Leptin and adiponectin are associated with the glucocorticoid dose and androgen concentrations in children and young persons with congenital adrenal hyperplasia: data from the CAH-UK cohort

Bacila Irina A; Lawrence Neil R; Sabah Alvi; Cheetham Timothy D; Elizabeth Crowne; Urmi Das; Dattani Mehul T; Davies Justin H; Evelien Gevers; Brian Keevil; Krone Ruth E; Allan Lawrie; Leena Patel; Tabitha Randell; Ryan Fiona J; Ajay Thankamony; Ahmed S Faisal; Krone Nils P

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ESPE Abstracts (2024) 98 P1-8

ESPE2024 Poster Category 1 Adrenals and HPA Axis 1 (9 abstracts)

Leptin and adiponectin are associated with the glucocorticoid dose and androgen concentrations in children and young persons with congenital adrenal hyperplasia: data from the CAH-UK cohort.

Irina A Bacila ^1,2 , Neil R Lawrence ¹ , Sabah Alvi ³ , Timothy D Cheetham ^4,5 , Elizabeth Crowne ⁶ , Urmi Das ⁷ , Mehul T Dattani ⁸ , Justin H Davies ⁹ , Evelien Gevers ^10,11 , Brian Keevil ¹² , Ruth E Krone ¹³ , Allan Lawrie ¹⁴ , Leena Patel ¹⁵ , Tabitha Randell ¹⁶ , Fiona J Ryan ¹⁷ , Ajay Thankamony ¹⁸ , S Faisal Ahmed ¹⁹ & Nils P Krone ^1,2

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Author affiliations

¹University of Sheffield, Sheffield, United Kingdom. ²Sheffield Children’s Hospital, Sheffield, United Kingdom. ³Leeds General Infirmary, Leeds, United Kingdom. ⁴Great North Children's Hospital, Newcastle, United Kingdom. ⁵University of Newcastle, Newcastle, United Kingdom. ⁶University Hospitals Bristol Foundation Trust, Bristol, United Kingdom. ⁷Alder Hey Children's Hospital, Liverpool, United Kingdom. ⁸Great Ormond Street Hospital, London, United Kingdom. ⁹United Kingdom University of Southampton, Southampton, United Kingdom. ¹⁰Centre for Endocrinology, William Harvey Research Institute, London, United Kingdom. ¹¹London and Barts Health NHS Trust, London, United Kingdom. ¹²Manchester University NHS Foundation Trust, Manchester, United Kingdom. ¹³Birmingham Women's & Children's Hospital, Birmingham, United Kingdom. ¹⁴Faculty of Medicine, National Heart & Lung Institute, Imperial College London, London, United Kingdom. ¹⁵Paediatric Endocrine Service, Royal Manchester Children's Hospital, Manchester University NHS Foundation Trust, Manchester, United Kingdom. ¹⁶Nottingham Children’s Hospital, Nottingham, United Kingdom. ¹⁷Oxford Children's Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom. ¹⁸University of Cambridge, Cambridge, United Kingdom. ¹⁹Developmental Endocrinology Research Group, University of Glasgow, Glasgow, United Kingdom

Introduction: Patients with Congenital adrenal hyperplasia (CAH) have increased prevalence of obesity and metabolic problems. The underlining mechanisms are not clearly known. Adipokines are likely involved in this association, however, their role in it is not completely understood.

Objective: We studied adiponectin and leptin in children and young persons with CAH, in relation to their body mass, treatment, hormonal and metabolic biomarkers.

Methods: We analysed a national cohort of 102 patients with 21-hydroxylase deficiency (54 females, age 13.0±2.92 years) recruited between 2016–2019, from 13 centres in the United Kingdom, and 83 sex- and age-matched controls. We collected and analysed anthropometric measurements, data on hormone replacement, and blood samples for biochemical analysis, including an extended steroid profile (17-hydroxyprogesterone, androstenedione, testosterone, 11-hydroxyandrostenedione, 11-ketotestosterone), metabolic profiles, adiponectin and leptin. Blood samples were collected between 9:00-11:00, after the morning hydrocortisone dose.

Results: A difference in adipokines between patients and controls was only found for leptin in males (patients > control, P = 0.033). In patients, leptin had a positive relationship with BMI (leptin(ng/dl) = 4810 + 3939 × BMI-SDS, P < 0.01) and waist circumference (r_s = 0.38, P < 0.01), similar to controls. Adiponectin decreased significantly with the BMI only in patients (adiponectin(pg/dl) = 98 – 11 × BMI-SDS, P < 0.01). Regression analysis in patients showed that leptin increased with the insulin level and decreased with the morning relative hydrocortisone dose (leptin(ng/dl) = 11846 + 250 × insulin – 1316 × dose, P < 0.01), but not with the total daily glucocorticoid dose. However, the correlation between leptin and insulin, though significant, was weaker in patients (r_s = 0.31, P < 0.01) compared to controls (r_s = 0.58, P < 0.01). Of the measured plasma androgens, leptin was only found to correlate with testosterone (r_s = -0.29, P = 0.01). However, a negative correlation was found between adiponectin and 17-hydroxyprogesterone (r_s = -0.34, P < 0.00), androstenedione (r_s = -0.34, P < 0.01), testosterone (r_s = -0.33, P < 0.01), 11-hydroxyandrostenedione (r_s = -0.32, P < 0.01) and 11-ketotestosterone (r_s = -0.28, P = 0.01), which was not present in controls.

Conclusion: A suppressive effect of glucocorticoids on leptin may contribute to the weight gain and metabolic problems found in patients with CAH. The consistent association found between high adiponectin and effective androgen suppression indicate its potential use as a marker of metabolic and androgen control in CAH.