ESPE2021 ePoster Category 1 Adrenal A (10 abstracts)
Optimizing the timing of highest hydrocortisone dose in children and adolescents with 21-hydroxylase deficiency
Mariska A.M. Schröder 1,2 , Antonius E. van Herwaarden 2 , Paul N. Span 3 , Erica L.T. van den Akker 4 , Gianni Bocca 5 , Sabine E Hannema 6,7 , Hetty J. van der Kamp 8 , Sandra W.K. de Kort 9 , Christiaan F. Mooij 10 , Dina A. Schott 11 , Saartje Straetemans 12 , Vera van Tellingen 13 , Janiëlle A. van der Velden 1 , Fred C.G.J Sweep 2 & Hedi L. Claahsen-van der Grinten 1
1Amalia Children’s Hospital, Radboud University Medical Center, Department of Pediatrics, Nijmegen, The The Netherlands; 2Department of Laboratory Medicine, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University Medical Center, Nijmegen, The Netherlands; 3Radiotherapy & OncoImmunology Laboratory, Department of Radiation Oncology, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University Medical Center, Nijmegen, The Netherlands; 4Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; 5Beatrix Children’s Hospital, Department of Pediatrics, University Medical Center Groningen, Groningen, The Netherlands; 6Leiden University Medical Centre, Leiden, The Netherlands; 7Department of Pediatric Endocrinology, Emma Children’s Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands; 8Wilhelmina Children’s Hospital, Utrecht University Medical Center, Utrecht, The Netherlands; 9Department of Endocrinology, Juliana’s Children’s Hospital, The Hague, The Netherlands; 10Department of Pediatric Endocrinology, Emma Children’s Hospital, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands; 11Zuyderland Medical Center, Heerlen, The Netherlands; 12Maastricht University Medical Center, Maastricht, The Netherlands; 13Catharina Hospital, Eindhoven, The Netherlands
Context: Children with 21-hydroxylase deficiency (21OHD) require chronic glucocorticoid administration to substitute glucocorticoids and suppress adrenocorticotropic hormone-induced hyperandrogenemia. There is still no evidence about the best timing of the highest hydrocortisone (HC) dose. Administration of the highest dose in the morning aims to mimic the physiological rhythm of cortisol, while a high dose late in the evening may inhibit the early-morning increase in androgens more effectively.
Objective: The primary aim was to compare two standard HC timing strategies, either the highest dosage in the morning or the highest dosage in the evening, with respect to hormonal status throughout the day of children and adolescents with 21OHD. The secondary objective was to evaluate these treatment regimens with respect to nocturnal blood pressure, and sleep- and activity scores.
Design: A six-week cross-over study was performed.
Patients and interventions: Thirty-nine children and adolescents (age 4-19 years) with 21OHD were treated for three weeks with highest HC dose in the morning, followed by three weeks with highest dose in the evening (n = 21), or the other way around (n = 18). During the last two consecutive days of each treatment period, patients collected saliva at 5.00 am; 7.00 am; 3.00 pm; and 11.00 pm. Androstenedione (A4) and 17-hydroxyprogesterone (17OHP) levels in saliva were quantified using liquid chromatography-mass spectrometry. Overnight blood pressure was measured in the last week of each treatment period and sleeping and activity scores were reported for each day during the entire six-week period.
Results: Administration of the highest dose in the evening resulted in significantly lower 17OHP levels in the early morning (5.00 am) but not at 7.00 am, whereas the highest dose in the morning resulted in significantly lower 17OHP and A4 levels in the afternoon. Interestingly, a persistent circadian rhythm of 17OHP and A4 was observed during both treatment regimens. No substantial differences in overnight blood pressure, activity scores, or sleeping scores were found between the two treatment regimens.
Conclusion: The two treatment dose regimens were comparable with respect to overall daily hormonal control, nocturnal blood pressure, and subjective activity and sleep scores. A high-evening-dose regimen resulted in more effective inhibition of the 17OHP rise in the early morning, whereas a high-morning-dose regimen resulted in more effective 17OHP and A4 inhibition in the afternoon. We suggest to individually optimize dose distribution and recommend monitoring disease control at multiple timepoints a day, as single measurements do not reflect hormonal status throughout the day.
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