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.

• Authors: Mark Sherlock, Lucy Ann Behan, Mark J Hannon, Aurora Aragon Alonso, Christopher J Thompson, Robert D Murray, Nicola Crabtree, Beverly A Hughes, Wiebke Arlt, Amar Agha, Andrew A Toogood, Paul M Stewart
• Journal: European journal of endocrinology (Eur J Endocrinol) Vol. 173 Issue 5 Pg. 583-93 (Nov 2015) ISSN: 1479-683X [Electronic] England
• PMID: 26264718 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 European Society of Endocrinology.

Chemical References

• Glucocorticoids
• Adrenocorticotropic Hormone
• Hydrocortisone

Topics

• Adrenocorticotropic Hormone (deficiency)
• Adult
• Aged
• Body Composition (drug effects)
• Cross-Over Studies
• Cross-Sectional Studies
• Female
• Glucocorticoids (administration & dosage, metabolism, urine)
• Humans
• Hydrocortisone (administration & dosage, metabolism, urine)
• Hypopituitarism (drug therapy, metabolism, urine)
• Male
• Middle Aged
• Prospective Studies
• Waist-Hip Ratio
• Young Adult