Assessment of Adrenal Function in the Initial Phase of Meningococcal Disease

Abstract

Objective. To determine the status of the hypothalamic-pituitary-adrenal axis in children who had meningococcal disease and were admitted to 2 regional pediatric intensive care units. Methods. Sixty-five children (34 boys; median age: 2.5 years; range: 0.2–15 years) had cortisol and adrenocorticotropic hormone (ACTH) levels measured on admission, then at 8 am and 8 pm during the next 48 hours. At 48 hours, a low-dose short Synacthen test (LDST) (500 ng of 1–24 corticotropin/m2) was performed in 42 patients (19 boys). Normal ranges for 8 am cortisol and ACTH levels in unstressed children were 140 to 500 nmol/L and 2 to 11.3 pmol/L, respectively. Adrenal insufficiency (AI) was defined as a peak cortisol <500 nmol/L on the LDST or an 8 am cortisol value <140 nmol/L. Results. Five (7.7%) of the 65 children died, including 1 with primary AI. Cortisol levels were elevated on admission (median: 1122 mmol/L; range: 65–2110 nmol/L) with 81% of values more than the 8 am normal range. The median ACTH level on admission was within the 8 am normal range, but 40% of values were more than the 8 am normal range. However, 7% and 8% of cortisol and ACTH values, respectively, were less than the normal range. Both cortisol and ACTH levels fell thereafter and showed no diurnal variation during the 48-hour profile. Six (14%) of the 42 failed the LDST. These patients had significantly lower mean 8 am cortisol values than those with a normal peak value on the LDST. Five additional patients who did not have the LDST had 8 am cortisol values <140 nmol/L. In the diagnosis of AI, the sensitivity of the 8 am mean cortisol value at a cutoff of 400 nmol/L, judged against the LDST, was 83%; the specificity was 81%. Conclusions. During the initial phase of meningococcal disease, raised cortisol and ACTH levels indicate an appropriate stress response within the hypothalamic-pituitary-adrenal axis. However, a substantial subpopulation (11 [16.9%] of 65) has evidence of adrenal dysfunction during this period. Morning cortisol values in the initial phase of meningococcal disease could be used as a potential early index of AI.