Title: Diagnosis of relative adrenal insufficiency in critically ill patients
Abstract: Although critically ill patients generally show raised plasma cortisol concentrations, some patients have an inadequate production of cortisol in relation to the seriousness of their disease—so-called relative adrenal insufficiency. These intensive care patients may benefit from supplementation with stress doses of hydrocortisone.1Briegel J Forst H Haller M et al.Stress doses of hydrocortisone reverse hyperdynamic septic shock: a prospective, randomized, double-blind, single-center study.Crit Care Med. 1999; 27: 723-732Crossref PubMed Scopus (781) Google Scholar, 2Bollaert PE Charpentier C Levy B Debouverie M Audibert G Larcan A Reversal of late septic shock with supraphysiologic doses of hydrocortisone.Crit Care Med. 1998; 26: 645-650Crossref PubMed Scopus (744) Google Scholar Diagnosis of this syndrome is therefore of great importance. However, the best available clue to diagnosis is fast clinical and haemodynamic improvement after substitution with 100–200 mg hydrocortisone per day.3Lamberts SW Bruining HA de Jong FH Corticosteroid therapy in severe illness.N Engl J Med. 1997; 337: 1285-1292Crossref PubMed Scopus (434) Google Scholar Serum cortisol concentrations, stimulation tests with adreno-corticotropic hormone analogues (synacthen), or serum electrolyte disturbances are not very useful in this group of patients. In search of more refined aids to diagnosis, Albertus Beishuizen and colleagues (May 15, p 1675)4Beishuizen A Vermes I Hylkema BS Haanen C Relative eosinophilia and functional adrenal insufficiency in critically ill patients.Lancet. 1999; 353: 1675-1676Summary Full Text Full Text PDF PubMed Scopus (98) Google Scholar describe 40 patients with relative eosinophilia (>3% of total leucocyte count) out of 570 critically ill patients. Low-dose (1 μg) synacthen stimulation test was abnormal in ten patients with relative eosinophilia. Treatment with steroids resulted in haemodynamic improvement in seven patients. The investigators state that relative eosinophilia should be thought of as a warning sign of insufficient adrenocortical function. However, eosinophilia was used as inclusion criterion to enter the study; so we do not know which proportion of the remaining 530 patients, who did not show eosinophilia, might have had relative adrenal insufficiency (insufficient for the temporary increased needs). Furthermore, eosinophilia was not significantly different between the groups. Separation into groups on the basis of an abnormal synacthen test seems uncertain, because reference values are determined under standard circumstances and therefore cannot be applied to the whole population on the intensive care unit. The low basal cortisol concentrations in the group with so-called adequate response after 1 μg synacthen could suggest secondary adrenal insufficiency. However, would they also benefit from glucocorticoid administration? We are in need of tools to diagnose relative adrenal insufficiency syndrome, because this condition has therapeutic consequences in severely ill patients. However, we feel that relative eosinophilia is of little clinical value in making this diagnosis in the intensive care setting.