Trisomy of the short stature homeobox-containing gene (SHOX) due to duplication/deletion of the X chomosome: clinical implications on the stature.

BACKGROUND: The karyotypes of 2 patients with abnormal stature and different phenotypes revealed one similar structural abnormality in the X chromosome by conventional cytogenetic studies and fluorescence in situ hybridization analysis (FISH). FISH strongly suggested the presence of two copies of the SHOX gene in the der(X) chromosome. PATIENTS AND RESULTS: Patient 1 is a teenager girl with tall stature, behavioral disturbances and normal pubertal development. The abnormal X chromosome was present in all cells studied. Parent's karyotypes were normal. Patient 2 is a girl with gonadal dysgenesis, mild Turner syndrome phenotype and short stature. The karyotype was a mosaic 45,X/46,X,r(X) and der(X) chromosome presented in most metaphases of the cell lines. Parent's karyotypes were normal. Nearly all duplication of Xp and partial deletion of the long arm (Xq) from Xq27 or Xq21 to Xqter, in cases 1 and 2, respectively, were observed. In both patients, duplication of Xp translocated to deleted Xq occurred leading to a triplication of the pseudoautosomal region 1 (PAR1) where the SHOX gene is located (Xp22.3). CONCLUSIONS: We propose that in some cases of trisomy for the SHOX gene, the effect of overdosage per se may affect the stature, even in patients with preserved ovarian function (case 1), and that estrogen deprivation may not always be a contributor for tall stature (case 2).

Acute effects of testosterone infusion on the serum luteinizing hormone profile in eumenorrheic and polycystic ovary syndrome adolescents.

CONTEXT: Little is known about the neuroendocrine effects of androgens on the GnRH-LH unit in females. OBJECTIVE: Our objective was to evaluate androgen negative feedback on the GnRH-LH axis in eumenorrheic and polycystic ovary syndrome (PCOS) adolescents. DESIGN AND SETTING: We conducted a prospective, longitudinal, randomized, double-blind study at a pediatric endocrinology clinical research center. PARTICIPANTS: Seven nonobese PCOS adolescents and seven matched controls (C) were studied in the early follicular phase of three consecutive menstrual cycles or in three consecutive months. INTERVENTION: Pulsatile LH release was determined during saline [baseline (B)] and constant testosterone (T) infusions: low dose (T-LD) 0.75 and high dose (T-HD) 2.5 mg/12 h iv. Blood samples were drawn every 20 min overnight. MAIN OUTCOME MEASURES: LH (immunofluorometric assay) and T (electrochemiluminescence immunoassay) were determined at B, and during both T-LD and T-HD. LH profiles were analyzed by deconvolution and approximate entropy analyses. RESULTS: On T-LD, C and PCOS serum T levels increased 2- to 3-fold vs. B. On T-HD, T values doubled in both groups vs. T-LD. Controls on T-LD had greater 12-h pulsatile LH secretion rate (P < 0.05 vs. B) and on T-HD had lower mean, pulsatile, basal LH release and LH approximate entropy (vs. B, P < 0.05). PCOS did not respond to T-LD. High-dose T did not alter mean LH in PCOS but increased pulsatile and reduced basal LH secretion. CONCLUSIONS: PCOS adolescents have impaired suppression of pulsatile LH secretion rate consistent with reduced androgen negative feedback. Attenuation of T feedback in nonobese adolescents with PCOS extends the pathophysiology of this syndrome.