Thyroid Function in Normal, Hypothyroid, and Hyperthyroid States
The thyroid is the “gas pedal” of the body. Thyroid hormone governs the rate at which the metabolic processes of the body work. Thyroid hormone influences heart rate, body temperature, mental alertness and total body salt and water content. It also governs more subtle functions, as taste, bowel habits, and neurological reflex time.
Inadequate thyroid hormone levels (hypothyroidism) may cause increased body weight, primarily due to an accumulation of excess body fluid and salt. They also cause sleepiness and fatigue, a decreased taste for food, constipation, and slow heart rate. Muscle movement may be slowed, and there is a tendency for muscle cramps to occur.
Excess thyroid hormone levels (hyperthyroidism) may cause nervousness, sleeplessness, palpitations, reduced stamina, weight loss, and diarrhea. Because excess levels of thyroid hormone may raise blood levels of calcium too much in 10% of patients, their effect on appetite is variable. Many patients have increased appetite; some, including those with high serum calcium levels, have a decreased appetite. Patients usually lose weight. The caloric requirements per day may be extremely high. However, a minority of people do not lose much weight, because their daily caloric intake is also extremely high. In general, people with minimal weight loss or weight gain before treatment are at risk for substantial weight gain as treatment takes effect. This is because treatment normalizes how fast calories are burned (caloric utilization). The excess caloric intake before treatment is not balanced by excess caloric utilization with treatment. Thus, we try to alert our patients to the risks of weight gain when we start treatment, especially if they have not noticed major weight loss, before treatment is utilized.
How the Thyroid Works
The amount of thyroid tissue and the amounts of thyroid hormone that tissue makes are regulated by the brain and the pituitary gland. The area of brain just over the pituitary gland is called the hypothalamus. This area makes a hormone called TRH or thyrotropin releasing hormone. TRH stimulates the pituitary to make another hormone called TSH or thyroid stimulating hormone. TSH in turn stimulates the thyroid to grow and to make thyroid hormones. The secretion of TRH and TSH is elegantly regulated by the brain, and is based in large part on the blood levels of thyroid hormone. The more thyroid hormone the brain detects in the blood, the less TRH and TSH are secreted. The less thyroid hormone in the blood, the more TRH and TSH are released.
Doctors use this physiology of thyroid secretion to assess how much thyroid hormone is in the blood. Today, we measure TSH levels in the blood as the marker for how much thyroid hormone is in the blood. Given how TSH works, it is understandable that TSH levels move opposite to the levels of thyroid hormone in the blood. Persons with excess blood levels or thyroid hormone will have abnormally low TSH levels, as the brain and pituitary gland seeks to turn off thyroid hormone secretion. In contrast, persons with low levels of thyroid hormone in the blood will have high levels of TSH as the system seeks to stimulate the thyroid gland to make more thyroid hormone. Studies over the last two decades have clearly shown that TSH, which is not a thyroid hormone, is a better marker of blood levels of thyroid hormones and thyroid physiology than thyroid hormone levels themselves are.
The thyroid secretes two primary thyroid hormones: thyroxine or T4 and triodothyronine or T3. T3 is the active thyroid hormone. Under normal circumstances, the liver activates T4 to T3 as demand arises. Therefore, almost 99.9% of thyroid hormone in the blood is T4 and only 0.1% is T3, although the thyroid gland contains 10 to 100 times more T3 than it secretes.
It is very common for the thyroid to enlarge. Any enlargement of the thyroid is called a “goiter”. The term does not imply anything else but some enlargement. Goiters may be merely proportionate enlargements or imbalanced or asymmetrical enlargements. Goiters may be smooth or have nodules or bumps in them.
Approximately half of all patients with goiters have normal blood levels of thyroid: half do not. The presence of a goiter, by itself, does not mean that the level of thyroid hormones in the blood are always abnormal. Goiters can be associated with slight discomfort or pain locally, in the thyroid, generalized symptoms, such as fatigue, weight gain, or nervousness, are not attributable to the goiter, unless the blood levels of thyroid hormones are abnormal. Therefore, the clinical questions that arise in a patient with a goiter always involve consideration of whether thyroid hormone levels are normal, and the characteristics of the goiter itself.
Generalized enlargement of the thyroid can occur if there is an enzyme defect within the gland, involving the synthesis of thyroid hormone. When that happens, the pituitary gland increases TSH secretion to stimulate the thyroid to make more hormone. However, TSH also makes the gland enlarge. A condition known as Grave” Disease is also associated with a generalized enlargement of the thyroid. Here, the body is making an antibody against the thyroid, which acts on the thyroid much as TSH acts. Thus, the thyroid enlarges again.
Rarely, a symmetrical goiter may reflect the occurrence of cancer within the thyroid gland. A few, unusual thyroid cancers may present in this way. Such cancers may sometimes be associated with unusual symptoms, as flushing, nausea, or palpitations.
Multinodular goiters, or goiters with multiple lumps in them, are very common thyroid problems. These usually reflect some form of chronic inflammation in the thyroid gland. Thyroid inflammation is usually painless; however, patients occasionally complain of occasional low-grade tenderness in these glands. Commonly, patients will see that they feel as if someone is holding a fist to the area of the thyroid. A rare form of thyroid inflammation is a condition known as subacute thyroiditis, which is an acute viral infection of the thyroid gland. In contrast to most thyroid conditions, this thyroid disorder is very painful for a week or so. Acute bacterial infection of the thyroid gland is also very painful. It is associated with typical symptoms of serious bacterial infection.
As in patients with generalized goiters, thyroid hormone levels are normal in half of all patients with multinodular goiters. However, these patients are more likely to have the occurrence of low thyroid hormone levels (hypothyroidism) and are less likely to have high thyroid hormone levels (hyperthyroidism) than patients with generalized goiters. Also, patients with multinodular goiters are more likely to have thyroid cancer in them than patients with generalized goiters. This is especially true if one of the nodules is very prominent.
Most cases of thyroid cancer involve highly curable lesions, as long as the problem is not neglected. Part of the reason for the high success rate in treatment is that the thyroid is the only gland in the body that concentrates iodine. Therefore, ablation of the primary cancer, and even areas of spread (metastases), is usually possible because these sites will uptake radioactive iodine, without damage to nonthyroidal tissues.
Suspicion that a thyroid gland may have cancer in it often focuses on glands with nodules. Glands with solitary nodules have a greater risk than glands with multiple nodules. Other characteristics that suggest increased risk are growth of a nodule, whether a nodule in single or multiple glands, or the existence of a very large or prominent nodule in a gland with many nodules.
The usual approach to such nodules involves a fine needle aspiration of the suspicious nodule. If any question exists regarding how these cells appear in the nodule, surgical removal is recommended. If the lesion is felt to have malignant potential at surgery, the surgeon usually attempts to remove as much of the thyroid gland as possible. This assists in ongoing evaluation of whether the cancer has been totally cured, and reduces the complexity of further treatment.
Fine needle aspiration of the thyroid is a relatively painless procedure with limited risk. It involves preparing the skin with betadine antiseptic and inserting a small needle through the skin into the suspicious nodule. Material from the nodule is then allowed to “seep” into the needle, and is taken from the nodule. Usually, no anesthetic is given, because the procedure is so benign, and the administration of local anesthetic may make the nodule more difficult to precisely ample.