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OBJECTIVE Secondary adrenal insufficiency (sAI) is a severe endocrinological complication associated with non-functioning pituitary adenoma (NFPA). However, its prevalence is not simply related to tumor size. In this study, we aimed to detect the clinical characteristics of NFPAs that cause sAI. METHODS We retrospectively investigated the clinical data of 218 patients with newly diagnosed macro NFPA between April 2011 and March 2020. The patients for whom endocrinologists had prescribed hydrocortisone after comprehensive endocrinological evaluation were defined as having sAI. The seven clinical factors analyzed for association with sAI were age, sex, presence of neurological symptoms, hospitalization for emergency management of pituitary apoplexy, degree of optic chiasm compression, and Knosp grades on both sides. RESULTS Seventy-three patients (33%) were classified into the sAI group. Multinomial logistic regression revealed the strongest correlation between sAI and Knosp grade on the less extending side (p = 0.0001), followed by sex (male) (p = 0.0013) and pituitary apoplexy (p = 0.098). Tumors that extended bilaterally and had Knosp grades of 1-3 were frequently observed in sAI and were common in males. CONCLUSION The NFPAs that occupy the sella space and compress the walls on both sides of the cavernous sinus, but do not penetrate them, have a higher risk of developing sAI. This type is more common in males and is seen even in patients without visual field disturbances. This clinical finding will be beneficial in management of patients with NFPA.