Endocrine Connections (Sep 2023)

Pilot study shows suppression of mineralocorticoid precursors under high-dose glucocorticoid therapy in pediatric acute lymphoblastic leukemia

  • Paul-Martin Holterhus,
  • Alexandra Kulle,
  • Anne-Marie Till,
  • Caroline Stille,
  • Tabea Lamprecht,
  • Simon Vieth,
  • Melchior Lauten

DOI
https://doi.org/10.1530/EC-23-0002
Journal volume & issue
Vol. 12, no. 10
pp. 1 – 9

Abstract

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Glucocorticoids represent a key element in the treatment of pediatric acute lymphoblastic leukemia (ALL) and lead to adrenal suppression. We aimed to ass ess the differential response profile of adrenal steroids in children with ALL during BFM (Berlin–Frankfurt– Münster) induction treatment. Therefore, we performed liquid chromatography tandem– mass spectrometry (LC–MS/MS)-based steroid profiling of up to se ven consecutive leftover morning serum samples derived from 11 patients (pts) with ALL before (day 0) and during induction therapy at days 1–5, 6–12, 13–26, 27–29, 30–35 and 36–40. 17-hydroxyprogesterone (17OHP), 11-deoxycortisol (11S), cortisol, 11-deoxycorticosterone (DOC), corticosterone and aldosterone were determined in parallel. Subsequently, steroid concentrations were normalized by multiples of median (MOM) to adequately consider pediatric age- and sex-specific reference ranges. MOM-cortisol a nd its precursors MOM– 11S and MOM–17OHP were significantly suppressed by glucocorticoi d treatment until day 29 (P < 8.06 × 10−10, P < 5.102 × 10−5, P < 0.0076, respectively). Cortisol recovered in one of four pts at days 27–29 and in two of five pts at days 36–40. Amo ng the mineralocorticoids, corticosterone was significantly suppressed (P < 3.115 × 10−6). Aldosterone and DOC showed no significant changes when comparing day 0 to the treatm ent time points. However, two ALL patients with ICU treatment due to the sepsis showed significantly lower MOM–DOC (P = 0.006436) during that time and almost always the lowest aldost erone compared to all other time points. Suppression of mineralocorticoid precursors under high-dose glucocorticoid therapy suggests a functional cross talk of central glucocorticoid regulation and adrenal mineralocorticoid synthesis. Our data should stimulate prospective investigation to assess potential clinical relevance.

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