Hyper- and hypofunction

Imbalance in production of thyroid hormone

Thyroid hormone

The thyroid hormones, thyroxine and triiodothyronine , are tyrosine-based hormones produced by the thyroid gland primarily responsible for regulation of metabolism. An important component in the synthesis of thyroid hormones is iodine. The major form of thyroid hormone in the blood is thyroxine ,...

s arises from dysfunction of the thyroid gland itself, the pituitary gland

Pituitary gland

In vertebrate anatomy the pituitary gland, or hypophysis, is an endocrine gland about the size of a pea and weighing 0.5 g , in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain, and rests in a small, bony cavity covered by a dural fold...

, which produces thyroid-stimulating hormone

Thyroid-stimulating hormone

Thyrotrophin-stimulating hormone is a peptide hormone synthesized and secreted by thyrotrope cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid gland.- Physiology :...

 (TSH), or the hypothalamus

Hypothalamus

The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...

, which regulates the pituitary gland via thyrotropin-releasing hormone

Thyrotropin-releasing hormone

Thyrotropin-releasing hormone , also called thyrotropin-releasing factor , thyroliberin or protirelin, is a tropic tripeptide hormone that stimulates the release of thyroid-stimulating hormone and prolactin by the anterior pituitary...

 (TRH). Concentrations of TSH increase with age, requiring age-corrected tests. Hypothyroidism affects between three and ten percent of adults, with incidence higher in women and the elderly.

• Hypothyroidism
  Hypothyroidism
  Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by other causes such as several conditions of the thyroid gland or, less commonly, the pituitary gland or...
  
   (underactivity)
  • Hashimoto's thyroiditis
    Hashimoto's thyroiditis
    Hashimoto's thyroiditis or chronic lymphocytic thyroiditis is an autoimmune disease in which the thyroid gland is gradually destroyed by a variety of cell- and antibody-mediated immune processes. It was the first disease to be recognized as an autoimmune disease...
    
     / thyroiditis
    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.-Classification:...
    
    
  • Ord's thyroiditis
    Ord's thyroiditis
    Ord's thyroiditis is a common form of thyroiditis, an autoimmune disease where the body's own antibodies fight the cells of the thyroid. It is named after the physician, William Miller Ord, who first described it in 1877 and again in 1888...
    
    
  • Postoperative hypothyroidism
  • Postpartum thyroiditis
    Postpartum thyroiditis
    Postpartum thyroiditis is a phenomenon observed following pregnancy and may involve hyperthyroidism, hypothyroidism or the two sequentially. It affects about 5% of all women within a year after giving birth. The first phase is typically hyperthyroidism. Then, the thyroid either returns to normal...
    
    
  • Silent thyroiditis
    Silent thyroiditis
    Subacute lymphocytic thyroiditis is a form of thyroiditis that is also known as silent thyroiditis or painless 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...
    
    
  • Acute thyroiditis
  • Iatrogenic hypothyroidism
  • Thyroid hormone resistance
    Thyroid hormone resistance
    Thyroid hormone resistance describes a rare syndrome where the thyroid hormone levels are elevated but the thyroid stimulating hormone level is not suppressed, or not completely suppressed as would be expected.-Causes:...
    
    
  • Euthyroid sick syndrome
    Euthyroid sick syndrome
    Euthyroid sick syndrome, sick euthyroid syndrome, non-thyroidal illness syndrome or low T3 low T4 syndrome is a state of adaptation or dysregulation of thyrotropic feedback control where the levels of T3 and/or T4 are at unusual levels, but the thyroid gland does not appear to be dysfunctional...
    
    

• Hyperthyroidism
  Hyperthyroidism
  Hyperthyroidism is the term for overactive tissue within the thyroid gland causing an overproduction of thyroid hormones . Hyperthyroidism is thus a cause of thyrotoxicosis, the clinical condition of increased thyroid hormones in the blood. Hyperthyroidism and thyrotoxicosis are not synonymous...
  
   (overactivity)
  • Thyroid storm
  • Graves' disease
    Graves' disease
    Graves' disease is an autoimmune disease where the thyroid is overactive, producing an excessive amount of thyroid hormones...
    
    
  • Toxic thyroid nodule
  • Toxic nodular struma (Plummer's disease)
  • Hashitoxicosis

Anatomical problems

• Goitre
  Goitre
  A goitre or goiter , is a swelling in the thyroid gland, which can lead to a swelling of the neck or larynx...
  
  
  • Endemic goitre
    Endemic goitre
    Endemic goitre is a type of goitre that is associatedwith dietary iodine deficiency.Some inland areas where soil and water lacks in iodine compounds and consumption of marine foods is low are known for higher incidence of goitre. In such areas goitre is said to be "endemic".This type of goitre is...
    
    
  • Diffuse goitre
  • Multinodular goitre
• Lingual thyroid
• Thyroglossal duct cyst
  Thyroglossal cyst
  A thyroglossal cyst is a fibrous cyst that forms from a persistent thyroglossal duct.-Presentation:It usually presents as a midline neck lump that is usually painless, smooth and cystic, if infected pain can occur...
  
  

Tumors

• Thyroid adenoma
  Thyroid adenoma
  -Types:Almost all thyroid adenomas are follicular adenomas. Follicular adenomas can be described as "cold", "warm" or "hot" depending on their level of function...
  
  
• Thyroid cancer
  Thyroid cancer
  Thyroid neoplasm is a neoplasm or tumor of the thyroid. It can be a benign tumor such as thyroid adenoma, or it can be a malignant neoplasm , such as papillary, follicular, medullary or anaplastic thyroid cancer. Most patients are 25 to 65 years of age when first diagnosed; women are more affected...
  
  
  • Papillary
  • Follicular
  • Medullary
  • Anaplastic
• Lymphoma
  Lymphoma
  Lymphoma is a cancer in the lymphatic cells of the immune system. Typically, lymphomas present as a solid tumor of lymphoid cells. Treatment might involve chemotherapy and in some cases radiotherapy and/or bone marrow transplantation, and can be curable depending on the histology, type, and stage...
  
  s and metastasis
  Metastasis
  Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...
  
   from elsewhere (rare)

Deficiencies

• Cretinism
  Cretinism
  Cretinism is a condition of severely stunted physical and mental growth due to untreated congenital deficiency of thyroid hormones usually due to maternal hypothyroidism.-Etymology and use of cretin:...
  
  

Medication linked to thyroid disease includes amiodarone

Amiodarone

Amiodarone is an antiarrhythmic agent used for various types of tachyarrhythmias , both ventricular and supraventricular arrhythmias. Discovered in 1961, it was not approved for use in the United States until 1985...

, lithium salts, some types of interferon

Interferon

Interferons are proteins made and released by host cells in response to the presence of pathogens—such as viruses, bacteria, or parasites—or tumor cells. They allow communication between cells to trigger the protective defenses of the immune system that eradicate pathogens or tumors.IFNs belong to...

 and IL-2.
Defiency in adults causes Myxedema

Blood tests

• The measurement of thyroid-stimulating hormone
  Thyroid-stimulating hormone
  Thyrotrophin-stimulating hormone is a peptide hormone synthesized and secreted by thyrotrope cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid gland.- Physiology :...
  
   (TSH) levels is often used by doctors as a screening test. Elevated TSH levels can signify an inadequate thyroid hormone
  Thyroid hormone
  The thyroid hormones, thyroxine and triiodothyronine , are tyrosine-based hormones produced by the thyroid gland primarily responsible for regulation of metabolism. An important component in the synthesis of thyroid hormones is iodine. The major form of thyroid hormone in the blood is thyroxine ,...
  
   production, while suppressed levels can point at excessive unregulated production of hormone.
• If TSH is abnormal, decreased levels of thyroid hormones T4 and T3 may be present; T4 and T3 levels may be determined with blood tests to confirm that their levels are decreased.
• Autoantibodies
  Autoantibody
  An autoantibody is an antibody manufactured by the immune system that is directed against one or more of the individual's own proteins. It is derived from the Greek "auto" which means "self", "anti" which means "against" and "body"...
  
   may be detected in various disease states (anti-TG, anti-TPO
  Thyroid peroxidase
  Thyroid peroxidase or thyroperoxidase is an enzyme expressed mainly in the thyroid that liberates iodine for addition onto tyrosine residues on thyroglobulin for the production of thyroxine or triiodothyronine , thyroid hormones. In humans, thyroperoxidase is encoded by the TPO...
  
  , TSH receptor stimulating antibodies).
• There are two cancer markers for thyroid derived cancers. Thyroglobulin
  Thyroglobulin
  Thyroglobulin is a 660 kDa, dimeric protein produced by and used entirely within the thyroid gland. In earlier literature, Tg was referred to as colloid....
  
   (TG) for well differentiated papillary or follicular adenocarcinoma, and the rare medullary thyroid cancer has calcitonin
  Calcitonin
  Calcitonin is a 32-amino acid linear polypeptide hormone that is producedin humans primarily by the parafollicular cells of the thyroid, and in many other animals in the ultimobranchial body. It acts to reduce blood calcium , opposing the effects of parathyroid hormone . Calcitonin has been found...
  
   as the marker.
• Very infrequently, TBG
  Thyroxine-binding globulin
  Thyroxine-binding globulin binds thyroid hormone in circulation. It is one of three proteins responsible for carrying the thyroid hormones thyroxine and 3,5,3’-triiodothyronine in the bloodstream. Of these three proteins, TBG has the highest affinity for T4 and T3, but is present in the lowest...
  
   and transthyretin
  Transthyretin
  Transthyretin is a serum and cerebrospinal fluid carrier of the thyroid hormone thyroxine and retinol binding protein bound to retinol. 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. Thyroid-releasing hormone (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

Nodules of the thyroid may or may not be cancer

Cancer

Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

. Medical ultrasonography

Medical ultrasonography

Diagnostic sonography is an ultrasound-based diagnostic imaging technique used for visualizing subcutaneous body structures including tendons, muscles, joints, vessels and internal organs for possible pathology or lesions...

 can help determine their nature because some of the characteristics of benign and malignant nodules differ. The main characteristics of a thyroid nodule on high frequency thyroid ultrasound are as follows:

Possible cancer

Benign characteristics >- | irregular border

>- | hypoechoic (less echogenic than the surrounding tissue)

>- | microcalcifications

>- | taller than wide shape on transverse study

>- | significant intranodular blood flow by power Doppler

>- | -

"comet tail" artifact as sound waves bounce off intranodular colloid

Ultrasonography is not always able to separate benign from malignant nodules with complete certainty. In suspicious cases, a tissue sample is often obtained by biopsy for microscopic examination.

Radioiodine scanning and uptake

Thyroid scintigraphy

Scintigraphy

Scintigraphy is a form of diagnostic test used in nuclear medicine, wherein radioisotopes are taken internally, and the emitted radiation is captured by external detectors to form two-dimensional images...

, imaging of the thyroid with the aid of radioactive iodine, usually iodine-123

Iodine-123

Iodine-123 is a radioactive isotope of iodine used in nuclear medicine imaging, including single photon emission computed tomography . The isotope's half-life is 13.22 hours; the decay by electron capture to tellurium-123 emits gamma radiation with predominant energies of 159 keV and 127 keV...

 (¹²³I), is performed in the nuclear medicine

Nuclear medicine

In nuclear medicine procedures, elemental radionuclides are combined with other elements to form chemical compounds, or else combined with existing pharmaceutical compounds, to form radiopharmaceuticals. These radiopharmaceuticals, once administered to the patient, can localize to specific organs...

 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 radiodine scan) and tissue activity (a radioiodine uptake) of the thyroid gland.

A normal radioiodine scan shows even uptake and activity throughout the gland. Irregularity can reflect an abnormally shaped or abnormally located gland, or it can indicate that a portion of the gland is overactive or underactive, different from the rest. 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 hardly ever 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 counted as an indicator of the metabolic activity of the gland. A normal quantitation of radioiodine uptake demonstrates that about 8 to 35% of the administered dose can be detected in the thyroid 24 hours later. Overactivity or underactivity of the gland as may occur with hypothyroidism or hyperthyroidism is usually reflected in decreased or increased radioiodine uptake. Different patterns may occur with different causes of hypo- or hyperthyroidism.

Biopsy

A medical biopsy

Biopsy

A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...

 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 or by surgery

Surgery

Surgery is an ancient medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, or to help improve bodily function or appearance.An act of performing surgery may be called a surgical...

.

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 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 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.

Medical treatment

Levothyroxine

Levothyroxine

Levothyroxine, also L-thyroxine, synthetic T4, or 3,5,3',5'-tetraiodo-L-thyronine, is a synthetic form of thyroxine , used as a hormone replacement for patients with thyroid problems. The natural hormone is chemically in the chiral L-form, as is the pharmaceutical agent...

 is a stereoisomer of thyroxine which is degraded much slower and can be administered once daily in patients with hypothyroidism.
Natural thyroid hormone from pigs is also used, especially for people who cannot tolerate the synthetic version.
Graves' disease may be treated with the thioamide

Thioamide

Thioamide 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 character along the C-N bond, resulting in a larger rotational barrier...

 drugs propylthiouracil

Propylthiouracil

Propylthiouracil or 6-n-Propylthiouracil is a thioamide drug used to treat hyperthyroidism by decreasing the amount of thyroid hormone produced by the thyroid gland...

, carbimazole

Carbimazole

Carbimazole is used to treat hyperthyroidism. Carbimazole is a pro-drug as after absorption it is converted to the active form, methimazole. Methimazole prevents the thyroid peroxidase enzyme from coupling and iodinating the tyrosine residues on thyroglobulin, hence reducing the production of the...

 or methimazole

Methimazole

Methimazole is an antithyroid drug, and part of the thioamide group.-Indications:...

, or rarely with Lugol's solution. Hyperthyroidism as well as thyroid tumors may be treated with radioactive iodine.

Percutaneous Ethanol Injections, PEI, for therapy of recurrent thyroid cysts and metastatic thyroid cancer lymph nodes is an alternative to the usual surgical method.

Surgery

Thyroid surgery is performed for a variety of reasons. A nodule

Thyroid nodule

Thyroid nodules are lumps which commonly arise within an otherwise normal thyroid gland. They indicate a thyroid neoplasm, but only a small percentage of these are thyroid cancers.-Presentation:...

 or lobe of the thyroid is sometimes removed for biopsy

Biopsy

A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...

 or for the presence of an autonomously functioning adenoma

Thyroid adenoma

-Types:Almost all thyroid adenomas are follicular adenomas. Follicular adenomas can be described as "cold", "warm" or "hot" depending on their level of function...

 causing hyperthyroidism

Hyperthyroidism

Hyperthyroidism is the term for overactive tissue within the thyroid gland causing an overproduction of thyroid hormones . Hyperthyroidism is thus a cause of thyrotoxicosis, the clinical condition of increased thyroid hormones in the blood. Hyperthyroidism and thyrotoxicosis are not synonymous...

. A large majority of the thyroid may be removed, a subtotal thyroidectomy, to treat the hyperthyroidism of Graves' disease

Graves' disease

Graves' disease is an autoimmune disease where the thyroid is overactive, producing an excessive amount of thyroid hormones...

, or to remove a goitre

Goitre

A goitre or goiter , is a swelling in the thyroid gland, which can lead to a swelling of the neck or larynx...

 that is unsightly or impinges on vital structures.

A complete thyroidectomy

Thyroidectomy

A thyroidectomy is an operation that involves the surgical removal of all or part of the thyroid gland. Surgeons often perform a thyroidectomy when a patient has thyroid cancer or some other condition of the thyroid gland...

 of the entire thyroid, including associated lymph nodes, is the preferred treatment for thyroid cancer

Thyroid cancer

Thyroid neoplasm is a neoplasm or tumor of the thyroid. It can be a benign tumor such as thyroid adenoma, or it can be a malignant neoplasm , such as papillary, follicular, medullary or anaplastic thyroid cancer. Most patients are 25 to 65 years of age when first diagnosed; women are more affected...

. Removal of the bulk of the thyroid gland usually produces hypothyroidism

Hypothyroidism

Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by other causes such as several conditions of the thyroid gland or, less commonly, the pituitary gland or...

, unless the person takes thyroid hormone

Thyroid hormone

The thyroid hormones, thyroxine and triiodothyronine , are tyrosine-based hormones produced by the thyroid gland primarily responsible for regulation of metabolism. An important component in the synthesis of thyroid hormones is iodine. The major form of thyroid hormone in the blood is thyroxine ,...

 replacement. Consequently, individuals who have undergone a total thyroidectomy are typically placed on thyroid hormone replacement 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 gland

The parathyroid glands are small endocrine glands in the neck that produce parathyroid hormone. Humans usually have four parathyroid glands, which are usually located on the rear surface of the thyroid gland, or, in rare cases, within the thyroid gland itself or in the chest...

s and the recurrent laryngeal nerve

Recurrent laryngeal nerve

The recurrent laryngeal nerve is a branch of the vagus nerve that supplies motor function and sensation to the larynx . It travels within the endoneurium...

. Both are susceptible to accidental removal and/or injury during thyroid surgery. The parathyroid glands produce parathyroid hormone

Parathyroid hormone

Parathyroid hormone , parathormone or parathyrin, is secreted by the chief cells of the parathyroid glands as a polypeptide containing 84 amino acids...

 (PTH), a hormone needed to maintain adequate amounts of calcium in the blood. Removal results in hypoparathyroidism

Hypoparathyroidism

Hypoparathyroidism is decreased function of the parathyroid glands with under production of parathyroid hormone. This can lead to low levels of calcium in the blood, often causing cramping and twitching of muscles or tetany , and several other symptoms...

 and a need for supplemental calcium and vitamin D

Vitamin D

Vitamin D is a group of fat-soluble secosteroids. In humans, vitamin D is unique both because it functions as a prohormone and because the body can synthesize it when sun exposure is adequate ....

 each day. In the event 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

Larynx

The larynx , commonly called the voice box, is an organ in the neck of amphibians, reptiles and mammals involved in breathing, sound production, and protecting the trachea against food aspiration. It manipulates pitch and volume...

 except for the cricothyroid muscle

Cricothyroid muscle

The cricothyroid muscle is the only tensor muscle of the larynx, aiding with phonation. It attaches to the anterolateral aspect of the cricoid and the inferior cornu and lower lamina of the thyroid cartilage, and its action tilts the thyroid forward to help tense the vocal cords...

, 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 and their associated muscles, changing the voice quality.

Radioiodine therapy

Large goiters that cause symptoms but do not harbor cancer, after evaluation and biopsy of suspicious nodules, can be treated by an alternative therapy with radioiodine. The iodine uptake can be high in countries with iodine deficiency, but low in iodine sufficient countries. The 1999 release of recombinant human TSH, Thyrogen, in the USA, can boost the uptake to 50-60% allowing the therapy with Iodine 131. The gland shrinks by 50-60% but can cause hypothyroidism and rarely pain syndrome, which arises due to radiation thyroiditis. It is short lived and treated by steroids.

Further reading

• Brent, Gregory A. (Ed.), Thyroid Function Testing, New York : Springer, Series: Endocrine Updates, Vol. 28, 1st Edition., 2010. ISBN 978-1-4419-1484-2

External links

• Medline Plus Medical Encyclopedia entry for Thyroid Disease
• MyThyroid.com An evidence-based patient-centered website devoted to diseases of the thyroid
• Thyroid disease portal at About.com managed by health activist and patient advocate Mary Shomon
  Mary Shomon
  Mary Shomon, born 1961, is an American health activist and author whose primary focus is thyroid disease.-Published work:She is the author of one New York Times best-selling book, The Thyroid Diet: Manage Your Metabolism for Lasting Weight Loss, published by Harper Collins in 2004, along with a...
  
  
• Thyroid Disease Manager A group of thyroid experts offer an up-to-date analysis of all aspects of human thyroid disease and thyroid physiology
• Medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism from the American Association of Clinical Endocrinologists
• Clinical Thyroidology - Free online monthly magazine The Editor searches for the best new thyroid studies, summarizes them and provides expert commentary
• Clinical Thyroidology - Patient version The more accessible version of the magazine Clinical Thyroidology, directed at the patient