Hypothyroidism can be classified into different groups based on the organ responsible for the abnormality and the severity of disease, including
- "primary hypothyroidism" (hypothyroidism due to a thyroid gland abnormality) in which there is a decreased concentration of free T4 and an elevated concentration of TSH.
- "secondary hypothyroidism" (hypothyroidism due to a pituitary gland abnormality) in which there is a decreased concentration of both free T4 and TSH (the T4 is low since there is inadequate stimulation of the thyroid gland by TSH). When the TSH and free T4 are both low then a structural lesion in or around the pituitary gland should be ruled out with a radiologic test.
- "tertiary hypothyroidism" (hypothyroidism due to a hypothalamic or CNS abnormality)
- "subclinical hypothyroidism" in which there is an elevated TSH concentration but the free T4 level is normal. Many of these women become hypothyroid eventually, and many physicians use the presence of abnormally high levels of anti-thyroid antibodies to direct their treatment. If there are elevated anti-thyroid antibodies then the patient most likely will become hypothyroid, she may develop a goiter if untreated so treatment should be considered. If there is a minimal elevation in TSH and the patient is asymptomatic with normal anti-thyroid antibody levels then annual TSH levels to monitor the progression of disease could be considered.
Thyroid abnormalities are more common in women than in men. Hypothyroidism increases with aging. Up to 45% of women have evidence of thyroiditis, which is inflammation of the thyroid gland, usually secondary to an auto immune process. 15-20% (about 1 in 6) of women over 60 years of age have evidence of hypothyroidism.
Thyroid hormone is formed in the thyroid gland, which is present in the neck. Circulating iodide absorbed from the diet (by the small intestine) enters the thyroid gland (under the influence of thyroid stimulating hormone, TSH) where it is oxidized to iodine and is bound to tyrosine. Thyroxine (T4) and triiodothyronine (T3) are the two thyroid hormones that are stored in the thyroid gland within a colloid called thyroglobulin. TSH stimulates an enzyme that releases active thyroid hormone (T4 and T3) from the thyroglobulin storage compartment and enhances their secretion into the circulating blood. T4 is secreted from the thyroid gland at a rate 20 times greater than T3, but the bioactivity of T4 results predominantly from its conversion to the more active form T3 in the tissues of the body (mostly the liver and kidney). Circulating T4 and T3 are predominantly bound to proteins, with about 80% bound to TBG (thyroxine binding globulin) and about 20% bound to either thyroxine binding prealbumin and albumin. These binding proteins limit the bioactivity of the hormone, with the "free T4" and "free T3" fractions of the total T4 and total T3 reflecting the bioactive component.
Thyroid hormones secreted by the thyroid gland communicate with the hypothalamus and the pituitary gland of the brain to help maintain the circulating thyroid hormone concentration within a normal range (similar in principle to the ovarian feedback system). Circulating thyroid hormones suppress TRH secretion from the hypothalamus and decrease the pituitary sensitivity to available TRH, both of which reduce pituitary TSH secretion. The TSH secreted from the pituitary gland is very sensitive to circulating thyroid hormone levels so that a small change in free T4 in the circulation results in a large change in TSH.
Therefore, circulating free T4 and TSH concentrations are the best initial screening tests for thyroid disease. In the cost effective world of modern medicine, a single sensitive TSH concentration is initially all that is required. If the TSH is abnormal, then the free T4 should be checked.
The clinical appearance of hypothyroidism involves a spectrum of abnormalities from "unrecognized" to "overwhelming." The symptoms are often mild and go unnoticed, but may include
- menstrual irregularity or amenorrhea (due to an ovulatory dysfunction)
- cold intolerance (person always feels colder than others and cannot tolerate cold environments)
- decreased energy and exercise tolerance with easy fatiguability
- mental slowness with poor memory
- delayed reflexes
- water retention with periorbital (around the eye) edema (swelling)
Lab abnormalities associated with hypothyroidism may include
- elevated cholesterol (as well as elevated LDL-cholesterol fraction)
- hyponatriemia (decreased sodium due to water retention)
- elevated liver enzyme