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Monday, March 19, 2012

Hypothyroidism

thyroxine-binding globulin with thyroxine (magenta)
Author: Dr Paul Fitzgerald University of California San Francisco 2008-07-19

Hypothyroidism is a condition where the body’s thyroid hormone levels are too low. Because nearly all cells in the body need thyroid hormone, insufficient levels can have a profound effect on a person’s health. While there is no known cure for hypothyroidism, treatment with thyroid hormone is an effective therapy.

 
Glossary
Thyroid gland refers to the endocrine organ located in the low anterior (front) of the neck. The thyroid gland secretes two forms of thyroid hormone (T4 and T3) to regulate the body’s metabolism.   The thyroid gland weighs only about 15 grams (0.5 ounces) and is shaped something like a butterfly, with wings (lobes) flanking the trachea (windpipe) that connect to each other in front of the trachea.   The following link has an anatomical drawing of the thyroid gland:   http://www.med.umich.edu/1libr/aha/aha_thyroidg_art.htm

T4, thyroxine, and levothyroxine are synonyms that refer to the form of thyroid hormone that has four atoms of iodine in each molecule.  T4 is the main hormone secreted by the thyroid gland.  Over 99% of T4 circulates in the bloodstream attached to proteins (particularly thyroid binding globulin, TBG).  The unattached T4 is known as free T4 (FT4, free thyroxine) and only that tiny portion of T4 can leave the circulating blood to enter cells.

T3 triiodothyronine, and liothyronine are synonyms that refer to the form of thyroid hormone that has three atoms of iodine in each molecule. T3 is secreted by the thyroid gland and also made from T4 in cells outside of the thyroid gland that are capable of converting T4 to T3.  Over 99% of T3 circulates in the bloodstream attached to proteins (particularly thyroid binding globulin, TBG).  The unattached T3 is known as free T3 (F T3) and only that tiny portion of T3 can leave the circulating blood to enter cells.  Free T3 is active thyroid hormone and works by entering a cell’s nucleus (center) and binding to certain receptors (like a key in a lock) to regulate the activity of genes, particularly those affecting the metabolic rate. T3 receptors are found in nearly every cell of the body, from the brain to the skin, such that thyroid hormone’s effect is extremely widespread and profound.

TSH (Thyroid Stimulating Hormone) refers to a hormone that is produced by the pituitary gland, a small endocrine gland that lies at the base of the brain. TSH stimulates the thyroid gland to produce T4 and T3.  The normal pituitary gland secretes more TSH when thyroid hormone levels are too low (hypothyroidism).  The TSH level is elevated when the thyroid gland fails.

Myxedema is a homonym that has three different meanings:  1) Myxedema originally referred to the thickened skin that is seen with prolonged hypothyroidism.  2) Myxedema also refers generally to severe and prolonged hypothyroidism.  3) Pretibial Myxedema also refers to a skin condition that affects the shins in some patients with Graves’ disease; this is not a characteristic of hypothyroidism.

Hypothyroidism in Adults: Symptoms

Most adults with hypothyroidism complain of fatigue, weight gain, and feeling cold. There are many symptoms of hypothyroidism that vary considerably among individuals. Most people with hypothyroidism will have only a few of them.
Common Symptoms of Hypothyroidism: slow heart rate (bradycardia), high blood pressure, cold intolerance, fatigue, depression, mental dullness, puffiness in face or extremities, headache, slow speech, hoarse voice, heavy menstrual periods, joint and muscle pains, tingling feelings (paresthesias), carpal tunnel syndrome, hair breakage and thinning, brittle nails, decreased perspiration and dry skin, skin pallor or yellowing, weight gain.  There also may be an enlarged thyroid gland (goiter), due to stimulation of the gland by TSH and also by Hashimoto’s thyroiditis (see below), which can cause the thyroid to develop a firm “rubbery” texture, making it easier to see or feel in the neck.
Uncommon Symptoms of Hypothyroidism: trouble swallowing (dysphagia), breast milk secretion when not nursing (galactorrhea), shortness of breath, pneumonia, weight loss, decreased appetite, absent menstrual periods (amenorrhea), psychosis, sensitivity to narcotics, reduced consciousness and coma.

Hypothyroidism in Adults: Causes

Hashimoto’s thyroiditis & autoimmunity

Hashimoto’s thyroiditis (autoimmune thyroiditis) is the most common cause of hypothyroidism. Dr. Hakaru Hashimoto, a Japanese surgeon, first described the condition in 1912.  It’s an autoimmune condition in which the body’s immune system is turned against the thyroid.  White blood cells (B lymphocytes) invade the thyroid gland, such that the condition is also known as chronic lymphocytic thyroiditis. Meanwhile, the immune system makes antibodies (immune proteins) that are directed against the thyroid gland.  Such antithyroid antibodies are found in the blood of about 10% of most adult populations, but only a minority of these individuals develop hypothyroidism.  Hashimoto’s thyroiditis is usually a chronic condition that can eventually damage the thyroid and cause hypothyroidism. 
Autoimmune thyroiditis has a very strong genetic component.  Other members of the family frequently have hypothyroidism and may have other autoimmune conditions as well. Although autoimmune thyroiditis can occur at any age and in either sex, it typically affects women.  The sexual disparity is striking, with a female:male ratio of 10:1. Hashimoto’s thyroiditis can be caused by the drugs lithium, amiodarone, and interferon.   Dietary iodine supplementation also appears to increase the risk of autoimmune thyroiditis and hypothyroidism.
Although hypothyroidism from Hashimoto’s thyroiditis is usually permanent, up to 11% of patients experience a remission after several years. There are two causes for such a remission: 1) The Hashimoto’s thyroiditis may improve spontaneously for no apparent reason; 2) A stimulating antibody (Thyroid Stimulating Immunoglobulin, TSI) is produced that stimulates the thyroid’s TSH receptors, overwhelming the destructive effects of concurrent Hashimoto’s thyroiditis and causing the thyroid to produce more thyroid hormone.  Rarely, if the thyroid gland produces excessive amounts of thyroid hormone, the result is autoimmune hyperthyroidism, a condition known as Graves’ disease.
People with autoimmune thyroiditis have an overactive immune system that attacks their thyroid gland, but may attack other organs as well.  Sjöegren’s syndrome (dry eyes & mouth, usually mild) can occur fairly often, due to autoimmunity against the salivary and lacrimal glands.  Celiac disease, autoimmunity against the intestine (provoked by gluten, wheat) is also seen commonly.   Vitiligo (patches of white skin) can also occur.  Patients may also develop antibodies against other endocrine glands, such that a person with hypothyroidism from autoimmune thyroiditis is somewhat more prone to develop autoimmune adrenal insufficiency, autoimmune hypoparathyroidism (low serum calcium), or autoimmune type 1 diabetes mellitus.  When more than one endocrine gland is damaged by autoimmunity, it is termed polyglandular autoimmune syndrome.

Other causes of hypothyroidism

Other causes of hypothyroidism include thyroid surgery, and external beam radiation therapy to the head/neck region for treatment of cancer or skin conditions.   Radioiodine  (131I), received for treatment or from nuclear fallout, can also cause hypothyroidism.  Chemotherapy for cancer can also cause hypothyroidism.  Additional causes of hypothyroidism include chronic hepatitis, certain drugs  (propylthiouracil, methimazole, sulfonamides, interleukin-2), and sunitinib (Sutent chemotherapy).  In addition, iodine deficiency can cause hypothyroidism and goiter; certain foods (turnips, cassava) can aggravate iodine deficiency and are known as goitrogens.  Finally hypopituitarism (loss of function in the frontal lobe of the pituitary gland) can cause hypothyroidism, due to a deficiency of TSH.

The following links have additional information about Hashimoto’s thyroiditis, autoimmunity, and iodine:

Hypothyroidism in Adults: Testing

Screening tests

When the thyroid gland fails, the pituitary senses the diminished levels of thyroid hormone in the blood and secretes more Thyroid Stimulating Hormone (TSH).  Therefore, an elevated serum TSH level is the most sensitive test for hypothyroidism (exception: hypopituitarism).  In addition, with hypothyroidism, the serum free T4 (FT4) level is usually low or low normal.   Both the TSH and FT4 levels are determined by testing blood samples.  The blood can be drawn at any time of day and fasting is not required.
To screen for Hashimoto’s (autoimmune) thyroiditis, blood is assayed (tested) for antithyroid antibodies: anti-thyroperoxidase (TPO) antibodies, and anti-thyroglobulin (TG) antibodies.

Factors that can cause misleading testing for hypothyroidism

Misleadingly elevated serum TSH may occur in several conditions: recovery from an acute illness, acute psychiatric crises, sleep deprivation, and strenuous exercise just before testing.  Heroin or amphetamines can also elevate serum TSH. Falsely elevated serum TSH levels can also result from laboratory error or from assay interference by circulating antibodies.  TSH levels also tend to rise with age, such that elderly people without any thyroid problem can have a serum TSH that is somewhat above the “normal” range that has been determined for young adults.
Misleadingly low serum total T4 levels occur with malnourishment and factors that reduce serum protein levels, such as cirrhosis (scarring of the liver) and nephrotic syndrome (damage to the kidneys). Other conditions that can lower thyroid binding globulin (TBG) and result in a misleadingly low serum total T4 include anabolic steroid abuse and familial TBG deficiency.  Serum free T4 (FT4) levels are normal in these conditions; therefore the FT4 assay is superior to the total T4 assay.  However, misleadingly low serum FT4 levels can result from laboratory error or can be seen in severe illness, particularly congestive heart failure.  Certain drugs also cause low FT4 levels without hypothyroidism: high-dose corticosteroids (e.g., prednisone, dexamethasone), anti-seizure drugs (e.g., carbamazepine, phenytoin, phenobarbitol), and therapy with T3 (Cytomel).  In these conditions, while the serum FT4 may be low, the serum TSH is not elevated, and that distinguishes it from true hypothyroidism.

Other Laboratory Findings in Hypothyroidism

The first clues for hypothyroidism are often other abnormal laboratory test results.  Patients with hypothyroidism often have hyponatremia (low serum sodium), elevated liver enzymes, high serum prolactin, and anemia.   High serum lipids are commonly seen, including high LDL cholesterol, high triglycerides, and high lipoprotein (a).  In patients with autoimmune thyroiditis, serum antinuclear antibody (ANA) levels are usually elevated.  Such test abnormalities should prompt thyroid function testing.

Radiological Abnormalities in Hypothyroidism

Magnetic resonance imaging (MRI) of the head is sometimes done to evaluate the complaint of headaches, a common symptom in hypothyroidism.  The MRI may note an enlarged pituitary gland, due to an increased number of TSH-secreting cells.  This finding may be misinterpreted as showing a pituitary tumor.
Chest x-ray or computed tomography (CT) scan can show a mass in the front of the chest, behind the breast bone (mediastinum), due to an enlarged thyroid (goiter) that is located abnormally low in the chest. This is also known as a “retrosternal goiter”.  An enlarged thymus is commonly seen in the mediastinum in autoimmune thyroiditis.  The thymus is an organ that produces T-cell lymphocytes that are important for the body’s immune response; the thymus is largest during puberty.
The following link has additional information about testing for hypothyroidism:

 

Adults with Hypothyroidism: Treatment

History

Treatment for hypothyroidism first became available in 1892, when sheep thyroid glands were fried and eaten to treat this condition.  This was not particularly palatable or successful.  In 1900, a thyroid preparation was first introduced in the United States as desiccated (dried) sheep’s thyroid that had been freed from fat, cleaned, dried, and powdered.  It could be made into tablets whose dosage was measured as weight in an old measurement called grains, where 1 grain (not to be confused with the word gram) is equivalent to 60 milligrams (mg).  However, the original desiccated thyroid preparations differed in potency from batch to batch, although they have become more reliable and continue to be available.  Synthetic thyroxine was developed to be a more reliable thyroid medication and that is the type of thyroid preparation in greatest use today.
Synthetic thyroxine (T4) is the thyroid medication that is preferred by most clinicians for treating patients with hypothyroidism.  There are several thyroxine formulations and many dosage strengths.  Most formulations have accurate amounts of thyroxine in their tablets.  However, the bioavailability (absorption) of the different manufacturer’s thyroxine formulations can differ slightly. Therefore, it’s best for hypothyroid patients to be consistent and to take the same brand name of thyroxine or the same manufacturer’s generic thyroxine. 

Beginning therapy with thyroxine

Adults with hypothyroidism may be treated initially with thyroxine 50-75 mcg/d.  The ultimate daily dosage of thyroxine averages 1.7 mcg/kg body weight.  However, elderly patients tend to have lower thyroxine dose requirements, averaging 1.0 mcg/kg body weight.  Therefore, for older patients, the initial replacement dosage of thyroxine is no more than 25-50 mcg/d and increased as tolerated.  Much higher initial thyroxine doses are given to patients with myxedema crisis (see below).
Since thyroxine therapy increases the metabolic rate and the demand on the heart, hypothyroid patients with coronary disease can develop angina when treated with thyroxine. Therefore, the starting dosage of thyroxine for individuals with coronary disease is only 25 mcg/d, with increases in the dosage every 4-6 weeks as tolerated. If angina occurs, the thyroxine dosage is reduced until coronary blood flow can be restored.
Generally, for pregnant women or patients with severe hypothyroidism (see below), a full replacement dosage of thyroxine is given immediately.

Optimizing and Monitoring Treatment for Hypothyroidism

 While receiving optimal thyroxine replacement therapy, most people’s symptoms of hypothyroidism resolve fully.  Serum TSH (thyroid stimulating hormone) levels are used to monitor the adequacy of oral thyroxine replacement. The required dosage of thyroxine varies considerably, from 0.25 mcg/d to 300 mcg/d.  The thyroid dosage is adjusted to keep the serum TSH level between 0.4 mU/L and 2.0 mU/L, which is generally considered to be an optimal level.  For example, if the serum TSH remains above 2.0 mU/L, the dosage of thyroid hormone may need to be increased.  Similarly, if the serum TSH is low, the thyroid dosage may need to be reduced.  If a patient is unable to eat for a prolonged period, thyroxine may be given intravenously at a daily dose of about 75% of their usual oral dose.
Some treated hypothyroid individuals continue to have hypothyroid-type symptoms (e.g., fatigue, weight gain), despite having normal serum TSH and F T4 levels.  In such cases, it’s important to consider whether other conditions or drugs might be responsible.  However, if hypothyroid symptoms continue without another explanation, it is reasonable to try a slightly higher dosage of thyroid hormone replacement, unless there are contraindications such as angina or atrial fibrillation.  The increased dosage may be continued if there is clear clinical benefit and no symptoms of hyperthyroidism.
Some patients do not feel normal unless they receive thyroxine at a dosage that results in suppressed serum TSH or elevated FT4 levels.  There is concern that such replacement doses of thyroxine might increase the risk of osteoporosis or cardiac rhythm problems but in fact there is little risk in continuing such a dosage of thyroxine (with slightly suppressed serum TSH) if a patient feels distinctly better on the higher dose, has no symptoms or signs of hyperthyroidism, and has serum FT3 levels in the low-normal to mid-normal range.
In the United States, most clinicians prescribe pure T4 preparations.  However, since the normal thyroid gland secretes both T4 and T3, there have been studies comparing pure T4 thyroid preparations to combined T4/ T3 preparations; these studies have yielded conflicting results. A disadvantage of combined T4/ T3 preparations is that the T3 component peaks a few hours after taking the pill, with transiently elevated serum T3 levels.  Nevertheless, some patients state that they feel better when taking such T4/ T3 preparations.  A Dutch double-blind study of 141 hypothyroid individuals found that some patients preferred T4 /T3 over pure T4 preparations and that serum TSH levels were sometimes suppressed on the preferred doses.   Other studies have shown no advantage of combined T4/ T3therapy over pure T4 therapy, when the serum TSH is kept normal.  (See links, below).   Some patients’ preference for T4/ T3 over T4 therapy may be placebo effect, while some may like the feeling of being mildly hyperthyroid, and other subgroups of hypothyroid individuals may not adequately convert T4 to T3 in all tissues. 

Types of Thyroid Medications:

T4: levothyroxine (generic), Levoxyl, Synthroid, Levothroid, Unithroid.
T3: liothyronine (generic), Cytomel (oral), Triostat (intravenous)
T4/ T3 combinations:
         - Desiccated animal thyroid: generic or Armour Thyroid
         - Synthetic thyroid: Liotrix, Thyrolar

Factors that may affect thyroid hormone dose requirements:

Amiodarone (Cordarone) can decrease or increase thyroid hormone secretion and variably inhibits conversion of T4 to T3; follow the serum TSH levels carefully, adjusting the dose of thyroxine to keep the TSH levels normal.
Antacids (aluminum or calcium, sucralfate) reduce  the intestine’s uptake of  thyroid; take thyroid hormone at least one hour before or four hours after antacids.
Anti-tuberculosis antibiotics increase liver break-down of thyroxine, increasing thyroid hormone dose requirements:
         Rifabutin (Mycobutin)
         Rifampin (Rifadin, Rimactane)
Anti-sex hormone chemotherapy for breast cancer or prostate cancer reduces the liver’s TBG production, reducing thyroid hormone dose requirements:
         Leuprolide (Lupron, Lupron Depot)
Anti-seizure medications increase liver breakdown of thyroid, increasing thyroid hormone dose requirements:
         Carbamazepine (Tegretol)
         Phenobarbitol
         Primidone (Mysoline)
         Phenytoin (Dilantin)
Chemotherapy may cause ovarian failure, reducing estrogen levels and liver TBG production, and reducing thyroid hormone dose requirements.
Cholesterol-lowering bile acid-binding drugs reduce thyroxine absorption; separate thyroid hormone from them by at least six hours:
         Cholestiramine (Questran)
         Colestipol (Colestid)
Didanosine (ddi, Videx anti-HIV therapy) reduces thyroxine absorption; take thyroid hormone at least one hour before or four hours after didanosine.
Estrogens (especially oral) increase liver production of TBG, increasing thyroid hormone dose requirements:
           Oral contraceptives
           Oral estrogen replacement therapy
Imatinib chemotherapy (Gleevec) increases liver metabolism of thyroxine, increasing thyroid hormone dose requirements.
Iron supplements reduce thyroxine absorption; take thyroid hormone at least  one hour before or four hours after iron supplements:
         Ferrous bis-glycinate chelate/polysacharide complex (Niferex)
         Ferrous gluconate (Fergon)
         Ferrous sulfate
         Multivitamins with iron
Menopause reduces estrogen levels that reduce liver TBG production,  reducing thyroid hormone dose requirements.
Nephrotic Syndrome (kidney disease) causes protein loss in the urine, changing thyroid hormone dose requirements.
Proton Pump Inhibitors (PPIs) may cause atrophic gastritis and reduce the absorption of thyroxine (omeprazole, lansoprazole, pantoprazole, etc), increasing thyroid hormone dose requirements.
Raloxifene (Evista) reduces thyroxine absorption; take thyroid hormone 12 hours apart from raloxifene.

The following links have additional information about the treatment of hypothyroidism:

Pregnancy and Hypothyroidism

 Unsuspected maternal hypothyroidism appears to cause a 3.8% increase in miscarriage rate.
During pregnancy, the developing baby receives the mother’s thyroid hormones, which cross the placenta.  The baby is particularly dependent upon maternal thyroid during the first trimester when the fetal thyroid has not fully developed.  Maternal hypothyroidism can adversely affect the intellectual development of the baby.
Therefore, screening for hypothyroidism is reasonable for all women who are planning to become pregnant or who have become pregnant.   Screening should always be done for women with symptoms of hypothyroidism (see above) or who have a personal or family history of thyroid or autoimmune disorders.  Screening for hypothyroidism is done with a blood test for TSH.
Dietary iodine deficiency is surprisingly common during pregnancy and can cause hypothyroidism.  This can be prevented by ensuring adequate dietary iodine (iodized salt, tea, seafood) or by taking one prenatal multivitamin daily.  The multivitamin should contain 150 mcg iodine, the recommended daily requirement during pregnancy.  Excessive iodine supplements should be avoided, as this can cause the baby to develop a goiter.
Women with known hypothyroidism should have prenatal thyroid function testing to ensure they are at normal thyroid levels before becoming pregnant.  During pregnancy women’s thyroxine requirements predictably increase by as much as 50%.  Therefore, at the diagnosis of pregnancy the dosage of thyroxine is increased empirically by 20-30%.  It is prudent to monitor TSH levels every 6 weeks and adjust the thyroxine replacement to ensure that they are doing well clinically and to keep the TSH level below 2.0  µU/mL Following delivery, the thyroxine dosage may be tapered back gradually over several weeks to approximately the prenatal dosage. 
After delivery, some women develop postpartum thyroiditis, which refers to a painless but severe, acute autoimmune inflammation of the thyroid gland. The acute thyroid damage releases stored thyroid hormone and initially causes hyperthyroidism.  Once the store of thyroid hormone is depleted, hypothyroidism develops, due to thyroid damage.  The thyroid gland may recover normal function.  This condition is more generally known as painless thyroiditis or Hashitoxicosis and is termed postpartum thyroiditis when it occurs in women within 6 months after delivery.
The following links have additional information about hypothyroidism during pregnancy:

Newborns with Hypothyroidism

About 1 in 3000 newborn infants are born with hypothyroidism, which is also known as congenital hypothyroidism or neonatal hypothyroidism. 

Symptoms

Hypothyroid infants often appear lethargic and have a hoarse cry. They may nurse poorly and have abdominal bloating, constipation, choking, vomiting, and breathing problems with cyanosis (bluish skin).  Their posterior fontanelle (the soft spot in the back of the infant’s head) may be larger than normal.  Affected infants may also have neonatal jaundice (yellow skin due to high bilirubin levels) that persists for more than 3 days. The affected infant’s skin may be cool to touch and the skin may appear mottled.  The hands, feet, and genitals may be swollen.  Hypothyroid newborns can develop a large tongue or a belly button hernia (omphalocele). Rarely, an affected baby’s muscles may enlarge, a condition known as Kocher-Debré-Semelaigne syndrome.  In congenital hypothyroidism, the newborn may lack growth plates (epiphyses) at the knees.  
If congenital hypothyroidism is untreated, the baby’s brain and body gradually suffers irreversible damage, a condition known as cretinism.  With cretinism, the brain fails to develop normally, resulting in permanently but variably stunted mental development. By age 6 months, linear growth is slow, resulting in permanent short stature.  A cretin’s facial appearance becomes wide and short, Deafness often develops. If the condition is due to iodine deficiency, the thyroid may become very large (endemic goiter). 

Causes

Historically, the most common cause for congenital hypothyroidism, goiter, and cretinism has been severe iodine deficiency, particularly in certain regions of the world where the soils are deficient in iodine. With iodine supplementation of salt and the consumption of seafood, the incidence of iodine deficiency has declined dramatically, but still remains a problem in many areas.    In most developed countries, the main causes for congenital hypothyroidism include a failure of the thyroid to develop (thyroid aplasia), an underdeveloped thyroid (thyroid hypoplasia), or an abnormally located (ectopic) thyroid under the tongue (lingual thyroid) or on the side of the neck.  Congenital hypothyroidism can also be caused by thyroid enzyme defects.  Also, if the mother has Hashimoto’s thyroiditis, her antithyroid antibodies may cross the placenta into her baby.  This can result in neonatal hypothyroidism that can be permanent, but is usually transient.
If neonatal hypothyroidism is detected and treated before two weeks of age, it is likely that permanent brain damage can be avoided. Adequate therapy with thyroid hormone can be complicated if infants receive soy formula, which can interfere with the intestinal absorption of thyroxine.

Testing

Hypothyroidism is often not clinically recognized at birth, so a mandated screening process tests all newborns for congenital hypothyroidism, usually with blood obtained from a heel stick and absorbed onto filter paper.  The blood specimen is sent to a central laboratory to assess for inborn errors of metabolism and for TSH and/or T4.  TSH levels fluctuate a great deal during the first few days of life, so there may be false positive and false negative results. 
Transiently low serum T4 levels (with normal TSH) are commonly seen in newborns who are not hypothyroid, but who are premature, low birth weight, or who are sick from other causes.  Such newborns’ low serum T4 levels usually rise into the normal range after their recovery without any adverse outcome. However, repeat testing is advisable, since permanently low FT4 with low or normal TSH levels can be seen with congenital hypopituitarism, which is rare but must be suspected in babies with an abnormally slow growth.

Treatment

When screening tests (T4 and TSH) indicate hypothyroidism, confirmatory blood tests are drawn immediately and the infant is treated with thyroxine while the test results are pending.  To help ensure normal cognitive development, the starting dosage of thyroxine is aggressive: 10-15 mcg/kg body weight daily.  The thyroxine may be given intravenously initially, to ensure absorption. On this dosage, some newborns will become hyperthyroid, so parents and clinicians must be alert for signs of hyperthyroidism (shakiness, irritability, poor sleep) where serum TSH and FT4 should be measured immediately and the thyroxine dosage adjusted. Frequent monitoring of the FT4 and TSH levels is important and the FT4 level should be kept in the upper range of normal.  Testing is done at least every 1-2 months during the first year, every 3 months until age three years, and then every 6 months.  Thyroxine may be not be properly absorbed by the intestines of infants who receive concurrent formula containing soy, or supplements of calcium or iron.
About 10% of such newborns with hypothyroidism have  transient hypothyroidism that can reverse spontaneously.  Such transient hypothyroidism may be due to intrauterine exposure to maternal antithyroid antibodies or antithyroid drugs, or due to iodine deficiency during the pregnancy. When this is suspected, the clinician may be able to discontinue the thyroxine replacement after age 3 years, checking the serum FT4 and TSH levels after 6 weeks to make sure they have returned to normal.  If the thyroid tests have returned to normal, the thyroxine may be discontinued, but retesting of the serum TSH and FT4 is recommended at least every 6 months and immediately for any recurrent symptoms of hypothyroidism.

The following links have additional information about congenital hypothyroidism:

Children with Hypothyroidism

Children who develop hypothyroidism have a condition that is termed juvenile hypothyroidism. When hypothyroidism develops after age two, permanent mental deficiency does not typically occur. However, these children grow slowly and the eruption of adult teeth may be delayed. They may complain of feeling fatigued and cold and appear depressed and lethargic.  Their skin may be dry. They are usually constipated and may complain of abdominal pains.  Hypothyroid children also tend to be overweight.  Any of the adult symptoms of hypothyroidism (see above) may be present. They may develop problems with cognitive and attention deficits that may seem like a new learning disability. Girls may develop the early onset of menstrual periods before age 10 (precocious puberty) and may have heavy, painful, and irregular periods.  Some girls develop enlarged, cystic ovaries.  Delayed puberty may also occur. 
However, some children with hypothyroidism may not look particularly ill or have physical complaints. In fact, hypothyroid children are sometimes relatively good students because they lack some of the normal hyperactivity of childhood and pay attention in class.  This often leads to a delayed diagnosis of juvenile hypothyroidism.
The causes of juvenile hypothyroidism are similar to those of adult hypothyroidism (see above).  As with adults, Hashimoto’s thyroiditis is the most common cause of juvenile hypothyroidism.  Children with a family history of autoimmune disease and those with celiac disease (gluten sensitive enteropathy) are particularly prone to develop Hashimoto’s thyroiditis.  About 50% of children with Hashimoto’s thyroiditis go on to have hypothyroidism.  Additionally, some children have genetic conditions that predispose to hypothyroidism.  Such conditions include Pendred syndrome (hearing loss and hypothyroidism), Down syndrome (trisomy 21), and Turner syndrome. The latter is also known as 45XO, monosomy X, or gonadal dysgenesis.
Children with hypothyoidism are treated with thyroxine. Children and adolescents often require relatively more thyroxine (for their weight) than do adults - as much as 4 mcg/kg body weight.   Children may receive near-replacement doses of thyroxine from the outset. The dosage of thyroxine is adjusted, based upon serum TSH and FT4 measurements, which should be obtained frequently (every three to four months). Adolescents may neglect to take their thyroid medication regularly and require close medical supervision. 
The following links have additional information about children with hypothyroidism:

Myxedema Crisis

Myxedema crisis refers to severe, life-threatening  hypothyroidism.  It tends to affect elderly hypothyroid individuals who have had a stroke or who have simply run out of their prescription or have neglected to take their thyroid hormone medication.  Myxedema crisis usually occurs in a hypothyroid patient who develops another illness, such as pneumonia, influenza, or a urinary tract infection.
Symptoms of myxedema crisis include mental confusion, sleepiness, or even unconsciousness (myxedema coma).  The affected individual often struggles with their memory.  Sometimes, the condition can be precipitated when a hypothyroid person takes sedatives or narcotics, to which they are very sensitive.
In myxedema crisis, the signs of hypothyroidism (discussed above) are present but are more severe.  Affected individuals have skin that is dry, coarse, thickened, pale yellowish, and cool. A clue to the presence of hypothyroidism may be a neck scar from prior thyroid surgery, but such scars are often barely visible.   Hypothermia (low body temperature) is usually present, with rectal temperatures sometimes dropping to as low as 25 oC (77 oF).  Hypothermia can be missed if a mercury thermometer is used, particularly when it is not shaken down.  Electronic thermometers are more appropriate for this situation.   Bradycardia (slow heart beat) is usually present.  Hypotension (low blood pressure) is common and can progress to shock and death.
An underlying illness often precipitates myxedema crisis.  Such illness can be psychological, such as depression stemming from the loss of a spouse. Depression and dementia may cause a patient to neglect taking the prescribed thyroid hormone.
Blood testing for hypothyroidism must be done immediately.  The serum TSH level is elevated.  Serum FT4 levels are low.With myxedema crisis, the serum sodium is low (hyponatremia) and the serum glucose may also be low (hypoglycemia).  Patients have elevated serum levels of creatine phosphokinase (CK), lactate dehydrogenase (LDH) and other liver enzymes. Blood cultures may show sepsis. Screening tests for adrenal insufficiency are also obtained.  A urinalysis is obtained to look for urinary infection.  A chest x-ray is obtained to check for pneumonia.
With myxedema crisis, the blood oxygen level is usually low and this can be detected with pulse oximetry.   Arterial blood gases document the hypoxia, along with a high carbon dioxide level (hypercapnea). Pneumonia or pleural effusion (fluid around the lungs) may interfere with breathing.   Most patients need to have a breathing tube placed in the trachea (endotracheal intubation) and mechanical ventilation. 
Hypothermic patients are warmed with regular blankets gradually, since fast warming can precipitate shock.  Intravenous fluids are given cautiously, due to the danger of fluid retention. Intravenous glucose is given to avoid hypoglycemia (low blood sugar). All medications must be given intravenously, since oral medications are absorbed poorly in this condition.  
After blood tests have been drawn, thyroid hormone therapy is started based upon clinical suspicion for hypothyroidism.  Levothyroxine (T4) is given in a loading dosage of 400 mcg intravenously, followed by 50-100 mcg intravenously daily.  The lower dosage is given when coronary insufficiency is suspected.  In patients with myxedema coma, T3 (liothyronine, Triostat) may be given intravenously in doses of 5-10 mcg every 8 hours for the first 48 hours. 
While tests for adrenal insufficiency are pending, hydrocortisone is administered intravenously in doses of 50 mg every 6 hours.  If adrenal function is found to be normal, the hydrocortisone is discontinued.  When infection is suspected, antibiotics are given intravenously.
Without thyroxine replacement, the mortality rate for myxedema crisis is nearly 100%. Despite therapy, the mortality rate with myxedema crisis remains high (about 20%).   However, with optimal medical treatment, most patients eventually experience a full recovery.
The following links have additional information about myxedema crisis:

Additional general information about hypothyroidism

MESH Terms & Keywords: hypothyroidism, hypothyroid, thyroid, thyroxine, T4, levothyroxine, Levoxyl, Synthroid, Unithroid, T3, liothyronine, triiodothyronine, Cytomel, Triostat, desiccated thyroid, Armour Thyroid, Liotrix, Thyrolar, TSH, thyroid stimulating hormone, congenital hypothyroidism, neonatal hypothyroidism, cretin, cretinism, juvenile hypothyroidism, Hashimoto’s thyroiditis, silent thyroiditis, lymphocytic thyroiditis, Hashitoxicosis, maternal hypothyroidism, hypothyroidism in pregnancy, postpartum thyroiditis, goiter, myxedema, myxedema crisis, myxedema coma.


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