medwireNews: Adrenal crisis (AC) occurs in a “substantial proportion” of individuals with paediatric- onset adrenal insufficiency, say the authors of a prospective cohort study based in Japan.
After a median follow-up of 2.8 years, the incidence of AC in patients aged less than 20 years was 6.58 per 100 person–years and this was higher than in the full study population of patients aged from birth up to 57 years, at 4.27 per 100 person–years.
“Preventing AC and avoiding unnecessary deaths and morbidities remains a challenge”, Tomohiro Ishii, from Keio University School of Medicine in Tokyo, Japan, and co-authors therefore conclude in the Journal of Clinical Endocrinology & Metabolism.
The cohort included 349 patients (53% women) who were followed-up for a total of 961 person–years in specialist paediatric endocrinology clinics after developing primary (61%) or secondary (39%) adrenal insufficiency by the age of 15 years. The median age at diagnosis was younger than 1 year and the median age at the start of follow-up was 14.3 years. The average hydrocortisone dose was 12.9 mg/m2 per day, and 75% of the patients with primary adrenal insufficiency required fludrocortisone at an average dose of 0.06 mg/day.
Overall, 31 of the study participants had 41 AC events, with five patients experiencing two events, and two individuals experiencing three and four events. There were no fatal AC events but one patient had irreversible brain morbidity with deterioration from severe disability to a coma or vegetative state.
The most common symptoms of AC were vomiting (73%), fever (61%), abdominal pain (35%), impaired consciousness (32%), diarrhoea (22%) and convulsions (5%). The biochemical abnormalities hyponatraemia (29%), hypotension (28%), hypoglycaemia (26%) and hyperkalaemia (7%) were also common.
The researchers say that 61% of AC events were provoked by infection, most commonly gastroenteritis (29%), upper and lower respiratory tract infections (22.0 and 7.3%, respectively) and urinary tract infections (2%). There were no cases of AC associated with trauma and two children “rapidly” developed AC without a known cause, which emphasises the “important notion that AC may develop without any identified precipitating factors”, they write.
The median age at time of AC was 4.5 years, with the majority (61%) of AC events occurring in children younger than 8.5 years (25th percentile). The incidence among participants in this percentile was significantly higher than among those in the 25–75th, 50–75th and 75–100th percentile groups for age (12.1 vs 3.0, 1.6 and 1.2 per 100 person–years, respectively).
Multivariable analysis confirmed that younger age at the start of follow-up was a significant risk factor for adrenal insufficiency, with a relative risk (RR) of 0.93 after considering infections, female sex, primary versus secondary adrenal insufficiency and hydrocortisone dosage. An increasing number of infections was also a significant risk factor with a RR of 1.17.
And when the analysis was performed only in patients who were younger than 20 years at the end of observation, the number of infections was the only significant risk factor for AC, with a RR of 1.19. This prompted the researchers to write: “These results demonstrate, for the first time, that younger age remains a significant risk factor even after excluding the influence of recurrent infection, and vice versa.”
The team notes that all the patients received sick-day instruction and 61% of AC events occurred in patients taking oral stress-dosing glucocorticoids. Just one patient received intramuscular glucocorticoids before hospitalisation and the researchers explain that, as intramuscular self-injection has been approved in Japan since April 2020, it is “unclear” what proportion of patients were instructed to receive the injection.
“Based on these results, it is important to implement measures to avoid exposure to infectious diseases, such as not visiting crowded places during epidemic periods, and administering stress dosing or seeking emergency care when necessary, especially for young patients who have frequently experienced infections”, Ishii et al conclude.
By Lynda Williams
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