Glucocorticoid (GC)-induced diabetes mellitus (DM) is theoretically unlikely to occur in patients with adrenal insufficiency if adequate physiological replacement doses of GC are given. Herein we report a patient with holoprosencephaly who developed GC-induced DM due to frequent and prolonged administration of high-dose GC for suspected adrenal crisis (AC). GC treatment should be started whenever AC cannot be ruled out. However, the initial and subsequent doses should be adjusted to the severity of AC and to the pace of clinical recovery with treatment, respectively.