Exaggerated TSH Responses to TRH in Depressed
Patients With "Normal" Baseline TSH

Robert P. Kraus, F.R.C.P.(C), Elizabeth Phoenix, B.Sc.N.,
Merrill W. Edmonds, F.A.C.P., Ian R. Nicholson, C.Psych.,
Praful C. Chandarana, F.R.C.P.(C), and Sonya Tokmakejian, Ph.D., F.C.A.C.B.

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: Twentythree (38%) of 60 patients had an exaggerated TSH response to TRH. The 38% prevalence is significantly (c²=59.65, df=1, p<.001) greater than the 6% prevalence of positive TRHST results reported in the euthyroid general population. The prevalence of positive TRHST 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 TRHST 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.

(J Clin Psychiatry 1997;58:266_270)