Pediatric Drugs

, Volume 20, Issue 6, pp 567–573 | Cite as

The Challenges of Cortisol Replacement Therapy in Childhood: Observations from a Case Series of Children Treated with Modified-Release Hydrocortisone

  • Julie Park
  • Urmi Das
  • Mohammed Didi
  • Renuka Ramakrishnan
  • Matthew Peak
  • Paul Newland
  • Joanne BlairEmail author
Short Communication



Hydrocortisone is the preferred treatment for adrenal insufficiency in childhood. A small minority of children experience low cortisol concentrations and symptoms of cortisol insufficiency, poorly responsive to modifications in dosing. We speculated that treatment with modified-release hydrocortisone Plenadren® may be beneficial in these selected patients.


The aim of this article was to report cortisol profiles during treatment with standard formulation hydrocortisone and Plenadren, and growth and weight gain during treatment with Plenadren in selected children with adrenal insufficiency.

Patients and Methods

Data are reported as median (range). Eight patients (5 male) age 11.0 years (8.8–13.3), with adrenal insufficiency for 4.3 years (2.2–10.0) were treated with Plenadren in doses derived from cortisol concentrations measured during treatment with standard formulation hydrocortisone.


Plasma cortisol was 262 nmol/L (114–654) 2 h after the morning dose (hydrocortisone dose 6.1 mg/m2 [4.3–7.1]) of standard formulation hydrocortisone. After 4 h, cortisol concentration was 81 nmol/L (56–104) and was < 100 nmol/L in six patients. Two hours after Plenadren administration (hydrocortisone dose 12.1 mg/m2 [8.3–17.6]), plasma cortisol concentration was 349 nmol/L (150–466), and after 4 h it was 239 nmol/L (99–375) and < 100 nmol/L in one patient. Six hours after the Plenadren dose, cortisol concentration was < 100 nmol/L in four patients and after 8 h cortisol concentration was < 100 nmol/L in seven patients (sample not obtained in one patient). Six patients elected to continue treatment with Plenadren. After 4.2 years (2.7–6.0), change in height standard deviation score (SDS) was 0.1 SD (− 0.2 to 0.2) and body mass index SDS was 0.3 SD (0–1.1).


Smoother cortisol profiles and more sustained cortisol exposure were achieved during treatment with Plenadren, which was the preferred treatment in most patients. Robust clinical trials are required to determine the place of this medication in paediatric practice.


Compliance with Ethical Standards


No funding was received to support the work reported in this manuscript.

Conflict of interest

JB has a paid advisory role for a study of modified-release hydrocortisone (Chronocort) in adult patients with congenital adrenal hyperplasia. Authors JP, UD, MP, RR, MD and PN report no conflict of interest.


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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Department of EndocrinologyAlder Hey Children’s NHS Foundation TrustLiverpoolUK
  2. 2.NIHR Alder Hey Clinical Research FacilityAlder Hey Children’s NHS Foundation TrustLiverpoolUK
  3. 3.Department of Clinical BiochemistryAlder Hey Children’s NHS Foundation TrustLiverpoolUK

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