Session: OR21-HPA Axis: New Clinical Developments
Room 134 (Moscone Center)
Methods: Relationships between plasma B or F and features of metabolic syndrome were studied in: (i) am plasma samples from the Orkney Complex Disease Study cohort (ORCADES; n=2018); (ii) samples following overnight dexamethasone suppression (0.25mg) in the East Hertfordshire cohort (EH; n=279); and (iii) samples obtained 30 mins after Synacthen (1µg) in the EH cohort. B and F were measured by RIA and ELISA, respectively. In multiple linear regression analyses, we adjusted for age, gender, time of sample, body mass index and potentially confounding medications.
Results: In baseline am samples, higher fasting glucose and triglycerides were associated with both higher F and higher B, while systolic blood pressure was positively associated with F (β=0.02, p=0.001) but not B. After dexamethasone suppression, neither F nor B was associated with metabolic syndrome, other than an inverse association between B and insulin and HOMA-IR. After ACTH stimulation, B demonstrated a relatively enhanced response compared to F (basal vs stimulated B/F ratio 11.8% vs 18.9%, p<0.001). Higher ACTH-stimulated F was associated with glucose intolerance (β=0.146, p=0.006), increased total cholesterol (β=0.103, p=0.03) and triglycerides (β=0.32, p=0.01). In contrast, features of metabolic syndrome were associated with lower ACTH-stimulated B (fasting glucose (β=-0.03, p=0.01); HOMA-IR (β=-0.126, p=0.03)).
Conclusions: People with metabolic syndrome exhibit a shift in ACTH-stimulated glucocorticoid secretion in favour of F rather than B, in keeping with subtly altered adrenal steroidogenesis. This discrepancy is not manifest, however, in the unstressed state, when both B and F are raised in metabolic syndrome, consistent with subtle HPAA activation. Reduced B-dependent negative feedback of the HPAA may contribute to elevated F, and amplify the risk of metabolic syndrome, in conditions of high glucocorticoid output.
Nothing to Disclose: SDM, RMR, JB, JW, DIWP, BRW
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