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Hypothyroidism (also called ''underactive thyroid'', ''low thyroid'' or ''hypothyreosis'') is a disorder of the endocrine system in which the
thyroid gland The thyroid, or thyroid gland, is an endocrine gland Endocrine glands are ductless glands of the endocrine system The endocrine system is a messenger system comprising feedback loops of the hormones released by internal glands of an organis ...

thyroid gland
does not produce enough
thyroid hormone File:Thyroid_system.svg, upright=1.5, The thyroid 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 connec ...
. It can cause a number of symptoms, such as poor ability to tolerate cold, a ,
constipation Constipation refers to bowel movements that are infrequent or hard to pass. The stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the bowel movement. Complications ...
,
slow heart rate Bradycardia is a condition typically defined wherein an individual has a resting heart rateHeart rate is the speed of the heartbeat measured by the number of contractions (beats) of the heart The heart is a muscle, muscular Organ (anatomy ...
,
depression Depression may refer to: Mental health * Depression (mood), a state of low mood and aversion to activity * Mood disorders characterized by depression are commonly referred to as simply ''depression'', including: ** Dysthymia ** Major depressive ...
, and
weight gain Weight gain is an increase in body weight Human body weight refers to a person's mass or weight. Body weight is measured in kilogram The kilogram (also kilogramme) is the base unit of mass in the International System of Units (SI), the curr ...
. Occasionally there may be swelling of the front part of the neck due to
goiter A goitre, American and British English spelling differences#re er, or goiter, is a swelling in the neck resulting from an enlarged thyroid, thyroid gland. A goitre can be associated with a thyroid that is not functioning properly. Worldwide, over ...
. Untreated cases of hypothyroidism during
pregnancy Pregnancy, also known as gestation, is the time during which one or more offspring In biology, offspring are the young creation of living organisms, produced either by a Asexual reproduction, single organism or, in the case of sexual repr ...

pregnancy
can lead to delays in growth and intellectual development in the baby or
congenital iodine deficiency syndrome Congenital iodine deficiency syndrome (formerly known as cretinism) is a medical condition present at birth marked by impaired physical and mental development, due to insufficient thyroid hormone (hypothyroidism) often caused by insufficient dieta ...
. Worldwide, too little iodine in the diet is the most common cause of hypothyroidism.
Hashimoto's thyroiditis Hashimoto's thyroiditis, also known as chronic lymphocytic thyroiditis and Hashimoto's disease, is an autoimmune disease in which the thyroid, thyroid gland is gradually destroyed. Early on, symptoms may not be noticed. Over time, the thyroid m ...

Hashimoto's thyroiditis
is the most common cause of hypothyroidism in countries with sufficient dietary iodine. Less common causes include previous treatment with
radioactive iodine There are 37 known isotope Isotopes are two or more types of atoms that have the same atomic number (number of protons A proton is a subatomic particle, symbol or , with a positive electric charge Electric charge is the physical prop ...

radioactive iodine
, injury to the
hypothalamus The hypothalamus (from Ancient Greek wikt:ὑπό, ὑπό, "under", and wikt:θάλαμος, θάλαμος, "chamber") is a portion of the brain that contains a number of small Nucleus (neuroanatomy), nuclei with a variety of functions. One of ...

hypothalamus
or the
anterior pituitary A major Organ (anatomy), organ of the endocrine system, the anterior pituitary (also called the adenohypophysis or pars anterior) is the glandular, Anatomical terms of location#Usage in human anatomy, anterior lobe that together with the Anatomic ...
gland, certain medications, a lack of a functioning thyroid at birth, or previous thyroid surgery. The diagnosis of hypothyroidism, when suspected, can be confirmed with
blood test A blood test is a laboratory A laboratory (; ; colloquially lab) is a facility that provides controlled conditions in which or technological research, s, and may be performed. Laboratory services are provided in a variety of settings: ...

blood test
s measuring
thyroid-stimulating hormone Thyroid-stimulating hormone (also known as thyrotropin, thyrotropic hormone, or abbreviated TSH) is a pituitary hormone that stimulates the thyroid The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans it is in the ne ...
(TSH) and
thyroxine File:Thyroid_system.svg, upright=1.5, The thyroid 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 conne ...

thyroxine
levels.
Salt iodization An example of a commonly distributed packet of iodized salt, which can rapidly lose its iodine content in high temperature and high relative humidity conditions Iodised salt ( also spelled iodized salt) is table salt Salt is a mineral compo ...

Salt iodization
has prevented hypothyroidism in many populations. Thyroid hormone replacement with
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 Hashimoto's thyroiditis, Hashimoto's disease and a ...
treats hypothyroidism. Medical professionals adjust the dose according to symptoms and normalization of the thyroxine and TSH levels. Thyroid medication is safe in pregnancy. Although an adequate amount of dietary iodine is important, too much may worsen specific forms of hypothyroidism. Worldwide about one billion people are estimated to be iodine-deficient; however, it is unknown how often this results in hypothyroidism. In the United States, hypothyroidism occurs in 0.3–0.4% of people. Subclinical hypothyroidism, a milder form of hypothyroidism characterized by normal thyroxine levels and an elevated TSH level, is thought to occur in 4.3–8.5% of people in the United States. Hypothyroidism is more common in women than in men. People over the age of 60 are more commonly affected. Dogs are also known to develop hypothyroidism, as are cats and horses, albeit more rarely. The word ''hypothyroidism'' is from Greek ''hypo-'' 'reduced', ''thyreos'' 'shield', and ''eidos'' 'form'.


Signs and symptoms

People with hypothyroidism often have no or only mild
symptom Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower temperature than normal, raised or lowered blood pressure or an abnormality show ...
s. Numerous symptoms and signs are associated with hypothyroidism and can be related to the underlying cause, or a direct effect of having not enough thyroid hormones.
Hashimoto's thyroiditis Hashimoto's thyroiditis, also known as chronic lymphocytic thyroiditis and Hashimoto's disease, is an autoimmune disease in which the thyroid, thyroid gland is gradually destroyed. Early on, symptoms may not be noticed. Over time, the thyroid m ...

Hashimoto's thyroiditis
may present with the
mass effect ''Mass Effect'' is a military science fiction Military science fiction is a subgenre of science fiction that features the use of science fiction technology, mainly science fiction weapons, weapons, for military purposes and usually principal c ...
of a
goiter A goitre, American and British English spelling differences#re er, or goiter, is a swelling in the neck resulting from an enlarged thyroid, thyroid gland. A goitre can be associated with a thyroid that is not functioning properly. Worldwide, over ...
(enlarged thyroid gland). In middle-aged women, the symptoms may be mistaken for those of
menopause Menopause, also known as the climacteric, is the time in women's lives when menstrual periods stop permanently, and they are no longer able to bear children. Menopause usually occurs between the age of 48 and 52. Medical professionals often ...
. Delayed relaxation after testing the
ankle jerk reflexThe ankle jerk reflex, also known as the Achilles reflex, occurs when the Achilles tendon is tapped while the foot is dorsiflexion, dorsiflexed. It is a type of stretch reflex that tests the function of the gastrocnemius muscle and the nerve that su ...
is a characteristic sign of hypothyroidism and is associated with the severity of the hormone deficit.


Myxedema coma

Myxedema coma Myxedema coma is a state of decompensation, decompensated hypothyroidism. A person may have laboratory values identical to a "normal" hypothyroid state, but a stressful event (such as an infection, myocardial infarction, or stroke) precipitates th ...
is a rare but life-threatening state of extreme hypothyroidism. It may occur in those with established hypothyroidism when they develop an acute illness. Myxedema coma can be the first presentation of hypothyroidism. People with myxedema coma typically have a low body temperature without shivering,
confusion In medicine, confusion is the quality or state of being bewildered or unclear. The term "acute mental confusion"
, a
slow heart rate Bradycardia is a condition typically defined wherein an individual has a resting heart rateHeart rate is the speed of the heartbeat measured by the number of contractions (beats) of the heart The heart is a muscle, muscular Organ (anatomy ...
and reduced breathing effort. There may be physical signs suggestive of hypothyroidism, such as skin changes or enlargement of the tongue.


Pregnancy

Even mild or subclinical hypothyroidism leads to possible
infertility Infertility is the inability of a person, animal or plant to Sexual reproduction, reproduce by natural means. It is usually not the natural state of a healthy adult, except notably among certain eusocial species (mostly haplodiploid insects). I ...
and an increased risk of
miscarriage Miscarriage, also known in medical terms as a spontaneous abortion and pregnancy loss, is the natural loss of an embryo or fetus before it is fetal viability, able to survive independently. Some use the cutoff of 20 weeks of gestation, after whi ...
. Hypothyroidism in early pregnancy, even with limited or no symptoms, may increase the risk of
pre-eclampsia Pre-eclampsia is a disorder of pregnancy Pregnancy, also known as gestation, is the time during which one or more offspring In biology, offspring are the young creation of living organisms, produced either by a Asexual reproduction, si ...
, offspring with lower intelligence, and the risk of infant death around the time of birth. Women are affected by hypothyroidism in 0.3–0.5% of pregnancies. Subclinical hypothyroidism during pregnancy is associated with
gestational diabetes Gestational diabetes is a condition in which a woman without diabetes Diabetes mellitus (DM), commonly known as diabetes, is a group of metabolic disorders characterized by a high blood sugar level over a prolonged period of time. Symptoms of ...
and the birth of the baby before 37 weeks of pregnancy.


Children

Newborn children with hypothyroidism may have normal birth weight and height (although the head may be larger than expected and the
posterior fontanelle The posterior fontanelle (lambdoid fontanelle, occipital fontanelle) is a gap between bones in the human skull (known as fontanelle), triangular in form and situated at the junction of the sagittal suture and lambdoidal suture. It generally close ...
may be open). Some may have drowsiness, decreased muscle tone, a hoarse-sounding cry, feeding difficulties, constipation, an enlarged tongue,
umbilical hernia An umbilical hernia is a health condition where the abdominal wall behind the navel is damaged. It may cause the navel to bulge outwards—the bulge consisting of abdominal fat from the greater omentum or occasionally parts of the small intestine. ...
,
dry skin Xeroderma, xerosis or xerosis cutis, or simply dry skin, is a skin condition characterized by excessively dry skin. The medical term ''xeroderma'' is derived from the Greek language, Greek words meaning ''dry skin''. In most cases, dry skin can s ...
, a decreased body temperature, and
jaundice Jaundice, also known as icterus, is a yellowish or greenish pigmentation of the skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and s ...

jaundice
. A goiter is rare, although it may develop later in children who have a thyroid gland that does not produce functioning thyroid hormone. A goiter may also develop in children growing up in areas with
iodine deficiency Iodine deficiency is a lack of the mineral (nutrient), trace element iodine, an essential nutrient in the diet (nutrition), diet. It may result in metabolic problems such as goiter, sometimes as an endemic goiter as well as congenital iodine defi ...
. Normal growth and development may be delayed, and not treating infants may lead to an intellectual impairment (IQ 6–15 points lower in severe cases). Other problems include the following: difficulty with large scale and fine
motor skill A motor skill is a function that involves specific movements of the bodies muscles to perform a certain task. These tasks could include walking, running, or riding a bike. In order to perform this skill, the bodies nervous system, muscles, and br ...
s and
coordination Coordination may refer to: * Coordination (linguistics) In linguistics, coordination is a complex syntactic In linguistics, syntax () is the set of rules, principles, and processes that govern the structure of Sentence (linguistics), sentence ...

coordination
, reduced muscle tone, , decreased
attention span Attention span is the amount of time Time is the indefinite continued sequence, progress of existence and event (philosophy), events that occur in an apparently irreversible process, irreversible succession from the past, through the present, i ...

attention span
, and delayed speaking.
Tooth eruption Tooth eruption is a process in tooth development Tooth development or odontogenesis is the complex process by which tooth, teeth form from embryonic cells, cell growth, grow, and erupt into the human mouth, mouth. For human tooth, human teeth to ...
may be delayed. In older children and adolescents, the symptoms of hypothyroidism may include fatigue, cold intolerance, sleepiness, muscle weakness, constipation, a delay in growth, overweight for height, pallor, coarse and thick skin, increased body hair, irregular menstrual cycles in girls, and
delayed puberty Delayed puberty is when a person lacks or has incomplete development of specific sexual characteristics Sexual characteristics are physical or behavioral traits of an organism In biology, an organism (from Ancient Greek, Greek: ὀργαν ...
. Signs may include delayed relaxation of the ankle reflex and a slow heartbeat. A goiter may be present with a completely enlarged thyroid gland; sometimes only part of the thyroid is enlarged and it can be knobby.


Related disorders

Thyroid hormone abnormalities are common in major psychiatric disorders including
bipolar disorder Bipolar disorder, previously known as manic depression, is a mental disorder A mental disorder, also called a mental illness or psychiatric disorder, is a behavioral or mental pattern that causes significant distress or impairment of ...

bipolar disorder
; clinical research has shown there is a high rate of thyroid dysfunction in mood disorders and schizophrenia-spectrum disorders, concluding that there is a case for screening for the latter among people with thyroid illness.


Causes

Hypothyroidism is caused by inadequate function of the gland itself (primary hypothyroidism), inadequate stimulation by thyroid-stimulating hormone from the
pituitary gland upright=1.2, The Hypothalamus-Pituitary Complex. In vertebrate Vertebrates () comprise all species of animal Animals (also called Metazoa) are multicellular eukaryotic organisms that form the Kingdom (biology), biological kingd ...

pituitary gland
(secondary hypothyroidism), or inadequate release of
thyrotropin-releasing hormone Thyrotropin-releasing hormone (TRH) is a hypophysiotropic hormone produced by neurons in the hypothalamus The hypothalamus (from Ancient Greek wikt:ὑπό, ὑπό, "under", and wikt:θάλαμος, θάλαμος, "chamber") is a portion ...

thyrotropin-releasing hormone
from the brain's
hypothalamus The hypothalamus (from Ancient Greek wikt:ὑπό, ὑπό, "under", and wikt:θάλαμος, θάλαμος, "chamber") is a portion of the brain that contains a number of small Nucleus (neuroanatomy), nuclei with a variety of functions. One of ...

hypothalamus
(tertiary hypothyroidism). Primary hypothyroidism is about a thousandfold more common than central hypothyroidism.
Iodine deficiency Iodine deficiency is a lack of the mineral (nutrient), trace element iodine, an essential nutrient in the diet (nutrition), diet. It may result in metabolic problems such as goiter, sometimes as an endemic goiter as well as congenital iodine defi ...
is the most common cause of primary hypothyroidism and endemic goiter worldwide. In areas of the world with sufficient dietary iodine, hypothyroidism is most commonly caused by the autoimmune disease
Hashimoto's thyroiditis Hashimoto's thyroiditis, also known as chronic lymphocytic thyroiditis and Hashimoto's disease, is an autoimmune disease in which the thyroid, thyroid gland is gradually destroyed. Early on, symptoms may not be noticed. Over time, the thyroid m ...

Hashimoto's thyroiditis
(chronic autoimmune thyroiditis). Hashimoto's may be associated with a goiter. It is characterized by infiltration of the thyroid gland with
T lymphocytes A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system, and play a central role in the adaptive immune response. T cells can be easily distinguished from other lymphocytes by the presence of a T- ...
and
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 caused by such autoantibodies. Produ ...
against specific thyroid antigens such as
thyroid peroxidase Thyroid peroxidase, also called thyroperoxidase (TPO) or iodide peroxidase, is an enzyme Enzymes () are proteins that act as biological catalysts (biocatalysts). Catalysts accelerate chemical reactions. The molecules upon which enzymes may ac ...
,
thyroglobulin Thyroglobulin (Tg) is a 660 kDa, dimeric glycoprotein Glycoproteins are protein Proteins are large biomolecules or macromolecules that are comprised of one or more long chains of amino acid residue (biochemistry), residues. Proteins pe ...
and the TSH receptor. After women give birth, about 5% develop postpartum thyroiditis which can occur up to nine months afterwards. This is characterized by a short period 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. ...
followed by a period of hypothyroidism; 20–40% remain permanently hypothyroid. Autoimmune thyroiditis is associated with other immune-mediated diseases such as
diabetes mellitus type 1 Type 1 diabetes (T1D), previously known as juvenile diabetes, is an autoimmune disease An autoimmune disease is a condition arising from an abnormal immune response to a functioning body part. There are at least 80 types of autoimmune diseases ...
,
pernicious anemia Vitamin B12 deficiency anemia, of which pernicious anemia (PA) is a type, is a disease in which not enough red blood cell Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucl ...
,
myasthenia gravis Myasthenia gravis (MG) is a long-term neuromuscular disease A neuromuscular junction (or myoneural junction) is a chemical synapse between a motor neuron A motor neuron (or motoneuron) is a neuron A neuron or nerve cell is an electric ...
,
celiac disease Coeliac disease or celiac disease is a long-term autoimmune disorder An autoimmune disease is a condition arising from an abnormal immune response to a functioning body part. There are at least 80 types of autoimmune diseases. Nearly any bo ...
,
rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects synovial joint, joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and ...
and
systemic lupus erythematosus Lupus, technically known as systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary between people and may be mild to severe. Co ...
. It may occur as part of
autoimmune polyendocrine syndrome Autoimmune polyendocrine syndromes (APSs), also called polyglandular autoimmune syndromes (PGASs) or polyendocrine autoimmune syndromes (PASs), are a heterogeneous group of rare disease A rare disease is any disease A disease is a partic ...
(
type 1Type 1 or Type I or ''variant'', may refer to: Health *Diabetes mellitus type 1 (also known as "Type 1 Diabetes"), insulin-dependent diabetes *Female genital mutilation#Type I, Type I female genital mutilation *Type A and Type B personality theory, ...
and type 2).


Pathophysiology

Thyroid hormone is required for the normal functioning of numerous tissues in the body. In healthy individuals, the thyroid gland predominantly secretes thyroxine (T4), which is converted into
triiodothyronine Triiodothyronine, also known as T3, is a thyroid hormone File:Thyroid_system.svg, upright=1.5, The thyroid The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans it is in the neck and consists of two connected lobe (an ...

triiodothyronine
(T3) in other organs by the
selenium Selenium is a chemical element upright=1.0, 500px, The chemical elements ordered by link=Periodic table In chemistry Chemistry is the science, scientific study of the properties and behavior of matter. It is a natural science that ...

selenium
-dependent enzyme
iodothyronine deiodinase Iodothyronine deiodinases ( and ) are a subfamily of deiodinase enzymes important in the activation and deactivation of thyroid hormones. Thyroxine (T4), the precursor of 3,5,3'-triiodothyronine (T3) is transformed into T3 by deiodinase activity. ...

iodothyronine deiodinase
. Triiodothyronine binds to the
thyroid hormone receptor The thyroid hormone receptor (TR) is a type of nuclear receptor of a heterodimer of the nuclear receptors PPAR-γ (green) and Retinoid X receptor alpha, RXR-α (cyan) bound to double stranded DNA (magenta) and two molecules of the Nuclear recepto ...
in the
nucleus ''Nucleus'' (plural nuclei) is a Latin word for the seed inside a fruit. It most often refers to: *Atomic nucleus, the very dense central region of an atom *Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA ...

nucleus
of cells, where it stimulates the turning on of particular
gene In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular interactions, Physiology, physiological mecha ...

gene
s and the production of specific proteins. Additionally, the hormone binds to integrin αvβ3 on the
cell membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane A biological membrane, biomembrane or cell membrane is a selectively permeable membra ...

cell membrane
, thereby stimulating the
sodium–hydrogen antiporter The sodium–hydrogen antiporter or sodium–proton exchanger (Na+/H+ exchanger) is a membrane protein that transports Sodium, Na+ into the cell, and Proton, H+ out of the cell (Antiporter, antiport). Function They are found in the membranes of m ...
and processes such as and
cell growth Cell growth refers to an ''increase in the total mass Mass is both a property Property (''latin: Res Privata'') in the Abstract and concrete, abstract is what belongs to or with something, whether as an attribute or as a component of said ...
. In blood, almost all thyroid hormone (99.97%) is bound to plasma proteins such as
thyroxine-binding globulin Thyroxine-binding globulin (TBG) is a globulin The globulins are a family of globular protein 300px, 3-dimensional structure of hemoglobin, a globular protein. Globular proteins or spheroproteins are spherical ("globe-like") protein Protei ...
; only the free unbound thyroid hormone is biologically active. The thyroid gland is the only source of thyroid hormone in the body; the process requires
iodine Iodine is a chemical element In chemistry, an element is a pure Chemical substance, substance consisting only of atoms that all have the same numbers of protons in their atomic nucleus, nuclei. Unlike chemical compounds, chemical ele ...

iodine
and the
amino acid Amino acids are organic compound In , organic compounds are generally any s that contain - . Due to carbon's ability to (form chains with other carbon s), millions of organic compounds are known. The study of the properties, reactions, a ...

amino acid
tyrosine -Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acid Amino acids are organic compound , CH4; is among the simplest organic compounds. In chemistry, organic compounds are generally any chemi ...

tyrosine
. Iodine in the bloodstream is taken up by the gland and incorporated into
thyroglobulin Thyroglobulin (Tg) is a 660 kDa, dimeric glycoprotein Glycoproteins are protein Proteins are large biomolecules or macromolecules that are comprised of one or more long chains of amino acid residue (biochemistry), residues. Proteins pe ...
molecules. The process is controlled by the
thyroid-stimulating hormone Thyroid-stimulating hormone (also known as thyrotropin, thyrotropic hormone, or abbreviated TSH) is a pituitary hormone that stimulates the thyroid The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans it is in the ne ...
(TSH, thyrotropin), which is secreted by the
pituitary In vertebrate Vertebrates () comprise all species of animal Animals (also called Metazoa) are multicellular eukaryotic organisms that form the Kingdom (biology), biological kingdom Animalia. With few exceptions, animals Hetero ...

pituitary
. Not enough iodine, or not enough TSH, can result in decreased production of thyroid hormones. The hypothalamic–pituitary–thyroid axis plays a key role in maintaining thyroid hormone levels within normal limits. Production of TSH by the anterior pituitary gland is stimulated in turn by
thyrotropin-releasing hormone Thyrotropin-releasing hormone (TRH) is a hypophysiotropic hormone produced by neurons in the hypothalamus The hypothalamus (from Ancient Greek wikt:ὑπό, ὑπό, "under", and wikt:θάλαμος, θάλαμος, "chamber") is a portion ...

thyrotropin-releasing hormone
(TRH), released from the hypothalamus. Production of TSH and TRH is decreased by thyroxine by a
negative feedback Negative feedback (or balancing feedback) occurs when some function Function or functionality may refer to: Computing * Function key A function key is a key on a computer A computer is a machine that can be programmed to carry out se ...
process. Not enough TRH, which is uncommon, can lead to not enough TSH and thereby to not enough thyroid hormone production. Pregnancy leads to marked changes in thyroid hormone physiology. The gland is increased in size by 10%, thyroxine production is increased by 50%, and iodine requirements are increased. Many women have normal thyroid function but have immunological evidence of thyroid autoimmunity (as evidenced by autoantibodies) or are iodine deficient, and develop evidence of hypothyroidism before or after giving birth.


Diagnosis

Laboratory testing of thyroid stimulating hormone levels in the blood is considered the best initial test for hypothyroidism; a second TSH level is often obtained several weeks later for confirmation. Levels may be abnormal in the context of other illnesses, and TSH testing in hospitalized people is discouraged unless thyroid dysfunction is strongly suspected, as the cause of the acute illness. An elevated TSH level indicates that the thyroid gland is not producing enough thyroid hormone, and free T4 levels are then often obtained. Measuring T3 is discouraged by the AACE in the assessment for hypothyroidism. In England and Wales, the
National Institute for Health and Care Excellence The National Institute for Health and Care Excellence (NICE) is an executive non-departmental public body In the United Kingdom The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom (UK) or B ...

National Institute for Health and Care Excellence
(NICE) recommends routine T4 testing in children, and T3 testing in both adults and children if central hypothyroidism is suspected and the TSH is low. There are a number of symptom rating scales for hypothyroidism; they provide a degree of objectivity but have limited use for diagnosis. Many cases of hypothyroidism are associated with mild elevations in
creatine kinase Creatine kinase (CK), also known as creatine phosphokinase (CPK) or phosphocreatine kinase, is an enzyme () expressed by various tissues and cell types. CK catalyses the conversion of creatine and uses adenosine triphosphate (ATP) to create phospho ...
and liver enzymes in the blood. They typically return to normal when hypothyroidism has been fully treated. Levels of
cholesterol Cholesterol is any of a class of certain organic compound, organic molecules. A cholesterol is a sterol (or chemical modification, modified steroid), a type of lipid. Cholesterol is biosynthesis, biosynthesized by all animal Cell (biology)#Euk ...

cholesterol
,
low-density lipoprotein Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein which transport all fat molecules around the body in the extracellular water. These groups, from least dense to most dense, are chylomicrons (aka ULDL by the overall den ...
and lipoprotein (a) can be elevated; the impact of subclinical hypothyroidism on lipid parameters is less well-defined. Very severe hypothyroidism and myxedema coma are characteristically associated with low sodium levels in the blood together with elevations in
antidiuretic hormone Vasopressin, also called antidiuretic hormone (ADH), arginine vasopressin (AVP) or argipressin, is a hormone A hormone (from the Greek Greek may refer to: Greece Anything of, from, or related to Greece Greece ( el, Ελλάδα, , ...

antidiuretic hormone
, as well as acute worsening of kidney function due to a number of causes. In most causes, however, it is unclear if the relationship is causal. A diagnosis of hypothyroidism without any lumps or masses
felt Felt is a textile material that is produced by matting, condensing and pressing fibers together. Felt can be made of natural fibers such as wool Wool is the textile fiber obtained from sheep and other animals, including Cashmere wool, ca ...

felt
within the thyroid gland does not require thyroid imaging; however, if the thyroid feels abnormal, diagnostic imaging is then recommended. The presence of antibodies against
thyroid peroxidase Thyroid peroxidase, also called thyroperoxidase (TPO) or iodide peroxidase, is an enzyme Enzymes () are proteins that act as biological catalysts (biocatalysts). Catalysts accelerate chemical reactions. The molecules upon which enzymes may ac ...
(TPO) makes it more likely that thyroid nodules are caused by autoimmune thyroiditis, but if there is any doubt, a
needle biopsy Fine-needle aspiration (FNA) is a diagnostic procedure used to investigate lumps or masses. In this technique, a thin (23–25 Birmingham gauge, gauge (0.52 to 0.64 mm outer diameter)), hollow Hypodermic needle, needle is inserted into the mas ...
may be required.


Central

If the TSH level is normal or low and serum free T4 levels are low, this is suggestive of central hypothyroidism (not enough TSH or TRH secretion by the pituitary gland or hypothalamus). There may be other features of
hypopituitarism Hypopituitarism is the decreased (''hypo'') secretion of one or more of the eight hormone A hormone (from the Greek Greek may refer to: Greece Anything of, from, or related to Greece Greece ( el, Ελλάδα, , ), officially the Helleni ...
, such as
menstrual cycle The menstrual cycle is a series of natural changes in hormone A hormone (from the Greek Greek may refer to: Greece Anything of, from, or related to Greece Greece ( el, Ελλάδα, , ), officially the Hellenic Republic, is a country l ...

menstrual cycle
abnormalities and
adrenal insufficiency Adrenal insufficiency is a condition in which the adrenal glands do not produce adequate amounts of steroid hormones, primarily cortisol; but may also include impaired production of aldosterone (a mineralocorticoid), which regulates sodium conservat ...
. There might also be symptoms of a pituitary mass such as
headache Headache is the symptom of pain Pain is a distressing feeling often caused by intense or damaging stimuli. The defines pain as "an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or ...

headache
s and vision changes. Central hypothyroidism should be investigated further to determine the underlying cause.


Overt

In overt primary hypothyroidism, TSH levels are high and T4 and T3 levels are low. Overt hypothyroidism may also be diagnosed in those who have a TSH on multiple occasions of greater than 5mIU/L, appropriate symptoms, and only a borderline low T4. It may also be diagnosed in those with a TSH of greater than 10mIU/L.


Subclinical

Subclinical hypothyroidism is a milder form of hypothyroidism characterized by an elevated serum TSH level, but with a normal serum free thyroxine level. This milder form of hypothyroidism is most commonly caused by
Hashimoto's thyroiditis Hashimoto's thyroiditis, also known as chronic lymphocytic thyroiditis and Hashimoto's disease, is an autoimmune disease in which the thyroid, thyroid gland is gradually destroyed. Early on, symptoms may not be noticed. Over time, the thyroid m ...

Hashimoto's thyroiditis
. In adults it is diagnosed when TSH levels are greater than 5 mIU/L and less than 10mIU/L. The presentation of subclinical hypothyroidism is variable and classic signs and symptoms of hypothyroidism may not be observed. Of people with subclinical hypothyroidism, a proportion will develop overt hypothyroidism each year. In those with detectable antibodies against thyroid peroxidase (TPO), this occurs in 4.3%, while in those with no detectable antibodies, this occurs in 2.6%. Those with subclinical hypothyroidism and detectable anti-TPO antibodies who do not require treatment should have repeat thyroid function tests more frequently (e.g. yearly) compared with those who do not have antibodies.


Pregnancy

During pregnancy, the thyroid gland must produce 50% more thyroid hormone to provide enough thyroid hormone for the developing fetus and the expectant mother. In pregnancy, free thyroxine levels may be lower than anticipated due to increased binding to thyroid binding globulin and decreased binding to
albumin Albumin is a family In human society A society is a Social group, group of individuals involved in persistent Social relation, social interaction, or a large social group sharing the same spatial or social territory, typically subje ...
. They should either be corrected for the stage of pregnancy, or total thyroxine levels should be used instead for diagnosis. TSH values may also be lower than normal (particularly in the
first trimester Pregnancy, also known as gestation, is the time during which one or more offspring In biology, offspring are the young born of living organism, organisms, produced either by a single organism or, in the case of sexual reproduction, two orga ...
) and the normal range should be adjusted for the stage of pregnancy. In pregnancy, subclinical hypothyroidism is defined as a TSH between 2.5 and 10 mIU/l with a normal thyroxine level, while those with TSH above 10 mIU/l are considered to be overtly hypothyroid even if the thyroxine level is normal. Antibodies against TPO may be important in making decisions about treatment, and should, therefore, be determined in women with abnormal thyroid function tests. Determination of TPO antibodies may be considered as part of the assessment of
recurrent miscarriage Recurrent miscarriage is two or more consecutive pregnancy losses. In contrast, infertility Infertility is the inability of a person, animal or plant to Sexual reproduction, reproduce by natural means. It is usually not the natural state of a ...
, as subtle thyroid dysfunction can be associated with pregnancy loss, but this recommendation is not universal, and presence of thyroid antibodies may not predict future outcome.


Prevention

Hypothyroidism may be prevented in a population by adding iodine to commonly used foods. This
public health Public health has been defined as "the science and art of preventing disease", prolonging life and improving quality of life Quality of life (QOL) is defined by the World Health Organization The World Health Organization (WHO) is a s ...

public health
measure has eliminated endemic childhood hypothyroidism in countries where it was once common. In addition to promoting the consumption of iodine-rich foods such as dairy and fish, many countries with moderate
iodine deficiency Iodine deficiency is a lack of the mineral (nutrient), trace element iodine, an essential nutrient in the diet (nutrition), diet. It may result in metabolic problems such as goiter, sometimes as an endemic goiter as well as congenital iodine defi ...
have implemented universal
salt iodization An example of a commonly distributed packet of iodized salt, which can rapidly lose its iodine content in high temperature and high relative humidity conditions Iodised salt ( also spelled iodized salt) is table salt Salt is a mineral compo ...
(USI). Encouraged by the
World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations United Nations Specialized Agencies are autonomous organizations working with the United Nations and each other through the co-ordinating machinery of the Unit ...
, 130 countries now have USI, and 70% of the world's population are receiving iodized salt. In some countries, iodized salt is added to bread. Despite this, iodine deficiency has reappeared in some Western countries as a result of attempts to reduce salt intake. Pregnant and breastfeeding women, who require 66% more daily iodine requirement than non-pregnant women, may still not be getting enough iodine. The
World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations United Nations Specialized Agencies are autonomous organizations working with the United Nations and each other through the co-ordinating machinery of the Unit ...
recommends a daily intake of 250 µg for pregnant and breastfeeding women. As many women will not achieve this from dietary sources alone, the
American Thyroid Association The American Thyroid Association (ATA) is a professional organization of over 1700 medical specialists devoted to thyroid biology and to the prevention and treatment of thyroid disease through excellence in research, clinical care, education, an ...
recommends a 150 µg daily supplement by mouth.


Screening

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 T4 testing is required to pick up the rarer central causes of neonatal hypothyroidism. If T4 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 The United States Preventive Services Task Force (USPSTF) is "an independent panel of experts in primary care and prevention that systematically reviews the Evidence-based medicine, evidence of effectiveness and develops recommendations for clinica ...
) state that evidence is insufficient to support routine screening, while others (such as the
American Thyroid Association The American Thyroid Association (ATA) is a professional organization of over 1700 medical specialists devoted to thyroid biology and to the prevention and treatment of thyroid disease through excellence in research, clinical care, education, an ...
) recommend either intermittent testing above a certain age in all sexes or only in women. Targeted screening may be appropriate in a number of situations where hypothyroidism is common: other
autoimmune disease An autoimmune disease is a condition arising from an abnormal immune response An immune response is a reaction which occurs within an organism for the purpose of defending against foreign invaders. These invaders include a wide variety of differe ...

autoimmune disease
s, a strong
family history Genealogy (from el, γενεαλογία ' "study of family trees") is the study of families In human society, family (from la, familia) is a Social group, group of people related either by consanguinity (by recognized birth) or Affinity ...
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 Amiodarone is an antiarrhythmic medication used to treat and prevent a number of types of cardiac dysrhythmia, irregular heartbeats. This includes ventricular tachycardia (VT), ventricular fibrillation (VF), and wide complex tachycardia, as well as ...

amiodarone
or
lithium Lithium (from el, λίθος, lithos, lit=stone) is a chemical element In chemistry Chemistry is the study of the properties and behavior of . It is a that covers the that make up matter to the composed of s, s and s: the ...
, 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 Down syndrome or Down's syndrome, also known as trisomy 21, is a genetic disorder A genetic disorder is a health problem caused by one or more abnormalities in the genome In the fields of molecular biology and genetics Gen ...
, as they are at higher risk of thyroid disease. Guidelines for England and Wales from the National Institute for Health and Care Excellence (NICE) recommend testing for thyroid disease in people with type 1 diabetes and new-onset
atrial fibrillation Atrial fibrillation (AF or A-fib) is an abnormal heart rhythm (arrhythmia) characterized by the rapid and irregular beating of the atrial chambers of the heart. It often begins as short periods of abnormal beating, which become longer or cont ...

atrial fibrillation
, and suggests testing in those with depression or unexplained anxiety (all ages), in children with abnormal growth, or unexplained change in behaviour or school performance. On diagnosis of autoimmune thyroid disease, NICE also recommends screening for celiac disease.


Management


Hormone replacement

Most people with hypothyroidism symptoms and confirmed thyroxine deficiency are treated with a synthetic long-acting form of thyroxine, known as
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 Hashimoto's thyroiditis, Hashimoto's disease and a ...
(L-thyroxine). In young and otherwise healthy people with overt hypothyroidism, a full replacement dose (adjusted by weight) can be started immediately; in the elderly and people with heart disease a lower starting dose is recommended to prevent over supplementation and risk of complications. Lower doses may be sufficient in those with subclinical hypothyroidism, while people with central hypothyroidism may require a higher than average dose. Blood free thyroxine and TSH levels are monitored to help determine whether the dose is adequate. This is done 4–8 weeks after the start of treatment or a change in levothyroxine dose. Once the adequate replacement dose has been established, the tests can be repeated after 6 and then 12 months, unless there is a change in symptoms. Normalization of TSH does not mean that other abnormalities associated with hypothyroidism improve entirely, such as elevated
cholesterol Cholesterol is any of a class of certain organic compound, organic molecules. A cholesterol is a sterol (or chemical modification, modified steroid), a type of lipid. Cholesterol is biosynthesis, biosynthesized by all animal Cell (biology)#Euk ...

cholesterol
levels. In people with central/secondary hypothyroidism, TSH is not a reliable marker of hormone replacement and decisions are based mainly on the free T4 level. Levothyroxine is best taken 30–60 minutes before breakfast, or four hours after food, as certain substances such as food and calcium can inhibit the absorption of levothyroxine. There is no direct way of increasing thyroid hormone secretion by the thyroid gland.


Liothyronine

Treatment with
liothyronine Liothyronine is a manufactured form of the thyroid hormones, thyroid hormone triiodothyronine (T3). It is most commonly used to treat hypothyroidism and myxedema coma. It can be taken by mouth or by intravenous, injection into a vein. Side effe ...

liothyronine
alone has not received enough study to make a recommendation as to its use; due to its shorter half-life it would need to be taken more often than levothyroxine. Adding liothyronine (synthetic T3) to levothyroxine has been suggested as a measure to provide better symptom control, but this has not been confirmed by studies. In 2007, the British Thyroid Association stated that combined T4 and T3 therapy carried a higher rate of side effects and no benefit over T4 alone. Similarly, American guidelines discourage combination therapy due to a lack of evidence, although they acknowledge that some people feel better when receiving combination treatment. Guidelines by NICE for England and Wales discourage liothyronine. People with hypothyroidism who do not feel well despite optimal levothyroxine dosing may request adjunctive treatment with liothyronine. A 2012 guideline from the European Thyroid Association recommends that support should be offered with regards to the chronic nature of the disease and that other causes of the symptoms should be excluded. Addition of liothyronine should be regarded as experimental, initially only for a trial period of 3 months, and in a set ratio to the current dose of levothyroxine. The guideline explicitly aims to enhance the safety of this approach and to counter its indiscriminate use.


Desiccated animal thyroid

Desiccated thyroid extract Desiccated thyroid, also known as thyroid extract, is thyroid gland that has been dried and powdered for medication, medical use. It is used to treat hypothyroidism. It is less preferred than levothyroxine. It is taken by mouth. Maximal effects may ...
is an animal-based thyroid gland extract, most commonly from
pig The pig (''Sus domesticus''), often called swine, hog, or domestic pig when distinguishing from other members of the genus '' Sus'', is an omnivorous An omnivore () is an animal that has the ability to eat and survive on both plant and ani ...

pig
s. It is a combination therapy, containing forms of T4 and T3. It also contains
calcitonin Calcitonin is a 32 amino acid peptide hormonePeptide hormones or protein hormones are hormones whose molecules are peptides or proteins, respectively. The latter have longer amino acid chain lengths than the former. These hormones have an effect on ...

calcitonin
(a hormone produced in the thyroid gland involved in the regulation of calcium levels), T1 and T2; these are not present in synthetic hormone medication. This extract was once a mainstream hypothyroidism treatment, but its use today is unsupported by evidence; British Thyroid Association and American professional guidelines discourage its use, as does NICE.


Subclinical hypothyroidism

There is no evidence of a benefit from treating subclinical hypothyroidism in those who are not pregnant, and there are potential risks of
overtreatment Unnecessary health care (overutilization, overuse, or overtreatment) is health care Health care, health-care, or healthcare is the maintenance or improvement of health via the preventive healthcare, prevention, diagnosis, therapy, treatment, re ...
. Untreated subclinical hypothyroidism may be associated with a modest increase in the risk of
coronary artery disease Coronary artery disease (CAD), also called coronary heart disease (CHD), ischemic heart disease (IHD), or simply heart disease, involves the reduction of blood flow to the heart muscle Cardiac muscle (also called heart muscle or myocardium) i ...
when the TSH is over 10 mIU/l. A 2007 review found no benefit of thyroid hormone replacement except for "some parameters of lipid profiles and left ventricular function". There is no association between subclinical hypothyroidism and an increased risk of
bone fracture A bone fracture (abbreviated FRX or Fx, Fx, or #) is a medical condition in which there is a partial or complete break in the continuity of the bone. In more severe cases, the bone may be broken into several pieces. A bone fracture may be the r ...
s, nor is there a link with cognitive decline. Since 2008, consensus American opinion has been that in general people with TSH under 10 to 20 mIU/l do not require treatment. American guidelines recommend that treatment should be considered in people with symptoms of hypothyroidism, detectable antibodies against thyroid peroxidase, a history of heart disease or are at an increased risk for heart disease, if the TSH is elevated but below 10 mIU/l. NICE recommends that those with a TSH above 10 mIU/l should be treated in the same way as overt hypothyroidism. Those with an elevated TSH but below 10 mIU/l who have symptoms suggestive of hypothyroidism should have a trial of treatment but with the aim to stopping this if the symptoms persist despite normalisation of the TSH.


Myxedema coma

Myxedema coma Myxedema coma is a state of decompensation, decompensated hypothyroidism. A person may have laboratory values identical to a "normal" hypothyroid state, but a stressful event (such as an infection, myocardial infarction, or stroke) precipitates th ...
or severe decompensated hypothyroidism usually requires admission to the
intensive care Intensive care medicine, also called critical care medicine, is a medical specialty that deals with seriously or critically ill patients who have, are at risk of, or are recovering from conditions that may be life-threatening. It includes prov ...
, close observation and treatment of abnormalities in breathing, temperature control, blood pressure, and sodium levels.
Mechanical ventilation Mechanical ventilation, assisted ventilation or intermittent mandatory ventilationIntermittent Mandatory Ventilation (IMV) refers to any mode of mechanical ventilation where a regular series of breaths are scheduled but the ventilator senses p ...
may be required, as well as
fluid replacement Fluid replacement or fluid resuscitation is the medical practice of replenishing bodily fluid lost through sweating, bleeding, fluid shifts or other pathologic processes. Fluids can be replaced with oral rehydration therapy Oral rehydration ther ...
, vasopressor agents, careful rewarming, and
corticosteroid Corticosteroids are a class of steroid hormone A steroid hormone is a steroid A steroid is a biologically active organic compound In , organic compounds are generally any s that contain - . Due to carbon's ability to (form chains w ...
s (for possible
adrenal insufficiency Adrenal insufficiency is a condition in which the adrenal glands do not produce adequate amounts of steroid hormones, primarily cortisol; but may also include impaired production of aldosterone (a mineralocorticoid), which regulates sodium conservat ...
which can occur together with hypothyroidism). Careful correction of low sodium levels may be achieved with hypertonic saline solutions or
vasopressin receptor antagonist Vasopressin, also called antidiuretic hormone (ADH), arginine vasopressin (AVP) or argipressin, is a hormone A hormone (from the Greek participle , "setting in motion") is any member of a class of signaling molecules in multicellular or ...
s. For rapid treatment of the hypothyroidism, levothyroxine or liothyronine may be administered
intravenously Intravenous therapy (abbreviated as IV therapy) is a medical technique that delivers fluids, medications and nutrition directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrition ...
, particularly if the level of consciousness is too low to be able to safely swallow medication. While administration through a
nasogastric tube Nasogastric intubation is a medical process involving the insertion of a plastic tube (nasogastric tube or NG tube) through the nose A nose is a protuberance in vertebrate Vertebrates () comprise all species of animal Animals (also ...
is possible, this may be unsafe and is discouraged.


Pregnancy

In women with known hypothyroidism who become pregnant, it is recommended that serum TSH levels are closely monitored. Levothyroxine should be used to keep TSH levels within the normal range for that trimester. The first trimester normal range is below 2.5 mIU/L and the second and third trimesters normal range is below 3.0 mIU/L. Treatment should be guided by total (rather than free) thyroxine or by the free T4 index. Similarly to TSH, the thyroxine results should be interpreted according to the appropriate reference range for that stage of pregnancy. The levothyroxine dose often needs to be increased after pregnancy is confirmed, although this is based on limited evidence and some recommend that it is not always required; decisions may need to based on TSH levels. Women with anti-TPO antibodies who are trying to become pregnant (naturally or by assisted means) may require thyroid hormone supplementation even if the TSH level is normal. This is particularly true if they have had previous miscarriages or have been hypothyroid in the past. Supplementary levothyroxine may reduce the risk of preterm birth and possibly miscarriage. The recommendation is stronger in pregnant women with subclinical hypothyroidism (defined as TSH 2.5–10 mIU/l) who are anti-TPO positive, in view of the risk of overt hypothyroidism. If a decision is made not to treat, close monitoring of the thyroid function (every 4 weeks in the first 20 weeks of pregnancy) is recommended. If anti-TPO is not positive, treatment for subclinical hypothyroidism is not currently recommended. It has been suggested that many of the aforementioned recommendations could lead to unnecessary treatment, in the sense that the TSH cutoff levels may be too restrictive in some ethnic groups; there may be little benefit from treatment of subclinical hypothyroidism in certain cases.


Alternative medicine

The effectiveness and safety of using Chinese herbal medicines to treat hypothyroidism is not known.


Epidemiology

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
Caucasian Caucasian may refer to: Anthropology *Anything from the Caucasus region **Peoples of the Caucasus, humans from the Caucasus region **Languages of the Caucasus, languages spoken in the Caucasus region ** ''Caucasian Exarchate'' (1917–1920), an ...
s. There is a much higher rate of thyroid disorders, the most common of which is hypothyroidism, in individuals with
Down syndrome Down syndrome or Down's syndrome, also known as trisomy 21, is a genetic disorder A genetic disorder is a health problem caused by one or more abnormalities in the genome In the fields of molecular biology and genetics Gen ...
and
Turner syndrome Turner syndrome (TS), also known 45,X, or 45,X0, is a genetic condition in which a female is partly or completely missing an X chromosome. Signs and symptoms vary among those affected. Often, a short and webbed neck, low-set ears, low hairline at ...
. 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.


History

In 1811,
Bernard Courtois Bernard Courtois, also spelled Barnard Courtois, (8 February 1777 – 27 September 1838) was a French chemist A chemist (from Greek ''chēm(ía)'' alchemy; replacing ''chymist'' from Medieval Latin ''alchemist'') is a scientist A scientist ...
discovered iodine was present in
seaweed Seaweed, or macroalgae, refers to thousands of species of Macroscopic scale, macroscopic, Multicellular organism, multicellular, ocean, marine algae. The term includes some types of ''Rhodophyta'' (red), ''Phaeophyta'' (brown) and ''Chlorophyt ...

seaweed
, and iodine intake was linked with goiter size in 1820 by Jean-Francois Coindet.
Gaspard Adolphe Chatin Gaspard Adolphe Chatin (30 November 1813 – 13 January 1901) was a French physician, mycologist and botanist who was born in Isère, and died in Les Essarts-le-Roi. He was the first to prove that goiter was related of iodine deficiencies. He studi ...
proposed in 1852 that endemic goiter was the result of not enough iodine intake, and
Eugen Baumann Eugen Baumann (12 December 1846 – 3 November 1896) was a German chemist. He was one of the first people to create polyvinyl chloride (PVC), and, together with Carl Schotten, he discovered the Schotten-Baumann reaction. Life Baumann was born i ...

Eugen Baumann
demonstrated iodine in thyroid tissue in 1896. The first cases of myxedema were recognized in the mid-19th century (the 1870s), but its connection to the thyroid was not discovered until the 1880s when myxedema was observed in people following the removal of the thyroid gland (thyroidectomy). The link was further confirmed in the late 19th century when people and animals who had had their thyroid removed showed improvement in symptoms with transplantation of animal thyroid tissue. The severity of myxedema, and its associated risk of mortality and complications, created interest in discovering effective treatments for hypothyroidism. Transplantation of thyroid tissue demonstrated some efficacy, but recurrences of hypothyroidism was relatively common, and sometimes required multiple repeat transplantations of thyroid tissue. In 1891, the English physician
George Redmayne Murray George Redmayne Murray (20 June 1865 – 21 September 1939) was an England, English physician who pioneered in the treatment of endocrine disorders. In 1891, he introduced the successful treatment of myxedema, with injections of sheep thyroid extr ...
introduced subcutaneously injected sheep thyroid extract, followed shortly after by an oral formulation. Purified thyroxine was introduced in 1914 and in the 1930s synthetic thyroxine became available, although desiccated animal thyroid extract remained widely used. Liothyronine was identified in 1952. Early attempts at titrating therapy for hypothyroidism proved difficult. After hypothyroidism was found to cause a lower basal metabolic rate, this was used as a marker to guide adjustments in therapy in the early 20th century (around 1915). However, a low basal metabolic rate was known to be non-specific, also present in malnutrition. The first laboratory test to be helpful in assessing thyroid status was the serum protein-bound iodine, which came into use around the 1950s. In 1971, the thyroid stimulating hormone (TSH) radioimmunoassay was developed, which was the most specific marker for assessing thyroid status in patients. Many people who were being treated based on basal metabolic rate, minimizing hypothyroid symptoms, or based on serum protein-bound iodine, were found to have excessive thyroid hormone. The following year, in 1972, a T3 radioimmunoassay was developed, and in 1974, a T4 radioimmunoassay was developed.


Other animals

In veterinary practice, dogs are the species most commonly affected by hypothyroidism. The majority of cases occur as a result of primary hypothyroidism, of which two types are recognized: lymphocytic thyroiditis, which is probably immune-driven and leads to destruction and fibrosis of the thyroid gland, and idiopathic atrophy, which leads to the gradual replacement of the gland by fatty tissue. There is often lethargy, cold intolerance, exercise intolerance, and weight gain. Furthermore, skin changes and fertility problems are seen in dogs with hypothyroidism, as well as a number of other symptoms. The signs of myxedema can be seen in dogs, with prominence of skin folds on the forehead, and cases of myxedema coma are encountered. The diagnosis can be confirmed by blood test, as the clinical impression alone may lead to overdiagnosis. Lymphocytic thyroiditis is associated with detectable antibodies against thyroglobulin, although they typically become undetectable in advanced disease. Treatment is with thyroid hormone replacement. Other species that are less commonly affected include cats and horses, as well as other large domestic animals. In cats, hypothyroidism is usually the result of other medical treatment such as surgery or radiation. In young horses, congenital hypothyroidism has been reported predominantly in
Western Canada Western Canada, also referred to as the Western Provinces and more commonly known as the West, is a region In geography Geography (from Greek: , ''geographia'', literally "earth description") is a field of science devoted to the stud ...
and has been linked with the mother's diet.


References


External links

* * * * {{Thyroid disease Thyroid disease Wikipedia medicine articles ready to translate (full) Wikipedia neurology articles ready to translate Endocrine diseases Autoimmune diseases Iodine Metabolic disorders