Adrenocorticotropin-Dependent Precocious Puberty of Testicular Origin in a Boy with X-Linked Adrenal Hypoplasia Congenita Due to a Novel Mutation in the DAX1 Gene
Primary adrenal insufficiency is a rare condition in pediatric age, and its association with precocious sexual development is very uncommon. We report a 2-yr-old Brazilian boy with DAX1 gene mutation whose first clinical manifestation was isosexual gonadotropin-independent precocious puberty. He pre...
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Veröffentlicht in: | The journal of clinical endocrinology and metabolism 2001-09, Vol.86 (9), p.4068-4071 |
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Zusammenfassung: | Primary adrenal insufficiency is a rare condition in pediatric age,
and its association with precocious sexual development is very
uncommon. We report a 2-yr-old Brazilian boy with DAX1
gene mutation whose first clinical manifestation was isosexual
gonadotropin-independent precocious puberty. He presented with pubic
hair, enlarged penis and testes, and advanced bone age. T levels were
elevated, whereas basal and GnRH-stimulated LH levels were compatible
with a prepubertal pattern. Chronic GnRH agonist therapy did not reduce
T levels, supporting the diagnosis of gonadotropin-independent
precocious puberty. Testotoxicosis was ruled out after normal
sequencing of exon 11 of the LH receptor gene. At age 3 yr he developed
clinical and hormonal features of severe primary adrenal insufficiency.
The entire coding region of the DAX1 gene was analyzed
through direct sequencing. A nucleotide G insertion between nucleotides
430 and 431 in exon 1, resulting in a novel frameshift mutation and a
premature stop codon at position 71 of DAX-1, was identified.
Surprisingly, steroid replacement therapy induced a clear decrease in
testicular size and T levels to the prepubertal range. These findings
suggest that chronic excessive ACTH levels resulting from adrenal
insufficiency may stimulate Leydig cells and lead to
gonadotropin-independent precocious puberty in some boys with
DAX1 gene mutations. |
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ISSN: | 0021-972X 1945-7197 |
DOI: | 10.1210/jcem.86.9.7816 |