Hyperthyroidism
Encyclopedia
Hyperthyroidism is the term for overactive tissue within the thyroid
Thyroid
The thyroid gland or simply, the thyroid , in vertebrate anatomy, is one of the largest endocrine glands. The thyroid gland is found in the neck, below the thyroid cartilage...

 gland causing an overproduction of thyroid hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...

s (thyroxine
Thyroxine
Thyroxine, or 3,5,3',5'-tetraiodothyronine , a form of thyroid hormones, is the major hormone secreted by the follicular cells of the thyroid gland.-Synthesis and regulation:...

 or "T4" and/or triiodothyronine
Triiodothyronine
Triiodothyronine, C15H12I3NO4, also known as T3, is a thyroid hormone. It affects almost every physiological process in the body, including growth and development, metabolism, body temperature, and heart rate....

 or "T3"). Hyperthyroidism is thus a cause of thyrotoxicosis, the clinical condition of increased thyroid hormones in the blood. Hyperthyroidism and thyrotoxicosis are not synonymous. For instance, thyrotoxicosis could instead be caused by ingestion of exogenous
Exogenous
Exogenous refers to an action or object coming from outside a system. It is the opposite of endogenous, something generated from within the system....

 thyroid hormone or inflammation of the thyroid gland, causing it to release its stores of thyroid hormones. Its opposite is 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...

 which is an underproduction of the hormone.

Symptoms and signs

Hyperthyroidism may be asymptomatic, but when it is not, symptoms are due to an excess of thyroid hormone. Thyroid hormone is important at a cellular level, affecting nearly every type of tissue in the body. Thyroid hormone functions as a controller of the pace of all of the processes in the body. This pace is called the metabolic rate (see metabolism
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...

). If there is too much thyroid hormone, every function of the body tends to speed up. Therefore, some of the symptoms of hyperthyroidism are nervousness, irritability, increased perspiration, heart racing, hand tremors, anxiety, difficulty sleeping, thinning of the skin, fine brittle hair, and muscular weakness—especially in the upper arms and thighs. More frequent bowel movements may occur, but diarrhea is uncommon. Weight loss, sometimes significant, despite a good appetite may occur, vomiting, and, for women, menstrual flow may lighten and menstrual periods may occur less often. Thyroid hormone is critical to normal function of cells. In excess, it both overstimulates metabolism and exacerbates the effect of the sympathetic nervous system
Sympathetic nervous system
The sympathetic nervous system is one of the three parts of the autonomic nervous system, along with the enteric and parasympathetic systems. Its general action is to mobilize the body's nervous system fight-or-flight response...

, causing "speeding up" of various body systems and symptoms resembling an overdose of epinephrine
Epinephrine
Epinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...

 (adrenaline). These include fast heart beat and symptoms of palpitation
Palpitation
A palpitation is an abnormality of heartbeat that causes a conscious awareness of its beating, whether it is too slow, too fast, irregular, or at its normal frequency. The word may also refer to this sensation itself...

s, nervous system tremor
Tremor
A tremor is an involuntary, somewhat rhythmic, muscle contraction and relaxation involving to-and-fro movements of one or more body parts. It is the most common of all involuntary movements and can affect the hands, arms, eyes, face, head, vocal folds, trunk, and legs. Most tremors occur in the...

 such as of the hands and anxiety
Anxiety
Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...

 symptoms, digestive system hypermotility, unintended weight loss, and (in "lipid panel" blood tests) a lower and sometimes unusually low serum cholesterol
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...

.

Hyperthyroidism usually begins slowly. At first, the symptoms may be mistaken for simple nervousness due to stress. If one has been trying to lose weight by dieting, one may be pleased with weight loss success until the hyperthyroidism, which has quickened the weight loss, causes other problems.

Major clinical signs include weight loss
Weight loss
Weight loss, in the context of medicine, health or physical fitness, is a reduction of the total body mass, due to a mean loss of fluid, body fat or adipose tissue and/or lean mass, namely bone mineral deposits, muscle, tendon and other connective tissue...

 (often accompanied by an increased appetite
Appetite
The appetite is the desire to eat food, felt as hunger. Appetite exists in all higher life-forms, and serves to regulate adequate energy intake to maintain metabolic needs. It is regulated by a close interplay between the digestive tract, adipose tissue and the brain. Decreased desire to eat is...

), anxiety
Anxiety
Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...

, intolerance to heat
Heat
In physics and thermodynamics, heat is energy transferred from one body, region, or thermodynamic system to another due to thermal contact or thermal radiation when the systems are at different temperatures. It is often described as one of the fundamental processes of energy transfer between...

, hair loss, muscle aches, weakness, fatigue, hyperactivity, irritability, hypoglycemia
Hypoglycemia
Hypoglycemia or hypoglycæmia is the medical term for a state produced by a lower than normal level of blood glucose. The term literally means "under-sweet blood"...

, apathy
Apathy
Apathy is a state of indifference, or the suppression of emotions such as concern, excitement, motivation and passion. An apathetic individual has an absence of interest in or concern about emotional, social, spiritual, philosophical or physical life.They may lack a sense of purpose or meaning in...

, polyuria
Polyuria
Polyuria is a condition usually defined as excessive or abnormally large production or passage of urine . Frequent urination is sometimes included by definition, but is nonetheless usually an accompanying symptom...

, polydipsia
Polydipsia
Polydipsia is a medical symptom in which the patient displays excessive thirst. The word derives from the Greek πολυδιψία, which is derived from πολύς + δίψα...

, delirium
Delirium
Delirium or acute confusional state is a common and severe neuropsychiatric syndrome with core features of acute onset and fluctuating course, attentional deficits and generalized severe disorganization of behavior...

, tremor
Tremor
A tremor is an involuntary, somewhat rhythmic, muscle contraction and relaxation involving to-and-fro movements of one or more body parts. It is the most common of all involuntary movements and can affect the hands, arms, eyes, face, head, vocal folds, trunk, and legs. Most tremors occur in the...

, pretibial myxedema
Pretibial myxedema
Pretibial myxedema is an infiltrative dermopathy, resulting as a rare complication of Graves' disease, with an incidence rate of about 1-4% in patients.-Presentation:...

, and sweating. In addition, patients may present with a variety of symptoms such as palpitations and arrhythmias (the notable ones being atrial fibrillation
Atrial fibrillation
Atrial fibrillation is the most common cardiac arrhythmia . It is a common cause of irregular heart beat, identified clinically by taking a pulse. Chaotic electrical activity in the two upper chambers of the heart result in the muscle fibrillating , instead of achieving coordinated contraction...

), shortness of breath (dyspnea
Dyspnea
Dyspnea , shortness of breath , or air hunger, is the subjective symptom of breathlessness.It is a normal symptom of heavy exertion but becomes pathological if it occurs in unexpected situations...

), loss of libido
Libido
Libido refers to a person's sex drive or desire for sexual activity. The desire for sex is an aspect of a person's sexuality, but varies enormously from one person to another, and it also varies depending on circumstances at a particular time. A person who has extremely frequent or a suddenly...

, amenorrhea, nausea
Nausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...

, vomiting
Vomiting
Vomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...

, diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...

, gynaecomastia and feminization
Feminization
Feminization can refer to:*Feminization the hormonally induced development of female sexual characteristics*Feminization a sexual or lifestyle practice where a person assumes a female role...

. Long term untreated hyperthyroidism can lead to osteoporosis
Osteoporosis
Osteoporosis is a disease of bones that leads to an increased risk of fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered...

. These classical symptoms may not be present often in the elderly.

Neurological manifestations can include tremor
Tremor
A tremor is an involuntary, somewhat rhythmic, muscle contraction and relaxation involving to-and-fro movements of one or more body parts. It is the most common of all involuntary movements and can affect the hands, arms, eyes, face, head, vocal folds, trunk, and legs. Most tremors occur in the...

s, chorea
Chorea (disease)
Choreia is an abnormal involuntary movement disorder, one of a group of neurological disorders called dyskinesias. The term choreia is derived from the Greek word χορεία , see choreia , as the quick movements of the feet or hands are vaguely comparable to dancing or piano playing.The term...

, myopathy
Myopathy
In medicine, a myopathy is a muscular disease in which the muscle fibers do not function for any one of many reasons, resulting in muscular weakness. "Myopathy" simply means muscle disease...

, and in some susceptible individuals (in particular of Asian descent) periodic paralysis
Thyrotoxic periodic paralysis
Thyrotoxic periodic paralysis is a condition featuring attacks of muscle weakness in the presence of hyperthyroidism . Hypokalemia is usually present during attacks...

. An association between thyroid disease and myasthenia gravis
Myasthenia gravis
Myasthenia gravis is an autoimmune neuromuscular disease leading to fluctuating muscle weakness and fatiguability...

 has been recognized. The thyroid disease, in this condition, is autoimmune in nature and approximately 5% of patients with myasthenia gravis also have hyperthyroidism. Myasthenia gravis rarely improves after thyroid treatment and the relationship between the two entities is not well understood.

In Graves disease, which is the most common form or cause of hyperthyroidism, the eyes may look enlarged because the eye muscles swell and push the eye forward. This can only be resolved surgically by orbital decompression. Sometimes, one or both eyes may bulge. Some patients have swelling of the front of the neck from an enlarged thyroid gland (a goiter). Because hyperthyroidism, especially Graves’ disease, may run in families, examinations of the members of a family may reveal other individuals with thyroid problems.

Minor ocular (eye) signs, which may be present in any type of hyperthyroidism, are eyelid retraction ("stare"), extra-ocular muscle weakness, and lid-lag. In hyperthyroid stare (Dalrymple sign) the eyelids are retracted upward more than normal (the normal position is at the superior corneoscleral limbus, where the "white" of the eye begins at the upper border of the iris). Extra-ocular muscle weakness may present with double vision. In lid-lag (von Graefe's sign
Von Graefe's sign
Von Graefe's sign is the immobility or lagging of the upper eyelid on downward rotation of the eye, indicating exophthalmic goiter ....

), when the patient tracks an object downward with their eyes, the eyelid fails to follow the downward moving iris, and the same type of upper globe exposure which is seen with lid retraction occurs, temporarily. These signs disappear with treatment of the hyperthyroidism.

Neither of these ocular signs should be confused with exophthalmos
Exophthalmos
Exophthalmos is a bulging of the eye anteriorly out of the orbit. Exophthalmos can be either bilateral or unilateral . Measurement of the degree of exophthalmos is performed using an exophthalmometer...

 (protrusion of the eyeball), which occurs specifically and uniquely in hyperthyroidism caused by Graves' disease
Graves' disease
Graves' disease is an autoimmune disease where the thyroid is overactive, producing an excessive amount of thyroid hormones...

 (note that not all exopthalmos is caused by Graves' disease, but when present with hyperthyroidism is diagnostic of Graves' disease). This forward protrusion of the eyes is due to immune-mediated inflammation in the retro-orbital (eye socket) fat. Exophthalmos, when present, may exacerbate hyperthyroid lid-lag and stare.

Causes

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

The major causes in humans are:
  • Graves' disease
    Graves' disease
    Graves' disease is an autoimmune disease where the thyroid is overactive, producing an excessive amount of thyroid hormones...

    . An autoimmune disease (usually, the most common etiology with 50-80% worldwide, although this varies substantially with location- i.e., 47% in Switzerland (Horst et al., 1987) to 90% in the USA (Hamburger et al. 1981). Thought to be due to varying Iodine in the diet.
  • Toxic thyroid adenoma (the most common etiology in Switzerland, 53%, thought to be atypical due to a low level of dietary iodine in this country)
  • Toxic multinodular goitre
    Toxic multinodular goitre
    Toxic multinodular goitre is a form of hyperthyroidism - where there is excess production of thyroid hormones. It is characterized by functionally autonomous nodules...


High blood levels of thyroid hormones (most accurately termed hyperthyroxinemia
Hyperthyroxinemia
Hyperthyroxinemia or hyperthyroxinaemia is a thyroid disease where the serum levels of thyroxine are higher than expected.The term is sometimes used to refer to hyperthyroidism, but hyperthyroidism is a more general term.Types include:...

) can occur for a number of other reasons:
  • Inflammation
    Inflammation
    Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...

     of the thyroid is called 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:...

    . There are several different kinds of thyroiditis including 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...

    (immune-mediated), and subacute thyroiditis
    Subacute thyroiditis
    Subacute thyroiditis is a form of thyroiditis that can be a cause of both thyrotoxicosis and hypothyroidism. It is uncommon and can affect individuals of both sexes and all ages. It manifests as a sudden and painful enlargement of the thyroid gland accompanied with fever, malaise and muscle aches...

     (DeQuervain's). These may be initially associated with secretion of excess thyroid hormone, but usually progress to gland dysfunction and, thus, to hormone deficiency and hypothyroidism.
  • Oral consumption of excess thyroid hormone tablets is possible (surreptitious use of thyroid hormone), as is the rare event of consumption of ground beef contaminated with thyroid tissue, and thus thyroid hormone (termed "hamburger hyperthyroidism").
  • Amiodarone
    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...

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

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


Hypersecretion of thyroid stimulating hormone (TSH), which in turn is almost always caused by a pituitary adenoma
Pituitary adenoma
Pituitary adenomas are tumors that occur in the pituitary gland, and account for about 15% of intracranial neoplasms. Tumors which exceed 10 mm in size are defined as macroadenomas, and those smaller than 10 mm are referred to as microadenomas...

, accounts for much less than 1 percent of hyperthyroidism cases.

Diagnosis

Measuring the level 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), produced by the pituitary gland (which in turn is also regulated by the hypothalamus's TSH Releasing Hormone) in the blood is typically the initial test for suspected hyperthyroidism. A low TSH level typically indicates that the pituitary gland is being inhibited or "instructed" by the brain to cut back on stimulating the thyroid gland, having sensed increased levels of T4 and/or T3 in the blood. In rare circumstances, a low TSH indicates primary failure of the pituitary, or temporary inhibition of the pituitary due to another illness (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...

) and so checking the T4 and T3 is still clinically useful.

Measuring specific antibodies
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...

, such as anti-TSH-receptor antibodies in Graves' disease, or anti-thyroid-peroxidase in 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...

 — a common cause of 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...

 — may also contribute to the diagnosis.

The diagnosis of hyperthyroidism is confirmed by blood tests that show a decreased thyroid-stimulating hormone (TSH) level and elevated T4 and T3 levels. TSH is a hormone made by the pituitary gland in the brain that tells the thyroid gland how much hormone to make. When there is too much thyroid hormone, the TSH will be low. A radioactive iodine uptake test and thyroid scan together characterizes or enables radiologists and doctors to determine the cause of hyperthyroidism. The uptake test uses radioactive iodine injected or taken orally on an empty stomach to measure the amount of iodine absorbed by the thyroid gland. Persons with hyperthyroidism absorb too much iodine. A thyroid scan producing images is typically conducted in connection with the uptake test to allow visual examination of the over-functioning gland.

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...

 is a useful test to characterize (distinguish between causes of) hyperthyroidism, and this entity from thyroiditis. This test procedure typically involves two tests performed in connection with each other: an iodine uptake test and a scan (imaging) with a gamma camera
Gamma camera
A gamma camera, also called a scintillation camera or Anger camera, is a device used to image gamma radiation emitting radioisotopes, a technique known as scintigraphy...

. The uptake test involves administering a dose of radioactive iodine (radioiodine), traditionally Iodine-131
Iodine-131
Iodine-131 , also called radioiodine , is an important radioisotope of iodine. It has a radioactive decay half-life of about eight days. Its uses are mostly medical and pharmaceutical...

 or 131I, and more recently 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...

 or 123I . 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...

 may be the preferred radionuclide in some clinics due to its more favourable radiation dosimetry
Dosimetry
Radiation dosimetry is the measurement and calculation of the absorbed dose in matter and tissue resulting from the exposure to indirect and direct ionizing radiation...

 (i.e. less radiation dose to the patient per unit administered radioactivity) and a gamma photon energy more amenable to imaging with the gamma camera
Gamma camera
A gamma camera, also called a scintillation camera or Anger camera, is a device used to image gamma radiation emitting radioisotopes, a technique known as scintigraphy...

. For the imaging scan, I-123 is considered an almost ideal isotope of iodine for imaging thyroid tissue and thyroid cancer metastasis.

Typical administration involves a pill or liquid containing sodium iodide (NaI) taken orally, which contains a small amount of iodine-131
Iodine-131
Iodine-131 , also called radioiodine , is an important radioisotope of iodine. It has a radioactive decay half-life of about eight days. Its uses are mostly medical and pharmaceutical...

, amounting to perhaps less than a grain of salt. A 2-hour fast of no food prior to and for 1 hour after ingesting the pill is required. This low dose of radioiodine is typically tolerated by individuals otherwise allergic to iodine (such as those unable to tolerate contrast mediums containing larger doses of iodine such as used in CT scan, intravenous pyelogram
Intravenous pyelogram
An intravenous pyelogram is a radiological procedure used to visualize abnormalities of the urinary system, including the kidneys, ureters, and bladder.-Procedure:...

 (IVP), and similar imaging diagnostic procedures). Excess radioiodine that does not get absorbed into the thyroid gland is eliminated by the body in urine. Some patients may experience a slight allergic reaction to the diagnostic radioiodine, and may be given an antihistamine
Antihistamine
An H1 antagonist is a histamine antagonist of the H1 receptor that serves to reduce or eliminate effects mediated by histamine, an endogenous chemical mediator released during allergic reactions...

. The patient returns 24 hours later to have the level of radioiodine "uptake" (absorbed by the thyroid gland) measured by a device with a metal bar placed against the neck, which measures the radioactivity emitting from the thyroid. This test takes about 4 minutes while the uptake % is accumulated (calculated) by the machine software. A scan is also performed, wherein images (typically a center, left and right angle) are taken of the contrasted thyroid gland with a gamma camera
Gamma camera
A gamma camera, also called a scintillation camera or Anger camera, is a device used to image gamma radiation emitting radioisotopes, a technique known as scintigraphy...

; a radiologist will read and prepare a report indicating the uptake % and comments after examining the images. Hyperthyroid patients will typically "take up" higher than normal levels of radioiodine. Normal ranges for RAI uptake are from 10-30%.

In addition to testing the TSH levels, many doctors test for T3, Free T3, T4, and/or Free T4 for more detailed results. Typical adult limits for these hormones are: TSH (units): 0.45 - 4.50 uIU/mL; T4 Free/Direct (nanograms): 0.82 - 1.77 ng/dl; and T3 (nanograms): 71 - 180 ng/dl. Persons with hyperthyroidism can easily exhibit levels many times these upper limits for T4 and/or T3. See a complete table of normal range limits for thyroid function at the thyroid gland article.

Hyperthyroidism in pregnancy

Recognizing and evaluating hyperthyroidism in pregnancy is a diagnostic challenge. Thyroid hormones are naturally elevated during pregnancy and hyperthyroidism must also be distinguished from gestational transient thyrotoxicosis. See thyroid disease in pregnancy
Thyroid disease in pregnancy
Thyroid disorders are prevalent in women of child-bearing age and for this reason commonly present in pregnancy and the puerperium. Uncorrected thyroid dysfunction in pregnancy has adverse effects on fetal and maternal well-being. The deleterious effects of thyroid dysfunction can also extend...

 for details.

Thyroid storm

Thyrotoxic crisis (or thyroid storm) is a rare but severe complication of hyperthyroidism, which may occur when a thyrotoxic patient becomes very sick or physically stressed. Its symptoms can include: an increase in body temperature to over 40 degrees Celsius (104 degrees Fahrenheit), tachycardia, arrhythmia, vomiting, diarrhea, dehydration, coma, and death. Thyroid storm requires emergency treatment and hospitalization. The main treatment is to decrease the circulating thyroid hormone levels and decrease their formation. 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...

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

 are two agents that decrease thyroid hormone synthesis and are usually prescribed in fairly high doses. To inhibit thyroid hormone release from the thyroid gland, sodium iodide, potassium iodide, and/or Lugol's solution can be given. Beta blockers such as propranolol (Inderal, Inderal LA, Innopran XL) can help to control the heart rate, and intravenous steroids may be used to help support the circulation. Earlier in this century, the mortality of thyroid storm approached 100%. However, now, with the use of aggressive therapy as described above, the death rate from thyroid storm is less than 20%.

Hypothyroidism

Hyperthyroidism due to certain types of thryroiditis
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...

 can eventually lead to 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...

 (a lack of thyroid hormone)., as the thyroid gland is damaged. Also, radioiodine treatment of Graves' disease
Graves' disease
Graves' disease is an autoimmune disease where the thyroid is overactive, producing an excessive amount of thyroid hormones...

 often eventually leads to hypothyroidism. Such hypothyroidism may be avoided by regular thyroid hormone testing and oral thyroid hormone supplementation.

Management

The large and generally accepted modalities for treatment of hyperthyroidism in humans involve initial temporary use of suppressive thyrostatics medication (antithyroid drugs), and possibly later use of permanent surgical or radioisotope therapy. All approaches may cause under active thyroid function (hypothyroidism) which is easily managed with 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...

 or Triiodothyronine
Triiodothyronine
Triiodothyronine, C15H12I3NO4, also known as T3, is a thyroid hormone. It affects almost every physiological process in the body, including growth and development, metabolism, body temperature, and heart rate....

 supplementation.

Antithyroid drugs

Thyrostatics (antithyroid drugs) are drugs that inhibit the production of thyroid hormones, such as 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...

 (used in UK) and methimazole
Methimazole
Methimazole is an antithyroid drug, and part of the thioamide group.-Indications:...

 (used in US), and 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...

. Thyrostatics are believed to work by inhibiting the iodination of thyroglobulin by thyroperoxidase, and, thus, the formation of tetra-iodothyronine (T4). Propylthiouracil also works outside the thyroid gland, preventing conversion of (mostly inactive) T4 to the active form T3. Because thyroid tissue usually contains a substantial reserve of thyroid hormone, thyrostatics can take weeks to become effective, and the dose often needs to be carefully titrated over a period of months, with regular doctor visits and blood tests to monitor results.

A very high dose is often needed early in treatment, but, if too high a dose is used persistently, patients can develop symptoms of hypothyroidism. This titrating of the dose is difficult to do accurately, and so sometimes a "block and replace" attitude is taken. In block and replace treatments thyrostatics are taken in sufficient quantities to completely block thyroid hormones, the patient treated as though they have complete hypothyroidism.

Beta-blockers

Many of the common symptoms of hyperthyroidism such as palpitations, trembling, and anxiety are mediated by increases in beta adrenergic receptors on cell surfaces. Beta blockers, typically used to treat high blood pressure, are a class of drugs that offset this effect, reducing rapid pulse associated with the sensation of palpitations, and decreasing tremor and anxiety. Thus, a patient suffering from hyperthyroidism can often obtain immediate temporary relief until the hyperthyroidism can be characterized with the Radioiodine test noted above and more permanent treatment take place. Note that these drugs do not treat hyperthyroidism or any of its long-term effects if left untreated, but, rather, they treat or reduce only symptoms of the condition. Some minimal effect on thyroid hormone production however also comes with Propranolol - which has two roles in the treatment of hyperthyroidism, determined by the different isomers of propranolol. L-propranolol causes beta-blockade, thus treating the symptoms associated with hyperthyroidism such as tremor, palpitations, anxiety, and heat intolerance. D-propranolol inhibits Thyroxine deiodinase, thereby blocking the conversion of T4 to T3, providing some though minimal therapeutic effect. Other beta blockers are used to treat only the symptoms associated with hyperthyroidism. Propranolol in the US, and Metoprolol
Metoprolol
Metoprolol is a selective β1 receptor blocker used in treatment of several diseases of the cardiovascular system, especially hypertension. The active substance metoprolol is employed either as metoprolol succinate or metoprolol tartrate...

 in the UK, are most frequently used to augment treatment for hyperthyroid patients.

Permanent

Surgery as an option predates the use of the less invasive radioisotope therapy (radioiodine 131 thyroid ablation), but is still required in cases where the thyroid gland is enlarged and causing compression to the neck structures, or the underlying cause of the hyperthyroidism may be cancerous in origin. Some patients suffering from the related condition of thyroid eye disease leading to diplopia
Diplopia
Diplopia, commonly known as double vision, is the simultaneous perception of two images of a single object that may be displaced horizontally, vertically, or diagonally in relation to each other...

 because this condition can be worsened by radiotherapy treatment.

Surgery

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...

 (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...

 to remove the whole thyroid or a part of it) is not extensively used because most common forms of hyperthyroidism are quite effectively treated by the radioactive iodine method, and because there is a risk of also removing the parathyroid glands, and of cutting 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...

, making swallowing difficult, and even simply generalized staph infection as with any major surgery. Some Graves' disease patients, however, that cannot tolerate medicines for one reason or another, patients that are allergic to iodine, or patients that refuse radioiodine may opt for surgical intervention. Also, some surgeons believe that radioiodine treatment is unsafe in patients with unusually large gland, or those whose eyes have begun to bulge from their sockets, fearing that the massive dose of radioiodine 131 needed will only exacerbate the patient's symptoms.

Radioiodine

In iodine-131
Iodine-131
Iodine-131 , also called radioiodine , is an important radioisotope of iodine. It has a radioactive decay half-life of about eight days. Its uses are mostly medical and pharmaceutical...

 (radioiodine) radioisotope therapy, which was first pioneered by Dr. Saul Hertz
Saul Hertz
Saul Hertz, M.D. was an American physician who discovered the use of radioactive iodine for the treatment of thyroid disease.-Early life and education:...

, radioactive iodine-131 is given orally (either by pill or liquid) on a one-time basis, to severely restrict, or altogether destroy the function of a hyperactive thyroid gland. This isotope of radioactive iodine used for ablative treatment is more potent than diagnostic radioiodine (usually iodine-123 or a very low amount of iodine-131), which has a biological half life from 8–13 hours. Iodine-131, which also emits beta particles that are far more damaging to tissues at short range, has a half-life of approximately 8 days. Patients not responding sufficiently to the first dose are sometimes given an additional radioiodine treatment, at a larger dose. Iodine-131 in this treatment is picked up by the active cells in the thyroid and destroys them, rendering the thyroid gland mostly or completely inactive. Since iodine is picked more readily (though not exclusively) by thyroid cells, and (more important) is picked up even more readily by over-active thyroid cells, the destruction is local, and there are no widespread side-effects with this therapy. Radioiodine ablation has been used for over 50 years, and the only major reasons for not using it are pregnancy and breast-feeding (breast tissue also picks up and concentrates iodine). Once the thyroid function is reduced, replacement hormone therapy taken orally each day may easily provide the required amount of thyroid hormone the body needs. There is, however, a contrasting study noting increased cancer incidence after radioiodine treatment for hyperthyroidism.

The principal advantage of radioiodine treatment for hyperthyroidism is that it tends to have a much higher success rate than medications. Depending on the dose of radioiodine chosen, and the disease under treatment (Grave's vs. toxic goiter, vs. hot nodule etc.), success rate in achieving definitive resolution of the hyperthyroidism may vary from 75-100%. A major expected side-effect of radioiodine in patients with Graves' disease is the development of lifelong hypothyroidism, requiring daily treatment with thyroid hormone. Also, there are some indications that patients suffering from related eye disease experience a worsening of this condition, and for this reason some patients elect to have a surgical solution. On occasion, some patients may require more than one radioactive treatment, depending on the type of disease present, the size of the thyroid, and the initial dose administered. Many patients are initially unhappy at the thought of having to take a thyroid hormone pill for the rest of their lives. Nevertheless, as thyroid hormone is safe, inexpensive, and easy to take, and is identical to the thyroid hormone normally made by the thyroid, this therapy is, in general, extremely safe and very well tolerated by the vast majority of patients.

As radioactive iodine treatment results in destruction of thyroid tissue, there is often a transient period of several days to weeks when the symptoms of hyperthyroidism may actually worsen following radioactive iodine therapy. In general, this happens as a result of thyroid hormones being released into the blood following the radioactive iodine-mediated destruction of thyroid cells that contain thyroid hormone. In some patients, treatment with medications such as beta blockers (propranolol, atenolol, etc.) may be useful during this period of time. Many patients are able to tolerate the initial few weeks without any problem whatsoever.

Most patients do not experience any difficulty after the radioactive iodine treatment, usually given as a small pill. On occasion, neck tenderness or a sore throat may become apparent after a few days, if moderate inflammation in the thyroid develops and produces discomfort in the neck or throat area. This is usually transient, and not associated with a fever, etc.

Women breastfeeding should discontinue breastfeeding for at least a week, and likely longer, following radioactive iodine treatment, as small amounts of radioactive iodine may be found in breast milk even several weeks after the radioactive iodine treatment.

A common outcome following radioiodine is a swing from hyperthyroidism to the easily treatable hypothyroidism, which occurs in 78% of those treated for Graves' thyrotoxicosis and in 40% of those with toxic multinodular goiter or solitary toxic adenoma. Use of higher doses of radioiodine reduces the incidence of treatment failure, with penalty for higher response to treatment consisting mostly of higher rates of eventual hypothyroidism which requires hormone treatment for life.

There is increased sensitivity to radioiodine therapy in thyroids appearing on ultrasound scans
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...

 as more uniform (hypoechogenic), due to densely packed large cells, with 81% later becoming hypothyroid, compared to just 37% in those with more normal scan appearances (normoechogenic).

Thyroid storm

Thyroid storm presents with extreme symptoms of hyperthyroidism. It is treated aggressively with resuscitation measure along with a combination of the above modalities including: an intravenous beta blockers such as propranolol, followed by a thionamide such as methimazole
Methimazole
Methimazole is an antithyroid drug, and part of the thioamide group.-Indications:...

, an iodinated radiocontrast agent or an iodine solution if the radiocontrast agent is not available, and an intravenous steroid
Steroid
A steroid is a type of organic compound that contains a characteristic arrangement of four cycloalkane rings that are joined to each other. Examples of steroids include the dietary fat cholesterol, the sex hormones estradiol and testosterone, and the anti-inflammatory drug dexamethasone.The core...

 such as hydrocortisone.

Cats

In veterinary medicine, hyperthyroidism is one of the most common endocrine conditions affecting older domesticated felines (cats). Some veterinarians estimate that it occurs in up to 2% of cats over the age of 10. The disease has become significantly more common since the first reports of feline hyperthyroidism in the 1970s. In cats, one cause of hyperthyroidism tends to be benign tumors, but the reason those cats develop such tumors continues to be researched.

However, recent research published in Environmental Science & Technology, a publication of the American Chemical Society, suggests that many cases of feline hyperthyroidism are associated with exposure to environmental contaminants called polybrominated diphenyl ethers (PBDEs), which are present in flame retardants in many household products, in particular, furniture and some electronic products.

The study from which the report was based was conducted jointly by researchers at the EPA's National Health and Environmental Effects Laboratory and Indiana University. In the study, which involved 23 pet cats with feline hyperthyroidism, PDBE blood levels were three times as high as those in younger, non-hyperthyroid cats. In ideal circumstances, PBDE and related endocrine disruptors that seriously damage health would not be present in the blood of any animals or humans.

Mutations of the thyroid-stimulating hormone receptor that cause a constitutive activation of the thyroid gland cells have been discovered recently. Many other factors may play a role in the pathogenesis of the disease such as goitrogens (isoflavones such as genistein, daidzein, and quercertin) and iodine and selenium content in the diet.

The most common presenting symptoms are: rapid weight loss
Weight loss
Weight loss, in the context of medicine, health or physical fitness, is a reduction of the total body mass, due to a mean loss of fluid, body fat or adipose tissue and/or lean mass, namely bone mineral deposits, muscle, tendon and other connective tissue...

, tachycardia
Tachycardia
Tachycardia comes from the Greek words tachys and kardia . Tachycardia typically refers to a heart rate that exceeds the normal range for a resting heart rate...

 (rapid heart rate), vomiting
Vomiting
Vomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...

, diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...

, increased consumption of fluids (polydipsia
Polydipsia
Polydipsia is a medical symptom in which the patient displays excessive thirst. The word derives from the Greek πολυδιψία, which is derived from πολύς + δίψα...

) and food, and increased urine production (polyuria
Polyuria
Polyuria is a condition usually defined as excessive or abnormally large production or passage of urine . Frequent urination is sometimes included by definition, but is nonetheless usually an accompanying symptom...

). Other symptoms include hyperactivity, possible aggression, heart murmurs, a gallop rhythm
Gallop rhythm
A gallop rhythm refers to a rhythm of the heart on auscultation. It includes three or four sounds, thus resembling the sounds of a gallop....

, an unkempt appearance, and large, thick nails. About 70% of afflicted cats also have enlarged thyroid glands (goiter).

The same three treatments used with humans are also options in treating feline hyperthyroidism (surgery, radioiodine treatment, and anti-thyroid drugs). Drugs must be given to cats for the remainder of their lives, but may be the least expensive option, especially for very old cats. Radioiodine treatment and surgery often cure hyperthyroidism. Some veterinarians prefer radioiodine treatment over surgery because it does not carry the risks associated with anesthesia
Anesthesia
Anesthesia, or anaesthesia , traditionally meant the condition of having sensation blocked or temporarily taken away...

. Radioiodine treatment, however, is not available in all areas for cats. The reason is that this treatment requires nuclear radiological expertise and facilities, since the animal's urine, sweat, saliva, and stool are radioactive for several days after the treatment, requiring special inpatient handling and facilities usually for a total of 3 weeks (first week in total isolation and the next two weeks in close confinement). The guidelines for radiation levels vary from state to state; some states such as Massachusetts allow hospitalization for as little as two days before the animal is sent home with care instructions. Surgery tends to be done only when just one of the thyroid glands is affected (unilateral disease); however, following surgery, the remaining gland may become over-active. As in people, one of the most common complications of the surgery is hypothyroidism.

Dogs

Hyperthyroidism is very rare in canines (dogs) (occurring in less than 1 or 2% of dogs), who instead tend to have the opposite problem: hypothyroidism, which can manifest itself in a unhealthy-appearing coat and fertility problems in females. When hyperthyroidism does appear in dogs, it tends to be due to over-supplementation of the thyroid hormone during treatment for hypothyroidism. Symptoms usually disappear when the dose is adjusted.

On occasion, dogs will have functional carcinoma in the thyroid; more often (about 90% of the time), this is a very aggressive tumor that is invasive and easily metastasizes or spreads to other tissues (esp. the lungs), making prognosis very poor. While surgery is possible, it is often very difficult due to the invasiveness of the mass in surrounding tissue including the arteries, the esophagus
Esophagus
The esophagus is an organ in vertebrates which consists of a muscular tube through which food passes from the pharynx to the stomach. During swallowing, food passes from the mouth through the pharynx into the esophagus and travels via peristalsis to the stomach...

, and windpipe. It may only be possible to reduce the size of the mass, thus relieving symptoms and also allowing time for other treatments to work.

If a dog does have a benign functional carcinoma (appears in 10% of the cases), treatment and prognosis are no different from those of the cat. The only real difference is that dogs tend to appear to be asymptomatic, with the exception of having an enlarged thyroid gland appearing as a lump on the neck.

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

The source of this article is wikipedia, the free encyclopedia.  The text of this article is licensed under the GFDL.
 
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