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Hyperthyroidism (Grave's Disease) Print E-mail
by Ron Kennedy, M.D., Santa Rosa, CA

Dr. Kennedy Review of Thyroid Biochemistry

Thyroid Stimulating Hormone (TSH) is secreted by the pituitary gland in response to falling levels of T3 and T4. TSH activates the thyroid gland to release T3 an T4 which is stored as thyroglobulin (i.e. bound to protein). Thyroglobulin is enzymatically converted to T3, T4, and globulin and T3 and T4 are released. T4 is converted in the liver to T3 and reverse T3 (RT3). About 80% of T3 comes from T4 conversion and the other 20% comes directly from the thyroid gland. T3 is by far the most active of the thyroid hormones. Reverse T3 blocks the action of T3 and T4 by occupying cell receptor sites. Overproduction of RT3 results in Wilson's syndrome.

Clinical Manifestations of Hyperthyroidism

When excess T3 is present the condition is called hyperthyroidism. This speeds up metabolism and increases oxygen consumption. The body wants more fuel and therefore appetite is increased and overeating is usually present. Despite this, weight loss usually ensues. The heart grows larger due to increased protein synthesis and manifestations sometimes include widened pulse pressure, tachycardia, atrial fibrillation, and enhanced cardiac contractility. There can also be bone loss in postmenopausal women and hyperlipidemia (increased levels of fat in the blood) in anyone with hyperthyroidism.

Physical Exam Findings

On physical exam one may find rapid heart beat, tremor, increased systolic blood pressure, sagging eyelid, wide-eyed staring, palpitations of the heart, depression and anxiety.

Lab Findings

Serum TSH will be low in hyperthyroidism except for rare TSH-induced hyperthyroidism. Serum T4 and T3 will be elevated. T3 rises earlier and more markedly in hyperthyroidism.

In the pregnant woman free T3 and T4 must be measured because pregnancy induces increased thyroid binding by globulin and this is considered normal in pregnancy. However, free T3 and T4 will be normal in the absence of hyperthyroidism and elevated in its presence.

Radio-iodine Uptake Scan is a measure of the rate of uptake of radioactive iodine by the thyroid gland. It is high in most cases of hyperthyroidism and low in cases where the thyroid is not actively synthesizing hormone, e.g. inflammatory thyroiditis, and in people who are taking thyroid hormone. The pattern of uptake is diffuse in Graves disease and focal and multi-focal in nodular goiter.

Differential Diagnosis of Hyperthyroidism

Hyperthyroidism is defined as the production of excessive amounts of thyroid hormone by a hyperfunctional thyroid gland. The incidence of 2% in women, 0.2% in men, thus favoring women 10:1. The autoimmune version of hyperthyroidism (Grave's disease) accounts for 60-90% of cases of hyperthyroidism in different regions of the world. Graves disease is also referred to as Toxic Diffuse Goiter because the entire gland is uniformly overactive, unlike #1 below.

Less common types of hyperthyroidism include:

  1. Toxic Nodular Goitre (TNG)
  2. One or more lumps in the thyroid gland become overactive
  3. Thyroid Gland Inflammation (thyroiditis)
  4. Radiation injury to the gland
  5. Thyroid carcinoma
  6. Intake of unneeded thyroid hormone.
  7. Pituitary Adenoma (TSH-induced hyperthyroidism)


The information in this article is not meant to be medical advice.�Treatment for a medical condition should come at the recommendation of your personal physician.

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