Rathke's cleft cyst (RCC) and primary empty sella syndrome (PESS) are usually incidental findings on magnetic resonance imaging (MRI) scans. In most cases, these lesions do not cause mass effect symptoms and do not require surgical intervention. In patients with RCC or PESS, it is important to exclude secondary adrenal insufficiency (SAI), which may be a life-threatening condition. The incidence of SAI was assessed in patients with RCC or PESS detected by MRI, using the 1 μg Synacthen stimulation test. A total of 38 patients were analysed. Test results were linked to clinical symptoms and the type of cystic lesion. Assuming that cortisol levels < 14.6 μg/dL in Synacthen test are the criterion of SAI diagnosis, SAI was diagnosed only in 2 patients (5%). Adopting the traditional criterion of cortisol levels < 18 μg/dL, SAI would be diagnosed in 7 patients (18.4 %). Dizziness (Chi2 = 3.89; p = 0.049) and apathy (Chi2 = 3.87; p = 0.049) were significantly more frequent in the PESS group than in the RCC group. The incidence of SAI in the general patient population with empty sella syndrome and Rathke's cleft cysts is low. The 1 μg Synacthen test seems to be a valuable tool in the diagnosis of SAI among patients with RCC and PESS. Further studies are necessary to determine the sensitivity and specificity of the 1 μg Synacthen test with the standardization of test protocol and considering the cortisol level at the 20-minute timepoint. PESS patients report dizziness and apathy more frequently than RCC patients, which does not result from the disturbance of the hypothalamic-pituitary-adrenal axis, but probably from the different pathogenesis of these cystic lesions.