Unraveling thyroid disorders can be confusing because of the negative feedback loop and the numerous thyroid dysfunctions. The problem is compounded by the diverse presentation of thyroid disorders in educational materials. Thyroid abnormalities can be presented according to their causes such as hypothyroidism, hyperthyroidism, thyroiditis, nodules, goiters, cancers and causes of abnormal laboratory values. Since physicians are often confronted with abnormal laboratory values, this article will highlight the diagnostic approach to a low TSH.
A quick review of the negative feedback loop reminds us that TRH is released from the hypothalamus which in turn causes the release of TSH from the anterior pituitary. TSH then binds to the TSH receptor on the thyroid gland causing secretion of T4 and to a lesser degree, T3. T4 is converted to the active form, T3, in the periphery and also acts to suppress the release of TRH and TSH thus decreasing the secretion of more T4. Minor elevations in T4 can maximally suppress the release of TSH. A low TSH is either due to the pituitary’s inability to produce TSH or from excess T4 or T3 suppressing production.
Excessive levels of thyroid hormone is due to all forms of hyperthyroidism, thyroid replacement medications and, rarely, exogenous thyroid hormone producing tumors, known as Struma ovarii. The most common causes of hyperthyroidism include Grave’s Disease, Toxic Multinodular Goiter, Toxic Adenoma, and Subacute Thyroiditis, also known as DeQuervain’s Thyroiditis. In these cases, the TSH would be undetectable and the T4 or T3 levels elevated.
Although uncommon, one must consider the inability of the pituitary to produce TSH as a cause of low TSH. An undetectable TSH along with low levels of T4 and T3 readily identifies this condition. Causes include pituitary tumors, infiltrative diseases such as sarcoidosis, brain injury, rapid blood loss known as Sheehan’s syndrome and infections.
The clinician should use the TSH as the screening test for symptoms of thyroid dysfunction. TSH suppression or elevation is ultrasensitive to even minor changes in circulating T4 or T3. A normal TSH level indicates an intact hypothalamic-pituitary-thyroid axis. A normal TSH does not exclude the possibility of nodules, goiters and tumors. If the clinician obtains an abnormally low TSH, the next step is to obtain a free T4 and free T3. This will allow the clinician to distinguish between a thyroid and a pituitary disorder.
Radioactive Iodine Uptake, RAIU, testing will show excess uptake of iodine in the autonomously hyperfunctioning thyroid gland as in Grave’s disease, toxic multinodular goiter or toxic adenoma. In contrast, the RAIU will show little to no uptake in the hypofunctioning thyroid gland as in DeQuervain’s thyroiditis, thyroid replacement hormone usage or Struma ovarii. Pain in the anterior neck, tenderness to palpation of the thyroid, a low TSH and high free T4 is often all that is needed to diagnose DeQuervain’s thyroiditis. Additionally, in thyroiditis the serum thyroglobulin will be high (see table 1). In contrast, patients taking excessive thyroid hormone will have a low TSH, high free T4, low RAIU and a low serum thyroglobulin.
It is unlikely that the clinician will be able to read one article and have a comprehensive understanding of the pathophysiology and clinical approach to the management of thyroid disorders. Even the most advanced clinician may need to periodically review topics in thyroid disease and consult texts, articles and specialists if the patient’s presentation is not straight forward. This module, along with Part II, will present a variety of patient cases designed to illustrate common symptom presentations and management strategies.