Hypothyroidism:
ypothyroidism is a medical condition in which the thyroid does not produce enough thyroid hormone to meet the body's needs. The thyroid gland is an endocrine organ situated in the lower front of the neck, approximately 2 inches below the "Adam's apple." It is relatively flat and is normally the size and shape of a medium-sized butterfly. Each side has upper and lower lobes, connected in the middle by an "isthmus."
When functioning normally, the thyroid gland makes thyroid hormone, which goes via the bloodstream into all the cells of the body. Thyroid hormone molecules contain iodine atoms, and when these unique molecules enter a cell, they up regulate the cell's metabolism-running the Krebs citric acid cycle faster in the mitochondria.
Regulation of thyroid hormone production involves a feedback loop. When the thyroid releases thyroid hormone into the bloodstream, it affects all the body's cells, including specialized cells in the lower brain, called the hypothalamus. If the level of thyroid hormone is low, these cells release a molecule called "Thyrotropin Releasing Factor" (TRF).
TRF travels in a special local circulation from the hypothalamus to the pituitary gland, located below the brain. Pituitary cells release "Thyroid Stimulating Hormone" (TSH) in the presence of TRF. TSH causes the formation of thyroid hormone from colloid and iodine, released as thyroxine (T4, having four iodine atoms per molecule).
If the thyroid gland does not receive enough iodine from the diet, as occurs in land-locked famine-prone areas of Africa, TSH will be continually released, causing the thyroid gland to swell into a "nutritional" goiter, because TSH causes the thyroid gland to keep making colloid, which collects in spaces around the thyroid gland cells.
When the thyroid gland is "sick" from lack of iodine or radiation or autoimmune attack, the brain perceives a lack of thyroid hormone, and sends TSH to rev up the gland. Thus, hypothyroidism is typically seen with elevated TSH levels. Rarely, damage to the hypothalamus or pituitary may cause a person to be hypothyroid with a low TSH.
At one time, nutritional goiters were common in the central US. Residing significant distances from oceans and seas made it difficult to obtain fish and kelp, rich in iodine. Rates of nutritional goiter fell in the US and other countries with the introduction of iodized salt, refrigeration, and improved packaging of foods.
To make the diagnosis of hypothyroidism, the history, physical, and laboratory tests are checked. Symptoms of hypothyroidism are related to the systemic impact of thyroxine on cellular metabolism. Deficiency of thyroxine down regulates metabolism. Hence, symptoms of hypothyroidism include weight gain, cold temperature intolerance; fatigue, sleepiness; dry, puffy, flakey skin; slow pulse; slow reflexes; depression; irregular menstrual periods, and many more.
Physical examination reveals pallor, edema, slow heart rate, elevated BMI, slow reflexes, enlarged heart, heart failure, and pretibial myxedema (edema on the shin area). Laboratory analysis will show a TSH over 4.5 microunits/mL, though in some cases 2.5 serve as the upper limit of normal.
Radiological testing will show a low 24 hour radioactive iodine uptake by the thyroid. If a goiter is present, thyroid ultrasound may show enlargement with or without a mass or cyst. A thyroid isotope scan will help define the nature of a mass-a "cold" mass means decreased uptake of iodine, often seen in a tumor or neoplasm. When multiple masses and cysts exist in an enlarged thyroid, it is called a multinodular goiter.
A diagnosis is rendered, largely based on the TSH level. A TSH > 20 microunits/mL confirms the diagnosis of hypothyroidism due to failure of the thyroid gland.1 Severity of the disease is based on the history, physical, and laboratory findings.
Treatment of hypothyroidism is straightforward-the body needs thyroxine, so levothyroxine is given in replacement. People extremely low on thyroxine are given gradually increasing doses of levothyroxine, to "catch up" their metabolism. Once leveled out, 0.075 mg (75 micrograms) to 0.125 mg (125 micrograms) of levothyroxine is given daily. TSH levels are used to monitor the thyroxine replacement, keeping the TSH at about 1.0.
There exists a very active form of thyroid hormone called T3 or triiodothyronine (It has three iodine atoms on the molecule.) It is the usual practice to give the levothyroxine (T4) only. "What about the body's need for T3?" The thyroid gland secretes thyroxine, which is converted in the liver and other tissues to T3, so thyroxine tablets-Synthroid, Levoxyl, levothyroxine, and other generics are converted in the body as needed to T3.
Generics appear to be as effective as the brand name, but drug-drug interactions can occur, especially undesired impairment of absorption of T4 from the gut by binding agents. If there are any questions regarding the bioavailability of the drug, a TSH level will quickly resolve the issue.
Sources:
1. "Hypothyroidism" The Washington Manual of Medical Therapeutics 2007; pp. 625-628.
