TRH Stimulation When Basal TSH is Within the Normal Range: Is There "Sub-Biochemical" Hypothyroidism?

Abstract

The standard thyrotropin releasing hormone (TRH) test (200 μg) with synthetic TRH is no longer used commonly for the detection of primary hypothyroidism or hyperthyroidism. The reason has been that this test has been replaced by the development of more sensitive thyroid-stimulating hormone (TSH) assays, and hence suppression or elevation of TSH has been regarded as a sufficient criterion for the diagnosis of thyroid dysfunction in conjunction with measurements of free thyroid hormones. 1In the late 1990s it was recognized that depressed subjects with a normal serum TSH could have an exaggerated response to TRH stimulation. For the first time it was suggested that this could be evidence of a very mild degree of subclinical hypothyroidism that could not be diagnosed reliably with screening TSH alone. 2 In 1999, it was again suggested that hypothyroidism is an ongoing disease state starting with only a positive TRH test followed by TSH elevations and progressing to overt hypothyroidism and thyroid hormone failure. Indeed, these authors coined the term sub-biochemical hypothyroidism to denote this earliest phase of primary hypothyroidism in which serum free T4 and TSH levels are still within the reference range but the TRH response is exaggerated similar to established primary hypothyroidism. 3 Finally, in 2005, these observations were extended to pediatric subjects. 4 Again the authors concluded that if there is a goiter and serum TSH is in the upper half of the normal range, a TRH test is necessary to exclude hypothyroidism since basal TSH might not be enough to diagnose this earliest phase of subclinical hypothyroidism. We thus decided to look into a similar group of subjects with normal baseline TSH to see if these findings were reproducible in our population of patients.We retrieved records of TRH testing from our radioimmunoassay lab computer database that was performed between 2001 and 2005. Patients were referred to our dynamic testing facility for a TRH test if there was a strong suspicion of hypothyroidism, despite a normal basal TSH (either low [suggestive of central hypothyroidism] or low-normal free T4 [FT4] with suggestive clinical features). The patients were then followed in the endocrinology clinic, and those patients with an exaggerated response to TRH were considered, based on the individual merits of the case, for therapy along the lines of primary hypothyroidism. We did not evaluate response to therapy, but no patient started

Role of thyrotropin‐releasing hormone test in re‐evaluation of congenital hypothyroidism

“…Those with eutopic thyroid glands may only have transient neonatal hyperthyrotropinemia and are re‐evaluated at 3 years of age to decide whether hypothyroidism persists [3]. It has been suggested that hypothyroidism is an ongoing disease state starting with a positive thyrotropin‐releasing hormone (TRH) test, followed by TSH elevation, and subsequently to overt hypothyroidism and thyroid hormone failure [4–6]. Re‐evaluation mainly involves the levels of TSH, triiodothyronine (T3), thyroxine (T4), and free thyroxine (fT4), and the TRH test is also included in the re‐evaluation of CH [1].…”