Background: Glucocorticoid abuse is a very common situation in Vietnam, causing exogenous Cushing’s syndrome and drug-induced adrenal insufficiency. Determining the prevalence of adrenal insufficiency due to prolonged glucocorticoid therapy and related factors in order to alert physicians to these rarely recognized serious consequences of the drug. Methods: Cross-sectional study on 96 patients prolongedly treated with glucocorticoids at Nguyen Tri Phuong Hospital from May 2023 to February 2024. Insulin tolerance test was the gold standard for diagnosis of adrenal insufficiency. Results: The prevalence of adrenal insufficiency due to prolonged glucocorticoid therapy is 58.3%. In rheumatoid arthritis patients, the prevalence of adrenal insufficiency was statistically significantly higher than without adrenal insufficiency: 63.3% versus 36.7%. In lupus erythematosus group: 73.9% versus 26.1% and in exogenous Cushing’s syndrome group: 88.9% versus 11.1% (p < 0,001). Conversely, in pharyngitis patients, the prevalence of adrenal insufficiency was statistically significantly lower than without adrenal insufficiency: 22.2% versus 77.8%, and in sinusitis group: 25% versus 75% (p < 0,001). The median duration of treatment in adrenal insufficiency group with 12 months (6;24) was statistically significantly longer than that in non-adrenal insufficiency group with 3 months (1;9) (p < 0.001). After insulin tolerance test, the highest peak cortisol response in the group without adrenal insufficiency compared to adrenal insufficiency was 18.4 µg/dL (95% CI: 18-20.8) versus 11.8 µg/dL (95% CI: 7.8-15.1) (p < 0,001). Conclusion: Treatment of prolonged low dose glucocorticoid causing adrenal insufficiency, especially in chronic disease groups and the longer the duration of glucocorticoid therapy, the higher the risk of adrenal insufficiency.