Recomendaciones para el diagnóstico y tratamiento de pacientes con formas clásicas de hiperplasia suprarrenal congénita por déficit de 21-hidroxilasa / Recommendations for the diagnosis and treatment of classic forms of 21-hydroxylase-deficient congenital adrenal hyperplasia

La hiperplasia suprarrenal congénita debida al déficit de 21-hidroxilasa es una enfermedad autosómica recesiva causada por mutaciones en el gen CYP21A2. En las formas clásicas se produce defecto de cortisol y aldosterona (insuficiencia suprarrenal y pérdida salina) y virilizacion de la recién nacida afecta con ambigüedad genital. En este artículo ofrecemos algunas recomendaciones para el diagnóstico, que debe ser lo más precoz posible, y el tratamiento, adecuado e individualizado. El estudio genético del paciente y su familia es clave en el diagnóstico del propio afectado, y también permite establecer el consejo genético, así como el diagnóstico y tratamiento prenatales en futuros embarazos (AU)

Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is an autosomal recessive disorder caused by mutations in the CYP21A2 gene. Cortisol and aldosterone synthesis are impaired in the classic forms (adrenal insufficiency and salt-wasting crisis). Females affected are virilised at birth, and are at risk for genital ambiguity. In this article we give recommendations for an early as possible diagnosis and an appropriate and individualised treatment. A patient and family genetic study is essential for the diagnosis of the patient, and allows genetic counselling, as well as a prenatal diagnosis and treatment for future pregnancy (AU)

[Recommendations for the diagnosis and treatment of classic forms of 21-hydroxylase-deficient congenital adrenal hyperplasia]. / Recomendaciones para el diagnóstico y tratamiento de pacientes con formas clásicas de hiperplasia suprarrenal congénita por déficit de 21-hidroxilasa.

Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is an autosomal recessive disorder caused by mutations in the CYP21A2 gene. Cortisol and aldosterone synthesis are impaired in the classic forms (adrenal insufficiency and salt-wasting crisis). Females affected are virilised at birth, and are at risk for genital ambiguity. In this article we give recommendations for an early as possible diagnosis and an appropriate and individualised treatment. A patient and family genetic study is essential for the diagnosis of the patient, and allows genetic counselling, as well as a prenatal diagnosis and treatment for future pregnancy.

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. © 2016 S. Karger AG, Basel.

A follow-up study to monitor adult height among Spanish children with growth hormone deficiency who received biosimilar human recombinant growth hormone (Omnitrope®) during a phase III clinical trial.

INTRODUCTION: An initial Phase III clinical trial has evaluated the efficacy and safety of biosimilar recombinant human growth hormone (rhGH; Omnitrope(®), Sandoz) in Spanish children with growth hormone deficiency (GHD). At the end of the study, those patients still growing were offered to remain on treatment (as in usual clinical practice), and continued to be monitored. The aim of this study was to determine the adult height achieved by the Spanish children who participated in the initial Phase III clinical trial, and to evaluate the long-term safety of rhGH treatment. METHODS: This study was a multicenter, observational, retrospective follow-up study of patients who participated in the Phase III clinical trial (70 patients recruited). Auxological parameters [including height, height velocity, and their associated height standard deviation scores (HSDS)] were obtained from 39 patients. Safety was assessed by recording any adverse events (AEs). RESULTS: In total, 27 men and 12 women provided auxological data. At the start of the follow-up study, the mean age of the patients was 12.5 ± 2.7 years, mean height was 144.8 ± 13.9 cm and mean HSDS was -1.16 ± 0.63. By the end of the follow-up period, mean height had increased to 163.1 ± 7.6 cm (n = 36; men 165.5 ± 7.8 cm, women 157.6 ± 3.2 cm) and mean HSDS also increased to -1.01 ± 0.59 (n = 36; men -1.07 ± 0.52, women -0.86 ± 0.72). In terms of safety, no treatment-related AEs were reported during the study. CONCLUSION: This cohort of Spanish patients with GHD showed a positive response to rhGH treatment, achieving adult height within the local normal ranges. In addition, rhGH treatment was well tolerated, with no new or additional safety concerns.

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.

A novel dysfunctional growth hormone variant (Ile179Met) exhibits a decreased ability to activate the extracellular signal-regulated kinase pathway.

The pituitary-expressed GH1 gene was screened for mutation in a group of 74 children with familial short stature. Two novel mutations were identified: an Ile179Met substitution and a -360A-->G promoter variant. The Ile179Met variant was shown to exhibit a similar degree of resistance to proteolysis as wild-type GH, indicating that the introduction of Met does not cause significant misfolding. Secretion of Ile179Met GH from rat pituitary cells was also similar to that of wild type. Although receptor binding studies failed to show any difference in binding characteristics, molecular modeling studies suggested that the Ile179Met substitution might nevertheless perturb interactions between GH and the GH receptor loop containing the hotspot residue Trp169, thereby affecting signal transduction. The ability of the Ile179Met variant to activate a signal transducer and activator of transcription (STAT) 5-responsive luciferase reporter gene and induce phosphorylation of STAT 5 and ERK was therefore studied. In contrast to its ability to activate STAT 5 normally, activation of ERK by the Ile179Met variant was reduced to half that observed with wild type. Although differential effects on the activation of distinct signaling pathways by a mutant receptor agonist are unprecedented, these findings also suggest that the ERK pathway could play a role in mediating the action of GH.

Tos crónica refleja en el síndrome de Ross / Chronic reflex cough in the Ross's syndrome

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