Identifying patient-related predictors of permanent growth hormone deficiency.

Objective: Isolated childhood growth hormone deficiency (GHD) can persist into adulthood, and re-testing at the transition period is needed to determine whether continued growth hormone therapy is indicated. Here, our objective was to identify predictors of permanent GHD. Design: Retrospective single-centre study of patients with childhood-onset GHD who were re-tested after adult height attainment. Methods: Auxological, clinical, laboratory, and MRI data throughout follow-up were collected. Results: We included 101 patients. At GH treatment initiation, age was 8.1 ± 0.4 years, height -2.25 ± 0.8, and BMI -0.27 ± 0.1 SDS. The 29 (28.7%) patients with persistent GHD had lower height SDS (-2.57 ± 0.1 vs. -2.11 ± 0.1, p<0.001) and mean GH peaks (8.4 ± 1.0 vs.13.2 ± 0.5 mIU/L, p<0.001) at GHD diagnosis; at adult height, they had lower IGF1 (232 ± 19.9 vs. 331 ± 9.1 ng/mL, p<0.001) and higher BMI SDS (-0.15 ± 0.27 vs. -0.73 ± 0.13, p<0.005). By multivariate analysis, the best predictive model included height and BMI SDS, both GH peaks, and MRI findings at diagnosis. Patients with height at diagnosis <-3 SDS had a 7.7 (95% IC 1.4-43.1, p=0.02) fold higher risk of persistent GHD after adjustment on BMI SDS. An abnormal pituitary region by MRI was the strongest single predictor (7.2 times, 95% CI 2.7-19.8) and after multivariate analysis adjustment for GH peaks and height SDS at diagnosis, the risk increased to 10.6 (1.8 - 61.3) times. Conclusions: Height <-3 SDS at GHD diagnosis and pituitary MRI abnormalities should lead to a high index of suspicion for persistent GHD.

Correlation of body mass index to Ghrelin and IGF-1 among children with short stature

Abstract Objective: To assess the BMI among children with Growth Hormone Deficiency (GHD) and Idiopathic Short Stature (ISS) and its correlation to ghrelin, Growth Hormone (GH), and Insulin-like Growth Factor-1 (IGF-1) levels. Methods: A cross-sectional descriptive study in which 42 patients attending the Pediatric endocrine clinic were enrolled, allocated into two groups: group I: GHD children; group II: ISS children. Ghrelin, IGF-1 and GH in both groups were measured. Results: Ghrelin was significantly higher among GHD group (p < 0.001). Overall, there was a strong negative correlation between IGF-1 and ghrelin (r = -0.977, p-value = < 0.001) while a moderate positive correlation between ghrelin and BMI (r = 0.419, p-value = 0.006). There was a weak positive non-significant correlation between IGF-1 and BMI (r = 0.276, p-value = 0.077). In GHD group, there was a weak positive non-significant correlation between ghrelin and GHmax measurement (r = 0.052, p-value = 0.824), while a weak negative non-significant correlation between both variables in ISS group (r = -0.243, p-value = 0.288). In GHD group, there was a moderate positive correlation between ghrelin and BMI (r = 0.500, p-value = 0.021), but weak negative non-significant correlation between both variables in ISS group (r = -0.255, p-value = 0.265). Conclusion: There was a negative feedback loop between ghrelin and IGF-1, whereas a positive feedback between ghrelin and BMI. BMI was more affected in the ISS group but was non-signifi-cantly correlated with ghrelin. There was no significant compensatory response of ghrelin suggesting its contribution to the pathogenesis of ISS.

Correlation of body mass index to Ghrelin and IGF-1 among children with short stature.

OBJECTIVE: To assess the BMI among children with Growth Hormone Deficiency (GHD) and Idiopathic Short Stature (ISS) and its correlation to ghrelin, Growth Hormone (GH), and Insulin-like Growth Factor-1 (IGF-1) levels. METHODS: A cross-sectional descriptive study in which 42 patients attending the Pediatric endocrine clinic were enrolled, allocated into two groups: group I: GHD children; group II: ISS children. Ghrelin, IGF-1 and GH in both groups were measured. RESULTS: Ghrelin was significantly higher among GHD group (p < 0.001). Overall, there was a strong negative correlation between IGF-1 and ghrelin (r = -0.977, p-value = < 0.001) while a moderate positive correlation between ghrelin and BMI (r = 0.419, p-value = 0.006). There was a weak positive non-significant correlation between IGF-1 and BMI (r = 0.276, p-value = 0.077). In GHD group, there was a weak positive non-significant correlation between ghrelin and GHmax measurement (r = 0.052, p-value = 0.824), while a weak negative non-significant correlation between both variables in ISS group (r = -0.243, p-value = 0.288). In GHD group, there was a moderate positive correlation between ghrelin and BMI (r = 0.500, p-value = 0.021), but weak negative non-significant correlation between both variables in ISS group (r = -0.255, p-value = 0.265). CONCLUSION: There was a negative feedback loop between ghrelin and IGF-1, whereas a positive feedback between ghrelin and BMI. BMI was more affected in the ISS group but was non-significantly correlated with ghrelin. There was no significant compensatory response of ghrelin suggesting its contribution to the pathogenesis of ISS.

Genome-wide characterization and analysis of the CCT motif family genes in soybean (Glycine max).

MAIN CONCLUSION: Soybean possesses 19 CMF genes which mainly arose from duplication events. Their features and motifs are highly conserved but transcriptional data indicated functional diversity in metabolism and stress responses. CCT [for CONSTANS, CONSTANS-like (CO-like), and timing of CAB expression1 (TOC1)] domain-containing genes play important roles in regulating flowering, plant growth, and grain yield and are also involved in stress responses. The CMF (CCT motif family) genes, included in the CCT family, contain a single CCT domain as the only identifiable domain in their predicted protein sequence and are interesting targets for breeding programs. In this study, we identified 19 putative GmCMF genes, based on the latest soybean (Glycine max) genome annotation. The predicted GmCMF proteins were characterized based on conserved structural features, and a phylogenetic tree was constructed including all CMF proteins from rice and Arabidopsis as representative examples of the monocotyledonous (monocot) and dicotyledonous (dicot) plants, respectively. High similarities in the conserved motifs of the protein sequences and the gene structures were found. In addition, by analyzing the CMF gene family in soybean, we identified seven pairs of genes that originated from segmental chromosomal duplication events attributable to the most recent whole-genome duplication (WGD) event in the Glycine lineage. Expression analysis of GmCMF genes in various tissues and after specific treatments demonstrated tissue and stress-response specific differential expression. Gene expression analysis was complemented by the identification of putative cis-elements present in the promoter regions of the genes through a bioinformatics approach, using the existing soybean reference genome sequence and gene models. Co-functional networks inferred from distinct types of genomics data-including microarrays and RNA-seq samples from soybean-revealed that GmCMF genes might play crucial roles in metabolism and transport processes. The results of this study, the first systematic analysis of the soybean CCT gene family, can serve as a strong foundation for further elucidation of their physiological functions and biological roles.

Metabolomics as a potential tool for the diagnosis of growth hormone deficiency (GHD): a review.

Metabolomics uses several analytical tools to identify the chemical diversity of metabolites present in organisms. These metabolites are low molecular weight molecules (<1500 Da) classified as a final or intermediary product of metabolic processes. The application of this omics technology has become prominent in inferring physiological conditions through reporting on the phenotypic state; therefore, the introduction of metabolomics into clinical studies has been growing in recent years due to its efficiency in discriminating pathophysiological states. Regarding endocrine diseases, there is a great interest in verifying comprehensive and individualized physiological scenarios, in particular for growth hormone deficiency (GHD). The current GHD diagnostic tests are laborious and invasive and there is no exam with ideal reproducibility and sensitivity for diagnosis neither standard GH cut-off point. Therefore, this review was focussed on articles that applied metabolomics in the search for new biomarkers for GHD. The present work shows that the applications of metabolomics in GHD are still limited, since the little complementarily of analytical techniques, a low number of samples, GHD combined to other deficiencies, and idiopathic diagnosis shows a lack of progress. The results of the research are relevant and similar; however, their results do not provide an application for clinical practice due to the lack of multidisciplinary actions that would be needed to mediate the translation of the knowledge produced in the laboratory, if transferred to the medical setting.

Metabolomics as a potential tool for the diagnosis of growth hormone deficiency (GHD): a review

ABSTRACT Metabolomics uses several analytical tools to identify the chemical diversity of metabolites present in organisms. These metabolites are low molecular weight molecules (<1500 Da) classified as a final or intermediary product of metabolic processes. The application of this omics technology has become prominent in inferring physiological conditions through reporting on the phenotypic state; therefore, the introduction of metabolomics into clinical studies has been growing in recent years due to its efficiency in discriminating pathophysiological states. Regarding endocrine diseases, there is a great interest in verifying comprehensive and individualized physiological scenarios, in particular for growth hormone deficiency (GHD). The current GHD diagnostic tests are laborious and invasive and there is no exam with ideal reproducibility and sensitivity for diagnosis neither standard GH cut-off point. Therefore, this review was focussed on articles that applied metabolomics in the search for new biomarkers for GHD. The present work shows that the applications of metabolomics in GHD are still limited, since the little complementarily of analytical techniques, a low number of samples, GHD combined to other deficiencies, and idiopathic diagnosis shows a lack of progress. The results of the research are relevant and similar; however, their results do not provide an application for clinical practice due to the lack of multidisciplinary actions that would be needed to mediate the translation of the knowledge produced in the laboratory, if transferred to the medical setting.

Clinical features of girls with short stature among inv (9), Turner (45, X) and control individuals.

BACKGROUND: The clinical significance of pericentric inversion of chromosome 9 [inv (9)] remains unclear. METHODS: This case control study assessed girls with short stature. According to karyotypes, the subjects were divided into inv (9) [46,XX,inv (9)(p12q13) and 46,XX,inv (9)(p11q13)], Turner syndrome (45, X) and control (normal 46, XX) groups, respectively. Detailed clinical features were compared. RESULTS: Height standard deviation score (SDS) values at diagnosis were -2.51±0.58, -3.71±2.12 and -2.5±1.24 for inv (9), (45, X) and control groups, respectively (p=0.022). The inv (9) group showed lower body mass index (BMI) values compared with the (45, X) and control groups (F=5.097, p=0.008). Similar growth hormone deficiency (GHD) incidences were found in all groups. Interestingly, height SDS was positively correlated with mother height and patient BMI SDS (r=0.51, p=0.036; r=0.576, p=0.023, respectively) in the inv (9) group. In the (45, X) group, height SDS was positively correlated with birth weight (r=0.392, p=0.039). CONCLUSIONS: Short stature in inv (9) girls was correlated with low birth weight (LBW) and mother height.

Deficiência de hormônio do crescimento, hipotireoidismo e cromossomo 18 em anel: relato de caso / Growth hormone deficiency, hypothyroidism and ring chromosome 18: case report / Growth hormone deficiency, hypothyroidism and ring chromosome 18: case report

INTRODUÇÃO: A associação de síndrome do cromossomo 18 em anel com deficiência de hormônio de crescimento (DGH) é muito rara, com apenas dois relatos na literatura. RELATO DO CASO: Paciente feminina, negra, 1 ano de idade, encaminhada para investigação de crises de hipoglicemia desde os 6 meses, acompanhadas de crise convulsiva. Apresentava atraso do desenvolvimento neuropsicomotor e erro alimentar. Ao exame físico, criança desnutrida (escores z peso/idade de -6,95 e estatura/idade de -5,05), fenda palatina, prega epicântica e hipotonia generalizada. O diagnóstico de DGH foi feito em vigência de hipoglicemia e iniciado o tratamento com somatropina 0,1 U/kg aos 16 meses de idade. A RM do crânio evidenciou neuro-hipófise ectópica. O hipotireoidismo foi diagnosticado com 1 ano e 7 meses, sendo adicionada levotiroxina ao tratamento. O cariótipo 46XX r(18) (p11,2 ­ q.23), estabeleceu o diagnóstico de síndrome do cromossomo 18 em anel. Está em uso de GH há 3 anos, os episódios de hipoglicemia com crise convulsiva desapareceram mas não houve melhora da velocidade de crescimento. DISCUSSÃO: Não foram encontrados na literatura relatos da associação de DGH, hipotireoidismo e cromossomo 18 em anel. Crianças com cromossomo 18 em anel merecem investigação para DGH. A reposição com GH não melhorou o crescimento da nossa paciente.

INTRODUCTION: The association of 18-ring chromosome syndrome and growth hormone deficiency (GHD) is extremely rare, with only two reports in the literature. CASE REPORT: A one year-old, non-white female was referred due to hypoglycemic seizures. She had developmental delay and poor nutrition. Her physical examination was significant for a weight Z score of -6.95, height Z score of -5,05, cleft palate, epicanthic folds and generalized hypotony. Karyotype was 46XX r(18) (p11,2 ­ q.23) - 18 ring chromosome syndrome, the MRI showed an ectopic neurohypophysis. The diagnosis GHD was made due to low GH levels during spontaneous severe hypoglycemia at the age of 16 months. She was started on hGH 0.1 U/kg/day. Three months later, TSH deficiency was diagnosed and L-thyroxin therapy was started. During hGH replacement the hypoglycemic events stopped but after 3 years of hGH therapy, she did not improve growth velocity. DISCUSSION: We were unable to find any report of GHD and hypothyroidism associated with the 18-ring chromosome syndrome. Children with 18-ring chromosome should undergo investigation of GHD. In our child with 18-ring syndrome the hGH therapy did not improve growth velocity.