Hypothyroidism (Underactive thyroid) : Sign and Symptoms, Causes, Risk Factors, Mechanism, Diagnosis, Complications and Treatment

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Hypothyroidism is a condition where thyroid gland doesn't produce enough volume of thyroid hormones to meet human body’s needs. It’s also known as Underactive thyroid. Hypothyroidism may not cause noticeable symptoms in the early stages. But untreated hypothyroidism can cause a number of health problems, such as obesity, fatigue, constipation, weight gain, muscle weakness, puffy face, increased sensitivity to cold, hoarseness, dry skin, muscle aches, tenderness and stiffness, joint pain, stiffness or swelling in the joints, heavier than normal or irregular menstrual periods, fatigue infertility, thinning hair, depression, impaired memory, bradycardia, enlarged thyroid gland (goiter) etc.

The thyroid gland is divided into two lobes that are connected by the isthmus, which crosses the midline of the upper trachea at the second and third tracheal rings. In its anatomic position, the thyroid gland lies posterior to the sternothyroid and sternohyoid muscles, wrapping around the cricoids cartilage and tracheal rings. It is located inferior to the laryngeal thyroid cartilage, typically corresponding to the vertebral levels C5-T1.

Thyroid gland is responsible for the formation and secretion of the thyroid hormones as well as iodine homeostasis within the human body. The thyroid produces approximately 90% inactive thyroid hormone, or thyroxine (T4), and 10% active thyroid hormone, or triiodothyronine (T3). Inactive thyroid hormone is converted peripherally to either activated thyroid hormone or an alternative inactive thyroid hormone.

 Mechanism of Thyroid Hormones

The thyroid gland is responsible for the production of iodothyronines. The primary secretory product is inactive thyroxine, or T4; a prohormone of triiodothyronine, or T3. T4 is converted to T3 peripherally by type-1 deiodinase in the tissues with high blood flow, such as the liver and kidneys. In the brain, T4 is converted to active T3 by type-2 deiodinase produced by Glial cells. The third iodothyronine is called reverse T3, or rT3. rT3 is inactive and forms by type 3 deiodinase activity on T4.

These iodothyronines are composed of thyroglobulin and iodine. Thyroglobulin is formed from amino acids in a basal to apical fashion within the thyroid cells themselves. Thyroglobulin is then secreted into the follicular lumen, where it is enzymatically combined with iodine to form iodinated thyroglobulin. Endosomes containing this iodinated thyroglobulin then fuse with lysosomes, which enzymatically release the thyroglobulin from the resultant thyroid hormone. The thyroid hormones are next released from the cell while the remaining thyroglobulin is deiodinated and recycled for further use.

Function of Thyroid Hormones

Thyroid hormone induces effects on practically all nucleated cells in the human body, generally increasing their function and metabolism.

  1. Cardiac output, Stroke volume, and Resting heart rate increase through positive chronotropic and inotropic effects. Active thyroid hormone increases myocardial intracellular calcium to increase contraction force and speed. Concomitantly, vasculature in the skin, muscle, and heart dilate, resulting in decreased peripheral vascular resistance while blood volume increases through activation of the renin-angiotensin-aldosterone system.
  2. Basal Metabolic Rate (BMR), Heat production, and Oxygen consumption elevate through thyroid hormone activation of mitochondrial uncoupling proteins. Glucose and fatty acid uptake and oxidation also increase, which results in increased thermogenesis and necessitates increased heat dissipation. Heat intolerance in hyperthyroidism is attributable to this increase in thermogenesis. Compensation for increased thermogenesis is also mediated by thyroid hormone through increases in blood flow, sweating, and ventilation.
  3. Resting respiratory rate and minute ventilation undergo stimulation by active thyroid hormone, triiodothyronine (T3), to normalize arterial oxygen concentration in compensation for increased rates of oxidation. T3 also promotes oxygen delivery to the tissues by simulating erythropoietin and hemoglobin production and promoting folate and cobalamin absorption through the gastrointestinal tract.
  4. T3 is responsible for the development of fetal growth centers and linear bone growth, endochondral ossification, and epiphyseal bone center maturation following birth. Additionally, T3 simulates adult bone remodeling and degradation of mucopolysaccharides and fibronectin in extracellular connective tissue.
  5. T3 stimulates the nervous system resulting in increased wakefulness, alertness, and responsiveness to external stimuli. Thyroid hormone also stimulates the peripheral nervous system, resulting in increased peripheral reflexes and gastrointestinal tone, and motility.
  6. Thyroid hormone also plays a role in reproductive health and other endocrine organ function. It allows for the regulation of normal reproductive function in both men and women by regulating both the ovulatory cycle and spermatogenesis. Thyroid hormone also regulates pituitary function; growth hormone production and release are stimulated by thyroid hormone while inhibiting prolactin production and release. Additionally, renal clearance of many substances, including some medications, can be increased due to activated thyroid hormone stimulation of renal blood flow and glomerular filtration rate.

Sign and Symptoms of Hypothyroidism

The signs and symptoms of hypothyroidism vary from person to person and on the severity of the hormone deficiency. Problems tend to develop slowly, often over a number of years. Because of hypothyroidism develops slowly, person may not notice symptoms of the disease for months or even years and many of these symptoms, especially fatigue and weight gain, are common and do not necessarily mean person have a thyroid problem. Hypothyroidism may not cause noticeable symptoms in the early stages if it not treat properly in early stage than hypothyroidism can cause a number of health problems, such as obesity, fatigue, constipation, weight gain, muscle weakness, puffy face, increased sensitivity to cold, hoarseness, dry skin, muscle aches etc. Some common signs and symptoms of hypothyroidism may include:

  1. Weight gain (leads to Obesity),
  2. Fatigue,
  3. Constipation,
  4. Muscle weakness,
  5. Puffy face,
  6. Increased sensitivity to cold,
  7. Hoarseness,
  8. Dry skin,
  9. Muscle aches,
  10. Tenderness and stiffness,
  11. Joint pain,
  12. Stiffness or swelling in the joints,
  13. Heavier than normal or irregular menstrual periods,
  14. Fatigue infertility,
  15. Thinning hair,
  16. Depression,
  17. Confusion,
  18. Impaired memory,
  19. Bradycardia,
  20. Enlarged thyroid gland etc.

Hypothyroidism in Infants

Although hypothyroidism most often affects middle-aged and older women, anyone can develop the condition, including infants. Initially, babies born without a thyroid gland or with a gland that doesn't work properly may have few signs and symptoms. When newborns do have problems with hypothyroidism, the problems may include:

  1. Yellowing of the skin and whites of the eyes (jaundice). In most of the cases, this occurs when a baby's liver can't metabolize bilirubin.
  2. A large, protruding tongue.
  3. Difficulty breathing.
  4. Hoarse crying.
  5. An umbilical hernia etc.

As the disease progresses, infants are likely to have trouble feeding and may fail to grow and develop normally. They may also have:

  1. Constipation.
  2. Poor muscle tone.
  3. Excessive sleepiness.

When hypothyroidism in infants isn't treated, even mild cases can lead to severe physical and mental retardation.

Hypothyroidism in Children and Teens

In general, hypothyroidism in children and teens has the same signs and symptoms as adults do, but they may also experience:

  1. Poor growth, resulting in short stature.
  2. Poor mental development.
  3. Delayed development of permanent teeth.
  4. Delayed puberty etc.

Causes of Hypothyroidism

Hypothyroidism results when the thyroid gland fails to produce enough hormones, the balance of chemical reactions in your body can be upset. Hypothyroidism may be due to a number of factors, including:

  1. Autoimmune Disease: The most common cause of hypothyroidism is an autoimmune disorder known as Hashimoto's thyroiditis. Autoimmune disorders occur when body’s immune system produces antibodies that attack thyroid glands own tissues. Scientists aren't sure why this happens, but it's likely a combination of factors, such as genes and an environmental trigger. However it happens, these antibodies affect the thyroid glands and The thyroid becomes inflamed and can’t make enough thyroid hormones.
  2. Thyroiditis: Thyroiditis, an inflammation of thyroid glands, causes stored thyroid hormone to leak out of patient thyroid gland. At first, the leakage increases blood’s hormone levels, leading to thyrotoxicosis (a condition in which thyroid hormone levels are too high). The thyrotoxicosis may last for many months. After that, thyroid may become underactive and, over time, the condition may become permanent, requiring thyroid hormone replacement. Three types of thyroiditis can cause thyrotoxicosis followed by hypothyroidism.
    1. Subacute thyroiditis involves a painfully inflamed and enlarged thyroid.
    2. Postpartum thyroiditis develops after a woman gives birth.
    3. Silent thyroiditis is painless, even though thyroid may be enlarged. Experts think it is probably an autoimmune condition.
  3. Over-response to Hyperthyroidism Treatment: People with hyperthyroidism are often treated with radioactive iodine or anti-thyroid medications. The goal of these treatments is to get thyroid function back to normal. But sometimes, correcting hyperthyroidism can end up lowering thyroid hormone production too much, resulting in permanent hypothyroidism.
  4. Thyroid Gland Surgery: When patient suffering from hyperthyroidism or a large goiter or thyroid nodules (which are noncancerous tumors or lumps in the thyroid that can produce too much thyroid hormone) or small thyroid cancers in this condition surgeon remove part of the thyroid gland, the remaining part may produce normal amounts of thyroid hormone. But some people who have this surgery may develop hypothyroidism. Removing the entire thyroid always results in hypothyroidism. In that case, patient will need to take thyroid hormone for life.
  5. Radiation Therapy: Radiation used to treat cancers of the head and neck can affect thyroid gland and may lead to hypothyroidism. Radioactive iodine, a common treatment for hyperthyroidism, gradually destroys thyroid cells. If you receive radioactive iodine treatment, you probably will eventually develop hypothyroidism.
  6. Medications: A number of medications can contribute to hypothyroidism. Some medicines can interfere with thyroid hormone production and lead to hypothyroidism, including certain heart medicines, psychiatric disorder medicines, bipolar disorder medicines and cancer medicines. Several recently developed cancer medicines, in particular, can either affect the thyroid directly or affect it indirectly by damaging the pituitary gland.
  7. Congenital Disease: Some babies are born with a defective thyroid gland or no thyroid gland. In most cases, the thyroid gland didn't develop normally for unknown reasons, but some children have an inherited form of the disorder. Often, infants with congenital hypothyroidism appear normal at birth.
  8. Pituitary Disorder: A relatively rare cause of hypothyroidism is the failure of the pituitary gland to produce enough Thyroid Stimulating Hormone (TSH) - usually because of a benign tumor of the pituitary gland.
  9. Pregnancy: Some women develop hypothyroidism during or after pregnancy (postpartum hypothyroidism), often because they produce antibodies to their own thyroid gland. Left untreated, hypothyroidism increases the risk of miscarriage, premature delivery and preeclampsia (a condition that causes a significant rise in a woman's blood pressure during the last three months of pregnancy. It can also seriously affect the developing fetus.).
  10. Iodine Deficiency: The trace mineral iodine - found primarily in seafood, seaweed, plants grown in iodine-rich soil and iodized salt - is essential for the production of thyroid hormones. Too little iodine can lead to hypothyroidism, and too much iodine can worsen hypothyroidism in people who already have the condition. In some parts of the world, iodine deficiency is common, but the addition of iodine to table salt has virtually eliminated this problems.

Risk Factors of Hypothyroidism

Hypothyroidism can affect people of all ages, genders and ethnicities. Women, particularly older women, are more likely to develop hypothyroidism than men. Women are generally more likely to develop hypothyroidism after menopause than earlier in life. Although anyone can develop hypothyroidism, you're at an increased risk of hypothyroidism if you:

  1. Being a woman
  2. Race (being white or Asian)
  3. Age (growing older and especially older than 60 years.)
  4. Have a family history of thyroid disease.
  5. Pituitary Disorder
  6. Had an Autoimmune disorder such as type-1diabetes mellitus, multiple sclerosis, Sjoegren Syndrome, rheumatoid arthritisceliac disease, Addison's disease and vitiligo etc.
  7. Down syndrome.
  8. Iodine Deficiency
  9. Have been treated with radioactive iodine or anti-thyroid medications.
  10. Have any Congenital Disease.
  11. Received radiation to neck or upper chest.
  12. Have had thyroid surgery (partial thyroidectomy)
  13. Have been pregnant or delivered a baby within the past six months.
  14. Have Turner syndrome (a genetic disorder that affects women).
  15. Bipolar disorder etc.

Diagnosis of Hypothyroidism

It can actually be difficult to diagnose hypothyroidism because the symptoms can be easily confused with other conditions. A hypothyroidism diagnosis can’t be based on symptoms alone because many of its symptoms are the same as those of other diseases. Hypothyroidism can cause fertility problems; hence women who have trouble getting pregnant often get tested for thyroid problems.

The main way to diagnose hypothyroidism is a blood test along with medical history and physical examination.  That’s why doctor may use several blood tests (mainly TSH and T4 level) and imaging tests to confirm the diagnosis and find its cause.

A Thyroid Stimulating Hormone (TSH) test measures how much TSH pituitary gland is secreting. If thyroid isn’t producing enough hormones, the pituitary gland will boost TSH to increase thyroid hormone production. If the person had hypothyroidism; TSH levels will be high, as body is trying to stimulate more thyroid hormone activity. If he/she had hyperthyroidism; TSH levels will be low, as body is trying to stop excessive thyroid hormone production.

A Thyroxine (T4) level test is also useful in diagnosing hypothyroidism. T4 is one of the hormones directly produced by thyroid. Used together, T4 and TSH tests help evaluate thyroid function.

Typically, if the people have a low level of T4 along with a high level of TSH, he/she have hypothyroidism. However, there’s a spectrum of thyroid disease. Other thyroid function tests may be necessary to properly diagnose.

In addition, TSH tests are used to help diagnose a condition called Subclinical hypothyroidism, which usually causes no outward signs or symptoms. In this condition, people have normal blood levels of triiodothyronine and thyroxine, but higher than normal levels of TSH.

There are certain factors that can affect blood tests for thyroid problems. One is the blood-thinning medication called heparin. Another is biotin, a vitamin taken as a stand-alone supplement or as part of a multivitamin. Let doctor know about any medications or supplements take before having blood tests done.

 Complications of Hypothyroidism

Untreated hypothyroidism can lead to a number of health problems:

  1. Goiter: Constant stimulation of thyroid to release more hormones may cause the gland to become larger - a condition known as a goiter. Although generally not uncomfortable, a large goiter can affect appearance and may interfere with swallowing or breathing.
  2. Heart problems: Hypothyroidism may also be associated with an increased risk of heart disease and heart failure, primarily because of high levels of low-density lipoprotein (LDL) cholesterol (‘bad’ cholesterol)
  3. Mental health issues: Depression may occur early in hypothyroidism and may become more severe over time. Hypothyroidism can also cause slowed mental functioning.
  4. Peripheral Neuropathy: Long-term uncontrolled hypothyroidism can cause damage of peripheral nerves. These are the nerves that carry information from brain and spinal cord to the rest of the body. Peripheral neuropathy may cause pain, numbness and tingling in affected areas.
  5. Joint pain: Low levels of thyroid hormone can cause aches and pains in the joints and muscles, as well as tendonitis.
  6. Myxedema: This rare, life-threatening condition is the result of long-term, undiagnosed hypothyroidism. Its signs and symptoms include intense cold intolerance and drowsiness followed by profound lethargy and unconsciousness. A myxedema coma may be triggered by sedatives, infection or other stress on the body. If person have signs or symptoms of myxedema, he/she need immediate emergency medical treatment. Myxedema is the most severe form of hypothyroidism. A person with myxedema can lose consciousness or go into a coma, which can cause death.
  7. Infertility: Low levels of thyroid hormone can interfere with ovulation, which impairs fertility. In addition, some of the causes of hypothyroidism - such as autoimmune disorder; can also impair fertility.
  8. Birth defects: Babies born to women with untreated thyroid disease may have a higher risk of birth defects compared to babies born to healthy mothers. These children are also more prone to serious intellectual and developmental problems. Infants with untreated hypothyroidism present at birth are at risk of serious problems with both physical and mental development. But if this condition is diagnosed within the first few months of life, the chances of normal development are excellent.

Thyroid problems in a pregnant woman can affect the developing baby. During the first three months of pregnancy, the baby receives all thyroid hormone from its mother. If the mother has hypothyroidism, the baby does not get enough thyroid hormone. This can lead to problems with mental development.

Treatment of Hypothyroidism

A Standard treatment for hypothyroidism involves daily use of the synthetic thyroid hormone levothyroxine (Levo-T, Synthroid, others). This oral medication restores adequate hormone levels, reversing the signs and symptoms of hypothyroidism. Treatment with levothyroxine will likely be life-long, but because the dosage need may change, doctor is likely to check TSH level every year.

To determine the right dosage of levothyroxine initially, doctor generally checks the level of TSH after six to eight weeks. After that, blood levels are generally checked six months later. Excessive amounts of the hormone can cause side effects, such as increased appetite, Insomnia, Heart palpitations and or Shakiness. If person have coronary artery disease or severe hypothyroidism, doctor may start treatment with a smaller amount of medication and gradually increase the dosage. Progressive hormone replacement allows heart to adjust to the increase in metabolism.

Levothyroxine causes virtually no side effects when used in the appropriate dose and is relatively inexpensive. Certain medications, supplements and even some foods may affect ability to absorb levothyroxine. Talk to doctor if eat large amounts of soy products or a high-fiber diet or take other medications, such as Iron supplements or multivitamins that contain iron, Aluminum hydroxide, which is found in some antacids and Calcium supplements.

Levothyroxine is best taken on an empty stomach at the same time every day. Ideally, take the hormone in the morning and wait an hour before eating or taking other medications. If take the medicine at bedtime, wait for four hours after last meal or snack. If miss a dose of levothyroxine, take two pills of this medicine on the next day.

Once person have the correct dosage, he/she shouldn’t have any side effects from hormones. But don’t stop or skip medication, because hypothyroidism symptoms could come back.

 

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