Hypothyroidism | signs | causes and treatment


Hypothyroidism is a kind of thyroid disease. If you have hypothyroidism that means you have an underactive thyroid ("hypo-" means "under" or "below normal"). In people with hypothyroidism, the thyroid does not make enough thyroid hormone to keep the body running normally. Common causes of hypothyroidism are autoimmune disease, surgical removal of the thyroid, and radiation treatment.
The thyroid is a butterfly-shaped endocrine gland usually located in the lower front of the neck below the larynx (the voice box).
Hypothyroidism is a kind of thyroid disease



The thyroid's job is to make thyroid hormones, which are secreted into the blood and then carried to every tissue in the body. Thyroid hormone helps the body use energy, stay warm and keep the brain, heart, muscles, and other organs working as they should. The main hormone made by the thyroid is thyroxine, also called T4 because it contains four iodine molecules. Small amounts of another and more potent thyroid hormone containing three iodine molecules, triiodothyronine (T3) are also made by the thyroid gland. However, most of the T3 in the blood is made from T4 in other body tissues.




Low thyroid hormone levels cause the body's functions to slow down, leading to general symptoms like dry skin, fatigue, loss of energy, and memory problems. Hypothyroidism is diagnosed by a simple blood test for thyroid-stimulating hormone (TSH). Hypothyroidism is treated by replacing the missing thyroid hormone with synthetic thyroxine pills, which the person must take every day for life. With daily treatment, most patients recover completely.

Signs and symptoms of hypothyroidism

Symptoms of hypothyroidism include dry skin, cold intolerance, weight gain, constipation, weakness, lethargy, fatigue, muscle cramps, myalgia, stiffness, and loss of ambition or energy. In children, thyroid hormone deficiency may manifest as growth or intellectual retardation.

Physical signs include coarse skin and hair, cold or dry skin, periorbital puffiness, bradycardia, and slowed or hoarse speech. Objective weakness (with proximal muscles affected more than distal muscles) and slow relaxation of deep tendon reflexes are common. Reversible neurologic syndromes such as carpal tunnel syndrome, polyneuropathy, and cerebellar dysfunction may also occur.

Most patients with secondary hypothyroidism due to inadequate TSH production have clinical signs of generalized pituitary insufficiency, such as abnormal menses and decreased libido, or evidence of a pituitary adenoma, such as visual field defects, galactorrhea, or acromegaloid features.

Myxedema coma is a rare consequence of decompensated hypothyroidism manifested by hypothermia, advanced stages of hypothyroid symptoms, and altered sensorium ranging from delirium to coma. Mortality rates of 60% to 70% necessitate immediate and aggressive therapy.

Risk factors

  • Have a close relative, such as a parent or grandparent, with an autoimmune disease
  • Hypothyroidism can develop at any age, but risk for developing it increases with age.
  • Hypothyroidism is more common in women than men; and, much more so in young women than young men. The risk of hypothyroidism increases during pregnancy, after delivery and around menopause.
  • Hypothyroidism is more common in whites and Asians than in other races and ethnicities.
  • Have another autoimmune disorder, such as type 1 diabetes, rheumatoid arthritis, multiple sclerosis, celiac disease, Addison's disease, pernicious anemia, or vitiligo
  • Have been treated with radioactive iodine or received radiation to the neck or upper chest
  • Have had thyroid surgery
  • Have Down syndrome or Turner syndrome – genetic disorders
  • Have bi-polar disease (manic depression)

Causes

Autoimmune disease
The immune system normally protects the body against bacterial and viral "invaders." In autoimmune diseases ("auto" means "self"), the immune system attacks a normal part of the body. In autoimmune hypothyroidism, the immune system accidentally attacks cells in the thyroid. This causes the cells to become inflamed and damaged, interfering with their ability to make thyroid hormone.

Surgical removal of a part or all of the thyroid gland
 Some people with thyroid nodules, thyroid cancer, or Graves' disease need to have part or the entire thyroid removed. Hypothyroidism results when the entire thyroid is removed or when the remaining thyroid tissue no longer works properly.

Radiation treatment
Some people with Graves' disease, nodular goiter, or thyroid cancer are treated with radioactive iodine (131I). Radioactive iodine destroys the thyroid, which can result in hypothyroidism. Hodgkin's disease, lymphoma, or cancers of the head or neck are treated with radiation which can destroy the thyroid and result in hypothyroidism.

Congenital (from birth) hypothyroidism
About 1 in 4,000 babies each year are born without a thyroid or with a partly formed thyroid. A few babies have part or their entire thyroid in the wrong place (ectopic thyroid). In some babies, the thyroid cells or their enzymes do not function correctly or are affected by medications taken by the mother. In others, the thyroid may make enough hormone for a while but later stop stops functioning as the child gets older or becomes an adult. In the United States, all children are tested at birth for hypothyroidism.

Thyroiditis
Thyroiditis is an inflammation of the thyroid. It is usually caused by an autoimmune attack (such as Hashimoto’s disease, postpartum thyroiditis or silent thyroiditis) or by a viral infection. Thyroiditis can make the thyroid release its whole supply of stored thyroid hormone into the blood at once, causing the thyroid to become overactive (hyperthyroidism) for a brief period of time. Once the entire stored hormone has been released, the thyroid becomes underactive. Almost all people with viral thyroiditis recover their thyroid function, but about one-fourth of people with autoimmune thyroiditis have permanent hypothyroidism.

Medicines
Some medicines can interfere with the thyroid's ability to make thyroid hormone, leading to hypothyroidism. Lithium is one of the most common medicines that cause hypothyroidism. Others medicines that can cause hypothyroidism are amiodarone, interferon alpha, and interleukin-2. All of these drugs are most likely to trigger hypothyroidism in people who have a genetic tendency to autoimmune thyroid disease. Rarely, some people with the blood cancer multiple myeloma who are treated with thalidomide can develop hypothyroidism.

Too little or too much iodine
The thyroid must have iodine to make thyroid hormone. Iodine comes into the body in foods, mainly dairy products, chicken, beef, pork, fish, and iodized salt. The iodine then travels through the blood to the thyroid. Keeping thyroid hormone production in balance requires the right amount of iodine. People who live in undeveloped parts of the world may not get enough iodine in their diet. Worldwide, iodine deficiency is the most common cause of hypothyroidism, although it is a rare cause in the U.S.

Too much iodine can also cause or worsen hypothyroidism. The major source of too much iodine is dietary supplements containing kelp, a kind of seaweed. Most of these supplements are sold with the false promise of helping people lose weight. Other sources of too much iodine are x-ray dyes, medicines like amiodarone, and some older expectorants (medicines that help clear the lungs and throat).

Damage to the pituitary gland
The pituitary gland tells the thyroid how much hormone to make. If the pituitary gland is damaged by injury, a tumor, radiation, or surgery, it may no longer be able to give the thyroid the right instructions, and the thyroid may stop making enough hormone.


A rise in TSH level is the first evidence of primary hypothyroidism. Many patients have a free T4 level within the normal range (compensated hypothyroidism) and few, if any, symptoms of hypothyroidism. As the disease progresses, the free T4 drops below normal. The T3 concentration is often maintained in the normal range despite low T4. Antithyroid peroxidase antibodies and antithyroglobulin antibodies are usually elevated. The RAIU is not useful in evaluation of hypothyroidism because it can be low, normal, or elevated.

Pituitary failure (secondary hypothyroidism) should be suspected in patients with decreased T4 levels and inappropriately normal or low TSH levels.


Levothyroxine (l-thyroxine, T4) is the drug of choice for thyroid hormone replacement and suppressive therapy because it is chemically stable, relatively inexpensive, free of antigenicity, and has uniform potency. Other commercially available thyroid preparations can be used but are not preferred therapy. Once a particular product is selected, therapeutic interchange is discouraged. Because T3 (and not T4) is the biologically active form, levothyroxine administration results in a pool of thyroid hormone that is readily and consistently converted to T3.

In patients with long-standing disease and older individuals without known cardiac disease start therapy with levothyroxine 50 mcg daily and increase after 1 month.

The recommended initial dose for older patients with known cardiac disease is 25 mcg/day titrated upward in increments of 25 mcg at monthly intervals to prevent stress on the cardiovascular system.

The average maintenance dose for most adults is ~125 mcg/day, but there is a wide range of replacement doses, necessitating individualized therapy and appropriate TSH monitoring to determine an appropriate dose.

Although treatment of subclinical hypothyroidism is controversial, patients presenting with marked elevations in TSH (above 10 mIU/L) and high titers of thyroid peroxidase antibody or prior treatment with sodium iodide–131 may be most likely to benefit from treatment.

Levothyroxine is the drug of choice for pregnant women, and the goal is to decrease TSH to the normal reference range for pregnancy.

Cholestyramine, calcium carbonate, sucralfate, aluminum hydroxide, ferrous sulfate, soybean formula, dietary fiber supplements, and espresso coffee may impair the GI absorption of levothyroxine. Drugs that increase nondeiodinative T4 clearance include rifampin, carbamazepine, and possibly phenytoin. 

Amiodarone may block conversion of T4 to T3.

Thyroid USP (or desiccated thyroid) is usually derived from pig thyroid gland. It may be antigenic in allergic or sensitive patients. Inexpensive generic brands may not be bioequivalent.

Liothyronine (synthetic T3) has uniform potency but has a higher incidence of cardiac adverse effects, higher cost, and difficulty in monitoring with conventional laboratory tests.

Liotrix (synthetic T4:T3 in a 4:1 ratio) is chemically stable, pure, and has a predictable potency but is expensive. It lacks therapeutic rationale because ~35% of T4 is converted to T3 peripherally.

Excessive doses of thyroid hormone may lead to heart failure, angina pectoris, and myocardial infarction (MI). Hyperthyroidism leads to reduced bone density and increased risk of fracture.



References
https://www.mayoclinic.org/diseases-conditions/hypothyroidism/symptoms-causes/syc-20350284
https://www.webmd.com/women/hypothyroidism-underactive-thyroid-symptoms-causes-treatments
https://www.endocrineweb.com/conditions/thyroid/hypothyroidism-too-little-thyroid-hormone
https://www.thyroid.org/hypothyroidism/
https://www.niddk.nih.gov/health-information/endocrine-diseases/hypothyroidism
https://www.medicalnewstoday.com/articles/163729
https://emedicine.medscape.com/article/122393-overview
https://www.nhs.uk/conditions/underactive-thyroid-hypothyroidism/
https://my.clevelandclinic.org/health/diseases/12120-hypothyroidism
https://www.medicinenet.com/hypothyroidism/article.htm
https://www.womenshealth.gov/a-z-topics/thyroid-disease
https://medlineplus.gov/hypothyroidism.html
https://www.yourhormones.info/endocrine-conditions/hypothyroidism/
https://www.everydayhealth.com/hypothyroidism/guide/
https://www.hormone.org/diseases-and-conditions/hypothyroidism

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