Objective To explore the potential value of stromal cell proteins thrombospondin 1(TSP1) and osteocalcin (OCN) in evaluating hormonal exposure in patients with hypopituitarism (HP) receiving glucocorticoid (GC) replacement therapy at different doses, and to investigate whether the TSP1, OCN and their ratio can serve as a reference indicator for adequate exogenous glucocorticoid replacement. Methods From August 2022 to December 2024, 82 patients with HP who had received continuous GC replacement therapy for ≥6 months and were in a stable condition were enrolled as observation subjects at Xiangdong Hospital Affiliated to Hunan Normal University. Based on the GC dosage administered, the patients were divided into three groups: Group A (low physiological dose, n=19), Group B (physiological dose, n=36), and Group C (supraphysiological dose, n=27). Baseline (at enrollment) levels of TSP1 and OCN were measured, and their ratio was calculated. Furthermore, 19 patients from the above three groups were subdivided into three subgroups: Subgroup A1(n=7), Subgroup B1(n=6), and Subgroup C1(n=6). After 12 weeks of continued treatment, serum levels of bone-specific alkaline phosphatase (β-ALP), propeptide of type I procollagen (PINP), cross-linked C-telopeptide of type I collagen (CTX-I), TSP1, and OCN, as well as their respective ratios, were measured at baseline and after 12 weeks of treatment for comparison. In addition, the above parameters were compared between the 19 HP patients and 10 healthy controls at baseline. Results 1) Baseline comparisons revealed that OCN levels in the three groups gradually decreased with increasing GC dosage, and the differences were statistically significant (P<0.05).2) Intergroup comparisons among the three subgroups demonstrated that OCN and CTX-I levels decreased with increasing GC replacement doses (P<0.05). Compared with the respective baseline values, the A1 subgroup showed a decrease in PINP levels after 12 weeks of treatment, the B1 subgroup exhibited an increase in TSP1 levels, and the C1 subgroup showed a decrease in OCN levels along with an increase in the TSP1∶OCN ratio after treatment, all with statistically significant differences (all P<0.05).3) Compared with healthy controls, HP patients exhibited significantly lower levels of PINP, β-ALP, TSP1, and OCN (P<0.05). Conclusion 1) GC replacement therapy results in exogenous hormone exposure in patients with HP. Higher replacement doses are associated with lower OCN levels and an increased risk of osteoporosis. It is therefore postulated that OCN may serve as a potential biomarker for assessing the risk of exogenous glucocorticoid exposure. However, current evidence does not support the use of TSP1 or the TSP1∶OCN ratio as reference indicators for evaluating such risk. 2) Compared with healthy controls, patients with HP exhibit reduced levels of PINP, β-ALP, TSP1, and OCN, suggesting that glucocorticoids suppress bone formation. In contrast, no significant modulatory effect on bone resorption was observed.
Key words
glucocorticoid /
hypopituitarism /
thrombospondin 1 /
osteocalcin /
hormone exposure
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