{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T17:54:03Z","timestamp":1789408443576,"version":"build-2803163510"},"reference-count":35,"publisher":"The Endocrine Society","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2001,9,1]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1210\/jcem.86.9.7816","type":"journal-article","created":{"date-parts":[[2014,1,8]],"date-time":"2014-01-08T17:07:29Z","timestamp":1389200849000},"page":"4068-4071","source":"Crossref","is-referenced-by-count":50,"title":["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"],"prefix":"10.1210","volume":"86","author":[{"given":"Sorahia","family":"Domenice","sequence":"first","affiliation":[{"name":"Unidade de Endocrinologia do Desenvolvimento, Laborato\u0301rio de Hormo\u0302nios e Gene\u0301tica Molecular\/LIM 42 da Disciplina de Endocrinologia e Metabologia (S.D., A.C.L., V.N.B., I.J.P.A., B.B.M.), Caixa Postal 3671, Sao Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Claudia","family":"Latronico","sequence":"additional","affiliation":[{"name":"Unidade de Endocrinologia do Desenvolvimento, Laborato\u0301rio de Hormo\u0302nios e Gene\u0301tica Molecular\/LIM 42 da Disciplina de Endocrinologia e Metabologia (S.D., A.C.L., V.N.B., I.J.P.A., B.B.M.), Caixa Postal 3671, Sao Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinicius Nahime","family":"Brito","sequence":"additional","affiliation":[{"name":"Unidade de Endocrinologia do Desenvolvimento, Laborato\u0301rio de Hormo\u0302nios e Gene\u0301tica Molecular\/LIM 42 da Disciplina de Endocrinologia e Metabologia (S.D., A.C.L., V.N.B., I.J.P.A., B.B.M.), Caixa Postal 3671, Sao Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivo Jorge Prado","family":"Arnhold","sequence":"additional","affiliation":[{"name":"Unidade de Endocrinologia do Desenvolvimento, Laborato\u0301rio de Hormo\u0302nios e Gene\u0301tica Molecular\/LIM 42 da Disciplina de Endocrinologia e Metabologia (S.D., A.C.L., V.N.B., I.J.P.A., B.B.M.), Caixa Postal 3671, Sao Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Kok","sequence":"additional","affiliation":[{"name":"Departamento de Neurologia, Hospital das Cli\u0301nicas (F.K.), Universidade de Sa\u0303o Paulo, Caixa Postal 3671, Sao Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berenice Bilharinho","family":"Mendonca","sequence":"additional","affiliation":[{"name":"Unidade de Endocrinologia do Desenvolvimento, Laborato\u0301rio de Hormo\u0302nios e Gene\u0301tica Molecular\/LIM 42 da Disciplina de Endocrinologia e Metabologia (S.D., A.C.L., V.N.B., I.J.P.A., B.B.M.), Caixa Postal 3671, Sao Paulo, 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