[Endocrinological outcome in children and adolescents survivors of central nervous system tumours after a 5 year follow-up]. / Secuelas endocrinológicas en niños y adolescentes supervivientes de tumores del sistema nervioso central tras 5 años de seguimiento.

INTRODUCTION: Given the successful increase in survival rates with the current treatments for central nervous system tumours (CNST), survivors are at high risk for late adverse effects. PURPOSE: To evaluate the endocrine sequelae in children with CNST according to the type of tumour and treatment received. PATIENTS AND METHODS: A retrospective review of the clinical features, auxology, hormone determinations and imaging findings of 38 patients (36.8% females, 63.2% males) with CNST, with a minimum of 5 years follow-up, was performed. RESULTS: The mean age at diagnosis was 5.34 ± 3.07 years, with 76.3% of the patients having at least one hormone deficiency, of which growth hormone (GH) (73.7% of all patients) was the most prevalent, followed by thyrotropin (TSH) (68.4%), corticotropin (31.6%), antidiuretic hormone (28.9%), and gonadotropin (LH/FSH) (21.1%) deficiency. Precocious puberty was found in 21.1% of patients. After 5 years of follow-up, 28.9% were obese. Craniopharyngioma had more hormone deficiencies, obesity and recurrence rates. The most frequently administered treatment was surgery + chemotherapy + radiotherapy, in 47.4% of the patients. Mean final height (20 patients) was -1.2 1.6 SDS, with a mean difference of -0.53 SDS regarding their target height. CONCLUSIONS: 1) The type of tumour and treatment received influence the endocrinological sequelae. 2) The most frequent hormone deficiencies in all types of CNST, regardless of the treatment received, were GH and TSH. 3) Early diagnosis and prompt intervention of endocrine dysfunction can reduce the morbidity and improve quality of life over the long term.

Increased leptin/adiponectin ratio and free leptin index are markers of insulin resistance in obese girls during pubertal development.

BACKGROUND: Modifications in body fat in obese patients during puberty determine changes in adipokines that affect insulin sensitivity. AIMS: We hypothesized that the leptin/adiponectin (L/A) ratio and free leptin index (FLI) are good markers of insulin resistance (IR) and total body fat (TBF) during pubertal development. METHODS: A prospective study of 32 obese girls (OG) and age-matched control girls (CG) was performed. OG were divided into those that maintained a weight loss (WL) of >1 SD of initial body mass index (BMI) (WL group, n = 25) and those without WL (NWL group, n = 7). Oral glucose tolerance tests (OGTT) were performed to evaluate IR. Correlations of adipokines, L/A, and FLI with BMI, waist circumference, percentage of TBF (%TBF) and IR were performed over pubertal development. RESULTS: The L/A ratio and FLI were increased in OG at baseline. Both indexes decreased in the WL group as puberty progressed, with no change in CG or NWL. In the WL group, a correlation between L/A and FLI with OGTT and %TBF, and L/A and homeostasis model assessment (HOMA) was found throughout the study. CONCLUSION: The L/A ratio and FLI are good markers to follow changes in IR and %TBF after WL during puberty. Insulin more accurately reflects the changes in IR than HOMA.

[Response to 3 years of growth hormone therapy in small for gestational age children: clinical, hormonal and metabolic parameters]. / Respuesta al tratamiento con hormona de crecimiento durante 3 años en niños pequeños para la edad gestacional: parámetros clínicos, hormonales y metabólicos.

AIM: To analyze the effectiveness and safety of growth hormone (GH) treatment, administered over a 3 year period to children small for gestational age (SGA) without catch-up growth, followed up in the Department of Endocrinology at the University Hospital Niño Jesús in Madrid between 2003 and 2011. PATIENTS AND METHODS: Anthropometric and analytical data from 52 SGA patients receiving GH therapy (mean dose: 0.035mg/kg/day) were retrospectively examined in order to determine its influence on linear growth, body composition, bone maturation, carbohydrate and lipid metabolism, thyroid hormone profile and blood pressure. RESULTS: GH treatment induced a significant increase in growth velocity, with the highest rise occurring during the first 12 months of its administration and in children under 5 years of age. Insulin-like growth factor-I levels increased significantly, along with a significant acceleration in bone maturation, with both parameters remaining within normal limits. A progressive rise in fasting glucose levels, glycosylated hemoglobin, baseline insulin, and homeostasis model assessment index, were also found. Low density lipoprotein cholesterol (LDL-c) levels decreased and high density lipoprotein cholesterol levels (HDL-c) increased significantly. The atherogenic ratios of total-cholesterol/HDL-c and LDL-c/HDL-c also decreased significantly. CONCLUSION: GH treatment promotes physical growth in SGA patients, generates certain resistance to the action of insulin, and improves atherogenic risk ratios after 3 years of therapy. Long-term monitoring is required until adult height is reached.

[Testicular and paratesticular tumors during childhood and adolescence]. / Tumores testiculares y paratesticulares en la infancia y adolescencia.

INTRODUCTION: Testicular and paratesticular tumors represent 1-2% of the solid tumors in children. We present a retrospective series of 15 cases in patients less than 18 years of age. RESULTS: The mean age of the patients was 9.7 yrs, 6 of them prepubertal (mean age: 2.08 ± 1 yrs) and 9 pubertal (mean age: 15.1 ± 1.3 yrs). The most common clinical form of presentation was a painless testicular mass. The α-fetoprotein levels were high in 5 patients (yolk-sac tumors and embryonal carcinomas). The pathological study showed 11 primary testicular tumors and 4 paratesticular tumors (rhabdomyosarcomas), with 60% being germinal tumors and the rest non-germinal. Around 60% were malignant tumors (2 from the yolk-sac tumors, 2 embryonal carcinomas, one seminoma and 4 rhabdomyosarcomas). Among the benign tumors, the most common was the mature cystic teratoma. Surgery was the initial treatment in all of the cases (radical orchiectomy in 13 tumors and enucleation in 2 teratomas, with retroperitoneal lymphadenectomy in 4 cases). In 11 patients the tumor was in stage I, while 4 cases (2 embryonal carcinomas and 2 rhabdomyosarcomas) were in stage IV with pulmonary metastasis. Chemotherapy whether or not combined with radiotherapy was applied in 7 patients (4 rhabdomyosarcomas, 2 embryonal carcinomas and one seminoma). CONCLUSIONS: Testicular and paratesticular tumors in prepubertal children show epidemiological, histological, therapeutical and evolutional characteristics well differentiated from postpubertal or adult subjects.

[Primary hypoaldosteronism and moderate bilateral deafness in a child with a homozygous missense mutation (Thr318Met) in the CYP11B2 gene]. / Hipoaldosteronismo primario e hipoacusia bilateral moderada en un niño con una mutación sin sentido en homocigosis (Thr318Met) en el gen CYP11B2.

Isolated congenital hypoaldosteronism is a rare disorder that presents as chronic salt-wasting syndrome during infancy. Aldosterone synthase deficiency due to mutations in CYP11B2 is the underlying cause in most cases. Apart from the classical electrolyte disturbances (hyponatremia and hyperkalemia), no other extra-adrenal features have been described to date. We report a male child with congenital hypoaldosteronism due to a homozygous missense mutation (Thr318Met) in CYP11B2 who also presented with unexplained sensorineural hearing loss.

Increased circulating adiponectin levels and decreased leptin/soluble leptin receptor ratio throughout puberty in female ballet dancers: association with body composition and the delay in puberty.

INTRODUCTION: Ballet dancers (BDs) have a negative energy balance related to physical training that results in alterations in body composition, sexual development, and adipokine secretion. Our aims were to study anthropometric parameters, body composition, and their relationship with adipokines throughout pubertal development. SUBJECTS AND METHODS: We carried out a prospective follow-up study of 22 female Caucasian BDs (Tanner II stage) followed throughout puberty. Nutritional status was determined by measurement of height, weight, and body mass index (BMI). We calculated growth velocity, bone maturity, and body composition at Tanner stages II, III, and V by dual energy X-ray absorptiometry. Circulating leptin, adiponectin, and soluble leptin receptor (sObR) levels were determined. RESULTS: BDs presented a delay in skeletal maturation during puberty, without affectation of final height. Energy intake was deficient according to their physical exercise, and they had a delay of 1 year in the mean age of menarche. Leptin levels were decreased, whereas sObR and adiponectin levels were increased throughout puberty. The percentage of trunk fat, total fat mass, and fat of the extremities was decreased throughout the study period (P<0.01). Lean mass was increased in the lower extremities, and bone mineral density was normal. CONCLUSION: A negative energy balance together with maintained physical exercise induced modifications in body composition in BDs. Changes in leptin and adiponectin levels appear to be more related to total fat content than to BMI. Furthermore, the onset and delayed progress of puberty may be related with an inadequate energy balance due to increased exercise.

Maintained malnutrition produces a progressive decrease in (OPG)/RANKL ratio and leptin levels in patients with anorexia nervosa.

OBJECTIVE: Osteoprotegerin (OPG) and receptor activator of nuclear factor-kappaB ligand (RANKL) are key factors in bone remodeling in patients with anorexia nervosa (AN) and osteopenia. The purpose of this study was to investigate basal serum levels of OPG, RANKL and leptin, as well as bone mineral density (BMD) measured by DEXA at lumbar vertebrae L1-L4, and their evolution during one year in two groups of patients with AN. MATERIAL AND METHODS: Group I included 10 adolescent girls suffering from malnutrition and secondary amenorrhea with an evolution of more than one year at the beginning of the study who received oral estrogen treatment throughout the follow-up period. Group II comprised 10 girls with malnutrition and secondary amenorrhea with an evolution of less than one year who received nutritional treatment only. All parameters were compared with those of a control group of 19 healthy, age-matched girls with normal BMI and regular menstrual cycles. RESULTS: The OPG/RANKL ratio was significantly decreased (p<0.05) after 1 year in group I, a fact that was due to an increase (p<0.05) in serum RANKL values. A correlation between OPG/RANKL and BMD was found in group I at the beginning of the study (r = 0.95; p<0.001). Patients in this group showed lower BMD values (p<0.01), both at diagnosis and at the end of the study, than those of group II patients, who showed normal BMD values. CONCLUSION: The decrease in the OPG/RANKL ratio in girls with AN could partly explain the increase in bone loss that occurs in these patients.

[Familial hypobetalipoproteinemia secondary to a mutation in the apolipoprotein B gene]. / Hipobetalipoproteinemia familiar secundaria a mutación en el gen de la apolipoproteína B.

Familial hypobetalipoproteinemia (FHB) is a rare genetically heterogeneous disorder provoking abnormally low serum levels of apoprotein (apo) B, total cholesterol, and low-density lipoprotein (LDL-C). Patients carrying heterozygous mutations in the APOB (2p24) gene are usually asymptomatic, but homozygous mutations cause clinical disturbances as a result of intestinal fat malabsorption and fat-soluble vitamin deficiency. We present an asymptomatic boy, aged 8 years and 7 months, with low serum levels of apo-B, total cholesterol, triglyceride, LDL-C and very low-density lipoprotein (VLDL-C), as well as vitamin E deficiency. Three asymptomatic relatives also exhibited low apo-B, total cholesterol and LDL-C levels. The APOB (2p24) gene was fully sequenced, demonstrating a heterozygous mutation in exon 26 (G --> T) in all four members of this family. Familial genetic studies in FHB could be useful in the early detection and treatment of homozygous carriers.

[Triptorelin therapy in girls with central precocious puberty increases body mass index]. / El tratamiento con triptorelina en las niñas con pubertad precoz central provoca incremento del índice de masa corporal.

INTRODUCTION: The most important complications of central precocious puberty (CPP) in girls are loss of height and multiple psychosocial problems. OBJECTIVES: To study the effect of triptorelin therapy in a cohort of girls with CPP. PATIENTS AND METHODS: Thirty-four girls diagnosed with organic or idiopathic CPP and treated with monthly triptorelin were studied. Age, height in standard deviation (SD), bone age (Greulich and Pyle), height prediction (Bayle-Pinneau), body mass index (BMI) in SD, uterine size (pelvic ultrasound), target height, cranial magnetic resonance imaging, triptorelin dose, and treatment duration were studied. RESULTS: Triptorelin produced a statistically significant reduction in growth velocity and an increase in BMI after 1 year of therapy and these changes were maintained after discontinuation of therapy. Adult height in these patients was in accordance with their target genetic height, as well as with their predicted height according to the method of Bayley-Pinneau. No significant differences were found between age of menarche in our patients and in controls. Adult height in patients with organic CPP was significantly lower than that in patients with idiopathic CPP. CONCLUSIONS: 1. Triptorelin can increase BMI in girls with CPP. 2. The presence of an organic cause in patients with CPP worsens the prognosis for adult height. 3. The Bayley-Pinneau prediction method for "average" bone age is useful for establishing a prognosis of adult height in girls with CPP treated with triptorelin.

[Central precocious puberty is associated with a high prevalence of organic disease]. / La pubertad precoz central en niños está asociada a una elevada prevalencia de patología orgánica.

INTRODUCTION: The incidence of central precocious puberty (CPP) is lower in boys than in girls; however, the presence of organic disease is more common in boys. OBJECTIVES: To investigate the percentage of CPP secondary to organic disease in boys and to analyze their clinical and biological characteristics at diagnosis, during follow-up, and at the end of therapy. PATIENTS AND METHODS: Eight boys with a diagnosis of CPP treated with triptorelin every 28 days were included. Age, height in standard deviation (SD), body mass index (BMI) in SD, growth velocity in SD, bone age (Greulich and Pyle), predicted height (Bayle-Pinneau), and target height were analyzed. Testicular volume was measured (according to Prader standards) and peak lutein hormone (LH) values and testosterone levels were determined after gonadotropin-releasing hormone (GnRH) stimulus. RESULTS: Seventy-five percent of the patients with CPP had organic disease. After treatment with triptorelin, growth reduction significantly decreased. In contrast, no changes were seen in the difference between bone age and chronological age, due to the slight difference found at diagnosis. Likewise, during treatment, there was no LH peak and testosterone levels were lower than 0.5 ng/ml in response to GnRH stimulus. No changes were observed in weight or BMI. Three patients reached an adult height similar to their genetic height and their predicted height, as estimated by the Bayle-Pinneau method. CONCLUSIONS: 1. Among boys with CPP we found a substantial number of patients with organic disease. 2. Adult height after treatment with triptorelin can reach the normal range. 3. Determination of testosterone levels can be useful in the follow-up of these children during treatment.

[Transitory neonatal diabetes mellitus and pericentric chromosome 9 inversion]. / Diabetes mellitus neonatal transitoria e inversión pericéntrica del cromosoma 9.

Neonatal diabetes mellitus is an infrequent carbohydrate metabolism disorder with an estimated incidence of approximately one case every 400,000 to 600,000 live newborns. We present the case of a 1-month-old girl with irritability, polyuria, and a 24-h history of eagerness to feed, without fever or other associated symptoms. The patient's karyotype, obtained by amniocentesis, was 46XX with a pericentric chromosome 9 inversion. Her birth weight and length were 2,230 g (-2.65 SD) and 46 cm (-1.8 SD), respectively. Glycemic determinations during the first 72 h of extrauterine life oscillated between 90 and 157 mg/dl. Physical examination revealed general involvement, skin and mucosal pallor, evident signs of dehydration, and impaired awareness. Laboratory tests revealed glycemia: 1552 mg/dL, pH 7.16, pCO2: 23.7 mmHg; bicarbonate: 8.1 mEq/L, base excess: -19.1, and positive ketonemia. After initial stabilization, the patient was treated with intravenous fluids and continuous intravenous regular insulin infusion (initial dose 0.03-0.05 IU/kg/h). After intensive treatment, breast feeding was restored and a short-acting insulin analog was administered subcutaneously after every feed (0.1 to 0.3 IU according to capillary glycemic determinations). Insulin requirements decreased and were discontinued when the infant was 5 months old. Currently, the patient is 2 years and 7 months old and her glycemia and glycosylated hemoglobin levels are normal. Anti-islet (ICA and GAD) and anti-tyrosin phosphatase (IA2) antibodies were absent, as were mutations in the glucokinase gene (GCK).