Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2015) 37 GP04.02 | DOI: 10.1530/endoabs.37.GP.04.02

ECE2015 Guided Posters Steroids (9 abstracts)

The modulation of corticosteroid metabolism by hydrocortisone therapy in patients with hypopituitarism increases tissue glucocorticoid exposure

Mark Sherlock 1, , Lucy Ann Behan 4 , Mark Hannon 4 , Aurora Aragon Alonso 1 , Christopher Thompson 4 , Robert Murray 5 , Nicola Crabtree 6 , Beverly Hughes 1 , Wiebke Arlt 1 , Amar Agha 4 , Andrew Toogood 1 & Paul M Stewart 1

1Centre for Endocrinology, Diabetes and Metabolism, University of Birmingham, Birmingham, UK; 2Department of Endocrinology and Diabetes, Adelaide and Meath Hospitals, Incorporating the National Children’s Hospital, Dublin, Ireland; 3Trinity College Dublin, Dublin, Ireland; 4Department of Endocrinology, Diabetes and Metabolism, Beaumont Hospital and RCSI Medical School, Dublin, Ireland; 5Department of Endocrinology, Leeds Teaching Hospitals NHS Trust, St James’s University Hospital, Leeds, UK; 6Department of Nuclear Medicine, Queen Elizabeth Hospital, Birmingham, UK.

Context: Patients with hypopituitarism have increased morbidity and mortality. There is ongoing debate around the optimum glucocorticoid replacement therapy.

Objective: To assess the effect of glucocorticoid replacement in hypopituitarism on corticosteroid metabolism and its impact on body composition.

Design and patients: We assessed the urinary corticosteroid metabolite profile (using gas chromatography/mass spectrometry) and body composition (clinical parameters and full body DEXA) of 53 patients (19 females, median age 46 years) with hypopituitarism (33 ACTH deficient/20 ACTH replete) (study A). The corticosteroid metabolite profile of ten patients with ACTH deficiency was then assessed prospectively in a cross over study using three hydrocortisone dosing regimens (20/10, 10/10, and 10/5 mg) (study B) each for 6 weeks. 11β-HSD1 activity was assessed by urinary THF+5α-THF/THE.

Setting: Endocrine Centres within University Teaching Hospitals in UK and Ireland.

Main outcome measures: Urinary corticosteroid metabolite profile and body composition assessment.

Results: In study A, when patients were divided into three groups: patients not receiving HC, patients receiving HC <20 or >20 mg/day, patients in the group receiving the highest daily dose of HC had significantly higher WHR than the ACTH replete group. They also had significantly elevated THF+5α-THF/THE (P=0.0002) and total cortisol metabolites (P=0.015). In study B, patients on the highest hydrocortisone dose had significantly elevated total cortisol metabolites and all patients on hydrocortisone had elevated THF+5α-THF/THE ratios when compared to controls.

Conclusions: In ACTH deficient patients daily HC doses of >20 mg/day have increased WHR, THF+5α-THF/THE ratios and total cortisol metabolites. Glucocorticoid metabolism and induction of 11β-HSD1 may play a pivitol role in the development of the metabolically adverse hypopituitary phenotype.

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