Congenital Growth Hormone Deficiency Research Articles

Congenital growth hormone deficiency associated with hypopituitarism: experience from the endocrinology department of hedi chaker university hospital in sfax

Congenital growth hormone deficiency associated with hypopituitarism: experience from the endocrinology department of hedi chaker university hospital in sfax

Management of Neonatal Isolated and Combined Growth Hormone Deficiency: Current Status.

Congenital growth hormone deficiency (GHD) is a rare disease caused by disorders affecting the morphogenesis and function of the pituitary gland. It is sometimes found in isolation but is more frequently associated with multiple pituitary hormone deficiency. In some cases, GHD may have a genetic basis. The many clinical signs and symptoms include hypoglycaemia, neonatal cholestasis and micropenis. Diagnosis should be made by laboratory analyses of the growth hormone and other pituitary hormones, rather than by cranial imaging with magnetic resonance imaging. When diagnosis is confirmed, hormone replacement should be initiated. Early GH replacement therapy leads to more positive outcomes, including reduced hypoglycaemia, growth recovery, metabolic asset, and neurodevelopmental improvements.

Prevalence and associated factors related to combined hypopituitarism in patients with congenital Growth Hormone deficiency

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Morphological pituitary abnormalities in patients with congenital Growth Hormone deficiency

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Predictive clinical factors of stature gain in congenital growth hormone deficiency treated patients

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

What factors predict a favorable response to hormonal therapy in congenital growth hormone deficiency?

What factors predict a favorable response to hormonal therapy in congenital growth hormone deficiency?

Art and science: impact of semioccluded vocal tract exercises and choral singing on quality of life in subjects with congenital GH deficiency.

Currently, not much is known about the interactions between voice and growth hormone (GH). We have described large kindred with isolated GH deficiency (IGHD) due to a GHRH receptor mutation, resulting in severe short stature and high-pitched voice. These IGHD individuals have little interest in GH treatment, as they consider themselves "short long-lived people", rather than patients. Interestingly, they report normal general quality of life, but they rate their Voice-Related Quality of Life (V-RQOL) as low. Here, we assessed the social and auditory-perceptual impacts of artistic-intervention voice therapy with semioccluded vocal tract exercises (SOVTE) and choral singing, on their voices. Seventeen GH-naïve adult IGHD individuals were enrolled in a single-arm interventional pre-post study with 13 weekly sessions of choir singing over 90 days. Outcome measures were V-RQOL scores, self-assessment of voice, and auditory-perceptual analysis (GRBAS scale, G: grade of the severity of dysphonia; R: roughness; B: breathiness; A: asthenia; and S: strain). Marked improvements in total (p = 0.0001), physical (p = 0.0002), and socioemotional (p = 0.0001) V-RQOL scores and in self-assessment of voice (p = 0.004) were found. The general grades of vocal deviation (p = 0.0001), roughness (p = 0.0001), breathiness (p = 0.0001) and strain (p = 0.0001) exhibited accentuated reductions. Voice therapy with semioccluded vocal tract exercises and choral training improved social impact and perceptual voice assessments in IGHD subjects and markedly improved their voice-related quality of life. This is particularly important in a setting where GH replacement therapy is not widely accepted.

Somatropin therapy in italian adults with growth hormone deficiency

BackgroundIn adult population, Growth Hormone Deficiency (GHD) is a complex clinical condition with heterogeneity of causes and duration. Growth Hormone (GH) replacement therapy has beneficial effects entailing a chronic and expensive use. Therefore, entity, appropriateness and standardization of GHD treatment need to be accurately analysed.In Italy, the epidemiological surveillance on somatropin therapy is entrusted to the National Register of Growth Hormone Therapy (Registro Nazionale degli Assuntori dell’Ormone della Crescita-RNAOC) by the Italian Regulation, in accordance of which the RNAOC-database is collecting the notifications of somatropin prescriptions.MethodsAim of this study is to analyse data on somatropin-treated adult population communicated to the RNAOC by the specialist centres of 15 Italian regions and 2 autonomous provinces.ResultsFrom 2011 to 2019, the somatropin-treated adults were 970 with 4061 examinations (1.21 ± 0.33 visits/year).The diagnoses were: hypopituitarism (n = 579); hypophysectomy (n = 383); and congenital GHD (n = 3). Five subjects were addressed with diagnoses not included in the regulation.The starting posology of somatropin was 0.320 (± 0.212) mg/day, 0.292 (± 0.167) mg/day in male and 0.360 (± 0.258) in female patients, with 7 administrations/week in 70.31% of the prescriptions. The differences in posology by gender persisted at 10th year of the follow-up. Starting dosage was higher in patients diagnosed with adult GHD before the age of 30 (0.420 ± 0.225 mg/day), with a progressive decrease of the dosage during the follow-up.ConclusionsThis is the first report on adult GH treatment, describing numbers, diagnoses, and pharmaceutical prescriptions associated to somatropin therapy in a large cohort of Italian GHD-adults.

The utility of a random growth hormone level in determining neonatal growth hormone sufficiency

Background Random growth hormone (GH) levels have been used in the neonate to investigate congenital growth hormone deficiency (GHD). The cut-off value for use in this diagnosis is yet to be established. Methods This is a retrospective chart review of all random GH levels obtained in neonates ≤28 days of age. Neonates were divided into three groups: those diagnosed with congenital GHD, those at risk for GHD (ARF-GHD) and a non-growth hormone deficient (non-GHD) group. Mean GH levels for each group were compared, and ROC analysis was used to identify a cut-off for the diagnosis of GHD. Results The study included 138 neonates with the mean age of 9.07 ± 6.6 days, and 65% of these were born at term gestation. Mean GH levels were lower in the GHD group (2.73 ± 1.19 ng/ml) as compared to the ARF-GHD (9.4 ± 7.96 ng/ml, p = .002) and non-GHD groups (14.86 ± 14.42 ng/ml, p = .027). GH values were not significantly different between non-GHD and ARF-GHD groups. ROC analysis identified a cut-off of serum random GH level of 4.5 ng/ml that achieved 100% sensitivity and 83% specificity for the diagnosis of congenital GHD. Conclusion This study demonstrates that random GH levels obtained in the first 28 days of life can be useful in diagnosing congenital GHD. Moreover, a diagnostic cut-off for congenital GHD using random GH levels was identified.

Circulating microRNA profile in humans and mice with congenital GH deficiency.

Reduced inflammation, increased insulin sensitivity, and protection against cancer are shared between humans and mice with GH/IGF1 deficiency. Beyond hormone levels, miRNAs are important regulators of metabolic changes associated with healthy aging. We hypothesized that GH deficiency in humans alters the abundance of circulating miRNAs and that a subset of those miRNAs may overlap with those found in GH‐deficient mice. In this study, subjects with untreated congenital isolated GH deficiency (IGHD; n = 23) and control subjects matched by age and sex (n = 23) were recruited and serum was collected for miRNA sequencing. Serum miRNAs from young (6 month) and old (22 month) Ames dwarf (df/df) mice with GH deficiency and their WT littermates (n = 5/age/genotype group) were used for comparison. We observed 14 miRNAs regulated with a genotype by age effect and 19 miRNAs regulated with a genotype effect independent of age in serum of IGHD subjects. These regulated miRNAs are known for targeting pathways associated with longevity such as mTOR, insulin signaling, and FoxO. The aging function was overrepresented in IGHD individuals, mediated by hsa‐miR‐31, hsa‐miR‐146b, hsa‐miR‐30e, hsa‐miR‐100, hsa‐miR‐181b‐2, hsa‐miR‐195, and hsa‐miR‐181b‐1, which target the FoxO and mTOR pathways. Intriguingly, miR‐181b‐5p, miR‐361‐3p, miR‐144‐3p, and miR‐155‐5p were commonly regulated in the serum of humans and GH‐deficient mice. In vitro assays confirmed target genes for the main up‐regulated miRNAs, suggesting miRNAs regulated in IGHD individuals can regulate the expression of age‐related genes. These findings indicate that systemic miRNAs regulated in IGHD individuals target pathways involved in aging in both humans and mice.

Predictive factors of final height in children with congenital growth hormone deficiency in Tunisian children

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Predictive factors of final height in children with congenital growth hormone deficiency in Tunisian children

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Predictive factors of final height in children with congenital growth hormone deficiency in Tunisian children

Predictive factors of final height in children with congenital growth hormone deficiency in Tunisian children

Congenital GH deficiency in children: What are the differences between isolated and combined/total and partial somatotropic GH deficiency?

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Pituitary Hypoplasia Is the Best MRI Predictor of the Severity and Type of Growth Hormone Deficiency in Children With Congenital Growth Hormone Deficiency

Abstract Background and Objectives: Congenital idiopathic growth hormone deficiency(GHD) is associated with various MRI abnormalities, including both sellar anomalies such as pituitary hypoplasia, ectopic pituitary, empty sella and abnormalities of the pituitary stalk and extrasellar abnormalities such as Arnold Chiari malformation, corpus callosum agenesis, arachnoid cyst, septum pellucidum agenesis, enlarged ventricles, vermis dysplasia, and sphenoid cyst. However, it remains contentious whether MRI brain findings could provide an additional avenue for precisely predicting the differentiation of GHD based on severity(severe or partial) and type(isolated GHD or multiple pituitary hormone deficiency MPHD). This study aimed to ascertain the abnormality that is the best predictor of severe GHD and type of GHD amongst the different MRI findings. Methods: This was an analytical cross-sectional study conducted from 2018-2020. During the study period, we included a total of 100 subjects diagnosed to have idiopathic GHD after the exclusion of syndromic causes, system illness, presence of pituitary mass, and those with h/o cranial irradiation. Patients were divided into severe GHD and partial GHD based on peak stimulated GH of <5 ng/dl and ≥ 5 ng/dl respectively and into groups based on isolated GHD and MPHD. Patients were further divided into groups based on the presence of pituitary hypoplasia,extrasellar brain abnormalities (EBA), and presence of ectopic posterior pituitary and/or pituitary stalk abnormalities(EPP/PSA), respectively. Analyses were performed using SPSS version 24.0 software. Results: Amongst 100 subjects with idiopathic congenital GHD, 66 (66%) subjects had Isolated GHD while the remaining 34 (34%) had MPHD. 71 had severe GHD, and 29 had partial GHD. Amongst the MRI findings, pituitary hypoplasia was the most common finding observed in 53% of patients, while 23(23%) had EBA, and 25(25%) had EPP/PSA. Pituitary hypoplasia was observed to be the best predictor of severity of GHD with an odds ratio(OR) of 10.8 (95% CI 3.38-29.6) followed by ectopic posterior pituitary /pituitary stalk abnormalities (OR =2.8, 95% CI 1.5-9.5) while the presence of extrasellar abnormalities was the weakest predictor (OR =1.8, 95% CI 1.05-3.2). Pituitary hypoplasia was the only finding to significantly predict MPHD (OR=9.2). On ROC analysis, a Pituitary height SDS of -2.03 had a 73.2 % sensitivity and specificity of 79.3%(AUC =0.787,95% CI 0.7-0.873) for severe GHD and a sensitivity of 88.2 % and specificity of 66.7% (AUC =0.745, 95% CI 0.68-0.877) for MPHD. Conclusion: We observed Pituitary hypoplasia to be not only the most frequent MRI abnormality but also the best predictor of severe GHD and MPHD amongst various sellar and extrasellar abnormalities.

Individuals with isolated congenital GH deficiency due to a GHRH receptor gene mutation appear to cope better with SARS-CoV-2 infection than controls.

PurposeSeveral interactions exist between the GH/IGF axis and the immune system, including effects on innate immunity and humoral and cellular response. Acquired GH deficiency (GHD) has been recently proposed as a risk factor for severity of COVID-19 infections. However, acquired GHD is often associated to other factors, including pituitary tumors, surgery, radiotherapy, and additional pituitary hormones deficits and their replacements, which, together, may hinder an accurate analysis of the relationship between GHD and COVID-19. Therefore, we decided to assess the seroprevalence of SARS-CoV-2 antibodies and the frequency of symptomatic cases of COVID-19 in adults subjects with untreated isolated GHD (IGHD) due to a homozygous null mutation in the GHRH receptor gene.MethodsA cross-sectional study was carried out in 27 adult IGHD subjects and 27 age- and gender-matched local controls. Interview, physical examination, bio-impedance, hematological and SARS-CoV-2 IgM and IgG antibodies were analyzed.ResultsThere was no difference in the prevalence of positivity of anti-SARS-CoV-2 IgM and IgG antibodies between the two groups. Conversely, no IGHD individual had a previous clinical diagnosis of COVID-19 infection, while 6 control subjects did (p = 0.023).ConclusionThe production of anti-SARS-CoV-2 antibodies was similar between IGHD subjects due to a GHRH receptor gene mutation and controls, but the evolution to symptomatic stages of the infection and the frequency of confirmed cases was lower in IGHD subjects than in GH sufficient individuals.

Pituitary hypoplasia is the best MRI predictor of the severity and type of growth hormone deficiency in children with congenital growth hormone deficiency.

Congenital idiopathic growth hormone deficiency (GHD) is associated with various MRI abnormalities, including sellar and extrasellar abnormalities. However, it remains contentious whether MRI brain findings could provide an additional avenue for precisely predicting the differentiation of GHD based on severity and type {isolated GHD or multiple pituitary hormone deficiencies (MPHD)}. This study aimed to ascertain the abnormality that is the best predictor of severity and type of GHD amongst the different MRI findings. We conducted an analytical cross-sectional study, including 100 subjects diagnosed with idiopathic GHD. Patients were grouped into severe GHD, partial GHD, and MPHD and into groups based on the presence of pituitary hypoplasia, extrasellar brain abnormalities (EBA), and presence of ectopic posterior pituitary or pituitary stalk abnormalities (EPP/PSA) or both. Sixty six percentage of subjects had isolated GHD, 34% had MPHD, 71% had severe GHD, and 29% had partial GHD. Pituitary hypoplasia was the most common finding, observed in 53% of patients, while 23% had EBA, and 25% had EPP/PSA. Pituitary hypoplasia was observed to be the best predictor of severity of GHD with an odds ratio (OR) of 10.8, followed by EPP/PSA (OR=2.8), and EBA was the weakest predictor (OR=1.8). Pituitary hypoplasia was the only finding to predict MPHD (OR=9.2) significantly. On ROC analysis, a Pituitary height SDS of-2.03 had the best detection threshold for both severe GHD and MPHD. We observed Pituitary hypoplasia to be not only the most frequent MRI abnormality but also the best predictor of severe GHD and MPHD amongst various sellar and extrasellar abnormalities.

The utility of a random growth hormone level in determining neonatal growth hormone sufficiency.

Random growth hormone (GH) levels have been used in the neonate to investigate congenital growth hormone deficiency (GHD). The cut-off value for use in this diagnosis is yet to be established. This is a retrospective chart review of all random GH levels obtained in neonates ≤28days of age. Neonates were divided into three groups: those diagnosed with congenital GHD, those at risk for GHD (ARF-GHD) and a non-growth hormone deficient (non-GHD) group. Mean GH levels for each group were compared, and ROC analysis was used to identify a cut-off for the diagnosis of GHD. The study included 138 neonates with the mean age of 9.07±6.6days, and 65% of these were born at term gestation. Mean GH levels were lower in the GHD group (2.73±1.19ng/ml) as compared to the ARF-GHD (9.4±7.96ng/ml, p=.002) and non-GHD groups (14.86±14.42ng/ml, p=.027). GH values were not significantly different between non-GHD and ARF-GHD groups. ROC analysis identified a cut-off of serum random GH level of 4.5ng/ml that achieved 100% sensitivity and 83% specificity for the diagnosis of congenital GHD. This study demonstrates that random GH levels obtained in the first 28days of life can be useful in diagnosing congenital GHD. Moreover, a diagnostic cut-off for congenital GHD using random GH levels was identified.

Congenital growth hormone deficiency associated with hip dysplasia and Legg‐Calve‐Perthes disease

Growth hormone deficiency (GHD) is usually treated with recombinant human GH (rhGH), and this has been rarely associated with hip disorders. We analysed the clinical data of patients with congenital GHD receiving rhGH who had associated hip dysplasia or Legg-Calve-Perthes disease (LCPD), with a view to determining whether the hip dysplasia was associated with the underlying disease or with rhGH treatment. We performed a retrospective analysis of paediatric and adolescent patients seen between 1992-2018 with congenital GHD and hip disorders. Data were collected through a review of the patients' medical records and included demographics, clinical and imaging data, and the time frame between the onset of the symptoms related to the hip disorders and the onset of GH treatment. Of the 13 patients with hip disorders, hip dysplasia was present in ten patients and LCPD in three. Hip dysplasia was diagnosed before rhGH was initiated in 50% of cases. These patients had bilateral hip dysplasia and isolated GHD. LCPD was diagnosed in one patient before rhGH was commenced and did not progress. In two patients, LCPD was diagnosed after rhGH was started and did temporarily progress in one of them, but rhGH was not discontinued because LCPD did not seem to be related to rhGH treatment. This study suggests that hip dysplasia could be a manifestation of an underlying GHD. Additionally, rhGH treatment may not necessarily be causative of LCPD.

BASELINE CHARACTERISTICS OF PATIENTS WITH GROWTH HORMONE DEFICIENCY

Objective: The aim of this study was to describe the characteristics and the aetiological profile of patients with growth hormone deficiency (GHD) Material and Method: Among randomly selected 320 cases with short stature with a height SDS<-3SD, 203 patients with diagnosis of GHD were evaluated with respect to their characteristics at diagnosis. Results: 86 patients (42.4%) had idiopathic GHD, 79 patients (39%) had congenital GHD, 14 patients (6.9%) had defined syndromes with GHD and 10 patients (5%) had acquired GHD. Number of patients with isolated GHD was 154 (81.5%) and with multiple pituitary hormone deficiency (MPHD) was 35 (18.5%) among classified cases. The most common accompanying hormone deficiency was TSH deficiency in GHD aetiologies with MPHD. Hypophyseal pathologies were most commonly seen in congenital and acquired GHD cases. Noonan syndrome was the most common syndrome with an accompanying GHD. The bone age delay was found to be over 2 years in congenital GHD. The mean IGF-1 SD score and the mean peak growth hormone stimulation tests’ values were significantly low in congenital GHD. Conclusions: Precise assessment of auxological, clinical and laboratory data could provide substantial value in the evaluation of severely short statured children with GHD.