Oral Presentation The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2017

Adolescent inhalant abuse induces an endocrine disorder analogous to adrenal insufficiency (#27)

Rose Crossin 1 , Andrew J Lawrence 1 , Brian Oldfield 2 , Aneta Stefanidis 2 , Zane B Andrews 2 , Terence Pang 1 , Jhodie R Duncan 1
  1. Florey Insititute of Neuroscience and Mental Health, Parkville, VIC, Australia
  2. Monash Obesity and Diabetes Institute, Monash University, Melbourne, VIC, Australia

Background: Abuse of products containing toluene (e.g. glue sniffing) primarily occurs during adolescence and has been associated with metabolic symptoms consistent with adrenal insufficiency e.g. appetite suppression, impaired weight gain, and fasting hypoglycaemia. We aimed to characterise the metabolic phenotype arising from adolescent inhalant abuse and to identify whether adrenal insufficiency was present.

Methods: Adolescent male Wistar rats (postnatal-day 27) were exposed to inhaled toluene (10,000ppm) (n=30) or air (n=28) for 1 hour/day, 3 days/week for 4 weeks, followed by 4 weeks abstinence. To explore the role of inhalant-induced adrenal insufficiency a subset of toluene-exposed rats (n=9) were treated with corticosterone (25mg/L) throughout the exposure period, with a crossover design in abstinence. Energy intake and expenditure and parameters of growth were monitored. Adrenal histology, insulin tolerance, and stress responses were used to identify adrenal insufficiency.

Results: Toluene-exposure increased energy expenditure (p=0.028), suppressed appetite (p<0.000) and reduced weight gain (p<0.000); the latter persisting into sustained abstinence. Persistent adrenal hypertrophy was also observed after toluene-exposure, particularly in the zona fasiculata (p<0.008). Toluene-exposure increased ACTH (p=0.022) and, although basal corticosterone levels remained unchanged, they were increased during the insulin tolerance test. Toluene-exposure also resulted in hypo-responsivity to stress (p=0.004) and disrupted the relationship between corticosterone and blood glucose levels. Corticosterone treatment, either during exposure or abstinence, had no effect on these variables.

Conclusions: Toluene-exposure during adolescence results in a hyper-metabolic phenotype with persistent effects during sustained abstinence. Our results show, for the first time, that adolescent inhalant abuse is apparently associated with primary adrenal insufficiency. We conclude that this resultant affect is a driver of the observed metabolic phenotype, and presents a significant health risk for inhalant users. However, as corticosterone replacement was ineffective at the trialled dose; we hypothesise that decreased corticosterone sensitivity as a result of inhalants may also be occurring.