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

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The modulation of corticosteroid metabolism by hydrocortisone therapy in patients with hypopituitarism increases tissue glucocorticoid exposure. / Sherlock, Mark; Behan, Lucy Ann; Hannon, Mark J; Alonso, Aurora Aragon; Thompson, Christopher J; Murray, Robert D; Crabtree, Nicola; Hughes, Beverly A; Arlt, Wiebke; Agha, Amar; Toogood, Andrew A; Stewart, Paul M.

In: European Journal of Endocrinology, Vol. 173, No. 5, 11.2015, p. 583-93.

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Sherlock, Mark ; Behan, Lucy Ann ; Hannon, Mark J ; Alonso, Aurora Aragon ; Thompson, Christopher J ; Murray, Robert D ; Crabtree, Nicola ; Hughes, Beverly A ; Arlt, Wiebke ; Agha, Amar ; Toogood, Andrew A ; Stewart, Paul M. / The modulation of corticosteroid metabolism by hydrocortisone therapy in patients with hypopituitarism increases tissue glucocorticoid exposure. In: European Journal of Endocrinology. 2015 ; Vol. 173, No. 5. pp. 583-93.

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@article{9e2adb95cf32447895a8f89b0e9d1d69,
title = "The modulation of corticosteroid metabolism by hydrocortisone therapy in patients with hypopituitarism increases tissue glucocorticoid exposure",
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.",
author = "Mark Sherlock and Behan, {Lucy Ann} and Hannon, {Mark J} and Alonso, {Aurora Aragon} and Thompson, {Christopher J} and Murray, {Robert D} and Nicola Crabtree and Hughes, {Beverly A} and Wiebke Arlt and Amar Agha and Toogood, {Andrew A} and Stewart, {Paul M}",
note = "{\textcopyright} 2015 European Society of Endocrinology.",
year = "2015",
month = nov
doi = "10.1530/EJE-15-0490",
language = "English",
volume = "173",
pages = "583--93",
journal = "European Journal of Endocrinology",
issn = "0804-4643",
publisher = "BioScientifica",
number = "5",

}

RIS

TY - JOUR

T1 - The modulation of corticosteroid metabolism by hydrocortisone therapy in patients with hypopituitarism increases tissue glucocorticoid exposure

AU - Sherlock, Mark

AU - Behan, Lucy Ann

AU - Hannon, Mark J

AU - Alonso, Aurora Aragon

AU - Thompson, Christopher J

AU - Murray, Robert D

AU - Crabtree, Nicola

AU - Hughes, Beverly A

AU - Arlt, Wiebke

AU - Agha, Amar

AU - Toogood, Andrew A

AU - Stewart, Paul M

N1 - © 2015 European Society of Endocrinology.

PY - 2015/11

Y1 - 2015/11

N2 - 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.

AB - 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.

U2 - 10.1530/EJE-15-0490

DO - 10.1530/EJE-15-0490

M3 - Article

C2 - 26264718

VL - 173

SP - 583

EP - 593

JO - European Journal of Endocrinology

JF - European Journal of Endocrinology

SN - 0804-4643

IS - 5

ER -