Adrenal steroidogenic function in a black and Hispanic population with precocious pubarche

Area of Science:

• Pediatric Endocrinology
• Steroid Biochemistry
• Genetics

Background:

• Precocious pubarche (PP) is characterized by early development of pubic hair, raising concerns about underlying adrenal steroidogenic function.
• Evaluating adrenal steroid responses to ACTH stimulation is crucial for diagnosing conditions like congenital adrenal hyperplasia and other steroidogenic enzyme deficiencies.
• Distinguishing between normal variants and pathological conditions in PP requires precise assessment of specific steroid precursors and metabolites.

Purpose of the Study:

• To evaluate adrenal steroidogenic function in children with precocious pubarche (PP) using ACTH stimulation tests.
• To identify potential deficiencies in key steroidogenic enzymes, specifically 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD).
• To correlate specific steroid ratios with clinical and developmental parameters in children with PP.

Main Methods:

• Adrenal steroidogenic function was assessed in 34 children with PP and 16 normal controls via ACTH-(1-24) stimulation.
• Stimulated levels of 17-hydroxyprogesterone (17-OHP), 11-deoxycortisol, and desoxycorticosterone were measured to rule out 21-hydroxylase and 11 beta-hydroxylase deficiencies.
• Patients were categorized into PP1, PP2, and PP3 groups based on the delta 5-17-hydroxypregnenolone/17-OHP ratio to assess for 3 beta-HSD deficiency.

Main Results:

• All patients had normal stimulated levels of 17-OHP and 11-deoxycortisol, excluding 21-hydroxylase and 11 beta-hydroxylase deficiencies.
• Four patients (PP3 group) showed significantly elevated delta 5-17P/17-OHP ratios, suggesting a possible nonclassical 3 beta-HSD deficiency.
• These four patients also exhibited the greatest increase in delta 5-17P and dehydroepiandrosterone (DHEA) levels and the highest delta 5-17P/cortisol ratio.

Conclusions:

• The findings suggest a possible nonclassical 3 beta-HSD deficiency in a subset of children presenting with precocious pubarche.
• The elevated delta 5-17P/17-OHP ratio and increased androgen precursors are indicative of impaired 3 beta-HSD activity.
• Further investigation is warranted to confirm the diagnosis and understand the long-term implications of this potential deficiency in children with PP.