Mark Sherlock1, Lucy Ann Behan2, Mark J Hannon3, Aurora Aragon Alonso3, Christopher J Thompson3, Robert D Murray3, Nicola Crabtree3, Beverly A Hughes3, Wiebke Arlt3, Amar Agha3, Andrew A Toogood3, Paul M Stewart3. 1. Centre for EndocrinologyDiabetes and Metabolism, University of Birmingham, Birmingham, UKDepartment of Endocrinology and DiabetesAdelaide and Meath Hospitals, Incorporating the National Children's Hospital and Trinity College, Tallaght Hospital, Dublin 24, IrelandDepartment of EndocrinologyDiabetes and Metabolism, Beaumont Hospital and RCSI Medical School, Dublin, IrelandDepartment of EndocrinologyLeeds Teaching Hospitals NHS Trust, St James's University Hospital, Leeds, UKDepartment of Nuclear MedicineQueen Elizabeth Hospital, Birmingham, UKDepartment of Medicine and EndocrinologyUniversity of Leeds, Leeds, UK Centre for EndocrinologyDiabetes and Metabolism, University of Birmingham, Birmingham, UKDepartment of Endocrinology and DiabetesAdelaide and Meath Hospitals, Incorporating the National Children's Hospital and Trinity College, Tallaght Hospital, Dublin 24, IrelandDepartment of EndocrinologyDiabetes and Metabolism, Beaumont Hospital and RCSI Medical School, Dublin, IrelandDepartment of EndocrinologyLeeds Teaching Hospitals NHS Trust, St James's University Hospital, Leeds, UKDepartment of Nuclear MedicineQueen Elizabeth Hospital, Birmingham, UKDepartment of Medicine and EndocrinologyUniversity of Leeds, Leeds, UK sherloma@tcd.ie. 2. Centre for EndocrinologyDiabetes and Metabolism, University of Birmingham, Birmingham, UKDepartment of Endocrinology and DiabetesAdelaide and Meath Hospitals, Incorporating the National Children's Hospital and Trinity College, Tallaght Hospital, Dublin 24, IrelandDepartment of EndocrinologyDiabetes and Metabolism, Beaumont Hospital and RCSI Medical School, Dublin, IrelandDepartment of EndocrinologyLeeds Teaching Hospitals NHS Trust, St James's University Hospital, Leeds, UKDepartment of Nuclear MedicineQueen Elizabeth Hospital, Birmingham, UKDepartment of Medicine and EndocrinologyUniversity of Leeds, Leeds, UK Centre for EndocrinologyDiabetes and Metabolism, University of Birmingham, Birmingham, UKDepartment of Endocrinology and DiabetesAdelaide and Meath Hospitals, Incorporating the National Children's Hospital and Trinity College, Tallaght Hospital, Dublin 24, IrelandDepartment of EndocrinologyDiabetes and Metabolism, Beaumont Hospital and RCSI Medical School, Dublin, IrelandDepartment of EndocrinologyLeeds Teaching Hospitals NHS Trust, St James's University Hospital, Leeds, UKDepartment of Nuclear MedicineQueen Elizabeth Hospital, Birmingham, UKDepartment of Medicine and EndocrinologyUniversity of Leeds, Leeds, UK. 3. Centre for EndocrinologyDiabetes and Metabolism, University of Birmingham, Birmingham, UKDepartment of Endocrinology and DiabetesAdelaide and Meath Hospitals, Incorporating the National Children's Hospital and Trinity College, Tallaght Hospital, Dublin 24, IrelandDepartment of EndocrinologyDiabetes and Metabolism, Beaumont Hospital and RCSI Medical School, Dublin, IrelandDepartment of EndocrinologyLeeds Teaching Hospitals NHS Trust, St James's University Hospital, Leeds, UKDepartment of Nuclear MedicineQueen Elizabeth Hospital, Birmingham, UKDepartment of Medicine and EndocrinologyUniversity of Leeds, Leeds, UK.
Abstract
CONTEXT: Patients with hypopituitarism have increased morbidity and mortality. There is ongoing debate about the optimum glucocorticoid (GC) replacement therapy. OBJECTIVE: To assess the effect of GC 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 DXA) of 53 patients (19 female, 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 (HC) dosing regimens (20/10 mg, 10/10 mg and 10/5 mg) (study B) each for 6 weeks. 11 beta-hydroxysteroid dehydrogenase 1 (11β-HSD1) activity was assessed by urinary THF+5α-THF/THE. SETTING: Endocrine Centres within University Teaching Hospitals in the 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 and patients receiving HC≤20 mg/day or HC>20 mg/day - patients in the group receiving the highest daily dose of HC had significantly higher waist-to-hip ratio (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 HC dose had significantly elevated total cortisol metabolites and all patients on HC 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. GC metabolism and induction of 11β-HSD1 may play a pivitol role in the development of the metabolically adverse hypopituitary phenotype.
CONTEXT: Patients with hypopituitarism have increased morbidity and mortality. There is ongoing debate about the optimum glucocorticoid (GC) replacement therapy. OBJECTIVE: To assess the effect of GC 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 DXA) of 53 patients (19 female, 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 (HC) dosing regimens (20/10 mg, 10/10 mg and 10/5 mg) (study B) each for 6 weeks. 11 beta-hydroxysteroid dehydrogenase 1 (11β-HSD1) activity was assessed by urinary THF+5α-THF/THE. SETTING: Endocrine Centres within University Teaching Hospitals in the 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 and patients receiving HC≤20 mg/day or HC>20 mg/day - patients in the group receiving the highest daily dose of HC had significantly higher waist-to-hip ratio (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 HC dose had significantly elevated total cortisol metabolites and all patients on HC 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. GC metabolism and induction of 11β-HSD1 may play a pivitol role in the development of the metabolically adverse hypopituitary phenotype.
Authors: Annet Vulto; Isidor Minović; Laura V de Vries; Arwin C Timmermans; Martijn van Faassen; Antonio W Gomes Neto; Daan J Touw; Margriet F C de Jong; André P van Beek; Robin P F Dullaart; Gerjan Navis; Ido P Kema; Stephan J L Bakker Journal: Clin Transplant Date: 2020-03-03 Impact factor: 2.863
Authors: Rosemary Dineen; Lucy-Ann Behan; Grainne Kelleher; Mark J Hannon; Jennifer J Brady; Bairbre Rogers; Brian G Keevil; William Tormey; Diarmuid Smith; Christopher J Thompson; Malachi J McKenna; Wiebke Arlt; Paul M Stewart; Amar Agha; Mark Sherlock Journal: BMC Endocr Disord Date: 2020-10-10 Impact factor: 2.763