By: Lewis Blevins Jr., MD,
Medical Director, California Center for Pituitary Disorders at UCSF
Central hypothyroidism is a condition where the thyroid gland does not function very well because of lack of stimulation by the pituitary gland. A wide range of disorders affecting the pituitary gland and/or hypothalamus may result in insufficient thyroid stimulating hormone (TSH) production leading to diminished thyroid hormone production.
Symptoms may include weakness, fatigue, decreased energy, weight gain, increased need for sleep, and cold intolerance.
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 in patients with pituitary disease has not been processed well and the molecules not as biologically active as TSH in normal individuals. Second, TSH is secreted in pulses, with most of them occurring at night while we are sleeping, 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 replacement in hypopituitary patients.
Successful treatment involves the administration of thyroxine in the form of l-T4 in a majority of patients. Some patients also require T3 replacement.
One of the more common errors in management by primary physicians that I see in my practice is the erroneous discontinuation or lowering of the thyroid hormone dosage because the TSH level is found to be low. In patients who have primary hypothyroidism, it is usual and customary to lower the l-T4 dosage if the TSH is low. In patients with pituitary disorders, however, it is essential to recognize that that altered secretion of TSH caused the problem in the first place. Thus, TSH levels cannot be used to assess responses to treatment. I usually aim to maintain the free T4 level in the middle or slightly into the upper part of the normal range, and to resolve the symptoms of hypothyroidism, while ensuring that patients do not develop symptoms of hyperthyroidism.