Tests of Pituitary Function: Thyroid

From Dr. Lewis Blevins.  Thyroid stimulating hormone (TSH) is produced by the pituitary gland and leads to the secretion of T4 and T3 by the thyroid gland. Most circulating T3 is driveed from the peripheral conversion of T4 to T3 in the liver and the kidneys. TSH secretion is regulated by the hypothalamus and measurement of circulating T3 levels. TRH from the hypothalamus stimulates TSH secretion by the pituitary gland whereas somatostatin inhibits TSH.

The principal tests of the adequacy of pituitary TSH secretion are measurement of the serum TSH, free T4, and either the total or free T3 level.

Generally, the free T4 level is low or in the low normal range in patient’s with hypopituitarism. The same is true for T3 levels. T3 levels may be even lower if there is a genetic disorder or drug that impairs the conversion of T4 to T3.

TSH levels are unreliable in the diagnosis of pituitary failure leading to hypothyroidism. Most TSH levels are actually normal whereas 15-20 % are low and 5-10% are slightly elevated. I am often asked why TSH levels are normal and yet the thyroid fails in patients with pituitary disorders. There are 3 potential explanations. First, we know that TSH levels in patients with pituitary disease haven’t been processed well and are not as biologically active as TSH in normal individuals. Second, TSH is secreted in pulses, with most of them occurring at night while we’re sleep, and this pulsatility is important for thyroid function. The pulsatility is disrupted in patients with pituitary failure. Lastly, the TSH assay simply measures the level of TSH in the blood stream during the 5 seconds it takes for the tube to fill with blood. It tells us nothing about the 24-hour secretion of TSH. It is believed that those with pituitary deficiency, even though they may secrete TSH that is measurable as “normal,” secrete far less TSH in a day than normal individuals. Thus, the thyroid is not properly stimulated and T4 levels fall leading to hypothyroidism. As a result, TSH levels are not as useful in evaluating for possible pituitary deficiency nor are they useful in the evaluation of the adequacy of the dose of thyroid hormone.

Thus, a diagnosis of pituitary hypothyroidism rest on the assessment of the T4 and T3 levels taking into consideration the clinical symptoms and signs of the affected patients.

TSH secreting pituitary adenomas usually present with hyperthyroidism as evidenced by elevations in T4 and T3 along with inappropriately normal or elevated TSH levels. TSH levels are usually quite low in patients with hyperthyroidism due to thyroid disease such as Graves’ disease or toxic multinodular goiter. Thus, a normal or elevated TSH in the setting of high T4 and T3 levels is considered inappropriate and suggests either a TSH producing pituitary adenoma or central resistance to thyroid hormone.

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