Hypothyroidism
Specialty	Endocrinology

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

Signs and symptoms

In adults, hypothyroidism is associated with the following symptoms:^[1][2][3]

Early

• Poor muscle tone (muscle hypotonia)
• Fatigue
• Cold intolerance, increased sensitivity to cold
• Depression
• Muscle cramps and joint pain
• Carpal Tunnel Syndrome
• Goitre
• Thin, brittle fingernails
• Thin, brittle hair
• Paleness
• Osteoporosis
• Decreased sweating
• Dry, itchy skin
• Weight gain and water retention^[4][5][6]
• Bradycardia (low heart rate – fewer than sixty beats per minute)
• Constipation

Late

• Slow speech and a hoarse, breaking voice – deepening of the voice can also be noticed, caused by reinke's edema.
• 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

Uncommon

• Impaired memory^[7]
• Impaired cognitive function (brain fog) and inattentiveness.^[8]
• A slow heart rate with ECG changes including low voltage signals. Diminished cardiac output and decreased contractility.
• Reactive (or post-prandial) hypoglycemia^[9]
• Sluggish reflexes
• Hair loss
• Anemia caused by impaired haemoglobin synthesis (decreased EPO levels), impaired intestinal iron and folate absorption or B₁₂ deficiency^[10] 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^[11] to vitamin A
• Impaired renal function with decreased glomerular filtration rate
• Elevated serum cholesterol
• Acute psychosis (myxedema madness) (a rare presentation of hypothyroidism)
• Decreased libido^[12] due to impairment of testicular testosterone synthesis
• Decreased sense of taste and smell (anosmia)
• Puffy face, hands and feet (late, less common symptoms)
• Gynecomastia

Causes

About three percent of the general population is hypothyroidic.^[13] Factors such as iodine deficiency or exposure to Iodine-131 (I-131) can increase that risk. There are a number of causes for hypothyroidism. Iodine deficiency is the most common cause of hypothyroidism worldwide.^{[citation needed]} In iodine-replete individuals hypothyroidism is generally caused by Hashimoto's thyroiditis, or otherwise as a result of either an absent thyroid gland or a deficiency in stimulating hormones from the hypothalamus or pituitary.

Hypothyroidism can result from postpartum thyroiditis, a condition that affects about 5% of all women within a year of giving birth.^{[citation needed]} The first phase is typically hyperthyroidism; the thyroid then 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.^{[citation needed]}

Hypothyroidism is also a relatively common disease in domestic dogs, with some specific breeds having a definite predisposition.^[14]

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^{[clarification needed]}:^[15][16]

General psychological associations

Hypothyroidism can be caused by lithium-based mood stabilizers, usually used to treat bipolar disorder (previously known as manic depression).^{[citation needed]}

In addition, patients with hypothyroidism and psychiatric symptoms may be diagnosed with:^[17]

• 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

Diagnosis

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^[18]
• 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

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.^[19]

T₄ and T₃ in Combination

This treatment protocol involves administering both synthetic L-T₄ and L-T₃ simultaneously in combination.^[20]

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.^[21]

Treatment controversy

A 2000 paper suggested "clear improvements in both cognition and mood" from combination therapy,^{[20] [22]} and another in 2001 concluded that combined treatment seemed to be more effective than treatment with T4 alone on eight main symptoms of hypothyroidism.^[21]

However, more recent studies have shown no improvement in mood or mental abilities for those on combination therapy, and possibly impaired well-being from subclinical hyperthyroidism.^[23] Another 2006 study which looked at the correlation between free T3 and free T4 levels and psychological well being in a randomized controlled trial of combined treatment found a strong correlation for free T4, but none for T3.^[24]. A 2007 metaanalysis of the nine controlled studies so far published found no significant difference in the effect on psychiatric symptoms.^[25].

In addition, a metaanlysis of 11 randomized controlled trials which looked at a wider range of symptoms including: bodily pain, anxiety, fatigue, body weight and a range of other factors, found no difference between the combined treatment and therapy with T4 alone.^[26]

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.^[27]

Subclinical hypothyroidism

Subclinical hypothyroidism occurs when thyrotropin (TSH) levels are elevated but thyroxine (T₄) and triiodothyronine (T₃) levels are normal.^[13] Prevalence estimates range 3–8%, increasing with age; incidence is more common in women than in men.^[28] 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.^[29] 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."^[30] A more recent metanalysis looking into whether subclinical hypothyroidism may increase the risk of cardiovascular disease, as has been previously suggested,^[31] found a possible modest increase and suggested further studies be undertaken with coronary heart disease as an end point "before current recommendations are updated."^[32]

Alternative treatments

Alternative practitioners may combine conventional serum tests with less conventional tests to assess thyroid hormone function, or simply look at symptoms. Many have found that compounded slow release T3 used in combination with T4 may help to mitigate many of the symptoms of functional hypothyroidism and improve quality of life, although this is still controversial and is rejected by the conventional medical establishment.^[33]