Exaggerated TSH Responses to TRH in Depressed Patients With “Normal” Baseline TSH

Background: Subclinical hypothyroidism (elevated thyroid-stimulating hormone [TSH] with normal thyroid hormone levels) can present with depression. This may be confirmed by an exaggerated TSH response to thyrotropin-releasing hormone (TRH) on the TRH stimulation test (TRHST). The objective of this study was to determine the prevalence of exaggerated TRHST results in a sample of depressed patients with “high-normal” screening TSH levels.

Method: Depressed patients with TSH levels of 3.00_5.50 mIU/L underwent a TRHST. After baseline TSH was drawn, TRH 400 mg was injected intravenously, and TSH samples were drawn at +20 min, +30 min, and +40 min postinjection. A rise in TSH after TRH (peak value minus baseline) of >25 mIU/L represented an exaggerated TSH response.

Results: Twenty-three (38%) of 60 patients had an exaggerated TSH response to TRH. The 38% prevalence is significantly (χ²=59.65, df=1, p<.001) greater than the 6% prevalence of positive TRH-ST results reported in the euthyroid general population. The prevalence of positive TRH-ST results was not attributable to differential patterns of psychotropic or thyroid hormone treatment. Unexpected observations were a lack of correlation in TSH levels week to week (r=.17, N.S.) and a lack of correlation between screening TSH value and subsequent TRH-ST results (r=.28, N.S.).

Conclusion: Subtle thyroid underfunction may be contributing to depression in some patients with TSH in the upper half of the range usually considered normal. If so, then the TRH-ST may be more sensitive in identifying this than measurement of TSH alone.