Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2009) 19 P244

SFEBES2009 Poster Presentations Pituitary (56 abstracts)

Abnormal cortisol metabolism in growth hormone deficient adults; the role of hydrocortisone replacement therapy and effect on body composition

M Sherlock 1 , A Aragon Alonso 1 , E McGregor 1 , B Hughes 1 , R Murray 2 , AA Toogood 1 & PM Stewart 1


1Department of Endocrinology, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK; 2Department of Endocrinology, Leeds Teaching Hospitals NHS Trust, D Floor, Brotherton Wing, Leeds General Infirmary., Leeds, UK.


GH deficiency (GHD) in adults shares several clinical features with syndromes of glucocorticoid excess. Many patients with GHD also receive glucocorticoid therapy. GH inhibits the generation of active glucocorticoid by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), but the confounding effect of ACTH deficiency/ cortisol replacement therapy has not been evaluated.

Aims: To assess corticosteroid exposure and metabolism and body composition in patients with adult GHD who were ACTH replete or deficient receiving hydrocortisone (HC).

Patients and methods: Fifty three patients (19 female, median age 46 years) with severe adult GHD (20 ACTH replete /33 ACTH deficient) had 24 h urinary corticosteroid metabolites analysed by gas chromatography/mass spectrometry. Body composition was determined by DXA.

Results: Of 11β-HSD1 activity (THF+alloTHF/THE) was positively correlated with WHR (r=0.36, P=0.01) and negatively correlated with GH peak during dynamic testing (r=−0.39, P=0.006). There was no correlation with IGF-I (r=−0.11. P=0.45). Total daily hydrocortisone replacement dose was correlated with WHR (r=0.38, P=0.0059), THF+alloTHF/THE (r=0.5, P=0.004) and total urinary cortisol metabolites (r=0.37, P=0.013), but not urinary free cortisol (r=0.216, P=0.25). The group was divided according to their steroid replacement dose, ACTH replete (HC0), <20 mg (HC<20) and >20 mg (HC>20). WHR was greater in HC>20 vs HC0 (0.95 (IQR 0.92–0.99) vs 0.91 (IQR 0.85–0.94), P=0.0068). HC>20 also had significantly elevated THF+alloTHF/THE (0.86 (IQR 0.72–1.09) vs 1.59 (IQR 1.25–2.23), P=0.0002) and total F metabolites (8469 μg/24 h (IQR 5986–12973) vs 20136 (9710–26169), P=0.015) despite urinary free cortisol levels being similar to the ACTH replete group (P=0.23).

Conclusions: In adults with GH deficiency daily HC doses >20 mg/ day are associated with increased WHR and abnormalities in cortisol metabolism. The raised THF+alloTHF/THE ratio suggests increased activity of 11β-HSD1; the ensuing local glucocorticoid excess in key tissues such as liver and fat may account for the phenotypic features of adult GHD.

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