Hypothyroidism

Hypothyroidism

Hypothyroidism is the disease state in humans and in animals caused by insufficient production of thyroid hormone by the thyroid gland. Cretinism is a form of hypothyroidism found in infants.

Causes

About three percent of the general population is hypothyroidic.[1] Factors such as iodine deficiency or exposure to Iodine-131 (I-131) can increase that risk. There are a number of causes for hypothyroidism. Historically, and still in many developing countries, iodine deficiency is the most common cause of hypothyroidism worldwide. In iodine-replete individuals, hypothyroidism is mostly caused by Hashimoto's thyroiditis, or by a lack of the thyroid gland or a deficiency of hormones from either the hypothalamus or the pituitary.

Hypothyroidism can result from postpartum thyroiditis, a condition that 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 or a woman develops hypothyroidism. Of those women who experience hypothyroidism associated with postpartum thyroiditis, one in five will develop permanent hypothyroidism requiring life-long treatment.

Hypothyroidism can also result from sporadic inheritance, sometimes autosomal recessive.

Hypothyroidism is also a relatively common sex disease in domestic dogs, with some specific breeds having a definite predisposition.[2]

Temporary hypothyroidism can be due to the Wolff-Chaikoff effect. A very high intake of iodine can be used to temporarily treat hyperthyroidism, especially in an emergency situation. Although iodine is substrate for thyroid hormones, high levels prompt the thyroid gland to take in less of the iodine that is eaten, reducing hormone production.

Hypothyroidism is often classified by the organ of origin:[3][4]

General psychological associations

Hypothyroidism can be caused by lithium-based mood stabilizers, usually used to treat bipolar disorder (previously known as manic depression).

In addition, patients with hypothyroidism and psychiatric symptoms may be diagnosed with:[6]

Atypical depression (which may present as dysthymia)
Bipolar spectrum syndrome (including bipolar I or bipolar II disorder, cyclothymia, or premenstrual syndrome)
Inattentive ADHD or sluggish cognitive tempo

Hypothyroidism Symptoms

In adults, hypothyroidism is associated with the following symptoms:[5][7][8]

Early symptoms
Poor muscle tone (muscle hypotonia)
Fatigue
Cold intolerance, increased sensitivity to cold
Depression
Muscle cramps and joint pain
Carpal Tunnel Syndrome
Goiter
Thin, brittle fingernails
Thin, brittle hair
Paleness
Decreased sweating
Dry, itchy skin
Weight gain and water retention[9][10][11]
Bradycardia (low heart rate – less than sixty beats per minute)
Constipation

Late symptoms

Slow speech and a hoarse, breaking voice – deepening of the voice can also be noticed
Dry puffy skin, especially on the face
Thinning of the outer third of the eyebrows (sign of Hertoghe)
Abnormal menstrual cycles
Low basal body temperature

Less common symptoms

Impaired memory[12]
Impaired cognitive function (brain fog) and inattentiveness
A slow heart rate with ECG changes including low voltage signals. Diminished cardiac output and decreased contractility.
Reactive (or post-prandial) hypoglycemia[13]
Sluggish reflexes
Hair loss
Anemia caused by impaired haemoglobin synthesis (decreased EPO levels), impaired intestinal iron and folate absorption or B12 deficiency[14] from pernicious anemia
Difficulty swallowing
Shortness of breath with a shallow and slow respiratory pattern.
Increased need for sleep
Irritability and mood instability
Yellowing of the skin due to impaired conversion of beta-carotene[15] to vitamin A
Impaired renal function with decreased GFR.
Elevated serum cholesterol
Acute psychosis (myxedema madness) is a rare presentation of hypothyroidism
Decreased libido[16] due to impairment of testicular testosterone synthesis.
Decreased sense of taste and smell (anosmia)
Puffy face, hands and feet (late, less common symptoms)
Gynecomastia

Hypothyroidism Diagnostic testing

To diagnose primary hypothyroidism, many doctors simply measure the amount of thyroid-stimulating hormone (TSH) being produced by the pituitary gland. High levels of TSH indicate that the thyroid is not producing sufficient levels of thyroid hormone (mainly as thyroxine (T4) and smaller amounts of triiodothyronine (T3)). However, measuring just TSH fails to diagnose secondary and tertiary hypothyroidism, thus leading to the following suggested blood testing if the TSH is normal and hypothyroidism is still suspected:

Free triiodothyronine (fT3)
Free levothyroxine (fT4)
Total T3
Total T4

Additionally, the following measurements may be needed:

24 hour urine free T3[17]
Antithyroid antibodies — for evidence of autoimmune diseases that may be damaging the thyroid gland
Serum cholesterol — which may be elevated in hypothyroidism
Prolactin — as a widely available test of pituitary function
Testing for anemia, including ferritin
Basal body temperature

Hypothyroidism Treatment

Hypothyroidism is treated with the levorotatory forms of thyroxine (L-T4) and triiodothyronine (L-T3). Both synthetic and animal-derived thyroid tablets are available and can be prescribed for patients in need of additional thyroid hormone. Thyroid hormone is taken daily, and doctors can monitor blood levels to help assure proper dosing. There are several different treatment protocols in thyroid replacement therapy:

T4 Only
    This treatment involves supplementation of levothyroxine alone, in a synthetic form. It is currently the standard treatment in mainstream medicine.[18]

T4 and T3 in Combination
    This treatment protocol involves administering both synthetic L-T4 and L-T3 simultaneously in combination.[19]

Desiccated Thyroid Extract
    Desiccated thyroid extract is an animal based thyroid extract, most commonly from a porcine source. It is also a combination therapy, containing natural forms of L-T4 and L-T3.[20]

Treatment controversy

The current standard treatment in thyroid therapy is levothyroxine only, and the American Association of Clinical Endocrinologists (AACE) states that desiccated thyroid hormone, combinations of thyroid hormone, or triiodothyronine should not generally be used for replacement therapy.[18] Nevertheless, there exists some controversy about whether this treatment protocol is optimal, and recent studies have given conflicting results.

Two recent studies comparing synthetic T4 versus synthetic T4 + T3 have shown "clear improvements in both cognition and mood" from combination therapy.[19] [21] Another study comparing synthetic T4 and desiccated thyroid extract showed marked improvements in virtually all symptom categories when certain patients were switched from synthetic T4 to desiccated thyroid extract.[20]

However, other studies have shown no improvement in mood or mental abilities for those on combination therapy, and possibly impaired well-being from subclinical hyperthyroidism.[22] Also, a 2007 metaanalysis of the nine controlled studies so far published found no significant difference in the effect on psychiatric symptoms.[23]

There is also concern among some practitioners about the use of T3 due to its short half life. T3 when used on its own as a treatment results in wide fluctuations across the course of a day in the thyroid hormone levels, and with combined T3/T4 therapy there continues to be wide variation throughout each day.[24]

Subclinical hypothyroidism

Subclinical hypothyroidism occurs when thyrotropin (TSH) levels are elevated but thyroxine (T4) and triiodothyronine (T3) levels are normal.[1] Prevalence estimates range 3–8%, increasing with age; incidence is more common in women than in men.[25] In primary hypothyroidism, TSH levels are high and T4 and T3 levels are low. Endocrinologists are puzzled because TSH usually increases when T4 and T3 levels drop. TSH prompts the thyroid gland to make more hormone. Endocrinologists are unsure how subclinical hypothyroidism affects cellular metabolic rates (and ultimately the body's organs) because the levels of the active hormones are adequate. Some have proposed treating subclinical hypothyroidism with levothyroxine, the typical treatment for overt hypothyroidism, but the benefits and the risks are unclear. Reference ranges have been debated as well. The American Association of Clinical Endocrinologists (ACEE) considers 0.45–4.5 mIU/L, with the ranges down to 0.1 and up to 10 mIU/L requiring monitoring but not necessarily treatment.[26] There is always the risk of overtreatment and hyperthyroidism. Some studies have suggested that subclinical hypothyroidism does not need to be treated. A meta-analysis by the Cochrane Collaboration found no benefit of thyroid hormone replacement except "some parameters of lipid profiles and left ventricular function."[27] A more recent metanalysis looking into whether subclinical hypothyroidism may increase the risk of cardiovascular disease, as has been previously suggested,[28] found a possible modest increase and suggested further studies be undertaken with coronary heart disease as an end point "before current recommendations are updated."[29]

Hypothyroidism
Norovirus Marfan syndrome Nasal Cancer Marburg Hemorrhagic Fever Malignant Hyperthermia Male Breast Cancer Lyme disease Lung cancer Legionellosis Latex Allergy Lassa Fever Jaundice / Kernicterus Hypothyroidism Kawasaki disease Genetic-Brain-Disorders Gallbladder-Diseases Fetal alcohol syndrome Diabetes Crimean-Congo Hemorrhagic Fever Dengue-and-Dengue-Hemorrhagic-Fever Chikungunya-Fever Cat Scratch Disease Cancer Larynx Cancer Among Children Borderline Personality Disorder Bladder cancer Baylisascaris Infection Benign tumor Skin Cancer African trypanosomiasis Coming Soon	Hypothyroidism Hypothyroidism is the disease state in humans and in animals caused by insufficient production of thyroid hormone by the thyroid gland. Cretinism is a form of hypothyroidism found in infants. Causes About three percent of the general population is hypothyroidic.[1] Factors such as iodine deficiency or exposure to Iodine-131 (I-131) can increase that risk. There are a number of causes for hypothyroidism. Historically, and still in many developing countries, iodine deficiency is the most common cause of hypothyroidism worldwide. In iodine-replete individuals, hypothyroidism is mostly caused by Hashimoto's thyroiditis, or by a lack of the thyroid gland or a deficiency of hormones from either the hypothalamus or the pituitary. Hypothyroidism can result from postpartum thyroiditis, a condition that 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 or a woman develops hypothyroidism. Of those women who experience hypothyroidism associated with postpartum thyroiditis, one in five will develop permanent hypothyroidism requiring life-long treatment. Hypothyroidism can also result from sporadic inheritance, sometimes autosomal recessive. Hypothyroidism is also a relatively common sex disease in domestic dogs, with some specific breeds having a definite predisposition.[2] Temporary hypothyroidism can be due to the Wolff-Chaikoff effect. A very high intake of iodine can be used to temporarily treat hyperthyroidism, especially in an emergency situation. Although iodine is substrate for thyroid hormones, high levels prompt the thyroid gland to take in less of the iodine that is eaten, reducing hormone production. Hypothyroidism is often classified by the organ of origin:[3][4] General psychological associations Hypothyroidism can be caused by lithium-based mood stabilizers, usually used to treat bipolar disorder (previously known as manic depression). In addition, patients with hypothyroidism and psychiatric symptoms may be diagnosed with:[6] Atypical depression (which may present as dysthymia) Bipolar spectrum syndrome (including bipolar I or bipolar II disorder, cyclothymia, or premenstrual syndrome) Inattentive ADHD or sluggish cognitive tempo Hypothyroidism Symptoms In adults, hypothyroidism is associated with the following symptoms:[5][7][8] Early symptoms Poor muscle tone (muscle hypotonia) Fatigue Cold intolerance, increased sensitivity to cold Depression Muscle cramps and joint pain Carpal Tunnel Syndrome Goiter Thin, brittle fingernails Thin, brittle hair Paleness Decreased sweating Dry, itchy skin Weight gain and water retention[9][10][11] Bradycardia (low heart rate – less than sixty beats per minute) Constipation Late symptoms Slow speech and a hoarse, breaking voice – deepening of the voice can also be noticed Dry puffy skin, especially on the face Thinning of the outer third of the eyebrows (sign of Hertoghe) Abnormal menstrual cycles Low basal body temperature Less common symptoms Impaired memory[12] Impaired cognitive function (brain fog) and inattentiveness A slow heart rate with ECG changes including low voltage signals. Diminished cardiac output and decreased contractility. Reactive (or post-prandial) hypoglycemia[13] Sluggish reflexes Hair loss Anemia caused by impaired haemoglobin synthesis (decreased EPO levels), impaired intestinal iron and folate absorption or B12 deficiency[14] from pernicious anemia Difficulty swallowing Shortness of breath with a shallow and slow respiratory pattern. Increased need for sleep Irritability and mood instability Yellowing of the skin due to impaired conversion of beta-carotene[15] to vitamin A Impaired renal function with decreased GFR. Elevated serum cholesterol Acute psychosis (myxedema madness) is a rare presentation of hypothyroidism Decreased libido[16] due to impairment of testicular testosterone synthesis. Decreased sense of taste and smell (anosmia) Puffy face, hands and feet (late, less common symptoms) Gynecomastia Hypothyroidism Diagnostic testing To diagnose primary hypothyroidism, many doctors simply measure the amount of thyroid-stimulating hormone (TSH) being produced by the pituitary gland. High levels of TSH indicate that the thyroid is not producing sufficient levels of thyroid hormone (mainly as thyroxine (T4) and smaller amounts of triiodothyronine (T3)). However, measuring just TSH fails to diagnose secondary and tertiary hypothyroidism, thus leading to the following suggested blood testing if the TSH is normal and hypothyroidism is still suspected: Free triiodothyronine (fT3) Free levothyroxine (fT4) Total T3 Total T4 Additionally, the following measurements may be needed: 24 hour urine free T3[17] Antithyroid antibodies — for evidence of autoimmune diseases that may be damaging the thyroid gland Serum cholesterol — which may be elevated in hypothyroidism Prolactin — as a widely available test of pituitary function Testing for anemia, including ferritin Basal body temperature Hypothyroidism Treatment Hypothyroidism is treated with the levorotatory forms of thyroxine (L-T4) and triiodothyronine (L-T3). Both synthetic and animal-derived thyroid tablets are available and can be prescribed for patients in need of additional thyroid hormone. Thyroid hormone is taken daily, and doctors can monitor blood levels to help assure proper dosing. There are several different treatment protocols in thyroid replacement therapy: T4 Only This treatment involves supplementation of levothyroxine alone, in a synthetic form. It is currently the standard treatment in mainstream medicine.[18] T4 and T3 in Combination This treatment protocol involves administering both synthetic L-T4 and L-T3 simultaneously in combination.[19] Desiccated Thyroid Extract Desiccated thyroid extract is an animal based thyroid extract, most commonly from a porcine source. It is also a combination therapy, containing natural forms of L-T4 and L-T3.[20] Treatment controversy The current standard treatment in thyroid therapy is levothyroxine only, and the American Association of Clinical Endocrinologists (AACE) states that desiccated thyroid hormone, combinations of thyroid hormone, or triiodothyronine should not generally be used for replacement therapy.[18] Nevertheless, there exists some controversy about whether this treatment protocol is optimal, and recent studies have given conflicting results. Two recent studies comparing synthetic T4 versus synthetic T4 + T3 have shown "clear improvements in both cognition and mood" from combination therapy.[19] [21] Another study comparing synthetic T4 and desiccated thyroid extract showed marked improvements in virtually all symptom categories when certain patients were switched from synthetic T4 to desiccated thyroid extract.[20] However, other studies have shown no improvement in mood or mental abilities for those on combination therapy, and possibly impaired well-being from subclinical hyperthyroidism.[22] Also, a 2007 metaanalysis of the nine controlled studies so far published found no significant difference in the effect on psychiatric symptoms.[23] There is also concern among some practitioners about the use of T3 due to its short half life. T3 when used on its own as a treatment results in wide fluctuations across the course of a day in the thyroid hormone levels, and with combined T3/T4 therapy there continues to be wide variation throughout each day.[24] Subclinical hypothyroidism Subclinical hypothyroidism occurs when thyrotropin (TSH) levels are elevated but thyroxine (T4) and triiodothyronine (T3) levels are normal.[1] Prevalence estimates range 3–8%, increasing with age; incidence is more common in women than in men.[25] In primary hypothyroidism, TSH levels are high and T4 and T3 levels are low. Endocrinologists are puzzled because TSH usually increases when T4 and T3 levels drop. TSH prompts the thyroid gland to make more hormone. Endocrinologists are unsure how subclinical hypothyroidism affects cellular metabolic rates (and ultimately the body's organs) because the levels of the active hormones are adequate. Some have proposed treating subclinical hypothyroidism with levothyroxine, the typical treatment for overt hypothyroidism, but the benefits and the risks are unclear. Reference ranges have been debated as well. The American Association of Clinical Endocrinologists (ACEE) considers 0.45–4.5 mIU/L, with the ranges down to 0.1 and up to 10 mIU/L requiring monitoring but not necessarily treatment.[26] There is always the risk of overtreatment and hyperthyroidism. Some studies have suggested that subclinical hypothyroidism does not need to be treated. A meta-analysis by the Cochrane Collaboration found no benefit of thyroid hormone replacement except "some parameters of lipid profiles and left ventricular function."[27] A more recent metanalysis looking into whether subclinical hypothyroidism may increase the risk of cardiovascular disease, as has been previously suggested,[28] found a possible modest increase and suggested further studies be undertaken with coronary heart disease as an end point "before current recommendations are updated."[29]
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