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Cited by 13Adrenal Hormones and DisordersStress Responses and CortisolThyroid Disorders and Treatments

Adrenal crisis in infants and young children with adrenal insufficiency: Management and prevention

Open access
Bizzarri, Carla, Capalbo, Donatella, Wasniewska, Malgorzata Gabriela, Baronio, Federico, Grandone, Anna, Cappa, Marco·2023·Frontiers in Endocrinology
DOI 10.3389/fendo.2023.1133376PMC PMC9968740
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Abstract

Background: Despite the optimization of replacement therapy, adrenal crises still represent life-threatening emergencies in many children with adrenal insufficiency. Objective: We summarized current standards of clinical practice for adrenal crisis and investigated the prevalence of suspected/incipient adrenal crisis, in relation to different treatment modalities, in a group of children with adrenal insufficiency. Results: Fifty-one children were investigated. Forty-one patients (32 patients <4 yrs and 9 patients >4 yrs) used quartered non-diluted 10 mg tablets. Two patients <4 yrs used a micronized weighted formulation obtained from 10 mg tablets. Two patients <4 yrs used a liquid formulation. Six patients >4 yrs used crushed non-diluted 10 mg tablets. The overall number of episodes of adrenal crisis was 7.3/patient/yr in patients <4yrs and 4.9/patient/yr in patients >4 yrs. The mean number of hospital admissions was 0.5/patient/yr in children <4 yrs and 0.53/patient/yr in children >4 yrs. There was a wide variability in the individual number of events reported. Both children on therapy with a micronized weighted formulation reported no episode of suspected adrenal crisis during the 6-month observation period. Conclusion: Parental education on oral stress dosing and switching to parenteral hydrocortisone when necessary are the essential approaches to prevent adrenal crisis in children.

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Crossref · 10.3389/fendo.2023.1133376

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9 of 9 references verified0 citation errors · 0 not checkable

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Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Adults with PAI for X-ALD can benefit from the dual-release HC formulation (DRHC).

    “Adults with PAI for X-ALD can benefit from the dual-release HC formulation (DRHC), consisting in a system based on an outer layer for immediate release and an inner retard formulation.”

    From X-linked adrenoleukodystrophy and primary adrenal insufficiency (2023) · cites this paper as [42]

    The Hydrocortisone formulations section (page unavailable) describes the dual-release formulation and reports benefits in adults with adrenal insufficiency. It does not establish those benefits specifically for adults with primary adrenal insufficiency due to X-ALD. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • DRHC is considered off-label in children with PAI.

    “Hitherto, this formulation is considered off-label in children with PAI (42).”

    From X-linked adrenoleukodystrophy and primary adrenal insufficiency (2023) · cites this paper as [42]

  • DRHC has proved in comparative studies to have a more natural cortisol profile.

    “DRHC has proved in comparative studies to have a more natural cortisol profile.”

    From X-linked adrenoleukodystrophy and primary adrenal insufficiency (2023) · cites this paper as [42]

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Percentages, sums and reported differences re-computed from the paper’s own numbers.

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Cites

Flagged first, then by citations

Research works printed but not linked: 14

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  4. [9]Miller BS Spencer SP Geffner ME Gourgari E Lahoti A Kamboj MK. Emergency management of adrenal insufficiency in children: Advocating for treatment options in outpatient and field settings. J Investig Med (2020) 68(1): 16– 25. doi: 10.1136/jim-2019-000999 PMC6996103 30819831 · DOI
  5. [11]Charmandari E Johnston A Brook CG Hindmarsh PC. Bioavailability of oral hydrocortisone in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. J Endocrinol (2001) 169(1): 65– 70. doi: 10.1677/joe.0.1690065 11250647 · DOI
  6. [13]Andersson A Lindemalm S Eksborg S. Dividing the tablets for children – good or bad? Pharm Methods (2016) 7(1): 23–7. doi: 10.5530/phm.2016.7.4 · DOI
  7. [14]Madathilethu J Roberts M Peak M Blair J Prescott R Ford JL. Content uniformity of quartered hydrocortisone tablets in comparison with mini-tablets for paediatric dosing. BMJ Paediatr Open (2018) 2(1): e000198. doi: 10.1136/bmjpo-2017-000198 PMC5843003 29637186 · DOI
  8. [15]Barillas JE Eichner D Van Wagoner R Speiser PW. Iatrogenic cushing syndrome in a child with congenital adrenal hyperplasia: Erroneous compounding of hydrocortisone. J Clin Endocrinol Metab (2018) 103(1): 7– 11. doi: 10.1210/jc.2017-01595 29029106 · DOI · Paper page
  9. [17]Manchanda A Laracy M Savji T Bogner RH. Stability of an alcohol-free, dye-free hydrocortisone (2 mg/mL) compounded oral suspension. Int J Pharm Compd. (2018) 22(1): 66– 75. 29385387
  10. [18]Nilsson AG Bergthorsdottir R Burman P Dahlqvist P Ekman B Engström BE. Long-term safety of once-daily, dual-release hydrocortisone in patients with adrenal insufficiency: A phase 3b, open-label, extension study. Eur J Endocrinol (2017) 176(6): 715–25. doi: 10.1530/EJE-17-0067 PMC5425941 28292927 · DOI
  11. [19]Merke DP Mallappa A Arlt W Brac de la Perriere A Lindén Hirschberg A Juul A. Modified-release hydrocortisone in congenital adrenal hyperplasia. J Clin Endocrinol Metab (2021) 106(5): e2063–77. doi: 10.1210/clinem/dgab051 PMC8063257 33527139 · DOI · Paper page
  12. [20]Neumann U Whitaker MJ Wiegand S Krude H Porter J Davies M. Absorption and tolerability of taste-masked hydrocortisone granules in neonates, infants and children under 6 years of age with adrenal insufficiency. Clin Endocrinol (Oxf). (2018) 88(1): 21–9. doi: 10.1111/cen.13447 28815660 · DOI · Paper page
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Authors
Bizzarri, C., Capalbo, D., Wasniewska, M. G., Baronio, F., Grandone, A., & Cappa, M.
Affiliations
  • Bambino Gesù Children's Hospital (IT)
  • Federico II University Hospital (IT)
  • University of Messina (IT)
  • IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola (IT)
  • University of Campania "Luigi Vanvitelli" (IT)
Corresponding author
Cappa, Marco
ORCID
Venue
Frontiers in Endocrinology
Publisher
Frontiers Media SA
Published
2023-02-13
Volume
14
Pages
1133376-1133376
ISSN
1664-2392 (ISSN-L)
DOI
10.3389/fendo.2023.1133376
PMC
PMC9968740
OpenAlex
W4320495335
Cited by
13
References
9
Citations by year
2026: 4 · 2025: 1 · 2024: 5 · 2023: 3
FWCI
2.67
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Endocrinology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Archivio Istituzionale della Ricerca - Università degli Studi della Campania "Luigi Vanvitelli" (submittedVersion)
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 › Thyroid Disorders and Treatments
Keywords
adrenal crisis, adrenal insufficiency, children, hydrocortisone replacement, crisis prevention, hospitalization, pediatric endocrinology
MeSH terms
Acute Disease, Adrenal Insufficiency, Child, Child, Preschool, Educational Status, Humans, Hydrocortisone, Infant, Hormone Replacement Therapy

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