Características auxológicas en pacientes pediátricos con déficit aislado permanente o transitorio de hormona del crecimiento. Respuesta al tratamiento y talla final / Auxological characteristics of pediatric patients with permanent or transient isolated growth hormone deficiency. Response to treatment and final height

Introducción: El tratamiento con hormona de crecimiento recombinante (rhGH) ha demostrado mejorar la talla adulta de los pacientes pediátricos con déficit de GH (DGH). Sin embargo, cuando los pacientes son reevaluados al llegar a la talla final, se evidencia que existen pacientes en los que el déficit de GH es permanente (DPGH) y otros en los que el déficit ha sido transitorio (DTGH). El objetivo es evaluar, en una cohorte de pacientes pediátricos con DGH, si existen diferencias en la respuesta al tratamiento con GH en función de que dicho déficit sea permanente o transitorio. Materiales y métodos: Estudio retrospectivo de 89 pacientes con DGH, que fueron seguidos desde el diagnóstico y durante todo el seguimiento hasta la talla adulta. Se obtuvieron parámetros clínicos, auxológicos, radiológicos y analíticos al diagnóstico, así como tras el primer año de tratamiento y en la revisión de la talla final. Resultados: El 28% de los pacientes presentaron un DPGH. Talla inicial de −2,46 ± 0,86 DE en el DPGH y −2,24 ± 0,68 DE en el DTGH. El valor pico de GH al diagnóstico fue de 4,26 ± 2,78 y 6,20 ± 2,01 ng/mL, respectivamente (p < 0,01). Tras el primer año de tratamiento el incremento de la velocidad de crecimiento fue mayor en el grupo de DPGH: 4,33 ± 3,53 DE vs. 2,95 ± 2,54 DE (p = 0,043). Talla final de −0,81 ± 0,87 DE los DPGH y de −0,95 ± 0,83 DE los DTGH (p = 0,47). Conclusiones: Los pacientes con DPGH obtienen un mayor beneficio del tratamiento con rhGH tanto a corto como a largo plazo. Además, muestran niveles más bajos de GH en las pruebas de estímulo al diagnóstico, como ha sido descrito previamente

Introduction: Treatment with recombinant human growth hormone (rhGH) has been shown to improve adult height in pediatric patients with GH deficiency (GHD). However, reassessment of patients after they reach their final height shows some of them have permanent GH deficiency (PGHD), while others had a transient deficiency (TGHD). The study objective was to assess, in a cohort of pediatric patients with GHD, potential differences in response to treatment with rhGH depending on whether deficiency is permanent or transient. Materials and methods: A retrospective study of 89 patients with GHD, who were monitored from diagnosis to adult height. Clinical, auxological, radiographic and laboratory variables were collected at diagnosis, after the first year of treatment, and when they had reached their adult height. Results: PGHD was found in 28% of patients. Initial height was −2.46 ± 0.86 SD and −2.24 ± 0.68 SD in subjects with PGHD and TGHD respectively. Peak GH level at diagnosis was 4.26 ± 2.78 and 6.20 ± 2.01 ng/mL (p < 0.01) in the PGHD and TGHD groups respectively. After the first year of treatment, increase in growth velocity was greater in the PGHD group: 4.33 ± 3.53 SD vs. 2.95 ± 2.54 SD in the PGHD group (p = 0.043). Final height was −0.81 ± 0.87 SD in the PGHD and −0.95 ± 0.83 SD in the TGHD group (p = 0.47). Conclusions: Patients with PGHD had a better short- and long-term response to rhGH. They also showed lower GH levels in stimulation tests at diagnosis, as previously reported

Auxological characteristics of pediatric patients with permanent or transient isolated growth hormone deficiency. Response to treatment and final height. / Características auxológicas en pacientes pediátricos con déficit aislado permanente o transitorio de hormona del crecimiento. Respuesta al tratamiento y talla final.

INTRODUCTION: Treatment with recombinant human growth hormone (rhGH) has been shown to improve adult height in pediatric patients with GH deficiency (GHD). However, reassessment of patients after they reach their final height shows some of them have permanent GH deficiency (PGHD), while others had a transient deficiency (TGHD). The study objective was to assess, in a cohort of pediatric patients with GHD, potential differences in response to treatment with rhGH depending on whether deficiency is permanent or transient. MATERIALS AND METHODS: A retrospective study of 89 patients with GHD, who were monitored from diagnosis to adult height. Clinical, auxological, radiographic and laboratory variables were collected at diagnosis, after the first year of treatment, and when they had reached their adult height. RESULTS: PGHD was found in 28% of patients. Initial height was -2.46 ± 0.86 SD and -2.24 ± 0.68 SD in subjects with PGHD and TGHD respectively. Peak GH level at diagnosis was 4.26 ± 2.78 and 6.20 ± 2.01 ng/mL (p < 0.01) in the PGHD and TGHD groups respectively. After the first year of treatment, increase in growth velocity was greater in the PGHD group: 4.33 ± 3.53 SD vs. 2.95 ± 2.54 SD in the PGHD group (p = 0.043). Final height was -0.81 ± 0.87 SD in the PGHD and -0.95 ± 0.83 SD in the TGHD group (p = 0.47). CONCLUSIONS: Patients with PGHD had a better short- and long-term response to rhGH. They also showed lower GH levels in stimulation tests at diagnosis, as previously reported.

The Brain-Lung-Thyroid syndrome (BLTS): A novel deletion in chromosome 14q13.2-q21.1 expands the phenotype to humoral immunodeficiency.

Genetic defects of NKX2-1 are classically associated with hypothyroidism, benign chorea and neonatal respiratory distress. The purpose of this study was to identify the genetic pathogenesis of the "NKX2-1 triad" in a 10 year-old female presenting additional features barely described in the disorder. In the neonatal period, she presented with generalized hypotonia and respiratory distress, with later episodes of frequent wheezing. At 3 month-age developmental dysplasia of the hip was diagnosed and at 10 months, primary hypothyroidism was detected and treated. Subsequently, delayed achievement of developmental milestones and then subtle choreic movements of extremities were identified at 2 years of age. Furthermore, delayed teeth eruption and agenesis of some dental pieces, short stature and joint hyperlaxity were also noticed. At 10 years, a poor immune response to polysaccharide antigens and hypogammaglobulinemia, including all IgG subclasses were detected. Surprisingly, no mutations were identified in the complete coding region of NKX2-1 by PCR and Sanger sequencing. MLPA showed a de novo loss of gene dosage in all 3 probes located in NKX2-1 exons. A CGH-array identified a deletion of 3.32 Mb in chromosome 14q13.2-q21.1 containing 20 genes, including NKX2-1, PAX9 and two candidate genes (NFKB1A and PPP2R3C) involved in immune response. The Brain-Lung-Thyroid syndrome (OMIM#610978; ORPHA:209905) associated with other clinical phenotypes should suggest monoallelic deletions of chromosome 14 causing haploinsufficiency of NKX2-1, and other contiguous genes like PAX9 (hypodontia) or other dosage-sensitive genes in the chromosomal vicinity that emerge as candidates for hypogammaglobulinemia, mainly NFKBIA.