Philipp Augsburger, Jani Liimatta, Christa E Flück

Update on Adrenarche – Still a Mystery

  • Biochemistry (medical)
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry
  • Endocrinology, Diabetes and Metabolism
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Abstract Context Adrenarche marks the timepoint of human adrenal development when the cortex starts secreting androgens in increasing amounts, in healthy children at age 8-9 years, with premature adrenarche (PA) earlier. Because the molecular regulation and significance of adrenarche are unknown, this prepubertal event is characterized descriptively, and PA is a diagnosis by exclusion with unclear consequences at long-term. Evidence acquisition We searched the literature of the past five years including original articles, reviews, and meta-analyses from PubMed, ScienceDirect, Web of Science, Embase, and Scopus, using search terms “adrenarche”, “pubarche”, “DHEAS”, “steroidogenesis”, “adrenal”, and “zona reticularis”. Evidence synthesis Numerous studies addressed different topics of adrenarche and PA. Although basic studies on human adrenal development, zonation and zona reticularis function enhanced our knowledge, the exact mechanism leading to adrenarche remains unsolved. Many regulators seem involved. A promising marker of adrenarche (11-ketotestosterone) was found in the 11-oxy androgen pathway. With current definition the prevalence of PA can be as high as 9-23% in girls and 2-10% in boys, but only a subset of these children might face related adverse health outcomes. Conclusion New criteria for defining adrenarche and PA are needed to identify children at risk for later disease and spare children with a normal variation. Further research is therefore required to understand adrenarche. Prospective, long-term studies should characterize prenatal or early postnatal developmental pathways that modulate trajectories of birth size, early postnatal growth, childhood overweight/obesity, adrenarche and puberty onset, and lead to abnormal sexual maturation, fertility, and other adverse outcomes.

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