Response to ‘Hydrocortisone suspension formulations are not necessarily the same in the treatment of children with congenital adrenal hyperplasia’

in European Journal of Endocrinology
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  • 1 Department of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Freie Universitaet Berlin, Berlin, Germany
  • 2 Graduate Research Training Program, PharMetrX, Berlin, Germany
  • 3 Department of Pharmaceutical Technology and Chemistry, School of Pharmacy and Nutrition, Universidad de Navarra, Pamplona, Spain
  • 4 Charité-Universitätsmedizin, Berlin, Germany
  • 5 Diurnal Limited, Cardiff, UK
  • 6 Institute of Mathematics, Universität Potsdam, Germany
  • 7 University of Sheffield, Sheffield, UK

Correspondence should be addressed to C Kloft; Email: charlotte.kloft@fu‐berlin.de

We were delighted to see the letter to the editor by Sarafoglou et al. (1). The authors highlight important points made in our recent paper on paediatric population pharmacokinetic modelling to assess hydrocortisone replacement dosing regimens in young congenital adrenal hyperplasia (CAH) patients (2).

We acknowledge that extemporaneously compounded hydrocortisone suspensions from specific pharmacies can provide adequate replacement therapy as referenced by Sarafoglou et al. (3, 4). However, as discussed by Sarafoglou, extemporaneously compounded drugs are not subject to the same quality control measures as commercial medications licensed by the US Food and Drug Administration (FDA), which can lead to inconsistent quality between different compounding pharmacies or between batches, and varied results in patients with some patients becoming Cushingoid and some adrenally insufficient (5). In the United States of America (US), there has been little innovation in hydrocortisone therapies for the treatment of CAH over the last 60 years and, currently, there is still no licenced paediatric-specific preparation of hydrocortisone in the US. We acknowledge that in our, Europe-focussed study, this was not referenced.

Lastly, we agree that there is a need for new biomarkers to guide hydrocortisone replacement in CAH to optimise long-term health. In healthy children, considerable interindividual variability in cortisol concentrations exists and in CAH patients, there is variability in response to hydrocortisone replacement therapy. Therefore, we agree that the measurement of cortisol alone is not sufficient to optimise therapy, especially as the current treatment does not replicate the physiological circadian rhythm of cortisol, and so measuring cortisol exposure does not take in to account the impact of unphysiological maximum and minimum concentrations of cortisol replacement therapy. As Sarafoglou et al., suggest, future research is required to determine the biomarkers that in the short term will allow optimisation of hydrocortisone replacement therapy in CAH to improve long-term health outcomes.

In conclusion, both new, easy-to-administer paediatric hydrocortisone formulations with low dose strengths and the consideration of pharmacodynamics biomarkers are avenues that should be investigated further in both Europe and the US to reach the aim of effectively treating our young CAH patients with paediatric appropriate medication.

Declaration of interest

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of this letter.

Funding

This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

References

  • 1

    Sarafoglou K, Jaber M, Al-Kofahi M & Brundage R Hydrocortisone suspension formulations are not necessarily the same in the treatment of children with congenital adrenal hyperplasia. European Journal of Endocrinology 2020 183 L27–L28. (https://doi.org/10.1530/EJE20-0938)

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  • 2

    Michelet R, Melin J, Parra-Guillen ZP, Neumann U, Whitaker JM, Stachanow V, Huisinga W, Porter J, Blankenstein O & Ross RJ Paediatric population pharmacokinetic modelling to assess hydrocortisone replacement dosing regimens in young children. European Journal of Endocrinology 2020 183 357368. (https://doi.org/10.1530/EJE-20-0231)

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  • 3

    Sarafoglou K, Gonzalez-Bolanos MT, Zimmerman CL, Boonstra T, Addo OY & Brundage R Comparison of cortisol exposures and pharmacodynamic adrenal steroid responses to hydrocortisone suspension vs. commercial tablets. Journal of Clinical Pharmacology 2015 55 452457. (https://doi.org/10.1002/jcph.424)

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  • 4

    Al-Rayess H, Fleissner K, Jaber Mt BRC & Sarafoglou K Manipulation of hydrocortisone tablets leads to iatrogenic Cushing syndrome in a 6-year-old girl with CAH. Journal of the Endocrine Society 2020 4 111. (https://doi.org/10.1210/jendso/bvaa091)

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  • 5

    Barillas JE, Eichner D, Van Wagoner R & Speiser PW Iatrogenic Cushing syndrome in a child with congenital adrenal hyperplasia: erroneous compounding of hydrocortisone. Journal of Clinical Endocrinology and Metabolism 2018 103 711. (https://doi.org/10.1210/jc.2017-01595)

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  • 1

    Sarafoglou K, Jaber M, Al-Kofahi M & Brundage R Hydrocortisone suspension formulations are not necessarily the same in the treatment of children with congenital adrenal hyperplasia. European Journal of Endocrinology 2020 183 L27–L28. (https://doi.org/10.1530/EJE20-0938)

    • Search Google Scholar
    • Export Citation
  • 2

    Michelet R, Melin J, Parra-Guillen ZP, Neumann U, Whitaker JM, Stachanow V, Huisinga W, Porter J, Blankenstein O & Ross RJ Paediatric population pharmacokinetic modelling to assess hydrocortisone replacement dosing regimens in young children. European Journal of Endocrinology 2020 183 357368. (https://doi.org/10.1530/EJE-20-0231)

    • Search Google Scholar
    • Export Citation
  • 3

    Sarafoglou K, Gonzalez-Bolanos MT, Zimmerman CL, Boonstra T, Addo OY & Brundage R Comparison of cortisol exposures and pharmacodynamic adrenal steroid responses to hydrocortisone suspension vs. commercial tablets. Journal of Clinical Pharmacology 2015 55 452457. (https://doi.org/10.1002/jcph.424)

    • Search Google Scholar
    • Export Citation
  • 4

    Al-Rayess H, Fleissner K, Jaber Mt BRC & Sarafoglou K Manipulation of hydrocortisone tablets leads to iatrogenic Cushing syndrome in a 6-year-old girl with CAH. Journal of the Endocrine Society 2020 4 111. (https://doi.org/10.1210/jendso/bvaa091)

    • Search Google Scholar
    • Export Citation
  • 5

    Barillas JE, Eichner D, Van Wagoner R & Speiser PW Iatrogenic Cushing syndrome in a child with congenital adrenal hyperplasia: erroneous compounding of hydrocortisone. Journal of Clinical Endocrinology and Metabolism 2018 103 711. (https://doi.org/10.1210/jc.2017-01595)

    • Search Google Scholar
    • Export Citation