Objective To analyze the diagnostic approaches to differentiate thyrotropin(TSH)-secreting pituitary adenomas(TSHoma)and resistance to thyroid hormone(RTH). Methods This was a retrospective single center study. All patients with insuppressible TSH despite elevated free-T4 and free-T3 levels from 2004 to 2014 were enrolled. Results Twenty-seven patients were diagnosed as TSHoma, 20 as RTH, and 14 remained undetermined. Palpitation was observed in 54% patients as the main symptom. There was no significant difference in gender, serum levels of sex hormone-binding globulin, and free thyroid hormones between patients with TSHoma and RTH. The ages of patients at diagnosis and disease onset were older in TSHoma patients than RTH patients[(45.59±11.32 vs 31.80±11.32)years, P=0.012; (42.16±12.53 vs 23.30±15.77)years, P<0.01]. The course of disease was shorter in TSHoma patients than RTH patients[(3.44±4.55 vs 8.50±9.95)years, P=0.049]. Five RTH patients showed pituitary adenoma by MRI. TSHoma patients showed blunt TSH response to thyrotropin hormone releasing hormone(TRH)stimulation while RTH patients showed normal TRH stimulation[(2.35±1.61 vs 9.48±2.94)fold, P<0.01]. TSHoma patients showed significantly suppressed serum TSH by somatostatin analogs as compared with RTH patients[(77.02±13.43)%vs(52.33±15.02)%, P<0.01]. Twelve RTH patients had thyroid hormone receptor beta (TRβ) mutation. Conclusion A later age of disease onset and shorter disease course suggested TSHoma other than RTH. TRH stimulating test was the most accurate test to distinguish RTH and TSHoma as compared with pituitary MRI, somatostatin suppression test, and TRβ mutation analysis. (Chin J Endocrinol Metab, 2015, 31: 925-931) Key words: Thyrotropin-secreting pituitary adenoma; Resistance to thyroid hormones