ESPE Yearbook of Paediatric Endocrinology

Brief summary: This single-centre retrospective study evaluated cortisol responses during febrile episodes in children with cancer. Low cortisol responses were common and were unrelated to current steroid therapy.

Random serum cortisol and ACTH were measured in 75 children and adolescents with cancer while admitted for fever during chemotherapy; 47/75 patients received glucocorticoids as part of their treatment (steroid group). A low cortisol response (LCR) was defined as cortisol <14.6 mcg/dL during fever. In total, 52/75 (69%) patients had LCR without significant difference between patients receiving steroid therapy or not. In the steroid group, most patients with low cortisol (30/32) had low or normal ACTH; only 2/32 patients had low cortisol and high ACTH.

The high doses of glucocorticoids used in cancer treatment can suppress the hypothalamic pituitary adrenal (HPA) axis for several months, causing impaired stress response to infections. Many authors recommend steroid replacement therapy during periods of serious stress. In this study, the equivalent cumulative dexamethasone (DXM) dose did not correlate with cortisol and ACTH levels during fever. Large inter-individual variability in stress responses was observed, especially when comparing patients who received the same equivalent cumulative steroid dose and had the same interval from the last dose. Patients with LCR did not show a more severe clinical course, with no difference in clinical presentation, duration of fever or hospital stay. In the steroid naive group, all 20 patients with LCR had low or normal ACTH levels and 4/20 patients were treated with posaconazole; none had LCR and high ACTH levels.

Few studies have assessed adrenal function in children undergoing treatment for cancer and none have assessed adrenal function during stress (e.g. fever). The strength of the study is its focused attention on this relevant clinical problem. Unfortunately, the results did not definitively answer the question, as there was no difference in cortisol response even between patients treated with steroids or not. Methodological limitations include the random sampling of cortisol and ACTH, regardless of time of the day and fasting and without contextual evaluation of blood sugar. Likewise, ACTH stimulation testing was not performed to assess adrenal reserve, with the questionable assumption that fever represents a sufficient stimulus for a cortisol response. Similarly, the cut-off values used to define LCR could also be questioned. Finally, no stratification was made by severity of infection (viral or bacterial, localized or generalized).

New prospective studies are desirable in children with cancer during stressful situations to better define the adrenal response to stress, taking into consideration ongoing or prior steroid therapy and the concomitant use of drugs (such as posaconazole) that interfere with adrenal function.