Hypothalamic-pituitary-adrenal axis activity and vascular function in healthy adults

Objective: The objective of this study is to assess the relationship between hypothalamic-pituitary-adrenal (HPA) axis activity, vascular function and insulin sensitivity in healthy adults. Design: Open observational study. Patients: Thirty healthy adults were studied at the Endocrine Research Unit, Repatriation General Hospital, Adelaide, SA, Australia. Measurements: HPA activity was assessed from the serum cortisol 30 min after 1 µg ACTH_1-24 (Novartis Pharmaceuticals). Subjects with a cortisol below (n = 15) and above (n = 15) the median were categorized as low and high responders, respectively. Reactive hyperaemia index (RHI) was measured fasting to estimate endothelial function. Matsuda index was calculated from glucose and insulin concentrations collected fasting and 30 minutely for 2 h after a mixed meal (10 kcal/kg, 45% carbohydrate, 15% protein, 40% fat). The primary endpoint was the difference in RHI between low and high responders. Results: There were no significant differences in age (61 ± 9 vs. 64 ± 7 years, p =.19), body mass index (BMI; 26 ± 3 vs. 24 ± 4 kg/m², p =.25) and sex (p =.71) between low and high responders. High responders had a lower RHI (2.1 ± 0.2 vs. 2.6 ± 0.2, p =.04) than low responders and there was a negative association between RHI and peak cortisol post ACTH_1-24 (β = −.56, p <.01). There were no significant differences in Matsuda index (15.0 ± 2.4 vs. 22.7 ± 5.2, p =.19) between high and low responders. Conclusion: In healthy adults, endothelial dysfunction is likely to contribute to the association between HPA hyperactivity and increased cardiovascular risk. As insulin sensitivity was not different in high and low responders, endothelial dysfunction is not primarily secondary to insulin resistance.