Central Precocious Puberty: Treatment with Triptorelin 11.25 mg

Background. Few data are available on quarterly 11.25 mg GnRH analog treatment in central precocious puberty (CPP). Aim. To assess the efficacy of triptorelin 11.25 mg in children with CPP. Patients. 17 patients (16 females) with CPP (7.9 ± 0.9 years) were treated with triptorelin 11.25 mg/90 days. Methods. Gonadotropins, basal-, and GnRH-stimulated peak, gonadal steroids, and pubertal signs were assessed at preinclusion and at inclusion visit, 3 months, 6 months, and 12 months of treatment. Results. At 3, 6, and 12 months, all patients had suppressed LH peak (<3 IU/L after GnRH stimulation), as well as prepubertal oestradiol levels. Mean LH peak values after GnRH test significantly decreased from 25.7 ± 16.5 IU/L at baseline to 0.9 ± 0.5 IU/L at M3 (P < 0.0001); they did not significantly changed at M6 and M12. Conclusions. Triptorelin 11.25 mg/90 days efficiently suppressed the pituitary-gonadal axis in children with CPP from first administration

Burosumab for X-linked hypophosphatemia in children and adolescents: opinion based on early experience in seven European countries

Given the relatively recent introduction of burosumab in the management of X-linked hypophosphatemia (XLH), there is limited real-world data to guide its use in clinical practice. As a group of European physicians experienced with burosumab treatment in clinical practice, we convened with the objective of sharing these practice-based insights on the use of burosumab in children and adolescents with XLH. We attended two virtual meetings, then discussed key questions via Within3, a virtual online platform. Points of discussion related to patient selection criteria, burosumab starting dose, dose titration and treatment monitoring. Our discussions revealed that criteria for selecting children with XLH varied across Europe from all children above 1 year to only children with overt rickets despite conventional treatment being eligible. We initiated burosumab dosing according to guidance in the Summary of Product Characteristics, an international consensus statement from 2019 and local country guidelines. Dose titration was primarily guided by serum phosphate levels, with some centers also using the ratio of tubular maximum reabsorption of phosphate to glomerular filtration rate (TmP/GFR). We monitored response to burosumab treatment clinically (growth, deformities, bone pain and physical functioning), radiologically (rickets and deformities) and biochemically (serum phosphate, alkaline phosphatase, 1,25-dihydroxyvitamin D, 25-hydroxyvitamin D, urine calcium-creatinine ratio and TmP/GFR). Key suggestions made by our group were initiation of burosumab treatment in children as early as possible, from the age of 1 year, particularly in those with profound rickets, and a need for clinical studies on continuation of burosumab throughout adolescence and into adulthoo

Maternal characteristics during pregnancy and risk factors for positive HIV RNA at delivery: a single-cohort observational study (Brescia, Northern Italy)

<p>Abstract</p> <p>Background</p> <p>Detectable HIV RNA in mothers at delivery is an important risk factor for HIV transmission to newborns. Our hypothesis was that, in migrant women, the risk of detectable HIV RNA at delivery is greater owing to late HIV diagnosis. Therefore, we examined pregnant women by regional provenance and measured variables that could be associated with detectable HIV RNA at delivery.</p> <p>Methods</p> <p>A observational retrospective study was conducted from January 1999 to May 2008. Univariate and multivariable regression analyses (generalized linear models) were used, with detectable HIV RNA at delivery as dependent variable.</p> <p>Results</p> <p>The overall population comprised 154 women (46.8% migrants). Presentation was later in migrant women than Italians, as assessed by CD4-T-cell count at first contact (mean 417/mm³versus 545/mm³, respectively; p = 0.003). Likewise, HIV diagnosis was made before pregnancy and HAART was already prescribed at the time of pregnancy in more Italians (91% and 75%, respectively) than migrants (61% and 42.8%, respectively). A subgroup of women with available HIV RNA close to term (i.e., ≤30 days before labour) was studied for risk factors of detectable HIV RNA (≥50 copies/ml) at delivery. Among 93 women, 25 (26.9%) had detectable HIV RNA. A trend toward an association between non-Italian nationality and detectable HIV RNA at delivery was demonstrated by univariate analysis (relative risk, RR = 1.86; p = 0.099). However, by multivariable regression analysis, the following factors appeared to be more important: lack of stable (i.e., ≥14 days) antiretroviral therapy at the time of HIV RNA testing (RR = 4.3; p < 0.0001), and higher CD4+ T-cell count at pregnancy (per 50/mm³, RR = 0.94; p = 0.038).</p> <p>Conclusions</p> <p>These results reinforce the importance of extensive screening for HIV infection, earlier initiation of antiretroviral therapy and stricter monitoring of pregnant women to reduce the risk of detectable HIV RNA at delivery. Public health interventions should be particularly targeted to migrant women who are frequently unaware of their HIV status at the time of pregnancy.</p

Adult height after spontaneous pubertal growth or GnRH analog treatment in girls with early puberty: a meta-analysis

Early puberty (EP) has been defined as the onset of puberty in the low-normal range; it may be a cause for concern regarding a possible impairment of adult height (AH). This paper meta-analysed data on AH after spontaneous growth or after gonadotropin-releasing hormone (GnRH) analog treatment in girls with EP. A computerized literature search was conducted from 1980 to June 30, 2016. Only published studies in English were considered. Eight papers were selected (483 cases). In untreated girls (n = 300), predicted adult height (PAH) at start of follow-up (â\u88\u920.559 SDS (95%CI â\u88\u921.110 to 0.001); P = 0.050) was close to mid-parental height (MPH) (â\u88\u920.557 SDS (95%CI â\u88\u920.736 to â\u88\u920.419); P < 0.0001) and AH (â\u88\u920.663 SDS (95%CI â\u88\u920.803 to â\u88\u920.524); P < 0.0001). In GnRH analog treated girls (n = 183), PAH before the start of treatment was slightly reduced (â\u88\u920.939 SDS (95%CI â\u88\u921.401 to â\u88\u920.477; P < 0.0001) vs MPH (â\u88\u920.678 SDS (95%CI â\u88\u920.942 to â\u88\u920.414); P < 0.0000), but AH (â\u88\u920.604 SDS (95%CI â\u88\u920.877 to â\u88\u920.338); P < 0.0000) was close to MPH. Conclusion: Present meta-analysis indicates that girls with EP spontaneously reach their MPH and that GnRH analog treatment does not widely change growth outcome. Differences among the selected studies for definition of EP, inclusion criteria, treatment duration, age at discontinuation of therapy, definition of AH may affect results.What is Known:â\u80¢ Early puberty represents a main cause of consultation in paediatric endocrinology offices due to concerns of both practitioners and parents.â\u80¢ Treatment with GnRH analogs is sometimes attempted with the aim to improve adult height.Whatis New:â\u80¢ Untreatedand GnRH analog treated girls with early puberty reached similar adult height.â\u80¢ Adult height was consistent with mid-parental height in both untreated and GnRH analog treated girls with early puberty

Normal Volumetric Bone Mineral Density and Bone Turnover in Young Men with Histories of Constitutional Delay of Puberty

It has been suggested that an appropriate timing of puberty is necessary for normal bone mineral density (BMD) acquisition, which may not be achievable in children with constitutional delay of puberty (CDP). To assess the effect of pubertal delay on BMD, we measured areal BMD (aBMD) at lumbar spine, by dual-energy x-ray absorptiometry (DEXA), in a group of patients with CDP (n=21; mean age, 21.8+/-1.7 yr) at final height and in healthy controls (n=12; mean age, 19.3+/-1.3 yr). A subset of seven patients (group a) were untreated, whereas six subjects (group b) had received im testosterone depot (100 mg/month, for 6-12 months) and 8 boys (group c) oral oxandrolone (1.25-2.5 mg/daily, for 6-28 months) for their pubertal delay. Volumetric BMD (vBMD) was calculated from DEXA measurements. aBMD was reduced in patients with CDP (1.101+/-0.134 g/cm2), in comparison with controls (1.222+/-0.091 g/cm2; P < 0.009); no significant differences were found among the groups (group a, 1.089+/-0.133 g/cm2; group b, 1.111+/-0.118 g/cm2; group c, 1.103+/-0.160 g/cm2). vBMD was not significantly different in patients with CDP (0.327+/-0.021 g/cm3) and in controls (0.337+/-0.017 g/cm3; P= not significant); no significant differences were found among the groups (group a, 0.326+/-0.016 g/cm3; group b, 0.332+/-0.022 g/cm3; group c, 0.330+/-0.021 g/cm3). No differences were found in mineral metabolism and in bone markers between patients and controls; patients did not report an increased fracture rate, compared with controls. Our data indicate that: 1) men with CDP have normal vBMD; 2) the reduced aBMD may be the result of uncritical use of DEXA measurements in subjects with altered growth pattern; and 3) androgen administration during pubertal years did not improve BMD in young men with a history of CDP

Central Precocious Puberty in Boys and Girls: Similarities and Differences

Central precocious puberty (CPP) is due to the premature activation of the hypothalamic–pituitary–gonadal axis, which is responsible for the appearance of secondary sexual characteristics. It occurs before the age of 8 and 9 in girls and boys, respectively. CPP shows higher incidence in females than in males. Causes of CPP are similar in both sexes, but the idiopathic form is more frequent in girls, while organic forms are more frequent in males. Recent studies demonstrated a role of some genetic variants in the pathogenesis of CPP. The diagnostic evaluation based on accurate physical examination, assessment of the pituitary–gonadal axis, pelvic sonography in girls, and determination of bone age. Magnetic resonance of the central nervous system should be done in all boys and selected girls. Since the 1980s, pharmacologic treatment involves the use of gonadotropin-releasing hormone (GnRH) analogs. These drugs are characterized by few side effects and long-term safety. Many data are available on the outcome of GnRH analog treated female patients, while poor data are reported in boys. Adult height is improved in both sexes

Central Precocious Puberty: Adult Height in Girls Treated with Quarterly or Monthly Gonadotropin-Releasing Hormone Analog Triptorelin

Treatment with quarterly gonadotropin-releasing hormone (GnRH) analogs may improve compliance and optimize outcome in girls with central precocious puberty (CPP), but long-term comparative data between the new and the monthly formulations are very scarce. Methods: A group of girls with idiopathic CPP (n = 13; age 7.9 ± 0.6 years) were treated from the beginning with quarterly triptorelin (11.25 mg/90 days) and followed up to the achievement of adult height (AH). A group of girls with idiopathic CPP (n = 12; age 8.0 ± 0.6 years) treated with monthly triptorelin (3.75 mg/28 days) served as controls. Results: The AH (157.1 ± 4.9 cm) of girls treated with quarterly triptorelin was not significantly different from their mid-parental height (159.7 ± 3.8 cm) and significantly increased in comparison with predicted AH (average tables) at the beginning of GnRH analog therapy. The AH of girls treated with quarterly triptorelin was not significantly different in comparison with that of girls treated with the monthly formulation (158.1 ± 6.6 cm; mid-parental height 158.4 ± 5.0 cm). Conclusion: Treatment with quarterly triptorelin formulation permitted to achieve an AH adequate for mid-parental height in girls with CPP. Significant differences of AH between girls with CPP treated with quarterly or monthly formulations were not found