ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 63 GP197 | DOI: 10.1530/endoabs.63.GP197

Optimizing mineralocorticoid replacement therapy in patients with congenital adrenal hyperplasia and Addison's disease

Riccardo Pofi1,2, Alessandro Prete3, Vivien Thornton-Jones1, Jilian Bryce4, Salma Ali4, Faisal Ahmed4, Birgit Koehler5, Antonio Balsamo6, Carlo Acerini7, Amalia Cannuccia8, Ayla Guven9, Tulay Guran10, Feyza Darendeliler11, Claire Higham12, Walter Bonfig13, Liat De Vries14, Berenice B Mendonca15, Violeta Iotova16, Nils P Krone17, Ruth Krone18, Andrea Lenzi2, Wiebke Arlt3, Richard Ross17, Andrea M Isidori2 & Jeremy W Tomlinson1


1Department of Endocrinology, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM) and NIHR Oxford Biomedical Research Centre, Churchill Hospital, University of Oxford, Oxford, UK; 2Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy; 3University of Birmingam, Birmingham, UK; 4Department Academic Child Health, Glasgow, UK; 5Department of Ecology and Genetics, Uppsala, Sweden. 6Dipartimento Della Donna, Del Bambino E Delle Malattie Urologiche, Policlinico S. Orsola-Malpighi, Bologna, Italy; 7Department of Paediatrics, University of Cambridge, Cambridge, UK. 8Division of Endocrinology, Department of System Medicine, Section of Reproductive Endocrinology, Tor Vergata University of Rome, Rome, Italy; 9Istanbul Medeniyet University, Goztepe Education and Research Hospital, Pediatric Endocrinology Clinic, Istambul, Turkey; 10Marmara University, Department of Pediatric Endocrinology and Diabetes, Pendik, Istambul, Turkey; 11Istanbul Faculty of Medicine, Department of Pediatrics, Pediatric Endocrinology Unit, Istambul, Turkey; 12Department of Endocrinology, Christie Hospital Nhs Foundation Trust, Manchester, University Of Manchester, Manchester Academic Health Science Centre, Manchester, UK; 13Department of Pediatrics, Technical University München, Munich, Germany; 14The Jesse Z and Sara Lea Shafer Institute for Endocrinology And Diabetes, National Center For Childhood Diabetes, Schneider Children’s Medical Center Of Israel, Petah Tikva, Israel; 15Unidade De Endocrinologia Do Desenvolvimento, Laboratório De Hormônios E Genética Molecular/Lim42, Hospital Das Clinicas Hcfmusp, Faculdade De Medicina, Universidade De Sao Paulo, Sao Paulo, Brazil; 16Clinic Of Paediatric Endocrinology - Umhat ’St. Marina’, Medical University of Varna, Varna, Bulgaria; 17The University of Sheffield, Sheffield, UK; 18Birmingham Children’s Hospital NHS Foundation Trust, Birmingam, UK.


Background: Adrenal insufficiency (AI) results from deficient production/action of glucocorticoids (GCs), with or without deficiency of mineralocorticoids (MC) and adrenal androgens. GC treatment is essential but some patient needs MC therapy to allow sodium(Na+) retention, potassium(K+) excretion and to maintain normal plasma volume and blood pressure. Much attention has focused on optimization of GC replacement but no consensus exists for optimization of MC therapy in primary AI. Our aim was to explore the relationship between MC dose, Plasma renin concentration (PRC) and clinically important variables to determine the most helpful in guiding MC dose titration.

Design: We performed an observational, retrospective analysis on 1107 assessments from 281 patients (242 with salt-wasting CAH(SW-CAH) and 39 with Addison’s disease(AD)) recruited from local databases and the international congenital adrenal hyperplasia registry (www.i-cah.org). Subgroup analysis was made in adult patients (age>=18years) and a longitudinal analysis performed in 92 patients with SW-CAH(median time between assessments 560 days,range 33–2082). PRC, electrolytes, BP and anthropometric parameters were assessed for their utility in optimizing MC replacement dose.

Results: PRC (normal range 11-32 μUI/mL) was low, normal or high in 30%,15% and 55% of patients respectively with wide variability in MC dose (37.7%, 16.6%, 15.4% and 11.7% of patients were on fludrocortisone 100.50.150 and 200 μg/day respectively) and PRC (median 47 μUI/mL, range 0.1–3166). Patients with high PRC had lower Na+ levels (with no change in K+), higher mean arterial pressure (MAP), BMI, age and were on the highest total daily MC dose. Univariate analysis demonstrated a direct relationship between MC dose and PRC (P<0.001), and an inverse correlation with potassium (P<0.001). Using multiple regression modelling, only Na+ was able to predicted PRC. MC dose predicted K+, but not MAP or PRC. In the longitudinal analysis, Na+ concentration at final follow-up visit was associated with the change (Δ) in PRC (B=139.538, P<0.001). There was no relationship between ΔPRC and final MAP, K+ or MC dose. No correlation was found between ΔMC dose and ΔPRC,K+, Na+ or MAP. Observations were similar in patients with SW-CAH and AD.

Conclusions: The lack of relationship between MC dose and PRC calls into question its utility as an aid to optimise and titrate MC replacement dose. This may reflect variability in sampling with respect to posture, timing and concomitant medications, but suggests that in clinical practice, emphasis should be placed on ensuring normalization of serum electrolytes in the optimization of MC replacement.

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