[Long-term outcomes after hypospadias surgery: Sexual reported outcomes and quality of life in adulthood]. / Vie sexuelle des jeunes adultes opérés dans l'enfance d'un hypospadias postérieur.

OBJECTIVE: To evaluate outcomes and long-term sexual quality of life after hypospadias surgery. Seventeen-years-old patients operated for a posterior hypospadias in childhood were included in a transversal study. PATIENTS AND METHODS: Fifteen patients, among the forty children treated since 1997, accepted to participate. These young men (mean age at the first surgery was 27.9±20months) were clinically reviewed and responded to questionnaires (EUROQOL 5, IIEF15 and non-validated questionnaire). This study arises about 8.4±5years after the last visit in paediatric department. RESULTS: Mean study age was 21.2±4.7years. One third of patients thought that global quality of life was distorted. Although 33% of the patients had erectile dysfunction, 80% were satisfied with their sexual quality of life. The most important complains were relative to the penile appearance. Number of procedures was not predictive of patient's satisfaction about penile function and appearance. Thirty-three percents of the patients would have been satisfied to have psychological and medical support. They would be interested in having contact with patients who suffered from the same congenital abnormality. CONCLUSION: These patients had functional and esthetical disturbances. This visit leads to a specific visit in 20% cases. In this study, medical follow-up does not seem to be counselling and had to be adapted. Adequate follow-up transition between paediatric and adult departments especially during adolescence seems to be necessary.

[Central precocious puberty due to hypothalamic hamartoma in Cameroon]. / Puberté précoce de cause rare au Cameroun: L'Hamartome hypothalamique.

Hypothalamic hamartoma is an uncommon cause of central precocious puberty and sometimes of gelastic epilepsy and delayed development. The purpose of this report is to describe a case of central precocious puberty in an 18-month-old girl who was referred to our department for further investigation of vaginal bleeding that had appeared during the 8th month of life. The patient's puberty was compatible with Tanner stage 3, her psychomotor development was normal, and epilepsy was not observed. Diagnosis was based on abnormal hormonal workup findings and discovery of a hypothalamic hamartoma on brain magnetic resonance imaging. Neurosurgery was not performed. Administration of long-acting gonadotropin releasing hormone analog to slow puberty led to clinical improvement. Hypothalamic hamartoma must always be suspected in case of central precocious puberty. Although magnetic resonance imaging is the most reliable modality, it is not always available nor affordable in low-income countries. Neurosurgery is not indicated in patients without epileptic seizure. Gonadotropin releasing hormone agonists are usually indicated to slow down puberty and improve the adult height. However, the cost is prohibitive in developing countries.

Undervirilization in XY newborns may hide a 5α-reductase deficiency: report of three new SRD5A2 gene mutations.

The observation of ambiguous genitalia in the newborn signals a medical, surgical and psychological emergency. The most crucial decision will be the choice of sex assignment. Rapid and precise diagnosis is thus essential. In XY newborns with normal/high plasma testosterone (T), partial androgen insensitivity syndrome (PAIS) is usually the first diagnosis evoked, which implies an androgen receptor (AR) defect. The diagnosis of steroid-5-alpha-reductase deficiency is rarely considered by the paediatrician. We report three new SRD5A2 gene mutations in four newborns from France, Morocco and Turkey. The newborns presented with ambiguous genitalia and normal plasma T values and the initial diagnosis\PAIS. In all four cases, normal sequences of the complete AR gene excluded this diagnosis and raised the hypothesis of 5α-reductase deficiency. The entire coding region (5 exons) of the SRD5A2 gene was assessed by PCR and direct sequencing analysis. For patient 1, we identified a new homozygous 2bp deletion in exon 1 (c.122_123delAG). Patient 2 had a known homozygous mutation, p.G115D, in exon 2. New compound heterozygous mutations in exon 4 (p.A215V) and exon 5 (p.X255Q) were found in patient 3. Patient 4 presented a new substitution in exon 1 (p.S14R) associated with a known polymorphism (p.V89L). Our data confirm our previous experience and clearly demonstrate that a 5-α reductase defect should be considered in all XY newborns with ambiguous genitalia and normal plasma T secretion, whatever their geographic area or ethnic group; moreover, this defect was not linked to specific phenotype. Early molecular diagnosis is indispensable for the crucial decision of the newborn's sex of rearing.

[Juvenile granulosa-cell tumor: clinical and molecular expression]. / Tumeurs juvéniles de la granulosa: expression clinique et moléculaire.

Ovarian sex cord-stromal tumors are rare tumors that originate from the nongerminal cells of ovary. Two decades ago, the identification of juvenile granulosa-cell tumors (GCT), as a specific entity inside this group, allowed a better treatment of these tumors in children. However, little data have been reported on the natural course of the disease and reliable prognostic factors have not been yet defined. We here review the clinical and genetics aspects of granulosa tumors, based on a series of 40 children. This national collaborative study involved the French Society of Children Cancer and eight clinical departments of pediatric endocrinology. We found that early diagnosis of a tumor, revealed by clinical signs of hyperoestrogeny, is an important prognostic factor. The pathophysiology of these tumors is still debatable and several cellular- and molecular-abnormal signals could be implicated in their development. The role of growth factors and oncogenes through the signaling pathway of MAP kinase is still discussed. According to our data, FSH signaling-transduction pathway, such as a constitutionally activated Galphas, could also be implicated in the induction of granulosa cell proliferation and seems to modulate the invasiveness of the tumor. Last, we have described a low-expression pattern or an extinction of an ovarian-determination gene, FOXL2, which is related to a worse prognosis of this tumor.

[Turner's syndrome and procreation. Ovarian function and Turner's syndrome]. / Syndrome de Turner et procréation. Fonction ovarienne et syndrome de Turner.

Ovarian failure is a typical feature in Turner's syndrome. The majority of follicles disappears prematurely after a normal determination of the ovary. This results from an accelerated loss of oocytes from the ovaries after the 18th week of fetal life or over a few postnatal years, usually before the onset of puberty. The cause and mechanism of this loss are unknown. X chromosomal anomaly due to deletions or haploinsufficiency of genes can explain the various degrees of ovarian failure. Spontaneous puberty occurs in 20-30% of Turner syndrome patients and their fertility rates vary from 5 to 10%. This indicates the possible presence and maturation of follicles in their ovaries in adolescence. In ovarian failure, the hormone replacement therapy (HRT) is necessary to achieve the development of normal female sexual characteristics, the self image or social functioning and to prevent osteoporosis. Pregnancy is now possible with oocyte donation. A careful cardiovascular follow-up is necessary. Cryoconservation represents one way for preserving the future fertility, but the optimal age of ovarian biopsy has to be studied.

[Growth follow-up of SGA children after 3 years of GH treatment]. / Suivi de la croissance chez les enfants de petite taille de naissance après 3 ans de traitement par hormone de croissance: l'expérience d'un centre français.

UNLABELLED: Eighty-five percent of children born with IUGR have spontaneous catch-up growth in the first 2 years of life; however, about 10 to 15% do not catch up. Numerous therapeutic trials have demonstrated the efficacy of GH treatment in these children. However, the duration of this treatment is still discussed. OBJECTIVE: The aim of this study was to describe the evolution of growth during and after the end of treatment. POPULATION AND METHODS: This study followed 33 children in our unit, treated with growth hormone under the French indication (3 years of treatment followed by 1 year off treatment) and with a mean follow-up of 3 years after cessation. RESULTS: During the 3 years of therapy, we confirmed an increase in growth velocity that resulted in a mean height above -2 standard deviation score (SDS) in 25 children at 3 years (mean height of 1.4 SDS). Among the 25 children who achieved a height above -2 SDS at three years and therefore stopped treatment, 15 resumed GH due to a secondary catch-down. Among children who didn't catch-up at 3 years, the continuation of GH treatment didn't seem to improve the growth.

[Construction of a neo-vagina by sigmoidocolpoplasty]. / Reconstruction vaginale par sigmoïdoplastie pour aplasie utérovaginale: Technique chirurgicale et avantages.

Construction of a neo-vagina by sigmoidocolpoplasty has been effective in the treatment of vaginal aplasia, a condition most commonly seen with the Mayer Rokitansky Syndrome. This article describes the surgical technique and principal complications, and reviews the literature to compare this technique with other methods of repair, particularly the Davydov technique.

[Contraception for adolescent : CNGOF Contraception guidelines]. / Contraception de l'adolescente. RPC Contraception CNGOF.

OBJECTIVE: The goal is to establish dialogue and determine the needs and skill levels of adolescence. This concerns sexuality, the prevention of STIs, the informed choice of contraception to avoid an unplanned pregnancy. MéTHODES: A systematic review based on literature about contraception AND teenagers was performed using Pubmed, Cochrane, national and international recommendations. RESULTS: The surveillance of the teenager contraception must integrate more specifically: global health with a stability of weight and corpulence, a sufficient calcium intake, the prevention of the sexually transmitted infections (STIs) and the vaccination against HPV. The 1st consultations with adolescent girls are an essential moment for dialogue in order to develop sexuality education. Main themes are: prevention of STIs with the use of condoms, detection of situations of precariousness or sexual abuse, and finally adherence to treatment to avoid unplanned pregnancy. Use of condoms associated with regular contraception is essential to assure a barrier against sexually transmitted infections (STIs) (NP1). To preserve the patient confidentiality, the patient is received alone (Grade B). She must be reassured about respect of anonymity and availability of free treatment. Clinical examination collects weight, height, BMI and blood pressure (Grade C). It is important to give them the choice of contraceptive method and provide objective information on the different contraceptive methods (NP2). If there are any contraindications, when the first prescription is a pill, it must be a 1st or 2nd generation pill with levonorgestrel. For some experts, it would be important to prescribe a pill at 30µg EE for better efficacy in case of forgetfulness in very young patients and for the good maintenance of bone mineralization (NP4). Information on long-acting reversible contraceptives, or LARCs, is essential. These contraceptive methods have proved their efficacy and their place in the first intention. (NP1). CONCLUSION: Prescribing contraception to a teenage girl requires the adaptation of the best treatment to her needs to prevent an unwanted pregnancy. This requires good information on prevention of STIs and on different methods of contraception in a confidence climate.

[Contraception: CNGOF Guidelines for Clinical Practice (Short Version)]. / Contraception : Recommandations pour la Pratique Clinique du CNGOF (texte court).

The French College of Obstetrics and Gynecology (CNGOF) releases its first global recommendations for clinical practice in contraception, to provide physicians with an updated synthesis of available data as a basis for their practice. The French Health Authority (HAS) methodology was used. Twelve practical issues were selected by the organizing committee and the task force members. The available literature was screened until December 2017, and allowed the release of evidence-based, graded recommendations. This synthesis is issued from 12 developed texts, previously reviewed by experts and physicians from public and private practices, with an experience in the contraceptive field. Male and female sterilization, as well as the use of hormonal treatments without contraceptive label were excluded from the field of this analysis. Specific practical recommendations on the management of contraception prescription, patient information including efficacy, risks, and benefits of the different contraception methods, follow up, intrauterine contraception, emergency contraception, local and natural methods, contraception in teenagers and after 40, contraception in vascular high-risk situations, and in case of cancer risk are provided. The short/mid-term future of contraception mostly relies on improving the use of currently available methods. This includes reinforced information for users and increased access to contraception for women, whatever the social and clinical context. That is the goal of these recommendations.

A case of trisomy 12 mosaicism with pituitary malformation and polycystic ovary syndrome.

We report the case of a patient (followed from birth to 15 years) presenting with trisomy 12 mosaicism, and focus on the endocrine phenotype associating a pituitary malformation and ovarian abnormalities. We describe the dysmorphic features and their evolution, the growth retardation and ovarian symptoms. Complete growth hormone deficiency was confirmed on auxological data, stimulation test and was related to pituitary stalk interruption, diagnosed by magnetic resonance imaging. Effect of growth hormone treatment was satisfactory resulting in a normal adult height. She also presented premature thelarche associated with right ovarian hypertrophy (4 to 5 fold the volume of the left ovary) which remained constant until 15 years of age. Diagnosis of trisomy 12 mosaicism was made on skin and ovarian karyotypes. The possible relation between these endocine findings and some genes located on chromosome 12 involved in pituitary and ovarian development is discussed.

A nationwide study of granulosa cell tumors in pre- and postpubertal girls: missed diagnosis of endocrine manifestations worsens prognosis.

BACKGROUND: There are very few data on the natural history of ovarian granulosa cell tumors (OGCT) in children. The aim of this study was to determine whether early recognition and diagnosis of the initial endocrine signs could improve the outcome of these tumors. METHODS: In a nationwide study from 1990 to 2004, we analyzed the clinical, biological and pathologic data from 40 pre- and postpubertal girls presenting an OGCT. RESULTS: 1. Among the prepubertal girls (n = 29), 17 OGCTs were diagnosed on the basis of precocious pseudopuberty. None of the 17 girls had a peritoneal spread of the tumor (100% FIGO stage Ia). Diagnosis based on a tumoral or acute abdomen (12 cases) was associated with frequent intraperitoneal ruptures of the tumor (50%) and a risk of relapse (2 cases). Of the eight girls who had had a misdiagnosed precocious pseudopuberty, five had a pre- or perioperative tumoral rupture. 2. Among the postpubertal girls (n = 11), endocrine manifestations such as secondary amenorrhea or virilization had been underevaluated in three of them and the diagnosis was established from a tumoral abdomen. This clinical presentation was associated with frequent ruptures of the mass in the peritoneum (80%) and a higher risk of recurrence (30%). 3. A delayed diagnosis of OGCT despite previous endocrine signs (11 cases; 8 pre- and 3 postpubertal) was associated with a high risk of pre- or peri-operative peritoneal tumor spreading (70% FIGO stage Ic or IIc, p <0.05). The mean delay for diagnosis ranged from 3 to 11 months. CONCLUSION: This study highlights the critical role of early diagnosis of OGCT in pre- and postpubertal girls, particularly at the first seemingly banal signs of endocrine disorder. Peritoneal spread of the tumor may thereby be prevented, which improves the prognosis.

Growth hormone (GH) retesting and auxological data in 131 GH-deficient patients after completion of treatment.

GH state and auxological data after completion of GH therapy are reported in 131 patients (79 males, 52 females). They were treated from 1980-1994 for partial (n = 98) or complete (n = 33) GH deficiency (GHD), either idiopathic (n = 121) or organic (n = 10). A single stimulation test (clonidine+betaxolol) was used, and only 50 patients (38%) maintained a blunted response (GH peak below 10 micrograms/L). Although 9 of the 10 patients with organic GHD had an abnormal low GH peak, 67% of patients with idiopathic GHD normalized their GH secretion. This was particularly true of partial GHD patients (71% vs. 36% of complete GH-deficient patients). Based on a retest GH peak below 5 micrograms/L, only 23% of the patients were considered to be GH deficient and therefore candidates for GH treatment during adulthood. We found no significant difference between hormonal state at completion of treatment and initial GH deficiency, pubertal state, or sex, although we did find a significantly lower GH peak value before and after treatment in patients with elevated body mass index. Of the 14 obese children who were treated, 50% had an abnormally low serum insulin-like growth factor-I level, arguing for true GHD, and only two children remained obese at cessation of treatment. Auxological data showed that with a mean duration of treatment of 3.6 +/- 2.0 yr, patients classified as having complete GHD before treatment had significantly greater catch-up growth as expressed in SDS for height than patients with partial GHD (0.6 +/- 1.1 vs. 1.1 +/- 0.7 SDS, P < 0.05), and that boys grew better than girls (1.4 +/- 0.8 vs. 1.6 +/- 0.6 SDS) for height, P < 0.01). That catch-up growth was not correlated with the result of GH peak after cessation of treatment.

Can some growth hormone (GH)-deficient children benefit from combined therapy with gonadotropin-releasing hormone analogs and GH? Results of a retrospective study.

Recombinant GH (rGH) treatment does not invariably correct height deficits in GH-deficient children once puberty has begun. The addition of GnRH analogs (GnRHa) to delay puberty has been advocated, but published results are few and sometimes conflicting. We retrospectively compared GH-deficient children treated with rGH and GnRHa for at least 1 yr after entering puberty and having attained their final height (n = 23) with a matched control group treated only with rGH. Overall, combined therapy did not significantly increase final height relative to rGH alone. However, the shortest girls at the onset of puberty (<25th percentile) benefited more than the tallest (>75th percentile) in both final height relative to predicted height and pubertal catch-up growth. In the control group, patients having experienced intrauterine growth retardation (IUGR) attained a lower mean final height than patients without IUGR (difference significant in boys, but not in girls). In the combined therapy group, IUGR did not affect the final height of either sex. Our results suggest that two populations might benefit most from combined GnRHa and rGH therapy: girls particularly short at the onset of puberty and patients who had experienced IUGR. Further prospective studies are required to confirm these preliminary hypothesis.

Growth hormone (GH) profiles in response to continuous subcutaneous infusion of GH-releasing hormone(1-29)-NH2 in children with GH deficiency.

Six children presenting with partial growth hormone (GH) deficiency (mean GH peak in two different tests, 8.0 +/- 1.3 micrograms/l) aged 8-10.3 years (mean, 2.7 +/- 0.9 years) were treated for 6 months by continuous subcutaneous infusion of GH-releasing hormone(1-29)-NH2 (GHRH(1-29)-NH2); 24-hour GH profiles and height velocity were measured. A biphasic effect of GHRH(1-29)-NH2 infusion was observed. After an early substantial increase in the 24-hour integrated concentration of GH, from 1.6 +/- 0.1 to 3.5 +/- 0.7 micrograms/l/minute, a subsequent consistent decrease occurred by 3 months, which was more pronounced after 6 months (mean 24-hour integrated concentration of GH, 1.9 +/- 0.9 micrograms/l/minute). This effect reflects modification of both pulse amplitude and frequency of GH secretion. At the end of the study, one child had complete suppression of GH secretion and two others showed only one peak above 5 micrograms/l during a 24-hour period. No correlation was found between these changes and height velocity. Three children did not grow significantly; the other three children who had a growth response to GHRH(1-29)-NH2 were those with the lowest 24-hour integrated GH concentration at the end of the study. The possible mechanisms involved in this biphasic effect, including GHRH antibodies, changes in somatostatin levels and/or desensitization of pituitary GHRH receptors, have been investigated.

[Androgen test: comparison of a low test and a high test in the development of the penis in male pseudohermaphroditism]. / Le test aux androgénes: comparaison d'un test faible et d'un test fort sur le développement du pénis dans les pseudohermaphrodismes masculins.

BACKGROUND: The androgen sensitivity test used in male pseudohermaphroditism for clinical assessment of the androgen sensitivity and prediction of penile development is an important element in choice of gender. However, there is a wide range of testosterone dosage and no standardized test. METHODS AND PATIENTS: Two doses (2.5 mg and 100 mg) of testosterone heptylate were used in six cases of male pseudohermaphrodism with sexual ambiguity and small penis (ages 6 to 18 months). The clinical results were compared with those of the study of androgen receptors. RESULTS: In two cases, both low-dose and high-dose tests resulted in only minimal changes in the penis. In two cases, the low-dose test gave a good result which was confirmed by the high-dose test; on the other hand, in two cases, the low-dose test was considered to be negative whereas the high-dose test led to the development of a normal-sized penis. In all cases except one, there was good concordance between the results of study of androgen receptors and those of the clinical test. CONCLUSION: The high-dose androgen test is thus useful in both diagnosis and treatment and facilitates the gender assignment.

[Precocious puberty and polycystic ovarian syndrome: apropos of 13 cases]. / Puberté précoce et syndrome des ovaires polykystiques: à propos de 13 observations.

BACKGROUND: Precocious puberty and polycystic ovarian syndrome are two different entities which appear at different stages of ovarian development. Their association is uncommon. POPULATION: Thirteen girls presented idiopathic central precocious puberty with sexual development before the age of 8 years; menstruations were seen at the age of 9.5 years in one patient. Nine of them were given medroxyprogesterone or cyproterone acetate and two patients LHRH analog. Menarche occurred at a mean age of 11.8 +/- 1.5 years. After a mean free interval of 22 months, these thirteen patients developed hirsutism with irregular menstruations (eight patients) and weight gain (seven patients). The diagnosis of polycystic ovarian syndrome was confirmed by increased plasma testosterone (mean 91.1 +/- 14 ng/dl) and LH levels during LHRH test and by ultrasonography or coelioscopy. The treatment included cyproterone acetate plus 17 beta oestradiol; it was discontinued in eleven cases after 2 years of treatment. Plasma testosterone levels were normal 6 months later in association with regular menstruations. But three patients presented clinical and hormonal recurrence one year later, requiring repeated treatment. CONCLUSION: This association seems to be related to the same gonadotropin dysfunction. It is necessary to regularly follow patients treated for precocious puberty.

[Morphological anomalies of breasts in adolescent girls and their surgical correction]. / Anomalies morphologiques des seins de l'adolescente et leur correction chirurgicale.

BACKGROUND: Morphological anomalies of the breast in adolescent girls cause considerable psychological distress. Plastic and reconstructive surgery offer the possibility of improving such conditions. The aims of this work were to define and illustrate the various types of anomalies, clarify their distribution and present the repair methods that can be used and the results obtained. POPULATION AND METHODS: A consecutive series of 33 girls under the age of legal majority, admitted over a 1-year period for surgical modifications of breast shape, was studied. The basic anomalies were classified as mammary hypertrophy, hypotrophy, asymmetry, and abnormal shape, among which were Poland's syndrome, tuberous breasts, thelorism and pute ptosis. The basic techniques used were reduction, augmentation with placement of an implant and breast remodeling. Distribution of anomalies was as follows: symmetrical bilateral hypertrophy, 33%; asymmetric bilateral hypertrophy, 30%; unilateral hypertrophy, 6%; combined hyper- and hypotrophy, 3%; unilateral hypotrophy with abnormal shape, 9%; abnormal shape with normal size, 15% and bilateral hypotrophy, 0.3%. Mean hospital stay was 3 days and there were no serious postoperative complications. DISCUSSION: Bilateral hypertrophy was the most frequent disorder and the main drawback was residual scaring. Bilateral hypotrophy was rarely seen since only congenital absence of mammary glands is surgically treated before legal coming of age. The main problem of implants was formation and contraction of fibrous capsules around the implants in 5% of cases. Asymmetry and anomalies of shape were more difficult to treat because each breast requires a different procedure. At the present time, because of the cost/benefit ratio of such procedures, they are reimbursed by health services. CONCLUSION: Although the results are not perfect, the psychological impact of such treatment is highly positive, suggesting that the requests of adolescent girls for this type of surgery may be encouraged.

[How to manage a symptomatic ovarian follicular cyst in a female child?]. / Que faire devant un kyste folliculaire ovarien symptomatique chez la petite fille?

BACKGROUND: --Ovarian cysts are common in childhood but most are non functioning. Treatment of those follicular cysts that develop in young children may be difficult. CASE REPORTS: Case no. 1.--A 1 1/2 month-old baby was admitted because of an acute abdominal syndrome. Ultrasonography showed a pelvic, heterogeneous mass without calcifications. Laparotomy showed right ovarian torsion with necrosis of a cyst requiring ovariectomy. At that time, there was an isolated increase in FSH after LHRH stimulation. A transitory premature thelarche without pubertal type response to LHRH was seen at the age of 3 months. Clinical and ultrasonographic controls remain normal with a follow-up of 1 year. Case no. 2.--A 4 yr 10 m-old girl was admitted because of an acute abdominal syndrome. Ovariectomy was necessary because laparotomy showed right ovarian torsion with necrosis of a cyst. Recurrent abdominal pain, 4 months later, was associated with an enlarged left ovary without sexual precocity. Gonadotropin were slightly increased after LHRH stimulation and the patient was given LHRH agonist that suppressed endogenous LHRH within 3 months. Clinical and ultrasonographic controls remain normal 1 year after cessation of treatment. Case no. 3.--A 19 month-old girl was admitted because of a genital hemorrhage with recent development of secondary sexual characteristics. Skeletal age was 2 yrs. Ultrasonography showed an enlarged uterus and a left ovarian cyst, heterogenous with calcifications. Plasma levels of estradiol were increased but gonadotropin were normal. Ovariectomy was performed, followed by disappearance of secondary sexual characteristics. However, the patient was given LHRH agonist at the age of 2 yr 7 mo because of recurrent pubertal activity. CONCLUSIONS: --These cases underline the difficulty in treating follicular cysts in young girls. The possibility of cyst recurrence with manifestations of pubertal activity after ovariectomy lead to discuss indication of LHRH agonists for an undetermined duration.