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Objectif: Étudier les délais diagnostiques des patients avec déficits en hormone de croissance (GHD) et syndrome d’interruption de tige pituitaire (SIT) et la sensibilité des critères auxologiques de la Growth Hormone Research Society (GHRS). Méthode: La performance de chaque critère de la GHRS a été étudiée sur une cohorte monocentrique de patients diagnostiqués entre 2000 et 2007, le délai diagnostique correspondant à la différence entre la date d’apparition du premier critère et la date du diagnostic, le retard diagnostique étant défini par un délai de plus d’un an. Résultats: 21 patients ont été inclus. Les médianes d’âge au diagnostic et de délai diagnostique étaient respectivement de 3,6 et 2,3 ans, avec un retard diagnostique chez 17 patients (81%). Le critère « taille inférieure à plus de 1,5 DS de la taille cible parentale » était le plus performant : 90% des patients l’ayant présenté avant le diagnostic, à un âge médian de 1 an, c’était le 1er critère à apparaître dans 84% des cas avec un gain diagnostique potentiel médian de 2,1 ans. Conclusion: Dans notre cohorte, le délai pour le diagnostic des GHD avec SIT était long et aurait pu être réduit par l’utilisation des critères de la GHRS. La spécificité d’une telle stratégie doit être testée sur des patients sans GHD. [ABSTRACT FROM AUTHOR]

Management of premature breast or pubic hair development in young girls. Precocious puberty is defined in girls as the development of sexual characteristics before the age of 8 years. It arises successively the two following questions: is the precocious development secondary to an abnormality, and what are the therapeutic indications? Each precocious development (breast or pubic or axillary hair) arises different questions if it is isolated. In the girls, the breast development between 2 and 8 years is secondary to an idiopathic central precocious puberty in the majority of cases. The indication to stop the pubertal development varies according to the presentation. The main difficulty is to distinguish abnormal precocious puberty from the variants of the normal, which are the premature thelarche and adrenarche. This distinction is based on the clinical features, biological and pelvic ultrasound if necessary, and on the follow., Competing Interests: R. Brauner déclare des essais cliniques et des travaux scientifiques pour Lilly France, Merck Serono.

Primary ovarian insufficiency (POI) is characterised by the arrest of normal ovarian function before the age of 40 years and affects 1 % of all women. POI shows familial inheritance suggesting a genetic contribution. NR5A1 is nuclear receptor that regulates the transcription of many genes involved in sexual developmental and reproduction. 18 NR5A1 mutations have been published associated with either anomalies of adrenal or testis development. We have identified NR5A1 mutations associated with POI, including familial cases with affected 46,XY individuals. This demonstrates that NR5A1 plays an important role in ovarian development and function. However several questions remain. What is the incidence of NR5A1 mutations in POI? Is there a genotype/phenotype relationship? Are mutations associated with a progressive loss of reproductive function? Answering these questions will lead to a better understanding of ovarian function and dysfunction and could lead to new therapies for treating POI.

This chapter presents guidelines for the follow-up of children with brain tumors, whether benign or malignant, in their transition to adulthood. The consequences of their disease and its treatment overlap greatly. The complications and long-term follow-up are detailed based on the specialists involved.

Central diabetes insipidus (DI) is extremely rare during the neonatal period. Most cases of central DI are secondary to a known aetiology. Substitutive treatment with desmopressin is effective with nasal or oral preparation, but doses are variable and must be tailored individually. We report on a case in a very low birth weight infant with an idiopathic central DI during the first month of life. He was successfully treated with oral desmopressin. The treatment was maintained after discharge with low doses desmospressin.

Precocious puberty (PP) is defined in girls by the occurrence of pubertal development before the age of 8. This development raises 3 questions: 1) Is it abnormal puberty or variant of the normal? 2) If abnormal puberty, is it of central, hypothalamic-pituitary, or peripheral, ovarian or adrenal origin? 3) If central, is it idiopathic or due to a lesion, and is there indication to treat it? The PP in a girl with no previous medical history is usually of central and idiopathic origin. However, isolated central PP may reveal a CNS lesion, particularly an optic glioma with its risk of blindness. Two independent predictors of CNS lesion are the age at PP onset of less than 6 years old, and increased plasma estradiol concentration. The selection of the girls for neuroradiological imaging should be based on these two parameters. However, neuroradiological imaging remains necessary until the prospective confirmation of their predictive value.

Unlabelled: Abnormalities of thyroid function, specially hypothyroidism, are common complications of head and neck irradiation for childhood cancer. Hyperthyroidism is rare and can be misdiagnosed. We report two observations of this condition., Observations: The first patient received conventional craniospinal irradiation for a localized medulloblastoma. Three years later, he presented with profuse sweating, irritability and paroxysmal tachycardia. Biologic evaluation revealed a peripheral hyperthyroidism. The patient was treated with antithyroidian hormonal treatment. The second patient received an irradiation for an undifferentiated nasopharyngeal carcinoma. Three years later, she developed a progressive thyrotoxicosis which was attributed to hyperthyroidism after six months of evolution. Hormonal treatment improved the clinical state after several weeks., Conclusion: Hyperthyroidism is a rare complication of head and neck irradiation. This condition justifies a periodic and prolonged evaluation of thyroid function.

Cranial irradiation may result in altered hypothalamo-pituitary function in patients treated for cancer distant from this area. Growth hormone (GH) deficiency is the most frequent complication. The frequency, delay of occurrence and severity of GH deficiency depend on the irradiation dose delivered to this area. The other factors influencing the frequency are the age at irradiation and the fractionation schedule. The frequency of other hypothalamo-pituitary changes is also dose-dependent: thyrotropin and gonadotropin deficiencies occur in 50-60% of cases after 50 Gray, and corticotrophin deficiency in 30%. Low dose cranial irradiation may also induce precocious puberty (onset < 8 yr in girls and < 10 yr in boys). The radiation-induced lesions seem to occur in the hypothalamus rather than in the pituitary. There is generally a good correlation between the GH peak and the growth velocity, but there may be normal growth in spite of GH deficiency after low dose or due to precocious puberty, decreased growth velocity in spite of normal GH peak, due to bone irradiation. Results on final height have been optimized by a better indication of GH therapy and by its association with treatment of precocious puberty.

During mammalian embryogenesis, the presence of the SRY gene determines the bipotential gonad to develop as a testis. 46,XY sex reversal has been described in man. It is associated with an essentially female phenotype and a streak gonad. In a collaborative study, we analysed 36 patients with a 46,XY sex reversal. The testis determining region of the Y chromosome was analysed by Southern blotting and by DGGE analysis of the SRY open reading frame (orf). We found a total of 7 mutations in the testis determining region including the SRY gene. This brings to 19 the total number of mutations in SRY associated with sex reversal. No relationship was found between the SRY status and the presence or absence of gonadoblastoma. However, a correlation was observed between the SRY genotype and the histology of the gonad. A mutant in SRY is associated with a completely dysgenetic gonad. The presence of immature testicular tubules is usually observed when SRY is normal. These latter results suggest the existence of as yet unidentified testis determining genes.

Background: Heart failure is a rare manifestation of neonatal hypocalcemia. This paper describes such a case resulting from maternal vitamin D deficiency., Case Report: A full-term boy, born in December after a normal pregnancy, was admitted at the age of 6 weeks because of dyspnea that appeared during suckling. Examination showed heart failure. Electrocardiogram showed that the corrected QT-interval was lengthened (0.54 s, normal < 0.45 s). Echocardiogram showed dilated, hypokinetic myocardiopathy. His serum calcium concentration was low (1.40 mmol/l) and phosphate was high (2.8 mmol/l); his alkaline phosphatase was 513 Ul/l. His blood PTH concentration was high (120 pg/ml) and his 25 (OH) D was low (5 ng/ml). The patient was given calcium (1 g/m2/day) and 1.25 (OH)2 D (2 micrograms/day orally). His serum calcium returned to normal within 4 days, and his cardiac abnormality was resolved within 3 months. His mother's blood 25 (OH) D concentration was very low (3 ng/ml), 6 weeks after birth., Conclusion: Neonatal hypocalcemia appears to have been compounded in this case by a maternal vitamin D deficiency. Hence, all pregnant women at risk of deficiency should be given vitamin D.

Background: The risk of secondary endocrine dysfunction in patients with thalassemia major remains high, despite improvements in the care of hematologic problems., Population and Methods: 31 patients (15 males, 16 females) with thalassemia major were studied. 28 of them had been regularly given blood transfusions since the age of 3.7 +/- 3.6 years. Iron chelation therapy had started before the age of 10 years in 9 patients, after this age in 15 patients; it was not performed or the time not specified in the 7 others. The mean dosage of deferoxamine was 20 +/- 6 mg/kg/day (9.6-34 mg/kg/day). Endocrine functions were evaluated at a mean age of 11.8 +/- 4.9 years and were monitored for 6.1 +/- 4.6 years (0 to 19 years). The hormones assay were: growth hormone (GH), thyroid, adrenal cortex, parathyroid and gonadal functions., Results: The GH peak after stimulation was normal, but plasma somatomedin CIGFI was low and did not increase at puberty. 6 patients had peripheral hypothyroidism. Plasma cortisol was normal in the 16 patients examined, but plasma dehydroepiandrosterone sulfate was low in 24; this might be partly responsible for the delayed development of pubic hair. 2 patients aged 20 and 27 years was suffered from diabetes mellitus. Hypoparathyroidism occurred in 7 patients and 12 of the 24 patients with impuberism had a gonadotropin deficiency. The mean final height was -1.3 +/- 1.0 SD in boys (n = 7, mean age: 20 +/- 1 yr) and -1.3 +/- 0.9 SD in girls (n = 7; mean age: 19 +/- 1 yr), whether puberty was spontaneous or induced., Conclusions: The most frequent endocrine complications in these patients are delayed puberty because of gonadotropin deficiency, hypoparathyroidism and peripheral hypothyroidism. Substitution therapy, using sex steroids at an appropriate age, can induce the pubertal growth spurt.

This study was designed to evaluate the diagnostic, therapeutic, and pathogenetic data provided by magnetic resonance imaging (MRI) in nonneoplastic hypothalamo-pituitary disorders. After determination of age-specific pituitary heights, 46 children with idiopathic growth hormone deficiency (GH peak < 8 ng/ml) were studied. Twenty-nine patients (group I) had pituitary stalk interruption syndrome and 17 (group II) had no anatomic abnormalities. Age-specific pituitary height was decreased by more than 2 SDs in all group I patients versus only 60% (10/17) of group II patients. The GH deficiency was transient in 4 of the 7 children with normal pituitary findings. Forty-seven girls with breast development before eight years of age were also studied: age-specific pituitary height was normal in all girls with premature thelarche and 68% of girls with mild form of central precocious puberty (CPP). Conversely, in 70% of girls with evolutive CPP, age-specific pituitary height was increased by more than 2 SDs. These data show that MRI is useful for the diagnosis of pituitary insufficiency and that multiple anterior pituitary deficiencies can be expected in patients with anatomic abnormalities. MRI is of diagnostic and prognostic usefulness in CPP and, therefore, is of assistance in making therapeutic decisions.

Background: Neonatal hyperthyroidism is a relatively rare condition. It can be severe and difficult to treat when the maternal hyperthyroidism has recently been recognized., Case Report: A baby was born at 37 weeks of gestational age to a mother whose hyperthyroidism was only suspected at the 34th week. The mother was not given propylthiouracil until the day before delivery. At birth, the newborn presented with meconial fluid; it weighed 2,380 grams, was 46 cm long and had a head circumference of 32 cm. Clinical examination showed exophthalmos, tachycardia, hepatosplenomegaly, restlessness, moderate goiter and premature craniosynostosis. Laboratory data showed elevated serum free T4 (76 pmol/l), unmeasurable TSH, and the presence of thyroid-stimulating immunoglobulins. The infant was given propranolol (10 mg/day), and carbimazol (3.75 mg/day) from day 13. Clinical and biological improvement allowed the carbimazol to be stopped at 1 month. A relapse was treated with carbimazol plus L-thyroxine. Both drugs were discontinued at the age of 4 months. At 12 months, the baby is perfectly well and has developed normally., Conclusion: This transient thyrotoxicosis was due to the transplacental passage of TSH receptor antibodies. Its management was difficult because the mother was treated late during her pregnancy.

Sixteen cases of pediatric hyperthyroidism treated by antithyroid drugs are reported. First-line treatment with carbimazole in a mean dose of 19 mg/m2 initially and 7 mg/m2 after one year ensured control of the disease within 6 weeks. Mean follow-up was 4 years. Only two children were able to discontinue the drug, after 9.1 years and 4.6 years. Two other patients had thyroidectomy, after 6.7 years and 3.4 years. The main disadvantages of antithyroid drugs are the need for prolonged treatment and the risk of recurrence. An attempt at treatment discontinuation is warranted in patients with good disease control of 2 to 3 years duration, goiter size reduction, improved exophthalmos, and decreased anti-TSH receptor antibodies.

Two new cases of diffuse hyperplasia of the pancreas are reported. This infrequent condition is caused by intermittent and variable insulin hypersecretion. The hyperinsulinism is responsible for severe, lasting and intractable hypoglycemia that causes seizures and mental retardation. Onset usually occurs in the neonatal period. The diagnosis of hyperinsulinism rests on four criteria: the presence of increased insulin levels in the face of hypoglycemia, the low urinary excretion of ketone bodies during hypoglycemic episodes, the need for more than 15/mg/kg/min glucose to maintain the serum glucose level above 2 mmol/l, and a positive response to glucagon. The topographic diagnosis is often disappointing. Medical treatment of the hypoglycemia with diazoxide is a transient measure. Subtotal pancreatectomy is indispensable. Postoperative results are variable. Insulin deficiency diabetes mellitus is common and unusual in that insulin induces an exaggerated response. Recovery can be observed. If hypoglycemia recurs, diazoxide is often effective.

Treatments given for childhood malignancies can alter gonadal function by several mechanisms: (1) cranial irradiation may cause either gonadotrophin deficiency or premature puberty. (2) Irradiation of the testes can induce germinal epithelium dysfunction even if the dose delivered is very low; Leydig cell failure occurs beyond 5-6 Gy and ovarian insufficiency beyond 6-7 Gy. (3) Chemotherapy is considerably more toxic for the germinal epithelium of the testes than for the ovaries; alkylating agents are especially toxic. Analysis of the consequences of preparation for bone marrow transplantation by chemotherapy or total body irradiation will be required when longer follow-up are available.