Objective: To evaluate the diagnostic value of the thyrotropin-releasing hormone (TRH) stimulation test in the diagnosis of central hypothyroidism in patients with Sheehan's syndrome. Design: TRH stimulation test was performed in 72 patients with Sheehan's syndrome. Basal free triiodothyronine (fT(3)) and free thyroxine (fT(4)) levels were measured. Serum thyrotropin (TSH) concentration was determined before and 30, 60, 90, and 120 minutes after 200 mu g TRH IV bolus injection. The peak TSH values < 5.5 mu IU/ml were defined as inadequate response. A peak TSH at 60 minutes or later was considered as delayed response. If TSH (60 minutes after peak), was more than 40% of the peak value it was considered as prolonged response. The diagnosis of central hypothyroidism (CH) was made if either serum fT(4) concentration was subnormal with an inappropriately low serum TSH concentration or inadequate response to TRH stimulation test and/or a delayed or prolonged response to TRH stimulation test. Main outcome: Fifty-six (77.7%) of the patients had low serum fT(4) and fT(3) levels with an inappropriately low serum TSH levels were defined as CH (CH0 group). Ten (13.8%) patients with normal and low-normal fT(4) levels had no response and/or delayed or prolonged response to TRH stimulation test (CH1group). Six (8.3%) patients had fT(3), fT(4), and TSH levels within normal limits and peak TSH responses >= 5.5 mu IU/ml consistent with euthyroidism (euthyroid group). Thus, 66 (91.6%) of 72 patients with Sheehan's syndrome had CH. Although fT4 levels were within normal reference range, TRH stimulation test revealed that 10 ( 13.8%) of these had CH. Conclusion: TRH stimulation test is useful in the diagnosis of central hypothyroidism, especially in whom fT(4) and/or TSH is low-normal and known to have hypothalamo-pituitary pathology.