Corticotropin (adrenocorticotropic hormone [ACTH]) deficiency due to transsphenoidal pituitary adenomectomy or Rathke’s cleft cysts extirpation is fairly low, mainly due to its monoclonal prevalence expression. It represents 20% of the cases, contrasting with other hypophyseal hormones, such as, antidiuretic hormone (arginine vasopressin), thyrotropin (thyroid-stimulating hormone), gonadotropins (follicle-stimulating hormone or luteinizing hormone) and growth hormone (GH) that may reach up to 40% to 50%. When low ACTH is found, it is generally permanent and close monitoring is vital. Statistics vary widely depending on tumor size and location, including the surgeon’s experience and/or compromise achieved by the medical team involved in this kind of process as well. Cortisol is of most importance, because a drop of circulating levels in the first 24 hours may be life-threatening, if replacement is not ensured with opportunity. Difficulties usually arise while attempting to establish the diagnosis and in delineating prognosis of hypocortisolism, which commonly relies on the accuracy of cortisol and corticotropin (ACTH) quantitative methods and/or qualitative clinical assessment. Preservation of ACTH/cortisol secretion when a tumor blockades the infundibulum or by surgical extension is not totally understood, albeit fragments of pituitary functional tissue have been found in neighboring zones like the ethmoid sinus or nasopharynx. A single morning or random serum cortisol quantitation in many cases do not necessarily correlate with impairment in cortisol secretion by the adrenal while attempting to evaluate intactness of the hypothalamic-pituitary-adrenal axis after a pituitary tumor removal. Nonetheless, the finding of a random serum cortisol 20 g/dL can rule out the possibility of adrenal insufficiency, whereas a concentration of cortisol 20 g/dL makes imperative a thorough investigation of adrenal deficit. Blood pressure monitoring and serum or urinary electrolytes (Na and K) with clinical assessment are effective auxiliary elements for diagnosis of hypocortisolism. It is important to bear in mind that circulating cortisol is transported by a cortisol-binding globulin (CBG), susceptible to cross react with other steroids like estrogen or testosterone or become altered in cases of liver disease (acute hepatitis) or hyperthyroidism able to induce high levels of cortisol, making necessary eventually to perform 24-hour urinary collections in order to obtain reliable amounts of free cortisol. Other sources for cortisol analysis that have proved to be useful are those in saliva or hair. Amounts of cortisol measured in saliva seem to be more accurate and specific because cross-reacting CBG is absent; however, experience under circumstances of surgical hypocorticotropism is scarce. Measurements of cortisol in hair apparently provide information to estimate time of tissue exposure to concentrations of cortisol. Potentially, this might be helpful in determining the quantities of hormonal replacement that need reduction or when to decide its withdrawal. Most methods currently available for measuring serum cortisol levels are automated immunoassays or by chemiluminescence, both susceptible to variations derived from cross-reacting material contained in biological fluids and consequently prone to erroneous readings.