The Triptorelin test had high accuracy for the differential diagnosis of CPP vs PT in girls providing a valid alternative to the classical GnRH test. This test also allowed a comprehensive evaluation of the pituitary-ovarian axis.
Commonly known for testosterone secretion, the testes also produce the protein hormones anti-müllerian hormone (AMH), inhibin B, and insulin-like factor 3 (INSL3). AMH and inhibin B are secreted by Sertoli cells, whereas INSL3 is a Leydig cell product. AMH is involved in fetal sex differentiation and induces the regression of the anlagen of the uterus and fallopian tubes. INSL3 participates in fetal testicular descent. Serum testicular protein hormone assessment can be very useful and complementary to testosterone measurements in patients with DSD. AMH and inhibin B determination is extremely helpful during childhood, when basal testosterone is normally low. Serum AMH and inhibin B above the female range are indicative of the presence of testicular tissue, and their circulating levels reflect the amount of functional Sertoli cells. In DSD patients with normal male levels of AMH and inhibin B, the diagnosis of gonadal dysgenesis can be ruled out, and isolated androgen secretion deficiency or androgen insensitivity should be suspected. In externally virilized XY patients with persistent müllerian ducts, serum AMH levels determine the diagnosis to AMH deficiency or resistance. At pubertal age, inhibin B levels serve to predict spermatogenic development.
BackgroundIn girls with Idiopathic Central Precocious Puberty (ICPP) concern has been raised by the potential impact of GnRH-analogues (GnRHa) treatment on body weight. We evaluated the effect of GnRHa on Body Mass Index (BMI) in girls with ICPP according to weight status at diagnosis.MethodsOne hundred seventeen ICPP girls were divided according to pretreatment weight status in: normal weight (NW), overweight (OW) and obese (OB). BMI at one and two years of treatment was assessed. BMI-SDS of 60 patients who reached adult height (AH) was compared to that of 33 ICPP untreated girls.ResultsNW girls significantly increased their baseline BMI-SDS at 1 and 2 years of treatment. OW girls only had a significant increment at one year of treatment while OB girls showed no BMI-SDS change. Patients evaluated at AH (at least four years after GnRHa withdrawal) showed a significant decrease on BMI compared to baseline and a significantly lower BMI than the untreated group.ConclusionIn ICPP girls the BMI increase under GnRHa was inversely related to the pretreatment weight status. In the long term follow-up, no detrimental effect of GnRHa on body weight was observed. BMI-SDS was lower in treated than in untreated girls.
Gonadotropin releasing hormone agonists (GnRHa) are standard of care for central precocious puberty (CPP). A 6-month subcutaneous injection has recently been approved by Food and Drug Administration.
Determine efficacy, pharmacokinetics and safety of 6-month 45 mg subcutaneous leuprolide acetate for CPP.
Phase 3 multicenter, open-label, single-arm study.
25 sites in 6 countries.
64 GnRHa naive children with CPP (age: 7.5±0.1 years) received study drug: 59 completed the study.
2 doses of 45 mg subcutaneous leuprolide acetate (0.375 mL) at 0 and 24 weeks, children followed for 48 weeks.
Main Outcome Measure(s)
Percentage of children with serum luteinizing hormone (LH) <4 IU/L 30 minutes following GnRHa stimulation at week 24.
54/62 (87%) children achieved post-stimulation LH <4 IU/L at week 24. 49/56 (88%) girls and 1/2 boys maintained peak LH <4 IU/L at week 48. Mean growth velocity decreased from 8.9 cm/year at week 4 to 6.0 cm/year at week 48. Mean bone age was advanced 3.0 years beyond chronological age at screening and 2.7 years at week 48. Breast pubertal stage regressed or was stable in 97% of girls and external genitalia development regressed in both boys. Adverse events were mild and did not cause treatment discontinuation.
A small volume of 45 mg subcutaneous leuprolide acetate administered at a 6-month interval effectively suppressed pubertal hormones and stopped or caused regression of pubertal progression. This long-acting GnRHa preparation of leuprolide acetate is a new effective and well-tolerated therapy for children with CPP.
Objective: To investigate the occurrence of abnormally elevated values of biomarkers of growth hormone (GH) action in short children on recombinant human GH (rhGH) therapy. Methods: Sixty-three prepubertal short children were examined: 31 with GH deficiency (GHD), 25 small for gestational age (SGA), and 9 with Turner syndrome (TS). The main outcomes were the following: standard deviation score (SDS) values of IGF-I, IGFBP-3, and IGF-I/IGFBP-3 molar ratio before, at the 1st and at the 2nd year on rhGH and Δheight (Ht)-SDS to evaluate GH treatment efficacy (adequate 1st-year ΔHt SDS: >0.4 SDS for GHD and >0.3 SDS for non-GHD). Results: Seventy-eight percent of GHD, 78% of SGA and 55% of TS children had adequate 1st-year ΔHt SDS. In GHD, 88% of IGF-I SDS and IGFBP-3 SDS that were ≤–2.0 SDS at baseline normalized on treatment. Abnormal IGF-I values >+2.0 SDS were observed in 52% of SGA and in 55% of TS patients on rhGH. Within each group, the IGF-I/IGFBP-3 molar ratio increased significantly from pretreatment and throughout therapy, remaining within normal range for most patients. ΔIGF-I/IGFBP-3 molar ratio SDS were significantly higher in children with an adequate response (p < 0.01). Conclusion: Non-GHD groups presented markedly elevated concentrations of GH biomarkers on rhGH and normal IGF-I/IGFBP-3 molar ratio in most patients. Since there is a lack of consensus regarding the molar ratio usefulness, we think that interventions towards a more physiological IGF-I serum profile should be implemented.
Background and aim of the studySerum anti-Müllerian hormone (AMH) is a reliable marker of ovarian reserve, and it has been shown to be correlated with reproductive outcomes in grouped analyses. However, practical data is scarce for the physician and the patients to predict these outcomes in an individual couple according to serum AMH measured prior to assisted reproduction technology (ART) procedures.Study DesignTo address this question, we performed an analytic observational study including 145 females undergoing intracytoplasmic sperm injection (ICSI) in a single center. Results were analyzed according to serum AMH; subgroup analyses were performed by grouping patients according to patient’s age and FSH levels.ResultsThe risk of cycle cancelation decreased from 64% in patients with serum AMH ≤3 pmol/L (0.42 ng/mL) to 21% with AMH ≥15 pmol/L (2.10 ng/mL). Cycle cancelation occurred in approximately two-thirds of the patients with AMH ≤ 3 pmol/L irrespective of the FSH level. However, with higher AMH values the risk of cycle cancelation decreased more significantly in patients with normal FSH. The rate of good response increased from almost null in patients with AMH ≤3 pmol/L to 61% in those with AMH ≥15 pmol/L. The positive correlation between good response and AMH was also significant, but with lower absolute rates, when patients were grouped according to their age or FSH levels. Pregnancy rate increased moderately, but significantly, from 31% with AMH ≤3 pmol/L to 35% with AMH ≥15 pmol/L.ConclusionsWe provide estimates of reproductive outcomes according to individualized values of serum AMH, in general and in subgroups according to patient’s age or serum FSH, which are helpful for the clinician and the couple in their decision making about starting an assisted reproductive treatment.
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