ECE2018 Poster Presentations: Adrenal and Neuroendocrine Tumours Steroid metabolism + action (2 abstracts)
Urinary steroid profile in patients with primary adrenal insufficiency under conventional glucocorticoid replacement: a case control study
Stéphanie Espiard 1, , Johanna McQueen 1, , Oskar Ragnarsson 1, , Ragnhildur Bergthorsdottir 1, , Pia Burman 3 , Per Dahlqvist 4 , Bertil Ekman 5 , Britt Edén Engström 6 , Anna G. Nilsson 1, , Stanko Skrtic 2, , Jeanette Wahlberg 5 , Mark Sherlock 8 , Paul M. Stewart 9 & Gudmundur Johannsson 1,
1Department of Endocrinology, Sahlgrenska University Hospital and, Göteborg, Sweden; 2Institute of Medicine, University of Gothenburg, Göteborg, Sweden; 3Department of Endocrinology, Skåne University Hospital Malmö, Malmö, Sweden; 4Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden; 5Department of Endocrinology, Department of Medical and Health Sciences, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; 6Department of Medical Sciences, Endocrinology and Metabolism, Uppsala University Hospital, Uppsala, Sweden; 7AstraZeneca R&D, Mölndal, Sweden; 8Department of Endocrinology and Diabetes, Beaumont Hospital, Dublin, Ireland; 9Faculty of Medicine and Health, University of Leeds, Leeds, UK.
Introduction: Primary adrenal insufficiency (PAI) leads to a drastically reduced production of steroids from the adrenal cortex, but a few patients may keep some residual adrenal steroid secretion that may simplify replacement therapy and prevent adrenal crisis. Irrespectively, the conventional glucocorticoid (GC) replacement therapy, using thrice-daily oral hydrocortisone, does not restore the patients’ physiological cortisol profile.
Objective: The primary objective was to study enzyme activity related to GC action, synthesis and degradation in patients with PAI and GC replacement by assessing urinary steroid profile. The secondary aim was to analyze if any residual adrenal function can be detected in patients with long-standing PAI.
Methods: Case-control study comparing patients with PAI >6 months after diagnosis, under stable thrice-daily hydrocortisone replacement (20-40mgs/day) with healthy controls. Urinary steroid profile was measured using gas chromatography/mass spectrometry. Activity of enzymes involved in synthesis and metabolism of steroid hormones was evaluated by calculation of ratios (substrates/products).
Results: Fifty PAI patients (22 females, mean age 47 years (range 19-71)) were compared with 124 healthy controls (73 females, mean age 48 years (range 20-81). Urinary cortisol (F) (P<0.001) and cortisone (E) (P<0.001) excretion were higher in patients compared to controls. In contrast, urinary metabolites of F (5α-THF and 11β-OH-etiocholanolone) and E (THE, 11-oxo-etiocholanolone) were similar in patients and controls. The urinary THF+5αTHF/THE ratio reflecting 11βHSD1 activity and the urinary F/E ratio reflecting 11βHSD2 activity was higher in patients than in controls (P<0.001 and P<0.01 respectively). The F/5αTHF (P<0.001), THB/αTHB (P<0.001) and androstenedione/etiocholanolone (P=0.023) ratios were higher in patients suggesting a lower 5α-reductase activity. Similarly, ratios evaluating 5β-reductase, 20αHSD and 20βHSD indicated a lower activity in patients. Androgens, mineralocorticoids and their precursors as well as the GC precursors were drastically decreased in patients, although residual secretion of one or more steroids was detected in 9 patients.
Conclusion: The urinary steroid metabolome showed that activity of important enzymes involved in the modulation of corticosteroid action and metabolism was markedly abnormal in PAI patients treated with conventional hydrocortisone therapy. This results in an abnormal cortisol metabolite profile that may contribute to adverse metabolic effects. Production of androgens, mineralocorticoids and GCs is markedly reduced in PAI patients, although 18% of them exhibited residual steroid secretion.
Volume 56
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Endocrine Abstracts
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