Raquel Corripio

Central Precocious Puberty in Children Living in Spain: Incidence, Prevalence, and Influence of Adoption and Immigration

CONTEXT No epidemiological data are available on central precocious puberty (CPP) in the general population or in adopted or immigrant children in Spain. OBJECTIVE We aimed to study the incidence and prevalence of CPP, assess the risk of developing this disorder among adopted and immigrant children, and analyze the predictive variables of CPP associated with intracranial pathology. DESIGN, SETTINGS, AND PATIENTS An observational study of children diagnosed with CPP in Spain was carried out between January 2008 and January 2010. A computer program was designed to process clinical and biological data and information on 250 patients treated in 34 pediatric endocrinology units throughout the country. RESULTS Of the patients registered, 226 were girls and 24 were boys. The global incidence rate of CPP was 5.66 cases per million person-years at risk, with an annual incidence ranging between 0.02 and 1.07 new cases per 100,000. The relative risk of CPP in domestic and internationally adopted children compared with those born in Spain was 27.82 (19.99-38.77), whereas the relative risk among immigrants was 1.55 (0.97-2.38). A logistic regression model developed for the study showed that the combined effect of four variables had a significant influence over the presence of organic disease: being male, having been adopted, age at diagnosis, and estimation of adult height. CONCLUSIONS CPP is a rare disease whose risk markedly increases with both national and international adoption but is not influenced by immigration. These results suggest a psychological influence on CPP.

Weight loss in prepubertal obese children is associated with a decrease in adipocyte fatty-acid-binding protein without changes in lipocalin-2: a 2-year longitudinal study

CONTEXT Lipocalin-2 and adipocyte fatty-acid-binding protein (A-FABP or FABP4) are adipokines potentially involved in the pathophysiology of obesity and metabolic syndrome in adults. In children, they have been scarcely studied. OBJECTIVE To analyze lipocalin-2 and A-FABP circulating levels before and after 2 years of a dieting and lifestyle intervention in a prepubertal obese cohort. DESIGN AND SETTING Case-control study with a prospective follow-up of cases for 2 years in our referral pediatric endocrine outpatient center. PATIENTS AND METHODS Seventy-three prepubertal obese children, 8.03 ± 1.08-years old, and 47 age- and gender-matched lean controls were studied. Anthropometric parameters, blood pressure, fasting oral glucose tolerance test, homeostatic model insulin resistance index (HOMA-IR), lipid profile, lipocalin-2, and A-FABP were evaluated. Weight loss was considered if z-score body mass index (BMI) decreased at least 0.5 s.d. RESULTS At baseline, lipocalin-2 and A-FABP were higher in prepubertal obese children than those in lean controls (P<0.001). A-FABP showed a gradual increase, according to the obesity degree (r(2)=0.632; P<0.001). After 2 years, obese patients who lost weight showed a decrease in A-FABP (a mean 2% reduction in BMI was associated with a mean 29% decrease in A-FABP (P<0.001)) without changes in lipocalin-2 levels. Regression model analysis adjusted by age, sex, BMI, and HOMA showed that A-FABP was lower in males (β=-5.77 (CI 95%: -9.7; -1.84)) and was modified by BMI (β=2.7 (CI 95%: 1.77-3.62), r(2)=0.659). Lipocalin-2 was not modified by any of these variables. CONCLUSIONS Prepubertal obese children show high plasma lipocalin-2 and A-FABP levels, but only A-FABP is influenced by weight loss.

Plasma brain-derived neurotrophic factor in prepubertal obese children: results from a 2-year lifestyle intervention programme.

Brain‐derived neurotrophic factor (BDNF) is a neurotrophin potentially involved in the pathophysiology of obesity and metabolic syndrome in adults. In children, it has scarcely been studied.

Pseudohypoaldosteronism without nephropathy masking salt-wasting congenital adrenal hyperplasia genetically confirmed

Salt-losing crisis with hypoglycaemia and shock are the main manifestations of congenital adrenal hyperplasia (CAH) during the first weeks of life, while hyponatremia and hyperpotassemia alone are seen on mineralocorticoid deficiency or resistance. During the neonatal period, high blood levels of adrenal steroids may lead to confusing laboratory tests not being able to identify the real level of each hormone. A 33-day-old male baby was admitted at the emergency department with severe salt-losing crisis (Na+ 99 mEq/l and K+ 9.4 mEq/l) and mild acidosis. No hypoglycaemia or hypotension was seen. Urinary tract infection was excluded. Despite treatment with hydrocortisone and fludrocortisone, hyperpotassemia was hard to control. Laboratory tests could not differentiate between pseudohypoaldosteronism and CAH as both the aldosterone (2454 pg/ml) and 17-OH-progesterone (656.6 ng/ml) levels were high. Diagnosis was made, thanks to the genetic study that proved classical mutations in both alleles of the 21-hydroxylase gene.

Disorder of sex development as a diagnostic clue in the first Spanish known newborn with P450 oxidoreductase deficiency

We report the first known case of p450 oxidoreductase deficiency (PORD) in a Spanish boy who presented ambiguous genitalia at birth as a unique feature. He had palpable gonads in the inguinal canal and a normal 46,XY karyotype. Blood tests showed increased lanosterol and androgen precursors (17-OH-pregnenolone and 17-OH-progesterone) and low adrenal androgens (dehydroepiandrosterone and its sulfate). Blood pressure and serum electrolytes were normal. As he had low-testosterone response to human chorionic gonadotropin stimulation but responded to exogenous testosterone with phallic growth, male sex was assigned. Testosterone/dihydrotestosterone ratio and inhibin B were normal. Adrenal insufficiency was detected by corticotropin test. Hydrocortisone replacement treatment was administered. Congenital adrenal hyperplasia was ruled out and molecular analysis of POR gene showed the missense mutation p.Gly539Arg in compound heterozygosity located at splice acceptor site of intron 2 and the coding variant p.Gly80Arg. Surgery for cryptorchidism and hypospadias was performed.

Changes in Body Mass Index in Girls with Idiopathic Central Precocious Puberty under Gonadotropin-Releasing Hormone Analogue Therapy: The Spanish Registry

Background: The influence of gonadotropin-releasing hormone analogue (GnRHa) treatment on body mass index (BMI) evolution in girls with idiopathic central precocious puberty (CPP) is unclear. Hence, we aimed to evaluate the effect of GnRHa treatment on BMI-standard deviation score (SDS) from diagnosis of idiopathic CPP until adult height. Methods: An observational study of girls diagnosed with CPP in Spain was carried out between January 2008 and December 2014. A computer program was designed to process clinical and biological data from patients treated in 55 departments of pediatric endocrinology throughout the country. The inclusion criteria were (1) girls diagnosed with CPP before 8 years of age; (2) born after 1992; (3) with a difference between bone and chronological age of at least 1 year, and (4) with a luteinizing hormone peak >7 U/l during luteinizing hormone-releasing hormone testing. The influence of GnRHa treatment on BMI-SDS evolution was analyzed. Results: Data from 333 girls (22.2% adopted) were evaluated. We report follow-up data at 6, 12, 24, 36, 48 and 60 months and adult height from 269, 232, 198, 153, 105, 56 and 49 girls, respectively. During treatment, there was an increase in BMI-SDS of 0.43 ± 1.17 (95% CI: 0.20-0.64). At adult height (n = 49), BMI-SDS was 1.51 ± 1.38, which was 0.60 ± 1.09 higher than at diagnosis (95% CI: 0.43-0.75). Conclusions: During treatment with GnRHa, girls experience a significant increase in BMI-SDS that persists after therapy is stopped and adult height has been reached.

Gastric Dilatation and Abdominal Compartment Syndrome in a Child with Prader-Willi Syndrome

Patient: Male, 5 Final Diagnosis: Abdominal compartment Symptoms: Abdominal distension • vomiting Medication: — Clinical Procedure: — Specialty: Pediatrics and Neonatology Objective: Rare disease Background: Prader-Willi syndrome (PWS) is a genetic disorder characterized by initial muscular hypotonia and feeding difficulties, and later an insatiable appetite, hyperphagia and obesity along with mild to moderate intellectual impairment. Affected individuals’ food-seeking behavior and suspected delayed gastric emptying can lead to gastric dilatation with subsequent necrosis and perforation. Case Report: We present the case of a 5-year-old boy diagnosed with Prader-Willi syndrome at neonatal age due to muscular hypotonia, who started growth hormone therapy at 20 months. He presented with two episodes of a rapidly progressing gastric dilatation that led to abdominal hypertension and secondary shock at the age of 2 and 5. No large amount of food was eaten before any of the episodes, and he had abdominal pain and vomiting on both occasions. On arrival at the emergency room, a nasogastric tube was placed and aspiration of food material was performed. Abdominal X-ray and CT scan revealed massive gastric dilatation. He was admitted at the Pediatric Intensive Care Unit and after a variable period of fasting, tolerated oral intake and could be discharged. Conclusions: Gastric dilatation due to gastroparesis in PWS is a rare complication. However, it is a life-threatening situation and physicians should therefore maintain a high level of suspicion for gastric dilatation when patients present with warning symptoms such as abdominal pain or discomfort and vomiting.