Central precocious puberty in a patient with X-linked adrenal hypoplasia congenita and Xp21 contiguous gene deletion syndrome

Abstract

X-linked adrenal hypoplasia congenita is caused by the mutation of DAX-1 gene (dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1), and can occur as part of a contiguous gene deletion syndrome in association with glycerol kinase (GK) deficiency, Duchenne muscular dystrophy and X-linked interleukin-1 receptor accessory protein-like 1 (IL1RAPL1) gene deficiency. It is usually associated with hypogonadotropic hypogonadism, although in rare cases, it has been reported to occur in normal puberty or even central precocious puberty. This study addresses a case in which central precocious puberty developed in a boy with X-linked adrenal hypoplasia congenita who had complete deletion of the genes DAX-1, GK and IL1RAPL1 (Xp21 contiguous gene deletion syndrome). Initially he was admitted for the management of adrenal crisis at the age of 2 months, and managed with hydrocortisone and florinef. At 45 months of age, his each testicular volumes of 4 mL and a penile length of 5 cm were noted, with pubic hair of Tanner stage 2. His bone age was advanced and a gonadotropin-releasing hormone (GnRH) stimulation test showed a luteinizing hormone peak of 8.26 IU/L, confirming central precocious puberty. He was then treated with a GnRH agonist, as well as steroid replacement therapy. In Korea, this is the first case of central precocious puberty developed in a male patient with X-linked adrenal hypoplasia congenita.

Central precocious puberty as a prelude to hypogonadism in a patient with Klinefelter syndrome

“…We searched the literature (Medline, PubMed, Embase, and CNKI) using the keywords “central precocious puberty,” “hypogonadism,” “Turner syndrome,” and similar terms, and the results showed that gonadal dysplasia with CPP is not unique to KFS. Similar to KFS, other disorders also occur along with CPP, including Turner syndrome adrenal hypoplasia congenita . All such disorders share the same features: a normal HPG axis, hypogonadism, and the presence of residual gonadal function.…”

“…Similar to KFS, other disorders also occur along with CPP, including Turner syndrome [16][17][18][19][20] adrenal hypoplasia congenita. 21,22 All such disorders share the same features: a normal HPG axis, hypogonadism, and the presence of residual gonadal function. All of these diseases are related to early activation of the HPG axis, leading us to conclude that CPP is a prelude to hypogonadism.…”

Adrenal Hypoplasia Congenita: A Rare Cause of Primary Adrenal Insufficiency and Hypogonadotropic Hypogonadism

“…A case of central precocious puberty has also been reported, adding more questions to the underlying mechanisms that affect puberty in patients with NR0B1 mutations. 13 …”

Central precocious puberty as a prelude of gonad dysplasia

“…AHC is classically known to cause hypogonadotropic hypogonadism, as NR0B1 mutations likely impair gonadotropin production by acting at both the hypothalamic and pituitary levels . However, the onset of puberty can be variable, from arrest of absent puberty to precocious puberty (PP) . The reported cases of PP present with extended mini‐puberty or temporary PP, and then progress to hypogonadotropic hypogonadism (HH).…”