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ACTH-dependent precocious pseudopuberty in an infant with DAX1 gene mutation
Diego Yeste1, Cristina González-Niño, Guiomar Pérez de Nanclares
1Pediatric Endocrinology Department, Hospital Universitario Vall d'Hebron, Autonomous University Barcelona, Paseo Vall d'Hebron, 119-129, 08035, Barcelona, Spain. dyeste@vhebron.net
European Journal of Pediatrics
|April 17, 2008
Summary
Mutations in the DAX1 gene cause adrenal hypoplasia congenita (AHC) and precocious puberty. Higher hydrocortisone doses were needed to normalize hormone levels in a patient with AHC and peripheral precocious puberty.
Area of Science:
- Endocrinology
- Genetics
- Molecular Biology
Background:
- The DAX1 gene (Xp21) is crucial for the development of the hypothalamo-pituitary-gonadal and adrenal axes, regulating steroidogenesis.
- Mutations in DAX1 lead to adrenal hypoplasia congenita (AHC) and hypogonadotropic hypogonadism.
Observation:
- A 9-month-old boy presented with macrogenitosomia, pubic hair development, neonatal adrenal crises, and peripheral precocious puberty.
- A novel DAX1 gene mutation (Trp291Arg) was identified, confirming the diagnosis of AHC.
Findings:
- Standard hydrocortisone (HC) replacement doses failed to inhibit adrenocorticotropic hormone (ACTH) and normalize testosterone levels.
- Elevated ACTH and testosterone normalized only after increasing HC dosage to 18 mg/m2/day.
Implications:
- Peripheral precocious puberty in DAX1 mutations may result from ACTH stimulation of Leydig cell melanocortin receptors.
- Loss of DAX1's transcriptional repression leads to overexpression of testicular steroidogenesis activators, contributing to precocious puberty.
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