We identified three plasma predictors of LO-CAH in patients presenting with PP. A selective strategy based on a 2-ng/ml basal 17-OHP plasma level threshold would have safely avoided 99% of the unnecessary ACTH tests among our patients.

Summary:findings are used to define the protocol survey and the indications for substitution treatment, and to propose a protocol for re-evaluating ovarian function to detect ovarian Ovarian failure is often brought about by the conditioning protocol used for bone marrow transplantation recovery. (BMT). We monitored ovarian function in 31 girls conditioned for BMT at 10.3 ؎ 0.6 (s.e., 3.2-17.5) years by chemotherapy alone (group 1, n = 8) or chemotherapy Patients and methods plus body irradiation (12 Gy, fractionated in group 2, n = 9, or 10 Gy single total body in group 3, n = 7, and A group of 31 girls who underwent BMT at 3.2-17.5 years were seen at 11.7-18.6 years at the Pediatric Endocrinology 5 or 6 Gy single thoraco-abdominal in group 4, n = 7, irradiation) at 13.4 ؎ 0.4 (11.7-18.6) years. BreastUnit for evaluation of their ovarian function. None of them had any CNS involvement, had been given additional crandevelopment was normal (n = 11), did not occur (n = 14), or did not progress spontaneously (n = 2) after ial or abdomino-pelvic irradiation, or had iron overload due to multiple blood transfusions. All patients had been suc-BMT. The other four girls who menstruated before BMT had permanent amenorrhea. Basal plasma gonacessfully transplanted, and all were considered to be free of their initial disease. Chronic graft-versus-host disease dotropin concentrations were measured in 29; folliclestimulating hormone was increased in them all and occurred in cases 15, 19, 25, 27, 28 and 31. They were assigned to one of four groups, according to luteinizing hormone in 23. At the last clinical evaluation at 16.3 ؎ 0.4 (12.1-21.6) years, 23 girls had complete the conditioning protocol used for BMT (Table 1): chemotherapy alone in group 1; chemotherapy plus body ovarian failure, two had partial ovarian failure, and six had normal ovarian function. Three of these were the irradiation in groups 2-4. Group 2 patients were given 12 Gy total body irradiation (TBI) as 6 fractions of 2 Gy youngest group 1 patients and those who had not received busulfan. We conclude that conditioning for over 3 consecutive days, group 3 patients 10 Gy TBI and group 4 patients 5 (cases 25 and 29) or 6 Gy thoraco-BMT given during childhood frequently prevents normal estrogen secretion at puberty. Adequate substitutabdominal irradiation (TAI) as a single 4-h exposure. At the Institut Curie, TBI was delivered using a 5.5 mV linear ive treatment may be necessary to induce growth acceleration and sexual development.accelerator at 50 cGy/min. Conditioning chemotherapy was melphalan (140 mg/m 2 ), cytarabine (18 g/m 2 ), etoposide Keywords: bone marrow transplantation; body irradiation; chemotherapy; ovarian function; puberty (400 mg/m 2 ) and carmustine (300 mg/m 2 ). At the Saint Louis Hospital, TBI was delivered using a 18 mV linear accelerator at 4.2 cGy/min. Conditioning chemotherapy was cyclophosphamide (120 mg/kg in cases 15, 18, 20, 21 The conditioning regimens used for bone marrow transplanand 23; 150 mg/kg in cases 26, 27, 28, 30 and 31;...

The features of central precocious puberty vary according to the aetiology, but it is impossible to exclude a central nervous system lesion in a given patient with central precocious puberty without performing central nervous system imaging. This imaging remains necessary in all cases of central precocious puberty. Most of the girls with idiopathic central precocious puberty had increased BMI, but we found no correlation between plasma leptin concentrations and gonadotrophin secretion.

BackgroundMutations of the NR5A1 gene encoding steroidogenic factor-1 have been reported in association with a wide spectrum of 46,XY DSD (Disorder of Sex Development) phenotypes including severe forms of hypospadias.Methodology/Principal FindingsWe evaluated the frequency of NR5A1 gene mutations in a large series of patients presenting with 46,XY DSD and hypospadias. Based on their clinical presentation 77 patients were classified either as complete or partial gonadal dysgenesis (uterus seen at genitography and/or surgery, n = 11), ambiguous external genitalia without uterus (n = 33) or hypospadias (n = 33). We identified heterozygous NR5A1 mutations in 4 cases of ambiguous external genitalia without uterus (12.1%; p.Trp279Arg, pArg39Pro, c.390delG, c140_141insCACG) and a de novo missense mutation in one case with distal hypospadias (3%; p.Arg313Cys). Mutant proteins showed reduced transactivation activity and mutants p.Arg39Pro and p.Arg313Cys did not synergize with the GATA4 cofactor to stimulate reporter gene activity, although they retained their ability to physically interact with the GATA4 protein.Conclusions/SignificanceMutations in NR5A1 were observed in 5/77 (6.5%) cases of 46,XY DSD including hypospadias. Excluding the cases of 46,XY gonadal dysgenesis the incidence of NR5A1 mutations was 5/66 (7.6%). An individual with isolated distal hypopadias carried a de novo heterozygous missense mutation, thus extending the range of phenotypes associated with NR5A1 mutations and suggesting that this group of patients should be screened for NR5A1 mutations.

Summary:Conditioning for bone marrow transplantation (BMT) may alter viability of germ cells and production of gonadal hormones. We analyzed the risk factors for gonadal failure after 12 Gy total body irradiation (TBI) given as six fractions (n = 31, group 1), 10 Gy (one dose) TBI (n = 20, group 2), 6 Gy (one dose) total lymphoid irradiation (TLI, n = 17, group 3) and chemotherapy alone (n = 7, group 4), given at 7.7 ± 0.4 (0.6-13.6) years. Among the 34 girls, seven (20.6%) had normal ovarian function with regular spontaneous menstruation and normal plasma follicle-stimulating (FSH) and luteinizing (LH) hormones, five (14.7%) had partial ovarian failure with regular menstruation but increased FSH and/or LH, and 22 (64.7%) had complete ovarian failure. The 24 girls with chronological and bone ages Ͼ13 years included similar percentages, with increased FSH or LH in all four groups. There was a positive correlation between age at BMT and FSH (r = 0.54, P Ͻ 0.01), but not with LH, and between FSH and LH (r = 0.8, P = 0.0003). Plasma FSH concentrations had returned to normal spontaneously in six cases, and those of LH in two cases. Among the 41 boys, 16 (39%) had normal testicular function and 25 (61%) had tubular failure and increased FSH. Of these, 10 also had Leydig cell failure (three complete and seven partial). The 18 boys with chronological and bone ages Ͼ15 years included similar percentages with increased FSH or LH in groups 1 to 3, and testicular volume was significantly lower in group 2 than in group 3 (P = 0.008). There was no correlation between age at BMT and FSH, LH or testosterone, but there was a negative correlation between FSH and inhibin B (rho = −0.87, P Ͻ 0.003). We conclude that girls are more likely to suffer ovarian failure the older they are at BMT, and that early ovarian recovery is possible. Keywords: bone marrow transplantation; fertility; inhibin; irradiation; ovary; testis Conditioning for bone marrow transplantation (BMT) may alter the production of gonadal hormones (estradiol and progesterone in girls, testosterone in boys) and the viability of germ cells. 1-3 Gonadal failure results in incomplete sexual development and growth at puberty, and sterility in adulthood. Gonadal hormones are required for the development of secondary sexual characteristics, and for the growth acceleration which normally occurs at puberty.The risk factors for gonadal failure in patients undergoing BMT are difficult to analyze because of the variety of conditioning regimens used, and the possibility of gonadal recovery. 4 This study analyzes the expression and frequency of gonadal failure in both sexes according to the conditioning protocol, and the significance of the age during childhood at which BMT is carried out. We also measured plasma inhibin B concentrations as an additional marker of tubular function in these young patients where semen analysis is not possible. PatientsThe gonadal function of 75 patients (34 girls and 41 boys) who received a BMT during childhood, and who were aged more than 10 years ...

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Short stature and gonad failure can be a side effect of total body irradiation (TBI). The purpose of the study was to evaluate the factors influencing final height and gonad function after TBI. Fifty young adults given TBI during childhood were included. Twenty-seven had been treated with growth hormone (GH). Those given single 10 Grays (Gy) or fractionated 12 Gy TBI had similar characteristics, GH peaks, final heights and gonad function. After the end of GH treatment, 11/20 patients evaluated had GH peak 410 lg/l. Final height was oÀ2 s.d. in 29 (58%). The height loss between TBI and final height (2.471.1 s.d.) was greater in those who were younger when irradiated (Po0.0001). When the GH-treated and -untreated patients were analyzed separately, this loss was correlated with the age at TBI at 4-8 years for the GHtreated and at 6-8 years for the untreated. Boys showed negative correlations between testicular volume and plasma follicle-stimulating hormone (FSH, P ¼ 0.0008) and between plasma FSH and inhibin B (P ¼ 0.005) concentrations. We concluded that the indications for GH treatment should be mainly based on the age at irradiation, taking into account the GH peak. The plasma FSH and inhibin B concentrations may predict sperm function.

Background/Aims: Hypothalamic hamartoma (HH) is one of the most frequent causes of organic central precocious puberty (CPP). We compared the clinical presentation and the magnetic resonance images (MRI) of 19 patients with HH aged 5.7 ± 4.1 (SD) years at the first endocrine evaluation. They had isolated CPP (group 1, n = 9), CPP plus gelastic seizures (group 2, n = 5), isolated seizures (group 3, n = 4), and 1 patient was asymptomatic. Methods/Results: All patients without neurological symptoms (group 1 and the asymptomatic patient) had pedunculated lesion (diameter 6.4 ± 3.6 (3–15) mm), suspended from the floor of the third ventricle. All patients with neurological symptoms (groups 2 and 3) had sessile lesion (diameter 18.3 ± 9.6 (10–38) mm, p = 0.0005 compared to the others), located in the interpeduncular cistern with extension to the hypothalamus. Seven patients were overweight. The growth hormone peak, free thyroxine, cortisol and prolactin concentrations, and the concomitant plasma and urinary osmolalities were normal in all the cases evaluated. The mean predicted or adult heights of 10 patients treated 5.2 ± 3.3 years for CPP with gonadotropin hormone releasing hormone (GnRH) analog were –0.3 ± 1.7 SD, similar to their target height –0.1 ± 0.9 SD. Conclusion: The clinical presentation of HH depends on its anatomy: small and pedunculated HH are associated with CPP, while large and sessile HH are associated with seizures. The hypothalamic-pituitary function in these cases is normal, which suggests that the absence of CPP is not due to gonadotropin deficiency. GnRH analog treatment preserves the growth potential in those with CPP.