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Review
. 2020 Aug;32(4):574-581.
doi: 10.1097/MOP.0000000000000928.

Update on adrenarche

Selma Feldman Witchel  1 , Bianca Pinto  1 , Anne Claire Burghard  2 , Sharon E Oberfield  2
Affiliations
Review

Update on adrenarche

Selma Feldman Witchel et al. Curr Opin Pediatr. 2020 Aug.

Abstract

Purpose of review: Adrenarche is the pubertal maturation of the innermost zone of the adrenal cortex, the zona reticularis. The onset of adrenarche occurs between 6 and 8 years of age when dehydroepiandrosterone sulfate (DHEAS) concentrations increase. This review provides an update on adrenal steroidogenesis and the differential diagnosis of premature development of pubic hair.

Recent findings: The complexity of adrenal steroidogenesis has increased with recognition of the alternative 'backdoor pathway' and the 11-oxo-androgens pathways. Traditionally, sulfated steroids such as DHEAS have been considered to be inactive metabolites. Recent data suggest that intracellular sulfated steroids may function as tissue-specific intracrine hormones particularly in the tissues expressing steroid sulfatases such as ovaries, testes, and placenta.

Summary: The physiologic mechanisms governing the onset of adrenarche remain unclear. To date, no validated regulatory feedback mechanism has been identified for adrenal C19 steroid secretion. Available data indicate that for most children, premature adrenarche is a benign variation of development and a diagnosis of exclusion. Patients with premature adrenarche tend to have higher BMI values. Yet, despite greater knowledge about C19 steroids and zona reticularis function, much remains to be learned about adrenarche.

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Conflict of interest statement

Conflicts of interest: No conflicts of interest, financial or otherwise exist. The authors have agreed on the order of authorship. No competing interests.

Figures

Figure 1.
Figure 1.
Steroid Pathways. A. Classical/Canonical Pathway; B. 11-oxo-Androgen Pathway; C. Alternative Backdoor Pathway. Abbreviations: CYP11A1: cholesterol side chain cleavage; HSD3B2, 3-beta hydroxysteroid dehydrogenase type 2; CYP17A1, 17-alpha hydroxylase/17,20 lyase; CYP21A2, 21-hydroxylase; CYP11B1, 11beta-hydroxylase; CYP11B2, aldosterone synthase; SRD5A1: 5a-reductase type 1, SRD5A2: 5a-reductase type 2, AKR1C1: Aldo-keto reductase type 1 C1, AKR1C2: Aldo-keto reductase type 1 C2, AKR1C3: Aldo-keto reductase type 1 C3, AKR1C4: Aldo-keto reductase type 1 C4, HSD17B3: 17B-hydroxysteroid dehydrogenase type 3, HSD17B6: 17B-hydroxysteroid dehydrogenase type 6
Figure 1.
Figure 1.
Steroid Pathways. A. Classical/Canonical Pathway; B. 11-oxo-Androgen Pathway; C. Alternative Backdoor Pathway. Abbreviations: CYP11A1: cholesterol side chain cleavage; HSD3B2, 3-beta hydroxysteroid dehydrogenase type 2; CYP17A1, 17-alpha hydroxylase/17,20 lyase; CYP21A2, 21-hydroxylase; CYP11B1, 11beta-hydroxylase; CYP11B2, aldosterone synthase; SRD5A1: 5a-reductase type 1, SRD5A2: 5a-reductase type 2, AKR1C1: Aldo-keto reductase type 1 C1, AKR1C2: Aldo-keto reductase type 1 C2, AKR1C3: Aldo-keto reductase type 1 C3, AKR1C4: Aldo-keto reductase type 1 C4, HSD17B3: 17B-hydroxysteroid dehydrogenase type 3, HSD17B6: 17B-hydroxysteroid dehydrogenase type 6
Figure 1.
Figure 1.
Steroid Pathways. A. Classical/Canonical Pathway; B. 11-oxo-Androgen Pathway; C. Alternative Backdoor Pathway. Abbreviations: CYP11A1: cholesterol side chain cleavage; HSD3B2, 3-beta hydroxysteroid dehydrogenase type 2; CYP17A1, 17-alpha hydroxylase/17,20 lyase; CYP21A2, 21-hydroxylase; CYP11B1, 11beta-hydroxylase; CYP11B2, aldosterone synthase; SRD5A1: 5a-reductase type 1, SRD5A2: 5a-reductase type 2, AKR1C1: Aldo-keto reductase type 1 C1, AKR1C2: Aldo-keto reductase type 1 C2, AKR1C3: Aldo-keto reductase type 1 C3, AKR1C4: Aldo-keto reductase type 1 C4, HSD17B3: 17B-hydroxysteroid dehydrogenase type 3, HSD17B6: 17B-hydroxysteroid dehydrogenase type 6
Figure 2.
Figure 2.
Algorithm to evaluate adrenarche. This algorithm provides guidance for evaluation of children with premature pubarche. For patients with CPP, breast development in girls and testicular enlargement in boys usually precedes pubic hair development. Rare forms of CAH include 3-hydroxysteroid dehydrogenase deficiency due to HSD3B2 mutations and 11-hydroxylase deficiency due to CYP11B1 mutations. Another rare genetic disorder is apparent cortisone reductase deficiency due to H6PD mutations.
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