Els glucocortidoides : inhibidors del creixement

L'article següent analitza el paper dels glucocorticoides en la inhibició del creixement fetal en humans. Fins ara, s'ha sabut que l'acció localitzada dels GCs sobre el cartíleg del creixement afecta directament a agents com els factors de creixement similiars a la insulina (IGFs). Tot i això, l'expressió in vivo de les senyals IGF-I i IGF-II sembla ser que depèn de la tècnica d'observació utilitzada i de l'edat de l'animal estudiat. Tot i això, és evident que la disrupció d'aquestes senyals genera un retard molt greu en el creixement intrauterí. Ara, i mitjançant l'estudi amb condròcits epifiseals fetals humans, s'ha pogut observar que el mecanisme inhibitori dels glucocorticoides afecta directament l'expressió gènica del cartíleg, és a dir, l'expressió de les senyals IGF-I però no d'IGF-II. En el cas humà cal remarcar que l'expressió d'IGF-II no varia segons el nivell de concentracions de GCs, demostrant que només l'expressió d'IGF-I és inhibida significativament durant el procés de creixement fetal del cartíleg humà.l siguiente artículo analiza el papel de los glucocorticoides (GCs) en la inhibición del crecimiento fetal en humanos. Hasta ahora, se ha sabido que la acción localizada de los GCs sobre el cartílago del crecimiento afecta directamente a agentes como los factores de crecimiento similares a la insulina (IGFs). Sin embargo, la expresión in vivo de las señales IGF-I y IGF-II parece ser que depende de la técnica de observación utilizada y de la edad del animal estudiado. Aun así, es evidente que la disrupción de estas señales genera un retraso muy grave en el crecimiento intrauterino. Ahora, y mediante el estudio con condrocitos epifiseales fetales humanos, se ha podido observar que el mecanismo inhibitorio de los glucocorticoides afecta directamente a la expresión génica del cartílago, es decir, la expresión de las señales IGF- I, pero no de IGF-II. En el caso humano hay que remarcar que la expresión de IGF-II no varía según el nivel de concentraciones de GCs, demostrando que sólo la expresión de IGF-I es inhibida significativamente durante el proceso de crecimiento fetal del cartílago humano.The following article analyses the role played by glucocorticoids in inhibiting foetal development in humans. Until now it was known that the localised action of GCs on growing cartilage directly affected agents such as insulin like growth factors (IGFs). Nevertheless, the in vivo expression of IGF-1 and IGF-2 signals seem to depend on the observation technique used and on the age of the animal being studied. What does seem clear however is that the disruption of these signals causes severe intrauterine growth retardation. By researching with human foetal epiphyseal chondrocytes, scientists were able to observe that the inhibiting mechanism of glucocorticoids directly affects the gene expression of cartilage, i.e. the expression of IGF-I but not of IGF-II signals. It must be highlighted that in the case of humans IGF-II expression does not vary according to the concentration levels of GCs. This demonstrates that only the IGF-I expression is inhibited significantly during the cartilage growth process in human foetuses

Clinical challenges in the management of isolated GH deficiency type IA in adulthood

Isolated GH deficiency type IA (IGHDIA) is an infrequent cause of severe congenital GHD, often managed by pediatric endocrinologists, and hence few cases in adulthood have been reported. Herein, we describe the clinical status of a 56-year-old male with IGHDIA due to a 6.7 kb deletion in GH1 gene that encodes GH, located on chromosome 17. We also describe phenotypic and biochemical parameters, as well as characterization of anti-GH antibodies after a new attempt made to treat with GH. The height of the adult patient was 123 cm. He presented with type 2 diabetes mellitus, dyslipidemia, osteoporosis, and low physical and psychological performance, compatible with GHD symptomatology. Anti-GH antibodies in high titers and with binding activity (>101 IU/ml) were found 50 years after exposure to exogenous GH, and their levels increased significantly (>200 U/ml) after a 3-month course of 0.2 mg/day recombinant human GH (rhGH) treatment. Higher doses of rhGH (1 mg daily) did not overcome the blockade, and no change in undetectable IGF1 levels was observed (<25 ng/ml). IGHDIA patients need lifelong medical surveillance, focusing mainly on metabolic disturbances, bone status, cardiovascular disease, and psychological support. Multifactorial conventional therapy focusing on each issue is recommended, as anti-GH antibodies may inactivate specific treatment with exogenous GH. After consideration of potential adverse effects, rhIGF1 treatment, even theoretically indicated, has not been considered in our patient yet. Learning points: Severe isolated GHD may be caused by mutations in GH1 gene, mainly a 6.7 kb deletion.Appearance of neutralizing anti-GH antibodies upon recombinant GH treatment is a characteristic feature of IGHDIA.Recombinant human IGF1 treatment has been tested in children with IGHDIA with variable results in height and secondary adverse effects, but any occurrence in adult patients has not been reported yet.Metabolic disturbances (diabetes and hyperlipidemia) and osteoporosis should be monitored and properly treated to minimize cardiovascular disease and fracture risk.Cerebral magnetic resonance imaging should be repeated in adulthood to detect morphological abnormalities that may have developed with time, as well as pituitary hormones periodically assessed

A Genome-Wide Pharmacogenetic Study of Growth Hormone Responsiveness

Individual patients vary in their response to growth hormone (GH). No large-scale genome-wide studies have looked for genetic predictors of GH responsiveness. To identify genetic variants associated with GH responsiveness. Genome-wide association study (GWAS). Cohorts from multiple academic centers and a clinical trial. A total of 614 individuals from 5 short stature cohorts receiving GH: 297 with idiopathic short stature, 276 with isolated GH deficiency, and 65 born small for gestational age. Association of more than 2 million variants was tested. Primary analysis: individual single nucleotide polymorphism (SNP) association with first-year change in height standard deviation scores. Secondary analyses: SNP associations in clinical subgroups adjusted for clinical variables; association of polygenic score calculated from 697 genome-wide significant height SNPs with GH responsiveness. No common variant associations reached genome-wide significance in the primary analysis. The strongest suggestive signals were found near the B4GALT4 and TBCE genes. After meta-analysis including replication data, signals at several loci reached or retained genome-wide significance in secondary analyses, including variants near ST3GAL6. There was no significant association with variants previously reported to be associated with GH response nor with a polygenic predicted height score. We performed the largest GWAS of GH responsiveness to date. We identified 2 loci with a suggestive effect on GH responsiveness in our primary analysis and several genome-wide significant associations in secondary analyses that require further replication. Our results are consistent with a polygenic component to GH responsiveness, likely distinct from the genetic regulators of adult height

Concentraciones plasmáticas de 25-OH-vitamina D en sangre de cordón umbilical tras los meses de verano

OBJECTIVE: Plasma vitamin D (25(OH)D) levels in the newborn are dependent on maternal stores. Several studies showing a high prevalence of vitamin D deficiency in pregnant women have been published last years. The aim of the study was to analyze 25(OH)D levels in cord blood after summer month, determine whether there is a relation with different variables. METHODS: 103 pregnant women were recruited between October and early December 2014, whose gestations took place during month of maximum sun exposure. Plasmatic 25(OH)D values were measured in cord blood at birth. Clinical record data were collected and a nutritional survey was made on maternal vitamin D and calcium intake and sun exposure. Statistical analysis was performed using SPSS. Comparisons were performed using Kruskal-Wallis and Mann-Whitney U tests, and correction for multiple comparisons using Bonferroni. P value smaller than 0.05 and smaller than 0.0083 for multiple comparisons were considered sta¬tistically significant. RESULTS: Mean 25(OH)D value in cord blood was 12.36± 7.2 ng/ml. Vitamin D deficiency was present in 83.4% of women. A statistically significant correlation was observed between lowvitamin D levels and low vitamin D intake (correlation coefficient 0.29); Ethnic group, with the highest level in caucasic group (17.9 ± 5.83 ng/ml) and the lowest in indopakistani group (6.68 ± 4.2 ng/ml); the use of traditional clothing (5.64 ± 3.09 ng/ml); low sun exposure and dark skin phototype with a correlation coefficient of 0.67 and -0.48, respectively. CONCLUSIONS: There is a high prevalence of vitamin D deficiency in pregnant women regardless of the season and increased sun exposure. Low vitamin D levels in cord blood were significantly related to ethnicity (Indopakistan and Maghreb), low sun exposure and dark skin phototype. No statistically significant differences were found between vitamin D levels and perinatal variables studied