypothyreosis'') is a disorder of the endocrine system in which the thyroid gland does not produce enough thyroid hormone. It can cause a number of symptoms, such as po ...
are:
Possible symptoms of
hyperthyroidism
Hyperthyroidism is the condition that occurs due to excessive production of thyroid hormones by the thyroid gland. Thyrotoxicosis is the condition that occurs due to excessive thyroid hormone of any cause and therefore includes hyperthyroidism ...
are:Note: certain symptoms and physical changes can be seen in both hypothyroidism and hyperthyroidism —fatigue, fine / thinning hair, menstrual cycle irregularities, muscle weakness / aches (
myalgia
Myalgia (also called muscle pain and muscle ache in layman's terms) is the medical term for muscle pain. Myalgia is a symptom of many diseases. The most common cause of acute myalgia is the overuse of a muscle or group of muscles; another likel ...
), and different forms of
myxedema
Myxedema is a term used synonymously with severe hypothyroidism. However, the term is also used to describe a dermatological change that can occur in hyperthyroidism and (rare) paradoxical cases of hypothyroidism. In this latter sense, myxedema ...
.
Diseases
Low function
Hypothyroidism
Hypothyroidism (also called ''underactive thyroid'', ''low thyroid'' or ''hypothyreosis'') is a disorder of the endocrine system in which the thyroid gland does not produce enough thyroid hormone. It can cause a number of symptoms, such as po ...
is a state in which the body is not producing enough thyroid hormones, or is not able to respond to / utilize existing thyroid hormones properly. The main categories are:
*
Thyroiditis
Thyroiditis is the inflammation of the thyroid gland. The thyroid gland is located on the front of the neck below the laryngeal prominence, and makes hormones that control metabolism.
Signs and symptoms
There are many different signs and symptom ...
: an inflammation of the thyroid gland
**
Hashimoto's thyroiditis
Hashimoto's thyroiditis, also known as chronic lymphocytic thyroiditis and Hashimoto's disease, is an autoimmune disease in which the thyroid gland is gradually destroyed. Early on, symptoms may not be noticed. Over time, the thyroid may enlarg ...
/ Hashimoto's disease
**
Ord's thyroiditis
**
Postpartum thyroiditis
Postpartum thyroiditis refers to thyroid dysfunction occurring in the first 12 months after pregnancy and may involve hyperthyroidism, hypothyroidism or the two sequentially. According to the National Institute of Health, postpartum thyroiditis a ...
**
Silent thyroiditis
Subacute lymphocytic thyroiditis is a form of thyroiditis. Subacute lymphocytic thyroiditis may occur at any age and is more common in females. A variant of subacute lymphocytic thyroiditis occurs postpartum: postpartum thyroiditis. Both of these ...
**
Acute thyroiditis
Acute infectious thyroiditis (AIT) also known as suppurative thyroiditis, microbial inflammatory thyroiditis, pyrogenic thyroiditis and bacterial thyroiditis.Melmed, Shlomo, Kenneth S. Polonsky, and P. R. Larsenthyroiditis vs subacute thyroiditis ...
**
Riedel's thyroiditis
Riedel's thyroiditis, is a chronic form of thyroiditis. It is now believed that Riedel's thyroiditis is one manifestation of a systemic disease that can affect many organ systems called IgG4-related disease. It is often a multi-organ disease affect ...
(the majority of cases do not affect thyroid function, but approximately 30% of cases lead to hypothyroidism)
* Iatrogenic hypothyroidism
** Postoperative hypothyroidism
** Medication- or radiation-induced hypothyroidism
*
Thyroid hormone resistance
Thyroid hormone resistance (also resistance to thyroid hormone (RTH), and sometimes Refetoff syndrome) describes a rare syndrome in which the thyroid hormone levels are elevated but the thyroid stimulating hormone (TSH) level is not suppressed, or ...
*
Euthyroid sick syndrome
Euthyroid sick syndrome (ESS) is a state of adaptation or dysregulation of thyrotropic feedback control wherein the levels of T3 and/or T4 are abnormal, but the thyroid gland does not appear to be dysfunctional. This condition may result from ...
*
Congenital hypothyroidism
Congenital hypothyroidism (CH) is thyroid hormone deficiency present at birth. If untreated for several months after birth, severe congenital hypothyroidism can lead to growth failure and permanent intellectual disability. Infants born with cong ...
: a deficiency of thyroid hormone from birth, which untreated can lead to
cretinism
Congenital iodine deficiency syndrome is a medical condition present at birth marked by impaired physical and mental development, due to insufficient thyroid hormone (hypothyroidism) often caused by insufficient dietary iodine during pregnancy. It ...
High function
Hyperthyroidism
Hyperthyroidism is the condition that occurs due to excessive production of thyroid hormones by the thyroid gland. Thyrotoxicosis is the condition that occurs due to excessive thyroid hormone of any cause and therefore includes hyperthyroidism ...
is a state in which the body is producing too much thyroid hormone. The main hyperthyroid conditions are:
*
Graves' disease
Graves' disease (german: Morbus Basedow), also known as toxic diffuse goiter, is an autoimmune disease that affects the thyroid. It frequently results in and is the most common cause of hyperthyroidism. It also often results in an enlarged thyr ...
*
Toxic thyroid nodule
*
Thyroid storm
The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans it is in the neck and consists of two connected lobes. The lower two thirds of the lobes are connected by a thin band of tissue called the thyroid isthmus. The thy ...
*
Toxic nodular struma (Plummer's disease)
*
Hashitoxicosis
Hashitoxicosis, which can be abbreviated "Htx", is a transient hyperthyroidism caused by inflammation associated with Hashimoto's thyroiditis disturbing the thyroid follicles, resulting in excess release of thyroid hormone. Robins Basic Pathology ...
: ''transient'' hyperthyroidism that can occur in Hashimoto's thyroiditis
Structural abnormalities
![Kone med stor struma](https://upload.wikimedia.org/wikipedia/commons/4/43/Kone_med_stor_struma.jpg)
*
Goiter
A goitre, or goiter, is a swelling in the neck resulting from an enlarged thyroid gland. A goitre can be associated with a thyroid that is not functioning properly.
Worldwide, over 90% of goitre cases are caused by iodine deficiency. The term is ...
: an abnormal enlargement of the thyroid gland
**
Endemic goiter
Endemic goiter is a type of goitre that is associated with dietary iodine deficiency.
Cause
Some inland areas where soil and water lacks in iodine compounds and consumption of Seafood, marine foods is low are known for higher incidence of goitre. ...
**
Diffuse goiter
**
Multinodular goiter
A goitre, or goiter, is a swelling in the neck resulting from an enlarged thyroid gland. A goitre can be associated with a thyroid that is not functioning properly.
Worldwide, over 90% of goitre cases are caused by iodine deficiency. The term is ...
* Lingual thyroid
*
Thyroglossal duct cyst
A thyroglossal cyst is a fibrous cyst that forms from a persistent thyroglossal duct. Thyroglossal cysts can be defined as an irregular neck mass or a lump which develops from cells and tissues left over after the formation of the thyroid gland d ...
Tumors
*
Thyroid adenoma
A thyroid adenoma is a benign tumor of the thyroid gland, that may be inactive or active (functioning autonomously) as a toxic adenoma.
Signs and symptoms
A thyroid adenoma may be clinically silent ("cold" adenoma), or it may be a functional tumor ...
: benign / non-cancerous tumor
*
Thyroid cancer
Thyroid cancer is cancer that develops from the tissues of the thyroid gland. It is a disease in which cells grow abnormally and have the potential to spread to other parts of the body. Symptoms can include swelling or a lump in the neck. C ...
**
Papillary
Papilla (Latin, 'nipple') or papillae may refer to:
In animals
* Papilla (fish anatomy), in the mouth of fish
* Basilar papilla, a sensory organ of lizards, amphibians and fish
* Dental papilla, in a developing tooth
* Dermal papillae, part of ...
**
Follicular
**
Medullary
**
Anaplastic
Anaplasia (from grc, ἀνά ''ana'', "backward" + πλάσις ''plasis'', "formation") is a condition of cells with poor cellular differentiation, losing the morphological characteristics of mature cells and their orientation with respect to ...
*
Lymphoma
Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). In current usage the name usually refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enlar ...
s and
metastasis
Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...
from elsewhere (rare)
Medication side effects
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
Amiodarone is an antiarrhythmic medication used to treat and prevent a number of types of cardiac dysrhythmias. This includes ventricular tachycardia (VT), ventricular fibrillation (VF), and wide complex tachycardia, as well as atrial fibrilla ...
(more commonly can lead to hypothyroidism, but can be associated with some types of hyperthyroidism)
*
Lithium salt
Lithium (from el, λίθος, lithos, lit=stone) is a chemical element with the symbol Li and atomic number 3. It is a soft, silvery-white alkali metal. Under standard conditions, it is the least dense metal and the least dense solid ele ...
s (hypothyroidism)
* Some types of
interferon
Interferons (IFNs, ) are a group of signaling proteins made and released by host cells in response to the presence of several viruses. In a typical scenario, a virus-infected cell will release interferons causing nearby cells to heighten the ...
and
IL-2
The Ilyushin Il-2 (Russian language, Russian: Илью́шин Ил-2) is a Ground attack aircraft, ground-attack plane that was produced by the Soviet Union in large numbers during the World War II, Second World War. The word ''shturmovík'' (C ...
(thyroiditis)
*
Glucocorticoid
Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebr ...
s,
dopamine agonist
A dopamine agonist (DA) is a compound that activates dopamine receptors. There are two families of dopamine receptors, D2-like and D1-like, and they are all G protein-coupled receptors. D1- and D5-receptors belong to the D1-like family and the ...
s, and
somatostatin analogs (block TSH, which can lead to hypothyroidism)
Pathophysiology
Most thyroid disease in the United States stems from a condition where the body's immune system attacks itself. In other instances, thyroid disease comes from the body trying to adapt to environmental conditions like iodine deficiency or to new physiologic conditions like pregnancy.
Autoimmune Thyroid Disease
Autoimmune thyroid disease is a general category of disease that occurs due to the immune system targeting its own body. It is not fully understood why this occurs, but it is thought to be partially genetic as these diseases tend to run in families.
In one of the most common types, Grave's Disease, the body produces antibodies against the TSH receptor on thyroid cells.
This causes the receptor to activate even without TSH being present and causes the thyroid to produce and release excess thyroid hormone (hyperthyroidism).
Another common form of autoimmune thyroid disease is Hashimoto thyroiditis where the body produces antibodies against different normal components of the thyroid gland, most commonly thyroglobulin, thyroid peroxidase, and the TSH receptor.
These antibodies cause the immune system to attack the thyroid cells and cause inflammation (lymphocytic infiltration) and destruction (fibrosis) of the gland.
Goiter
Goiter is the general enlargement of the thyroid that can be associated with many thyroid diseases. The main reason this happens is because of increased signaling to the thyroid by way of TSH receptors to try to make it produce more thyroid hormone.
This causes increased vascularity and increase in size (
hypertrophy
Hypertrophy is the increase in the volume of an organ or tissue due to the enlargement of its component cells. It is distinguished from hyperplasia, in which the cells remain approximately the same size but increase in number.Updated by Linda J ...
) of the gland.
In hypothyroid states or iodine deficiency, the body recognizes that it is not producing enough thyroid hormone and starts to produce more TSH to help stimulate the thyroid to produce more thyroid hormone.
This stimulation causes the gland to increase in size to increase production of thyroid hormone. In hyperthyroidism caused by Grave's Disease or toxic multinodular goiter, there is excess stimulation of the TSH receptor even when thyroid hormone levels are normal.
In Grave's Disease this is because of an autoantibodies (Thyroid Stimulating Immunoglobulins) which bind to and activate the TSH receptors in place of TSH while in toxic multinodular goiter this is often because of a mutation in the TSH receptor that causes it to activate without receiving a signal from TSH.
In more rare cases, the thyroid may become enlarged because it becomes filled with thyroid hormone or thyroid hormone precursors that it is unable to release or because of congential abnormalities or because of increased intake of iodine from supplementation or medication.
Pregnancy
There are many changes to the body during pregnancy. One of the major changes to help with the development of the fetus is the production of human chorionic gonadotropin (hCG). This hormone, produced by the placenta, has similar structure to TSH and can bind to the maternal TSH receptor to produce thyroid hormone.
During pregnancy, there is also an increase in estrogen which causes the mother to produce more thyroxine binding globulin, which is what carries most of the thyroid hormone in the blood.
These normal hormonal changes often make pregnancy look like a hyperthyroid state but may be within the normal range for pregnancy, so it necessary to use trimester specific ranges for TSH and free T4.
True hyperthyroidism in pregnancy is most often caused by an autoimmune mechanism from Grave's Disease.
New diagnosis of hypothyroidism in pregnancy is rare because hypothyroidism often makes it difficult to become pregnant in the first place.
When hypothyroidism is seen in pregnancy, it is often because an individual already has hypothyroidism and needs to increase their levothyroxine dose to account for the increased thyroxine binding globulin present in pregnancy.
Diagnosis
Diagnosis of thyroid disease depends on symptoms and whether or not a thyroid nodule is present. Most patients will receive a blood test. Others might need an ultrasound, biopsy or a radioiodine scanning and uptake study.
Blood tests
Thyroid function tests
There are several hormones that can be measured in the blood to determine how the thyroid gland is functioning. These include the
thyroid hormones
File:Thyroid_system.svg, upright=1.5, The thyroid system of the thyroid hormones T3 and T4
rect 376 268 820 433 Thyroid-stimulating hormone
rect 411 200 849 266 Thyrotropin-releasing hormone
rect 297 168 502 200 Hypothalamus
rect 66 216 386 25 ...
triiodothyronine
Triiodothyronine, also known as T3, is a thyroid hormone. It affects almost every physiological process in the body, including growth and development, metabolism, body temperature, and heart rate.
Production of T3 and its prohormone thyroxine ( ...
(T3) and its precursor
thyroxine
File:Thyroid_system.svg, upright=1.5, The thyroid system of the thyroid hormones T3 and T4
rect 376 268 820 433 Thyroid-stimulating hormone
rect 411 200 849 266 Thyrotropin-releasing hormone
rect 297 168 502 200 Hypothalamus
rect 66 216 386 25 ...
(T4), which are produced by the thyroid gland.
Thyroid-stimulating hormone
Thyroid-stimulating hormone (also known as thyrotropin, thyrotropic hormone, or abbreviated TSH) is a pituitary hormone that stimulates the thyroid gland to produce thyroxine (T4), and then triiodothyronine (T3) which stimulates the metabolism of ...
(TSH) is another important hormone that is secreted by the anterior pituitary cells in the brain. Its primary function is to increase the production of T3 and T4 by the thyroid gland.
The most useful marker of thyroid gland function is serum thyroid-stimulating hormone (TSH) levels. TSH levels are determined by a classic
negative feedback
Negative feedback (or balancing feedback) occurs when some function (Mathematics), function of the output of a system, process, or mechanism is feedback, fed back in a manner that tends to reduce the fluctuations in the output, whether caused by ...
system in which high levels of T3 and T4 suppress the production of TSH, and low levels of T3 and T4 increase the production of TSH. TSH levels are thus often used by doctors as a screening test, where the first approach is to determine whether TSH is elevated, suppressed, or normal.
* Elevated TSH levels can signify inadequate thyroid hormone production (hypothyroidism)
* Suppressed TSH levels can point to excessive thyroid hormone production (hyperthyroidism)
Because a single abnormal TSH level can be misleading, T3 and T4 levels must be measured in the blood to further confirm the diagnosis. When circulating in the body, T3 and T4 are bound to transport proteins. Only a small fraction of the circulating thyroid hormones are unbound or free, and thus biologically active. T3 and T4 levels can thus be measured as free T3 and T4, or total T3 and T4, which takes into consideration the free hormones in addition to the protein-bound hormones. Free T3 and T4 measurements are important because certain drugs and illnesses can affect the concentrations of transport proteins, resulting in differing total and free thyroid hormone levels. There are differing guidelines for T3 and T4 measurements.
* Free T4 levels should be measured in the evaluation of hypothyroidism, and low free T4 establishes the diagnosis. T3 levels are generally not measured in the evaluation of hypothyroidism.
* Free T4 and total T3 can be measured when hyperthyroidism is of high suspicion as it will improve the accuracy of the diagnosis. Free T4, total T3 or both are elevated and serum TSH is below normal in hyperthyroidism. If the hyperthyroidism is mild, only serum T3 may be elevated and serum TSH can be low or may not be detected in the blood.
* Free T4 levels may also be tested in patients who have convincing symptoms of hyper- and hypothyroidism, despite a normal TSH.
Antithyroid antibodies
Autoantibodies
An autoantibody is an antibody (a type of protein) produced by the immune system that is directed against one or more of the individual's own proteins. Many autoimmune diseases (notably lupus erythematosus) are associated with such antibodies.
Pr ...
to the thyroid gland may be detected in various disease states. There are several anti-thyroid antibodies, including
anti-thyroglobulin antibodies
Thyroglobulin (Tg) is a 660 kDa, Dimer (chemistry), dimeric protein, glycoprotein produced by the Thyroid epithelial cell, follicular cells of the thyroid and used entirely within the thyroid gland. Tg is secreted and accumulated at hundreds of ...
(TgAb),
anti-microsomal/
anti-thyroid peroxidase antibodies Antithyroid autoantibodies (or simply antithyroid antibodies) are autoantibodies targeted against one or more components on the thyroid. The most clinically relevant anti-thyroid autoantibodies are anti-thyroid peroxidase antibodies (anti-TPO antib ...
(TPOAb), and TSH receptor antibodies (TSHRAb).
* Elevated anti-thryoglobulin (TgAb) and anti-thyroid peroxidase antibodies (TPOAb) can be found in patients with Hashimoto's thyroiditis, the most common autoimmune type of hypothyroidism. TPOAb levels have also been found to be elevated in patients who present with subclinical hypothyroidism (where TSH is elevated, but free T4 is normal), and can help predict progression to overt hypothyroidism. The American Association Thyroid Association thus recommends measuring TPOAb levels when evaluating subclinical hypothyroidism or when trying to identify whether nodular thyroid disease is due to autoimmune thyroid disease.
* When the etiology of hyperthyroidism is not clear after initial clinical and biochemical evaluation, measurement of TSH receptor antibodies (TSHRAb) can help make the diagnosis. In Grave's disease, TSHRAb levels are elevated as they are responsible for activating the TSH receptor and causing increased thyroid hormone production.
Other markers
* There are two markers for thyroid-derived cancers.
**
Thyroglobulin
Thyroglobulin (Tg) is a 660 kDa, dimeric glycoprotein produced by the follicular cells of the thyroid and used entirely within the thyroid gland. Tg is secreted and accumulated at hundreds of grams per litre in the extracellular compartment o ...
(TG) levels can be elevated in well-differentiated papillary or follicular adenocarcinoma. It is often used to provide information on residual, recurrent or metastatic disease in patients with differentiated thyroid cancer. However, serum TG levels can be elevated in most thyroid diseases. Routine measurement of serum TG for evaluation of thyroid nodules is thus currently not recommended by the American Thyroid Association.
** Elevated
calcitonin
Calcitonin is a 32 amino acid peptide hormone secreted by parafollicular cells (also known as C cells) of the thyroid (or endostyle) in humans and other chordates. in the ultimopharyngeal body. It acts to reduce blood calcium (Ca2+), opposing the ...
levels in the blood have been shown to be associated with the rare
medullary thyroid cancer
Medullary thyroid cancer is a form of Thyroid cancer, thyroid carcinoma which originates from the parafollicular cells (C cells), which produce the hormone calcitonin.Hu MI, Vassilopoulou-Sellin R, Lustig R, Lamont JP"Thyroid and Parathyroid Cance ...
. However, the measurement of calcitonin levels as a diagnostic tool is currently controversial due to falsely high or low calcitonin levels in a variety of diseases other than medullary thyroid cancer.
* Very infrequently,
TBG and
transthyretin
Transthyretin (TTR or TBPA) is a transport protein in the plasma and cerebrospinal fluid that transports the thyroid hormone thyroxine (T4) and retinol to the liver. This is how transthyretin gained its name: ''transports thyroxine and retinol'' ...
levels may be abnormal; these are not routinely tested.
* To differentiate between different types of hypothyroidism, a specific test may be used.
Thyrotropin-releasing hormone
Thyrotropin-releasing hormone (TRH) is a hypophysiotropic hormone produced by neurons in the hypothalamus that stimulates the release of thyroid-stimulating hormone (TSH) and prolactin from the anterior pituitary.
TRH has been used clinicall ...
(TRH) is injected into the body through a vein. This hormone is naturally secreted by the hypothalamus and stimulates the pituitary gland. The pituitary responds by releasing thyroid-stimulating hormone (TSH). Large amounts of externally administered TRH can suppress the subsequent release of TSH. This amount of release-suppression is exaggerated in primary hypothyroidism, major depression, cocaine dependence, amphetamine dependence and chronic phencyclidine abuse. There is a failure to suppress in the manic phase of bipolar disorder.
Ultrasound
Many people may develop a thyroid nodule at some point in their lives. Although many who experience this worry that it is thyroid cancer, there are many causes of nodules that are benign and not cancerous. If a possible nodule is present, a doctor may order thyroid function tests to determine if the thyroid gland's activity is being affected. If more information is needed after a clinical exam and lab tests,
medical ultrasonography
Medical ultrasound includes diagnostic techniques (mainly medical imaging, imaging techniques) using ultrasound, as well as therapeutic ultrasound, therapeutic applications of ultrasound. In diagnosis, it is used to create an image of internal ...
can help determine the nature of thyroid nodule(s). There are some notable differences in ''typical'' benign vs. cancerous thyroid nodules that can particularly be detected by the high-frequency sound waves in an ultrasound scan. The ultrasound may also locate nodules that are too small for a doctor to feel on a physical exam, and can demonstrate whether a nodule is primarily solid, liquid (
cyst
A cyst is a closed sac, having a distinct envelope and cell division, division compared with the nearby Biological tissue, tissue. Hence, it is a cluster of Cell (biology), cells that have grouped together to form a sac (like the manner in which ...
ic), or a mixture of both. It is an imaging process that can often be done in a doctor's office, is painless, and does not expose the individual to any radiation.
The main characteristics that can help distinguish a benign vs. malignant (cancerous) thyroid nodule on ultrasound are as follows:
Although ultrasonography is a very important diagnostic tool, this method is not always able to separate benign from malignant nodules with certainty. In suspicious cases, a tissue sample is often obtained by biopsy for microscopic examination.
Radioiodine scanning and uptake
![Thyroid scintigraphy](https://upload.wikimedia.org/wikipedia/commons/0/0a/Thyroid_scintigraphy.jpg)
Thyroid
scintigraphy
Scintigraphy (from Latin ''scintilla'', "spark"), also known as a gamma scan, is a diagnostic test in nuclear medicine, where radioisotopes attached to drugs that travel to a specific organ or tissue (radiopharmaceuticals) are taken internally and ...
, in which the thyroid is imaged with the aid of
radioactive iodine
There are 37 known isotopes of iodine (53I) from 108I to 144I; all undergo radioactive decay except 127I, which is stable. Iodine is thus a monoisotopic element.
Its longest-lived radioactive isotope, 129I, has a half-life of 15.7 million year ...
(usually
iodine-123
Iodine-123 (123I) is a radioactive isotope of iodine used in nuclear medicine imaging, including single-photon emission computed tomography (SPECT) or SPECT/CT exams. The isotope's half-life is 13.2230 hours; the decay by electron capture to tellu ...
, which does not harm thyroid cells, or rarely,
iodine-131
Iodine-131 (131I, I-131) is an important radioisotope of iodine discovered by Glenn Seaborg and John Livingood in 1938 at the University of California, Berkeley. It has a radioactive decay half-life of about eight days. It is associated with nuc ...
),
is performed in the
nuclear medicine
Nuclear medicine or nucleology is a medical specialty involving the application of radioactive substances in the diagnosis and treatment of disease. Nuclear imaging, in a sense, is "radiology done inside out" because it records radiation emitting ...
department of a hospital or clinic. Radioiodine collects in the thyroid gland before being excreted in the urine. While in the thyroid, the radioactive emissions can be detected by a camera, producing a rough image of the shape (a ''radioiodine scan'') and tissue activity (a ''radioiodine uptake'') of the thyroid gland.
A normal radioiodine scan shows even uptake and activity throughout the gland. Irregular uptake can reflect an abnormally shaped or abnormally located gland, or it can indicate that a portion of the gland is overactive or underactive. For example, a nodule that is overactive ("hot") -- to the point of suppressing the activity of the rest of the gland—is usually a thyrotoxic adenoma, a surgically curable form of hyperthyroidism that is rarely malignant. In contrast, finding that a substantial section of the thyroid is inactive ("cold") may indicate an area of non-functioning tissue, such as thyroid cancer.
The amount of radioactivity can be quantified and serves as an indicator of the metabolic activity of the gland. A normal quantitation of radioiodine uptake demonstrates that about 8-35% of the administered dose can be detected in the thyroid 24 hours later. Overactivity or underactivity of the gland, as may occur with hyperthyroidism or hypothyroidism, is usually reflected in increased or decreased radioiodine uptake. Different patterns may occur with different causes of hypo- or hyperthyroidism.
Biopsy
A medical
biopsy
A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a diseas ...
refers to the obtaining of a tissue sample for examination under the microscope or other testing, usually to distinguish cancer from noncancerous conditions. Thyroid tissue may be obtained for biopsy by
fine needle aspiration
Fine-needle aspiration (FNA) is a diagnostic procedure used to investigate lumps or masses. In this technique, a thin (23–25 gauge (0.52 to 0.64 mm outer diameter)), hollow needle is inserted into the mass for sampling of cells that, aft ...
(FNA) or by
surgery
Surgery ''cheirourgikē'' (composed of χείρ, "hand", and ἔργον, "work"), via la, chirurgiae, meaning "hand work". is a medical specialty that uses operative manual and instrumental techniques on a person to investigate or treat a pat ...
.
Fine needle aspiration has the advantage of being a brief, safe, outpatient procedure that is safer and less expensive than surgery and does not leave a visible scar. Needle biopsies became widely used in the 1980s, but it was recognized that the accuracy of identification of cancer was good, but not perfect. The accuracy of the diagnosis depends on obtaining tissue from all of the suspicious areas of an abnormal thyroid gland. The reliability of fine needle aspiration is increased when sampling can be guided by ultrasound, and over the last 15 years, this has become the preferred method for thyroid biopsy in North America.
Treatment
Medication
Levothyroxine
Levothyroxine, also known as -thyroxine, is a manufactured form of the thyroid hormone thyroxine (T4). It is used to treat hypothyroidism, thyroid hormone deficiency (hypothyroidism), including a severe form known as myxedema coma. It may also ...
is a
stereoisomer
In stereochemistry, stereoisomerism, or spatial isomerism, is a form of isomerism in which molecules have the same molecular formula and sequence of bonded atoms (constitution), but differ in the three-dimensional orientations of their atoms in ...
of
thyroxine
File:Thyroid_system.svg, upright=1.5, The thyroid system of the thyroid hormones T3 and T4
rect 376 268 820 433 Thyroid-stimulating hormone
rect 411 200 849 266 Thyrotropin-releasing hormone
rect 297 168 502 200 Hypothalamus
rect 66 216 386 25 ...
(T4) which is degraded much more slowly and can be administered once daily in patients with hypothyroidism.
Natural thyroid hormone from pigs is sometimes also used, especially for people who cannot tolerate the synthetic version. Hyperthyroidism caused by Graves' disease may be treated with the
thioamide
A thioamide (rarely, thionamide, but also known as thiourylenes) is a functional group with the general structure R–CS–NR′R″, where R, R′, and R″ are organic groups. They are analogous to amides but they exhibit greater multiple bond ch ...
drugs
propylthiouracil
Propylthiouracil (PTU) is a medication used to treat hyperthyroidism. This includes hyperthyroidism due to Graves' disease and toxic multinodular goiter. In a thyrotoxic crisis it is generally more effective than methimazole. Otherwise it is t ...
,
carbimazole
Carbimazole (brand names Neo-Mercazole, Anti-Thyrox, etc.) is used to treat hyperthyroidism. Carbimazole is a pro-drug as after absorption it is converted to the active form, methimazole. Methimazole prevents thyroid peroxidase enzyme from iodin ...
or
methimazole
Thiamazole, also known as methimazole, is a medication used to treat hyperthyroidism. This includes Graves disease, toxic multinodular goiter, and thyrotoxic crisis. It is taken by mouth. Full effects may take a few weeks to occur.
Common s ...
, or rarely with
Lugol's solution. Additionally, hyperthyroidism and thyroid tumors may be treated with
radioactive iodine
There are 37 known isotopes of iodine (53I) from 108I to 144I; all undergo radioactive decay except 127I, which is stable. Iodine is thus a monoisotopic element.
Its longest-lived radioactive isotope, 129I, has a half-life of 15.7 million year ...
.
Ethanol
Ethanol (abbr. EtOH; also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound. It is an Alcohol (chemistry), alcohol with the chemical formula . Its formula can be also written as or (an ethyl ...
injections for the treatment of recurrent thyroid cysts and metastatic thyroid cancer in lymph nodes can also be an alternative to surgery.
Surgery
Thyroid surgery is performed for a variety of reasons. A
nodule or lobe of the thyroid is sometimes removed for
biopsy
A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a diseas ...
or because of the presence of an autonomously functioning
adenoma
An adenoma is a benign tumor of epithelial tissue with glandular origin, glandular characteristics, or both. Adenomas can grow from many glandular organs, including the adrenal glands, pituitary gland, thyroid, prostate, and others. Some adenom ...
causing
hyperthyroidism
Hyperthyroidism is the condition that occurs due to excessive production of thyroid hormones by the thyroid gland. Thyrotoxicosis is the condition that occurs due to excessive thyroid hormone of any cause and therefore includes hyperthyroidism ...
. A large majority of the thyroid may be removed (''subtotal thyroidectomy)'' to treat the hyperthyroidism of
Graves' disease
Graves' disease (german: Morbus Basedow), also known as toxic diffuse goiter, is an autoimmune disease that affects the thyroid. It frequently results in and is the most common cause of hyperthyroidism. It also often results in an enlarged thyr ...
, or to remove a
goiter
A goitre, or goiter, is a swelling in the neck resulting from an enlarged thyroid gland. A goitre can be associated with a thyroid that is not functioning properly.
Worldwide, over 90% of goitre cases are caused by iodine deficiency. The term is ...
that is unsightly or impinges on vital structures.
A complete
thyroidectomy
A thyroidectomy is an operation that involves the surgical removal of all or part of the thyroid gland. In general surgery, endocrine or head and neck surgeons often perform a thyroidectomy when a patient has thyroid cancer or some other conditi ...
of the entire thyroid, including associated
lymph nodes
A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that includ ...
, is the preferred treatment for
thyroid cancer
Thyroid cancer is cancer that develops from the tissues of the thyroid gland. It is a disease in which cells grow abnormally and have the potential to spread to other parts of the body. Symptoms can include swelling or a lump in the neck. C ...
. Removal of the bulk of the thyroid gland usually produces
hypothyroidism
Hypothyroidism (also called ''underactive thyroid'', ''low thyroid'' or ''hypothyreosis'') is a disorder of the endocrine system in which the thyroid gland does not produce enough thyroid hormone. It can cause a number of symptoms, such as po ...
unless the person takes
thyroid hormone
File:Thyroid_system.svg, upright=1.5, The thyroid system of the thyroid hormones T3 and T4
rect 376 268 820 433 Thyroid-stimulating hormone
rect 411 200 849 266 Thyrotropin-releasing hormone
rect 297 168 502 200 Hypothalamus
rect 66 216 386 25 ...
replacement. Consequently, individuals who have undergone a total thyroidectomy are typically placed on thyroid hormone replacement (e.g. Levothyroxine) for the remainder of their lives. Higher than normal doses are often administered to prevent recurrence.
If the thyroid gland must be removed surgically, care must be taken to avoid damage to adjacent structures, the
parathyroid gland
Parathyroid glands are small endocrine glands in the neck of humans and other tetrapods. Humans usually have four parathyroid glands, located on the back of the thyroid gland in variable locations. The parathyroid gland produces and secretes pa ...
s and the
recurrent laryngeal nerve
The recurrent laryngeal nerve (RLN) is a branch of the vagus nerve (cranial nerve X) that supplies all the intrinsic muscles of the larynx, with the exception of the cricothyroid muscles. There are two recurrent laryngeal nerves, right and le ...
. Both are susceptible to accidental removal and/or injury during thyroid surgery.
The parathyroid glands produce
parathyroid hormone
Parathyroid hormone (PTH), also called parathormone or parathyrin, is a peptide hormone secreted by the parathyroid glands that regulates the serum calcium concentration through its effects on bone, kidney, and intestine.
PTH influences bone re ...
(PTH), a hormone needed to maintain adequate amounts of calcium in the blood. Removal results in
hypoparathyroidism
Hypoparathyroidism is decreased function of the parathyroid glands with underproduction of parathyroid hormone (PTH). This can lead to low levels of calcium in the blood, often causing cramping and twitching of muscles or tetany (involuntary musc ...
and a need for supplemental calcium and
vitamin D
Vitamin D is a group of fat-soluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and many other biological effects. In humans, the most important compounds in this group are vitamin D3 (c ...
each day. In the event that the blood supply to any one of the parathyroid glands is endangered through surgery, the parathyroid gland(s) involved may be re-implanted in surrounding muscle tissue.
The recurrent laryngeal nerves provide motor control for all external muscles of the
larynx
The larynx (), commonly called the voice box, is an organ in the top of the neck involved in breathing, producing sound and protecting the trachea against food aspiration. The opening of larynx into pharynx known as the laryngeal inlet is about ...
except for the
cricothyroid muscle
The cricothyroid muscle is the only tensor muscle of the larynx aiding with phonation. It is innervated by the superior laryngeal nerve. Its action tilts the thyroid forward to help tense the vocal cords.
Structure
The cricothyroid muscle orig ...
, which also runs along the posterior thyroid. Accidental laceration of either of the two or both recurrent laryngeal nerves may cause paralysis of the
vocal cords
In humans, vocal cords, also known as vocal folds or voice reeds, are folds of throat tissues that are key in creating sounds through vocalization. The size of vocal cords affects the pitch of voice. Open when breathing and vibrating for speech ...
and their associated muscles, changing the voice quality.
Radioiodine
Radioiodine therapy
Iodine-131 (131I, I-131) is an important radioisotope of iodine discovered by Glenn Seaborg and John Livingood in 1938 at the University of California, Berkeley. It has a radioactive decay half-life of about eight days. It is associated with nuc ...
with iodine-131 can be used to shrink the thyroid gland (for instance, in the case of large goiters that cause symptoms but do not harbor cancer—after evaluation and biopsy of suspicious nodules has been done), or to destroy hyperactive thyroid cells (for example, in cases of thyroid cancer). The iodine uptake can be high in countries with iodine deficiency, but low in iodine sufficient countries. To enhance iodine-131 uptake by the thyroid and allow for more successful treatment, TSH is raised prior to therapy in order to stimulate the existing thyroid cells. This is done either by withdrawal of thyroid hormone medication or injections of recombinant human TSH (Thyrogen),
released in the United States in 1999. Thyrogen injections can reportedly boost uptake up to 50-60%. Radioiodine treatment can also cause hypothyroidism (which is sometimes the end goal of treatment) and, although rare, a pain syndrome (due to
radiation thyroiditis).
Epidemiology
In the United States, autoimmune inflammation is the most common form of thyroid disease while worldwide hypothyroidism and goiter due to dietary iodine deficiency is the most common.
According to the American Thyroid Association in 2015, approximately 20 million people in the United States alone are affected by thyroid disease.
Hypothyroidism affects 3-10% percent of adults, with a higher incidence in women and the elderly.
An estimated one-third of the world's population currently lives in areas of low dietary iodine levels. In regions of severe iodine deficiency, the prevalence of goiter is as high as 80%.
In areas where iodine-deficiency is not found, the most common type of hypothyroidism is an autoimmune subtype called
Hashimoto's thyroiditis
Hashimoto's thyroiditis, also known as chronic lymphocytic thyroiditis and Hashimoto's disease, is an autoimmune disease in which the thyroid gland is gradually destroyed. Early on, symptoms may not be noticed. Over time, the thyroid may enlarg ...
, with a prevalence of 1-2%.
As for hyperthyroidism,
Graves' disease
Graves' disease (german: Morbus Basedow), also known as toxic diffuse goiter, is an autoimmune disease that affects the thyroid. It frequently results in and is the most common cause of hyperthyroidism. It also often results in an enlarged thyr ...
, another autoimmune condition, is the most common type with a prevalence of 0.5% in males and 3% in females.
Although thyroid nodules are common, thyroid cancer is rare. Thyroid cancer accounts for less than 1% of all cancer in the UK, though it is the most common endocrine tumor and makes up greater than 90% of all cancers of the
endocrine gland
Endocrine glands are ductless glands of the endocrine system that secrete their products, hormones, directly into the blood. The major glands of the endocrine system include the pineal gland, pituitary gland, pancreas, ovaries, testes, thyroid ...
s.
See also
*
Hyperthyroidism
Hyperthyroidism is the condition that occurs due to excessive production of thyroid hormones by the thyroid gland. Thyrotoxicosis is the condition that occurs due to excessive thyroid hormone of any cause and therefore includes hyperthyroidism ...
**
Grave's Disease
*
Hypothyroidism
Hypothyroidism (also called ''underactive thyroid'', ''low thyroid'' or ''hypothyreosis'') is a disorder of the endocrine system in which the thyroid gland does not produce enough thyroid hormone. It can cause a number of symptoms, such as po ...
**
Hashimoto's Thyroiditis
Hashimoto's thyroiditis, also known as chronic lymphocytic thyroiditis and Hashimoto's disease, is an autoimmune disease in which the thyroid gland is gradually destroyed. Early on, symptoms may not be noticed. Over time, the thyroid may enlarg ...
*
Thyroid Nodule
Thyroid nodules are nodules (raised areas of tissue or fluid) which commonly arise within an otherwise normal thyroid gland. They may be hyperplastic or tumorous, but only a small percentage of thyroid tumors are malignant. Small, asymptomatic ...
*
Thyroid disease in pregnancy Thyroid disease in pregnancy can affect the health of the mother as well as the child before and after delivery. Thyroid disorders are prevalent in women of child-bearing age and for this reason commonly present as a pre-existing disease in pregnan ...
References
External links
*
Medline Plus Medical Encyclopedia entry for Thyroid DiseaseNational Institutes of Health
{{Congenital endocrine disorders