Adolescent inhalant abuse results in adrenal dysfunction and a hypermetabolic phenotype with persistent growth impairments.

<br>Background/aims: Abuse of toluene products (e.g. glue-sniffing) primarily occurs during adolescence and has been associated with appetite suppression and weight impairments. However, the metabolic phenotype arising from adolescent inhalant abuse has never been fully characterised, and its persistence during abstinence and underlying mechanisms remain unknown.

METHODS: Adolescent male Wistar rats (PND 27) were exposed to inhaled toluene (10,000ppm) (n=32) or air (n=48) for 1 hour/day, 3 days/week for 4 weeks, followed by 4 weeks abstinence. Twenty air-rats were pair-fed to the toluene group, to differentiate the direct effects of toluene from under-nutrition. Food intake, weight and growth were monitored. Metabolic hormones were measured after exposure and abstinence periods. Energy expenditure was measured using indirect calorimetry. Adrenal function was assessed using adrenal histology and hormone testing.

RESULTS: Inhalant abuse suppressed appetite and increased energy expenditure. Reduced weight gain and growth were observed in both toluene and pair-fed groups. Compared to the pair-fed group, and despite normalisation of food intake, the suppression of weight and growth for toluene-exposed rats persisted during abstinence. After exposure, toluene rats had low fasting blood glucose and insulin compared to air and pair-fed groups. Consistent with adrenal insufficiency, adrenal hypertrophy and increased basal adrenocorticotropic hormone was observed in toluene-exposed rats, despite normal basal corticosterone levels.

CONCLUSIONS: Inhalant abuse results in negative energy balance, persistent growth impairment, and endocrine changes suggestive of adrenal insufficiency. We conclude that adrenal insufficiency contributes to the negative energy balance phenotype, potentially presenting a significant additional health risk for inhalant users. <br>.