• The records of 72 pediatric and adolescent patients with multiple hypothalamic and/or pituitary hormone deficiencies of nontumoral origin who were followed up for years and receiving somatropin, thyroxine, and sex hormones at the appropriate age have been reviewed. According to their corticotropin-releasing factor–corticotropin–cortisol (CAC) axis function as evaluated by basal plasma cortisol levels and the response of cortisol to insulin hypoglycemia and to corticotropin-releasing factor, the patients were divided into three groups: group 1 (n=25), patients with multiple hypothalamic and/or pituitary hormone deficiencies with normal CAC axis; group 2 (n =38), patients with partial CAC deficiency without cortisol replacement therapy (hydrocortisone); and group 3 (n=9), patients with CAC deficiency receiving hydrocortisone therapy (5 to 10 mg/d). Repeated CAC axis evaluation in patients of group 2 over years revealed a progressive decrease in the basal and stimulated cortisol levels with age and pubertal advancement. Despite the low cortisol levels and the low cortisol response to insulin hypoglycemia, these patients did not have clinical symptoms until the end of puberty when nine of 24 patients complained of abdominal pain, weakness, or anorexia. Linear growth, which was followed up in all patients at regular intervals, showed a lower growth velocity and irregular growth in response to somatropin treatment in the patients receiving low doses of hydrocortisone (group 3 patients when compared with group 2 patients not receiving hydrocortisone).