News in diagnosis and therapeutics of secondary adrenal insufficiency

Immunotherapy and opioids treatment are new causes of secondary adrenal insufficiency (SAI). Prevalence of SAI with immunotherapy is more frequent with combined therapy (8% vs 4 to 10% with CTLA4 blocking antibody and 1% with PD1 blocking antibody). Although hypophysitis are more frequently observed with CTLA4 blocking antibody, some cases of Isolated SAI have been reported in patients treated by PD1 blocking antibody. SAI could be transient, requiring long-term monitoring. The use of opioid analgesics is increasing in many countries, thus becoming a public health problem. Prevalence of opioid-related SAI is unclear but recent prospective studies reveal a prevalence between 5 and 20%. The main risk factor to develop this pathology is morphine-equivalent daily dose. Diagnosis relies on 8.00 am plasma cortisol measurement and cortisol increase after Synacthen((R)) administration. Recent cortisol immuno-assays, in agreement with mass spectrometry, give lower reference values, encouraging reevaluation of the current cut-off of 500 nmol/L. New modified-release hydrocortisone preparations have been recently developed to better mimic the physiological cortisol rhythm and to improve compliance in adrenocortical deficient patients. Nowadays, continuous subcutaneous hydrocortisone infusion seems to be a unique replacement therapy allowing adequate circadian biorhythm but should be restricted to specific patients due to the complexity of this substituting strategy. (c) 2019 Published by Elsevier Masson SAS. All rights reserved.