Partial Growth Hormone Deficiency Research Articles

Optimal final adult height achieved by low-dose recombinant human growth hormone therapy.

Thailand has been administering the recombinant human growth hormone (rhGH) treatment for >20 years. Due to limited resources being available, efforts have been directed toward utilizing rhGH at the lowest feasible dose. However, there is currently a lack of evidence in terms of the efficacy and outcomes. To evaluate the auxological outcomes of growth hormone (GH) treatment and the GH secretion ability after reaching final adult height (FAH) and discontinuing rhGH. Data of 40 patients were retrospectively reviewed. The clinical characteristics, auxological data, and results of biochemical and endocrine investigations before and during rhGH treatment were evaluated. In addition, GH retesting was performed in 24 patients using the insulin tolerance test. Twenty patients (50%) had complete growth hormone deficiency (GHD), defined as peak stimulated GH level <5 ng/mL, and the remaining patients had partial GHD. Most patients were male (n = 25, 62.5%). The mean age at which rhGH was initiated was 8.9 years. Patients with partial GHD received a higher dose of rhGH than those with complete GHD (30.9 µg/kg/d vs. 26.2 µg/kg/d, P = 0.02). Patients with complete and partial GHD reached FAH at height standard deviation scores (SDSs) of -0.65 and -1.47, respectively. The factors associated with obtaining a good clinical response in terms of height gain included peak-stimulated GH level, age of puberty, and age of discontinuing rhGH. After completing the rhGH treatment, 13 of the 24 patients showed normal GH secretion. Patients with multiple pituitary hormone deficiency (MPHD) were likely to have persistent GHD through adulthood (n = 8, 88.9%). This study has demonstrated that the use of low-dose rhGH could result in healthy populations achieving optimal FAHs. Patients with MPHD might not require retesting as they were likely to have persistent GHD. The results obtained in this research highlight the benefits of the treatment. This treatment can be applied in resource-limited countries.

‘’Wait and See’’ as a Treatment Option for a Rathke’s Cleft Cyst Apoplexy in Pediatric Population: A Case Report

Introduction: Rathke cleft cyst apoplexy is exceedingly rare, particularly in infants. The most prevalent clinical manifestations include headaches, visual field defects, and endocrine dysfunction. Treatment options range from surgery to conservative methods, taking into consideration the balance of benefits and risks, especially during critical life stages such as childhood. Case Presentation: We present the case of a 12-year-old boy admitted due to the recent onset of headaches and diabetes insipidus. Magnetic resonance imaging revealed Rathke cleft cyst apoplexy. Given the absence of compressive symptoms in a child at the early stages of puberty and without abnormalities in basic endocrine tests, a conservative strategy was employed, involving regular clinical, biological, and radiological follow-ups. The child experienced normal puberty without any endocrine deficiencies except for a partial growth hormone deficiency. Conclusions: For clinically asymptomatic children diagnosed with Rathke's cleft cyst apoplexy, adopting a conservative management approach is recommended, provided there is thorough clinical, biological, and radiological surveillance.

Ambulatory blood pressure monitorisation in children with recombinant growth hormone treatment.

It is safe to use recombinant growth hormone in children. Studies have shown it to be effective and safe, except for a few side effects in the short and long term after treatment. The present study investigated the presence of hypertension in pediatric patients receiving growth hormone treatment using 24 h ambulatory blood pressure monitoring (ABPM). This study is a single-center, retrospective study. Eighty-four patients aged 5-16 years who received growth hormone treatment for at least 3months, who underwent 24 h ABPM were analyzed. They were compared with 67 patients who had no risk factors for hypertension. In the study, 84 rhGH-treated patients (45.2 % male, 54.8 % female) and 67 healthy control groups (49.3 % male, 50.7 % female) were analyzed. The mean age of the patient group was 10.83±2.85 years and the mean age of the healthy control group was 13.1±2.93 years. The diagnostic classification of the patients receiving treatment was as follows: 66.6 % (n=56) partial growth hormone deficiency, 22.6 % (n=19) growth hormone deficiency, 7.1 % (n=6) bioactive growth hormone, 2.3 % (n=2) idiopathic short stature, 1.1 % (n=1) low birth weight for gestational age (SGA). Body mass index was significantly lower in the treated group (p=0.013). The duration of treatment was 6.04±4.9months. Daytime diastolic blood pressure was significantly lower in the treated group (p=0.001). There was no correlation between BMI and ABPM parameters in the treatment group and the control group. The present study shows that growth hormone treatment is safe in terms of high blood pressure.

Beyond Growth Hormone: Association of Short Stature Types and Growth Hormones With Scoliosis.

Cross-sectional and retrospective cohort study. We investigated the effect of 3 types of short stature [partial growth hormone deficiency (GHD), GHD, and idiopathic short stature (ISS)] and recombinant human growth hormone (rhGH) therapy on scoliosis. In short stature, rhGH is widely used and the concentration of growth hormone varies among types. The epidemiologic characteristics of scoliosis and the role of rhGH in scoliosis remain unclear. A cross-sectional study was conducted among 3896 patients with short stature (partial GHD, GHD, and ISS), and a 1:1 age and sex-matched control group with preexisting whole-spine radiographs. The cohort study included 2605 subjects who underwent radiography more than twice to assess scoliosis development, progression, and the need for bracing and surgery. Adjusted logistic regression was used to assess differences in the prevalence of scoliosis among patients with partial GHD, GHD, ISS, and controls. The Kaplan-Meier method was used to analyze the time course of scoliosis development and progression. Cox regression was applied to assess the independent factors related to scoliosis development and progression. Mendelian randomization analyses were also performed. Compared with controls, patients with short stature had a higher incidence of scoliosis (34.47% in partial GHD, 31.85% in GHD, 32.94% in ISS vs . 8.83% in control, P < 0.001), a higher risk of scoliosis development [hazard ratio (HR) = 1.964 in partial GHD, P < 0.001; HR = 1.881 in GHD, P = 0.001; HR = 1.706 in ISS, P = 0.001), but not a higher risk of progression, brace, or surgery. Among the 3 types of short stature, there were no differences in the incidence, development, and progression of scoliosis or the need for bracing or surgery. RhGH treatment increased the risk of scoliosis development in each short-stature group (HR = 2.673 in partial GHD, P < 0.001; HR = 1.924 in GHD, P = 0.049; HR = 1.564 in ISS, P = 0.004). Vitamin D supplementation was protective against scoliosis development (HR = 0.456 in partial GHD, P = 0.003; HR = 0.42 in GHD, P = 0.013; HR = 0.838 in ISS, P = 0.257). More attention should be paid to the spinal curve in patients with partial GHD, GHD, or ISS. For short stature treated with rhGH, the risk of scoliosis development was increased. Vitamin D supplementation may be beneficial for prevention. Level III.

Hepatomegaly and fatty liver disease secondary to central hypothyroidism in combination with macrosomia as initial presentation of IGSF1 deficiency syndrome.

IGSF1 deficiency syndrome (immunoglobulin superfamily member 1) is considered the most common sex-linked cause of secondary congenital hypothyroidism and is characterized by a wide variety of other clinical and biochemical features, including hypoprolactinemia, transient and partial growth hormone deficiency, early/normal timing of testicular enlargement but delayed testosterone rise in puberty, and adult macro-orchidism. Congenital central hypothyroidism is a rare disease (1:65,000 births); the detection of which may be delayed and missed by neonatal screening programs since most neonatal screening programs are based on TSH determination in dried blood spots only. Untreated hypothyroidism may cause abnormal liver biochemistry and non-alcoholic fatty liver disease. Our aim is to report a case of secondary hypothyroidism in an infant with an uncommon initial presentation. A 3-month-old male baby was referred to our hospital due to elevated alpha-fetoprotein levels, hypercholesterolemia, and macrosomia. Initial investigations revealed enlarged fatty liver and central hypothyroidism. Pituitary insufficiency was biochemically excluded and a pituitary MRI showed normal findings. Upon genetic analysis, a hemizygous variant NM_001170961.1:c.2422dup, p.(His808Profs*14), in IGSF1 gene was detected, establishing the diagnosis of the IGSF1 deficiency syndrome. In our patient, no other clinical findings were identified. Treatment with levothyroxine led to the remission of liver disease. Liver disease may be the initial presentation of secondary hypothyroidism in neonates and infants. Macrosomia in patients with isolated secondary central hypothyroidism is a strong indicator of IGSF1 syndrome.

Electrocardiographic Findings in Children With Growth Hormone Deficiency.

Introduction It has been shown that cardiac functions begin to deteriorate in growth hormone (GH) deficiency even in childhood. However, little is known about how GH deficiency affects arrhythmogenesis. The aim of this study was to evaluate the parameters of P wave dispersion (Pd), QT dispersion (QTd), corrected QT (QTc) dispersion (QTcd), T wave peak-to-end (Tp-e) interval, Tp-e/QT ratio, and Tp-e/QTc ratio in children with GH deficiency. This study alsoaimed to evaluate the relationship of these parameters with insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP-3). Method In the study, records of children diagnosed with GH deficiency in Adana City Training and Research Hospital Pediatric Endocrine Outpatient Clinic between September 2021 and December 2022 were retrospectively reviewed. The control group consisted of children in the same age group who applied to the Emergency Outpatient Clinic with a complaint of chest pain and no pathological finding was detected. The electrocardiograms (ECGs) of all patients were retrospectively evaluated. Results There were a total of 82 children in the study, 41 of whom were diagnosed with GH deficiency and 41 in the healthy control group. The age and male/female ratio of children with GH deficiency were similar to those in the control group (p>0.05). There were 27 (66%) children with complete GH deficiency and 14 (34%) children with partial GH deficiency. P wave dispersion was similar in both GH-deficient children and control group children. It was also similar in children with complete and partial GH deficiency (p>0.05). QT and QTc dispersions were found to be increased in children with GH deficiency, although not statistically significant, compared to the control group (p>0.05). Tp-e interval, Tp-e/QTmax (longest QT interval), and Tp-e/QTcmax (longest QTc interval) ratios were increased in children with GH deficiency compared to the control group (p=0.001, p=0.003, and p=0.001, respectively). QT and QTc dispersion, Tp-e interval, Tp-e/QTmax, and Tp-e/QTcmax ratios were found to be increased in children with complete GH deficiency compared to children with partial GH deficiency, but the difference was not significant (p>0.05). No correlation was found between these ECG parameters and IGF-1, IGFBP-3, and peak GH levels after stimulation tests (p>0.05). Conclusion We found in our study that the Tp-e interval was longer and Tp-e/QT and Tp-e/QTc ratios were increased in children with GH deficiency. These results suggest that the risk of ventricular arrhythmias in children with GH deficiency may start to increase from childhood. However, further prospective studies are needed to confirm our results.

Evaluation of cardiac structure, exercise capacity and electrocardiography parameters in children with partial and complete growth hormone deficiency and their changes with short term growth hormone replacement therapy.

To evaluate cardiac structure, exercise capacity and electrocardiography (ECG) parameters of children with complete and partial growth hormone (GH) deficiency (GHD) and the effect of 12 months GH treatment on these. M-mode echocardiography, ECG and exercise test expressed as metabolic equivalent (MET) were performed in children with GHD, aged 9-14 years, divided into those with a peak GH response < 7µg/L (complete GHD; n = 30) and 7-10µg/L (partial GHD; n = 17) after two GH stimulation tests, at baseline and 12 months after GH initiation. Forty-eight healthy peers underwent the same tests once. Left ventricular mass (LVM) was significantly lower before treatment in both groups with GHD compared to healthy peers (p = 0.015 and p = 0.032) but LVM in the GHD groups was similar to controls after 12 months of treatment. The increase in LVM in the complete GHD group was significant (p = 0.044). LVM index was significantly reduced with treatment in children with partial GHD (p = 0.035). Max METs, VO2max and exercise duration were significantly increased in children with complete GHD after treatment (p = 0.022, p = 0.015 and p = 0.002, respectively). Significant changes in P wave and QTc dispersion on ECG between groups were within physiological limits. This study showed that children with both partial and complete GHD had smaller cardiac structures and less exercise capacity compared to their healthy peers prior to GH treatment but this improved with 12 months of treatment. The cardiac trophic effect of GH, as well as the effect of increasing exercise capacity, is greater in those with complete GHD than in those with partial GHD.

ODP393 Pfeiffer syndrome with growth hormone deficiency in a 4-year-old girl

Abstract Backgrounds Craniosynostosis syndrome has a variety of causes, one of which is an autosomal dominant disorder associated with FGFR1 or FGFR2 gene mutation known as Pfeiffer syndrome (PS; OMIM 101600). It is known that PS is clinically diagnosed, not genetic judgment. PS is divided into three subtypes depending on severity of specific phenotypes. Patients with PS type 1 are broad thumbs and great toes, brachydactyly or syndactyly. They have widely spaced eyes, midface hypoplasia and dental abnormalities but short stature is not typical phenotype of PS. We report the patient who were clinically diagnosed PS with short stature because of growth hormone deficiency (GHD). Case Report: A 4 years 7 month-old girl presented with a short stature below the 3rd percentile. She was born at 40 weeks of gestation with a birth weight of 2.9 kg. Her perinatal and neonatal histories were unremarkable. Her parents are non-consanguineous and her mother had micro- pituitary adenoma. She has healthy younger brother who aged 9 months old. In physical examination, height was 91.1 cm (-3.92 SDS), weight was 15.5 kg (-1.15 SDS). Wide thumb and great toes on both sides of her are observed. At the time of admission, bone age was advanced, measured 7 years. There were no specific findings other than a decrease in IGF-1 level (108.24 ng/ml) and increase in prolactin level (27.26 ng/ml) on the basic endocrine examination. The growth hormone (GH) induced stimulation test was performed after admission. She underwent GH induced stimulation test with combinations of 2 stimulants to assess GH secretion: levodopa 150 mg and arginine 0.5 g/kg. The peak GH level was 7.41 ng/ml in levodopa test and 5.58 ng/ml after 30 minutes’ response to arginine. She was diagnosed as a partial GHD defined by peak GH between 5 and 10 ng/ml in both test. There were no findings in karyotyping and chromosomal microarray. As a result of targeted panel sequencing of 233 genes related to hereditary short stature, c.2398dupT, a pathogenic variant that had not been previously reported in the FGFR2 gene, was observed in a heterozygous form as the cause of short stature. Subsequently, recombinant human GH has been administered in units of 0.1 per day according to her weight. The height was increased from 93.6 cm (SDS) in 4 years 10 months old to 98 cm in 5 years 2 months. Any side effects or adverse reactions were not observed during the treatment period. Conclusion It is suggested that a growth hormone test be performed for Pfeiffer syndrome patients with short stature. GH may help growth in patients with positive in the test. Presentation: No date and time listed

Short stature due to intrauterine growth retardation. Clinical and hormonal-metabolic features, possibilities of growth-stimulating therapy

The article presents data about short stature due to intrauterine development delay. This type of short stature - separate nosology, unites children born small for gestation age. The majority of them in the first years of life have accelerated growth rates, allowing the child to normalize their weight-growth indicators and catch up in the development of peers. In the absence of an accelerated growth rates, children have a high risk of lagging behind in physical development throughout childhood, achieving low final growth and becoming short adults. In addition, the fact of birth with small body sizes is associated with a number of hormonal and metabolic features, a risk of metabolic syndrome in adult years.It is assumed that the absence of postnatal growth acceleration is due to various damages to the GH-IGF1 axis (partial GH deficiency, partial resistance to GH, partial resistance to IGF1). Growth hormone therapy, initiated early in life, is able to normalize growth rates in childhood and ultimately significantly improve or normalize the final growth of short stature children born small for gestational age.

Identification of a novel MAP3K1 variant in a family with 46, XY DSD and partial growth hormone deficiency

The 46, XY disorder of sex development (DSD) is the main cause of birth defects; however, as it is a group of highly heterogeneous diseases, >50% of cases are not accurately diagnosed. Identification of more cases will improve understanding of the relationship between genotype and phenotype for DSD. The present study conducted a systematic analysis of the clinical characteristics of a proband with 46, XY DSD, applied genetic analysis by whole-exome sequencing to this pedigree and performed bioinformatics analysis of the identified variant. The proband presented with a short penis, lack of testicles and partial growth hormone (GH) deficiency at 1 year old. Histopathological examination revealed there were oviduct, epididymis and fibrous vascular tissue on both sides of the abdomen. The last follow-up at 5 years of age revealed that the patient exhibited restricted growth, a 1.5-cm penis and lack of testicles. Notably, a novel pathogenic mitogen-activated protein kinase kinase kinase 1 (MAP3K1) variant (c.3020A>G) was identified in the proband, resulting in a change in the 1,007th amino acid (glutamine) of the encoded protein. This variant caused the uncharged neutral glutamine to be replaced by a positively charged basic arginine. p.Gln1007 in MAP3K1 was confirmed to be conserved across various species. Pathogenicity analysis using bioinformatics tools suggested that this MAP3K1 variant may cause functional defects. In conclusion, the present study identified a novel MAP3K1 variant that was the cause of 46, XY DSD and partial GH deficiency. The present findings extend the mutation spectrum of MAP3K1 and provide novel characteristics of 46, XY DSD.

Covert actions of growth hormone: fibrosis, cardiovascular diseases and cancer.

Since its discovery nearly a century ago, over 100,000 studies of growth hormone (GH) have investigated its structure, how it interacts with the GH receptor and its multiple actions. These include effects on growth, substrate metabolism, body composition, bone mineral density, the cardiovascular system and brain function, among many others. Recombinant human GH is approved for use to promote growth in children with GH deficiency (GHD), along with several additional clinical indications. Studies of humans and animals with altered levels of GH, from complete or partial GHD to GH excess, have revealed several covert or hidden actions of GH, such as effects on fibrosis, cardiovascular function and cancer. In this Review, we do not concentrate on the classic and controversial indications for GH therapy, nor do we cover all covert actions of GH. Instead, we stress the importance of the relationship between GH and fibrosis, and how fibrosis (or lack thereof) might be an emerging factor in both cardiovascular and cancer pathologies. We highlight clinical data from patients with acromegaly or GHD, alongside data from cellular and animal studies, to reveal novel phenotypes and molecular pathways responsible for these actions of GH in fibrosis, cardiovascular function and cancer.

Molecular Genetics and Pathogenesis of the Floating Harbor Syndrome: Case Report of Long-Term Growth Hormone Treatment and a Literature Review.

Introduction: Floating Harbor syndrome (FHS) is an extremely rare disorder, with slightly more than a hundred cases reported worldwide. FHS is caused by heterozygous mutations in the SRCAP gene; however, little is known about the pathogenesis of FHS or the effectiveness of its treatment. Methods: Whole-exome sequencing (WES) was performed for the definitive molecular diagnosis of the disease. Identified variants were validated using Sanger sequencing. In addition, systematic literature and public data on genetic variation in SRCAP and the effects of growth hormone (GH) treatment was conducted. Results: We herein report the first case of FHS in the Russian Federation. The male proband presented with most of the typical phenotypic features of FHS, including short stature, skeletal and facial features, delayed growth and bone age, high pitched voice, and intellectual impairment. The proband also had partial growth hormone deficiency. We report the history of treatment of the proband with GH, which resulted in modest improvement in growth prior to puberty. WES revealed a pathogenic c.7466C>G (p.Ser2489*) mutation in the last exon of the FHS-linked SRCAP gene. A systematic literature review and analysis of available genetic variation datasets highlighted an unusual distribution of pathogenic variants in SRCAP and confirmed the lack of pathogenicity for variants outside of exons 33 and 34. Finally, we suggested a new model of FHS pathogenesis which provides possible basis for the dominant negative nature of FHS-causing mutations and explains limited effects of GH treatment in FHS. Conclusion: Our findings expand the number of reported FHS cases and provide new insights into disease genetics and the efficiency of GH therapy for FHS patients.

Response to growth hormone according to provocation test results in idiopathic short stature and idiopathic growth hormone deficiency.

Purpose To investigate growth response in children with either idiopathic short stature (ISS) or growth hormone (GH) deficiency (GHD).Methods The data of prepubertal GHD or ISS children treated using recombinant human GH were obtained from the LG Growth Study database. GHD children were further divided into partial and complete GHD groups. Growth response and factors predicting growth response after 1 and 2 years of GH treatment were investigated.Results This study included 692 children (98 with ISS, 443 partial GHD, and 151 complete GHD). After 1 year, changes in height standard deviation score (ΔHt-SDS) were 0.78, 0.83, and 0.96 in ISS, partial GHD, and complete GHD, respectively. Height velocity (HV) was 8.72, 9.04, and 9.52 cm/yr in ISS, partial GHD, and complete GHD, respectively. ΔHt-SDS and HV did not differ among the 3 groups. Higher initial body mass index standard deviation score (BMI-SDS) and midparental height standard deviation score (MPH-SDS) were predictors for better growth response after 1 year in ISS and the partial GHD group, respectively. In the complete GHD group, higher Ht-SDS and BMI-SDS predicted better growth response after 1 year. After 2 years of GH treatment, higher BMI-SDS and MPH-SDS predicted a better growth outcome in the partial GHD group, and higher MPH-SDS was a predictor of good growth response in complete GHD.Conclusions Clinical characteristics and growth response did not differ among groups. Predictors of growth response differed among the 3 groups, and even in the same group, a higher GH dose would be required when poor response is predicted.

Indexes of chronic low-grade inflammation in different models of insulin-resistance: Evaluation of lipocalin-2 in metabolic sindrome, partial and total growth hormone deficiency

Indexes of chronic low-grade inflammation in different models of insulin-resistance: Evaluation of lipocalin-2 in metabolic sindrome, partial and total growth hormone deficiency

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)

Impact of IGF-1 Normative Datasets on Indication and Outcome of Growth Hormone Stimulation Testing

In the Netherlands, the diagnosis of growth hormone deficiency in children follows the Dutch national guidelines for Triage and Diagnosis of Growth Disorders in Children. Initial biochemical evaluation includes an IGF-1 measurement as screening parameter for growth hormone deficiency. Based on the clinical probability of growth hormone deficiency and the IGF-1 Z-score, a growth hormone stimulation test is performed if serum IGF-1 Z-score is < 0 SD in case of a high probability and if serum IGF-1 Z-score is < -1 SD in case of low probability. An IGF-1 Z-score > 0 SD virtually excludes a growth hormone deficiency disorder. The interpretation of growth hormone stimulation testing is dependent on both the peak growth hormone concentration, but also on the baseline IGF-1 Z-score, particularly in cases of partial deficiency. Although, nation wide, Dutch laboratories have harmonized their measurement for IGF-1 (as was previously done for growth hormone), a Dutch harmonized normative data set has not been widely adopted. Moreover a clinical evaluation of the implementation of this dataset based on dynamic testing has not been published. To assess the impact of choice of a particular normative dataset on the diagnosis of growth hormone deficiency we recalculated Z-scores of IGF-1 measurements between 2016 and 2019, using our home reference values based on de normative dataset by Elmlinger (E)1, and using the normative datasets defined by Bidlingmaier (B)2 and by the Dutch IGF-1 harmonization program (NL). Based on these three Z-scores, the outcomes of growth hormone stimulation tests performed in this period (n=86) were reassessed according to the interpretation described in the Dutch guideline. Using all three normative datasets the same 4 patients were identified as likely to have a growth hormone deficiency, whereas 10(E), 10(B), or 8(NL) patients were identified as possible partial growth hormone deficiency. In 70(E), 66(B) or 72(NL) patients the growth hormone stimulation test was unaffected. Using normative dataset B, 6 patients displayed a pattern associated with a possible growth hormone resistance, or of bio-inactive growth hormone syndromes, which based on its incidence would be unlikely for a secondary care setting. A striking observation was however, that of all patients with a normal stimulation test 9 (E)/16 (B) or 30 (NL) had a IGF-1 Z-score of > 0 SD. This implies that, for the diagnosis of growth hormone deficiency, it is safe to implement the Dutch harmonized dataset, which in addition could result in a reduction in the number of growth hormone stimulation tests that have to be performed.

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 &amp;lt;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.

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.

Can plasma antioxidants prevent DNA damage in oxidative stress condition induced by growth hormone deficiency? A pilot study.

Adult growth hormone deficiency (GHD), a condition characterized by increased oxidative stress, is related to augmented cardiovascular, metabolic and oncological risk. A case-control observational study has been performed to evaluate DNA oxidative damage analysing the production of thymidine-glycol in lymphocytes and its correlation with plasma antioxidant levels, evaluated as Total Antioxidant Capacity (TAC). GHD was diagnosed using GHRH 50μg iv+arginine 0,5 g/Kg test, with peak GH response <9 μg/L when BMI was <30 kg/m2 or <4 μg/L when BMI was >30 kg/m2. Three groups were identified: total GHD (n = 16), partial GHD (n = 11), and controls (n = 12). Thymidine-glycol, TAC and IGF-1 have been determined respectively in lymphocytes, plasma and serum samples. When considering thymidine-glycol, we found a significant difference between total vs partial GHD and controls. Unexpectedly thymidine-glycol was lower in total GHD, also accompanied with a significant increase in plasmatic TAC. Our results showed that in adult GHD condition, the production of antioxidant species, in response to increased oxidative stress, could exert a protective effect on thymidine-glycol formation, and consequently on DNA intracellular damages. This pilot study could be inserted in the complex scenario of oxidative damage of GHD, a subtle, yet poorly defined condition, worthy of further insights.

Clinical and auxological characteristics of growth hormone deficiency in children of the southern region of Ukraine

Anotation. Regional clinical and auxological studies of growth hormone deficiency (GHD) in children contribute to a realistic assessment of the severity of the problem and prevent underdiagnostics of the disease. The aim of the study is to analyze the features of various forms of GHD in children of the Odessa region on the basis of the clinicians’ integrated assessment of history, physical examination, auxology, stature, growth velocity, bone age (BA), 2 growth hormone (GH) stimulation tests, insulin-like growth factor, magnetic resonance imaging in 92 children with GHD in the Odessa region. Parametric variables were assessed using criteria t-test and хі-square (χ2). The p value &lt;0,05 was considered statistically significant. Decrease in SDS height from - 2,1 tо - 6,6 was found. Isolated GHD (IGHD) was diagnosed in 65,2% of diseases, multiple pituitary hormone deficiency (MPHD) in 34,8% cases. IGHD was more often idiopathic and MPHD was more often arose on an organic basis. Chronological age (CA), BA and height of children with MPHD were lower at the start of therapy compared with IGHD. Complete GH deficiency was more common in children with MPHD (62,7%), while partial GH deficiency was more common in children with IGHD (81,7%). Very low values of the coefficient CA/BA (less than 0,55) were significantly more often detected in children with MPHD compared with IGHD. The regional clinical and auxological characteristics of GHD in children in the Odessa region can be considered in further study of population aspects and patterns of growth.