CYP21 mutations in Brazilian patients with 21-hydroxylase deficiency.

Congenital adrenal hyperplasia caused by 21-hydroxylase deficiency is a common autosomal recessive disorder resulting from mutations in the 21-hydroxylase (CYP21) gene. To develop a strategy to screen for the most commonly occurring CYP21 mutations in Brazil, we performed molecular genotype analysis on 73 children with CAH representing 71 unrelated families. The techniques used for CYP21 molecular genotype analysis were: restriction fragment length polymorphism, single-strand conformational polymorphism, allele-specific oligonucleotide hybridization, allele-specific polymerase chain reaction amplification, and heteroduplex analyses. Mutations were identified on all but eight affected alleles. The intron 2 splicing mutation was the most frequently identified mutation. Screening for the most common mutations detected at least one mutation on 132/142 (93%) alleles. Multiple CYP21 mutations were detected on 16.2% of alleles. The high frequency of multiple mutations on a single allele emphasizes the importance of thorough and accurate molecular genotype analysis of the complex CYP21 locus.

Rathke's cleft cyst as a cause of growth hormone deficiency and micropenis.

Rathke's cleft cyst has rarely been reported in pediatric patients, and such cysts are usually found by chance, in 2-33% of routine necropsies, as they have not interfered with pituitary function. In general, they are intrasellar with a single layer of ciliated cuboidal or columnar epithelium containing mucoid material. The age range in which symptomatic Rathke's cleft cysts occur is between 30 and 60 years. This paper reports an 8.1-year-old boy presenting with growth hormone deficiency and micropenis attributable to hypogonadotropic hypogonadism (HH), implying altered pituitary function since intrauterine life. At this age (before puberty) the diagnosis of HH can be made by means of the LHRH agonist stimulation test, since conventional LHRH is not able to discriminate HH from a normal prepubertal child. To our knowledge, this is the first case of micropenis caused by Rathke's cleft cyst interfering with gonadotropin and growth hormone secretion since intrauterine life.

Pituitary macroadenoma and Cushing's disease in pediatric patients: patient report and review of the literature.

Cushing's syndrome in pediatric patients has been rarely reported and most of the cases are due to adrenal tumors. When the etiology is an ACTH-secreting pituitary adenoma, most often it is a microadenoma. We report on a 9 year-old girl with an ACTH-secreting macroadenoma, whose surgical removal through transsphenoidal approach was extremely difficult due to invasion of the cavernous sinus as well as adjacent structures. After two surgical approaches and stereotactic radiotherapy, she still suffers from the deleterious effects of hypercortisolism, especially marked osteoporosis with vertebral collapse, which interferes with her walking and causes excruciating pain. Two months after the radiotherapy, we still had doubts about the prognosis regarding the persistence of the hypercortisolism. From six months on, her general health started improving, she lost weight, the backache disappeared and her cortisol level returned to normal.