The thyroid gland, a 2-inch-long, butterfly-shaped gland located just below the larynx (voice box), produces hormones responsible for one's metabolism (use of energy by the body). The pituitary gland, located at the base of brain, secretes thyroid-stimulating hormone (TSH), which makes the thyroid produce and release thyroxine, the main thyroid hormone. The pituitary is regulated by another area of the brain called the hypothalamus, which produces thyrotropin-releasing hormone (TRH). When thyroid function is too low, the pituitary increases its output of TSH to stimulate the thyroid to work harder. Subclinical (without obvious symptoms) hypothyroidism (low thyroid function) describes a situation in which thyroid function is only mildly low, so that the blood level of thyroxine remains within the normal range, but the blood level of TSH is elevated, indicating mild thyroid failure. Overt hypothyroidism, where the levels of thyroxine are actually below normal, is a more severe problem and may cause fatigue, weight gain, cold intolerance, dry skin, and an increased risk of heart problems. The September 22/29, 2010, issue of JAMA includes an article reporting that subclinical hypothyroidism is associated with an increased risk of coronary heart disease, especially if the levels of TSH are very high (10 mU/L or more).