Is physiological glucocorticoid replacement important in children?
Open accessAbstract
Cortisol has a distinct circadian rhythm with low concentrations at night, rising in the early hours of the morning, peaking on waking and declining over the day to low concentrations in the evening. Loss of this circadian rhythm, as seen in jetlag and shift work, is associated with fatigue in the short term and diabetes and obesity in the medium to long term. Patients with adrenal insufficiency on current glucocorticoid replacement with hydrocortisone have unphysiological cortisol concentrations being low on waking and high after each dose of hydrocortisone. Patients with adrenal insufficiency complain of fatigue, a poor quality of life and there is evidence of poor health outcomes including obesity potentially related to glucocorticoid replacement. New technologies are being developed that deliver more physiological glucocorticoid replacement including hydrocortisone by subcutaneous pump, Plenadren, a once-daily modified-release hydrocortisone and Chronocort, a delayed and sustained absorption hydrocortisone formulation that replicates the overnight profile of cortisol. In this review, we summarise the evidence regarding physiological glucocorticoid replacement with a focus on relevance to paediatrics.
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Salivary cortisone is of value in monitoring children with adrenal insufficiency to check for appropriate hydrocortisone replacement.
“This is especially of value in monitoring children with adrenal insufficiency to check for appropriate hydrocortisone replacement [13].”
From Bioavailability of Oral Hydrocortisone Corrected for Binding Proteins and Measured by LC-MS/MS Using Serum Cortisol and Salivary Cortisone (2018) · cites this paper as [13]
The Conclusions (page not provided) say salivary cortisone is a robust measure of blood cortisol and is attractive for studying new hydrocortisone formulations in children. They do not establish its use for routine monitoring of children with adrenal insufficiency to determine whether their replacement is appropriate. (LLM, conf=0.82)
Experimental — accuracy not yet measuredReplacing the natural circadian rhythm of cortisol is not addressed by Alkindi.
“However, replacing the natural circadian rhythm of cortisol is not addressed by Alkindi® (28).”
From Immediate-release granule formulation of hydrocortisone, Alkindi®, for treatment of paediatric adrenal insufficiency (Infacort development programme) (2018) · cites this paper as [28]
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“This is especially of value in monitoring children with adrenal insufficiency to check for appropriate hydrocortisone replacement [13].”
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- Porter, J., Blair, J., & Ross, R. J.
- Affiliations
- Diurnal (United Kingdom) (GB)
- Alder Hey Children's Hospital (GB)
- Corresponding author
- Ross, Richard J
- Venue
- Archives of Disease in Childhood
- Publisher
- BMJ
- Published
- 2016-08-31
- Volume
- 102
- Issue
- 2
- Pages
- 199-205
- ISSN
- 0003-9888 (ISSN-L)
- 1468-2044
- PMC
- PMC5284474
- OpenAlex
- W2507315643
- Cited by
- 50
- References
- 80
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 4 · 2023: 3 · 2022: 7 · 2021: 7 · 2020: 5 · 2019: 5 · 2018: 11 · 2017: 2 · 2016: 2
- FWCI
- 0.98
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Archives of Disease in Childhood (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- European Commission (281654)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Keywords
- adrenal insufficiency, cortisol, diurnal cortisol rhythm, pediatric patients, fatigue, obesity, modified-release hydrocortisone, jet lag, shift work
- MeSH terms
- Adolescent, Adrenal Insufficiency, Adrenal Hyperplasia, Congenital, Child, Child, Preschool, Circadian Rhythm, Drug Administration Schedule, Female, Glucocorticoids, Humans, Hydrocortisone, Hypothalamo-Hypophyseal System, Infant, Infant, Newborn, Male, Pituitary-Adrenal System, Hormone Replacement Therapy, Young Adult
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