Endocrine Abstracts (2011) 27 OC1.5

Deconvolution analysis of 24 h serum cortisol profiles informs the amount and distribution of hydrocortsione replacement therapy

Peter Hindmarsh1, Nathan Hill2, Mehul Dattani1, Catherine Peters1, Evangelia Charmandari3 & David Matthews2

1UCL Institute of Child Health, London, UK; 2Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford, UK; 3University of Athens Medical School, Athens, Greece.

Introduction: Glucocorticoid replacement therapy uses twice or thrice daily regimens of hydrocortisone (HC) with variable distribution of the dose over the day. Deconvolution analysis determines the mass of hormone that needs to be secreted to attain a particular serum concentration. We have used this methodology to determine the amount and distribution of cortisol over a 24 h period.

Methods: Seventy-nine adults (41M) aged 60–74 years and 30 children (24M) aged 5–9 years underwent 24 h serum cortisol profiles with samples drawn at 20 min intervals. Profiles were subjected to deconvolution analysis using a cortisol half-life of 80 min to yield the amount of cortisol released by the adrenal to generate the corresponding serum concentration.

Results: Cortisol secretion occurred in discrete bursts. Daily cortisol secretion was 8.3 (range 5.6–12.4) mg/m2 per day in adults and 10.6 (range 7.2–16.5) mg/m2 per day in children. Peak secretion was lower in adults than children (P<0.001) but nadir values were similar. Peak secretion occurred at 0720 h in both groups but the nadir was earlier in children (2245 h) compared to adults (2400 h). In adults the distribution of total cortisol over the 24 h period was 08.00–14.00 36%, 14.00–20.00 18%, 20.00–24.00 10%, 24.00–08.00 36% whereas the respective values in children were 27, 21, 7, 45%.

Conclusion: These observations suggest an optimal dosing and distribution regimen for HC replacement. The study raises the question whether a trial of thrice versus four times per day HC therapy should be considered.

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