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The aim of this review article is to highlight the consequences of COGHD after the end of linear growth on bone mass and body composition and the opposing beneficial effects of continuing GH replacement in the transition period and young adults. The role of growth hormone in the period of late adolescence and young adulthood is well established, mainly in achieving peak bone mass and a favorable body composition, characterized by muscle mass increase and fat mass reduction. Patients with childhood onset growth hormone deficiency (COGHD), after reaching the adult height, have a reduced bone mineral density and muscle mass with increased fat mass compared to healthy controls. Inadequate body composition is a predictor for cardiovascular risk, while low bone mass in early youth hallmarks the risk of osteoporosis and bone fractures in later life. Cessation of growth hormone replacement (GHr) after completion of growth will lead to delayed peak bone mass and unbalanced body composition with increased abdominal fat deposits. According to numerous clinical studies monitoring the effects of GH treatment on the physical and psychological status of patients with persistent GHD after completion of growth, we suggest continuing this treatment between 16 and 25 years of age. It is advised that GHr in the transition period be administered in intermediate doses between those for the pediatric population and those for the adult population. Usual daily GHr doses are between 0.3 and 0.5 mg but need to be individually optimized, with the aim of maintaining IGF-I in the age-specific normal range. [ABSTRACT FROM AUTHOR]

Short stature with IGF-1 receptor (IGF1R) gene alteration is known as small-for-gestational-age (SGA) short stature with elevated serum IGF1 levels. Its prevalence and clinical characteristics remain unclear. No adapted treatment is available for short stature related to IGF1R gene alteration in Japan, and genetic testing is not yet widely accessible. We investigated short stature with IGF1R gene alterations and analyzed the clinical data of 13 patients using the results of questionnaires issued to the Japanese Society for Pediatric Endocrinology. Four cases were caused by a deletion of chromosome 15q26.3, and eight were caused by heterozygous pathogenic variants in the IGF1R gene. Cases with deletions showed a more severe degree of growth impairment (–4.5 ± 0.43 SD) than those caused by pathological variants (–2.71 ± 0.15 SD) and were accompanied by neurodevelopmental delay. However, cases caused by pathological variants lacked distinctive features. Only three of the 12 cases demonstrated serum IGF1 values exceeding +2 SD, and the other three had values below 0 SD. Four patients did not meet the criteria for SGA at birth. Six patients received GH therapy for SGA short stature and showed improvement in growth rate without any side effects or elevated serum IGF1 levels during treatment. Elevated IGF1 levels (over +2 SD) after GH treatment should be considered a suspicious finding. Owing to the lack of distinctive features, there was a possibility of undiagnosed cases of this condition. Promoting genetic testing and clinical trials on GH administration for this condition is recommended.

Silver-Russell syndrome (SRS, OMIM, 180860) is a rare genetic disorder with a wide spectrum of symptoms. The most common features are intrauterine growth retardation (IUGR), poor postnatal development, macrocephaly, triangular face, prominent forehead, body asymmetry, and feeding problems. The diagnosis of SRS is based on a combination of clinical features. Up to 60% of SRS patients have chromosome 7 or 11 abnormalities, and <1% show abnormalities in IGF2 signaling pathway genes (IGF2, HMGA2, PLAG1 and CDKN1C). The underlying genetic cause remains unknown in about 40% of cases (idiopathic SRS). We report a novel IGF2 variant c.[-6-2A>G] (NM_000612) in a child with severe IUGR and clinical features of SRS and confirm the utility of targeted exome sequencing in patients with negative results to common genetic analyses. In addition, we report that long-term growth hormone treatment improves height SDS in this patient. [ABSTRACT FROM AUTHOR]

Thyroid nodules in children are less common than in adults but they are approximately two- to three-fold more likely to be malignant in children. Among thyroid nodular diseases, Plummer's adenoma occurs very rarely in pediatrics, and currently, there is no literature providing evidence of this diagnosis in patients with Prader–Willi syndrome (PWS). We report the case of a 9-year-old Caucasian boy affected by PWS presenting with a rapidly growing palpable mass in the thyroid lodge associated with subclinical hyperthyroidism. Laboratory and other examinations (thyroid ultrasound, fine-needle aspiration of the nodule, and scintigraphy) were strongly suggestive for Plummer's adenoma; therefore, the patient underwent left hemithyroidectomy surgery, and anatomo-pathological examination confirmed the diagnosis. Our case describes the first evidence of an isolated follicular adenoma in children with PWS. Surgery is the only therapeutic option in younger children. Further evidence is needed to assess the possible correlation between these two conditions and the existence of potential risk factors.

The aim of this review article is to highlight the consequences of COGHD after the end of linear growth on bone mass and body composition and the opposing beneficial effects of continuing GH replacement in the transition period and young adults. The role of growth hormone in the period of late adolescence and young adulthood is well established, mainly in achieving peak bone mass and a favorable body composition, characterized by muscle mass increase and fat mass reduction. Patients with childhood onset growth hormone deficiency (COGHD), after reaching the adult height, have a reduced bone mineral density and muscle mass with increased fat mass compared to healthy controls. Inadequate body composition is a predictor for cardiovascular risk, while low bone mass in early youth hallmarks the risk of osteoporosis and bone fractures in later life. Cessation of growth hormone replacement (GHr) after completion of growth will lead to delayed peak bone mass and unbalanced body composition with increased abdominal fat deposits. According to numerous clinical studies monitoring the effects of GH treatment on the physical and psychological status of patients with persistent GHD after completion of growth, we suggest continuing this treatment between 16 and 25 years of age. It is advised that GHr in the transition period be administered in intermediate doses between those for the pediatric population and those for the adult population. Usual daily GHr doses are between 0.3 and 0.5 mg but need to be individually optimized, with the aim of maintaining IGF-I in the age-specific normal range.

Silver-Russell syndrome (SRS, OMIM, 180860) is a rare genetic disorder with a wide spectrum of symptoms. The most common features are intrauterine growth retardation (IUGR), poor postnatal development, macrocephaly, triangular face, prominent forehead, body asymmetry, and feeding problems. The diagnosis of SRS is based on a combination of clinical features. Up to 60% of SRS patients have chromosome 7 or 11 abnormalities, and G] (NM_000612) in a child with severe IUGR and clinical features of SRS and confirm the utility of targeted exome sequencing in patients with negative results to common genetic analyses. In addition, we report that long-term growth hormone treatment improves height SDS in this patient.

Kei Takasawa,1 Hiroyo Mabe,2 Fusa Nagamatsu,2 Naoko Amano,3 Yuichi Miyakawa,4 Akito Sutani,4 Reiko Kagawa,5 Satoshi Okada,5 Yusuke Tanahashi,6 Shigeru Suzuki,6 Shota Hiroshima,7 Keisuke Nagasaki,7 Sumito Dateki,8 Shigeru Takishima,9 Ikuko Takahashi,10 Kenichi Kashimada1 1Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University (TMDU), Tokyo, Japan; 2Department of Pediatrics, Kumamoto University Hospital, Kumamoto, Japan; 3Department of Pediatrics, Saitama City Hospital, Saitama, Japan; 4Department of Pediatrics, Kawaguchi Municipal Medical Center, Saitama, Japan; 5Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan; 6Department of Pediatrics, Asahikawa Medical University, Asahikawa, Japan; 7Division of Pediatrics, Department of Homeostatic Regulation and Development, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan; 8Department of Pediatrics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan; 9Department of Pediatrics, Soka Municipal Hospital, Saitama, Japan; 10Department of Pediatrics, Akita University Graduate School of Medicine, Akita, JapanCorrespondence: Kei Takasawa, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan, Tel +81-3-5803-5246, Fax +81-3-5803-5249, Email ktakasawa.ped@tmd.ac.jpIntroduction: Although the treatment success of long-term growth hormone therapy (GHT) is dependent on maintaining patients’ adherence to treatment, marked variations in adherence levels among children with GHT (eg, 7– 71% nonadherence) have been reported. Barriers to or promoters of GHT adherence have been discussed and investigated, and digital health technologies, such as electronic GH injection devices, may have the potential to assess adherence to GHT more accurately. Thus, we conducted a multicenter, retrospective cohort study using GH injection log analysis of an electronic GH device, GROWJECTOR®L, to qualify adherence and explore the factors influencing adherence.Methods: This study enrolled 41 patients (median[range] age, 5.8[3.0 ~ 17.0] years) with short stature from nine Japanese medical institutions. The injection log data (12– 48 weeks) were read by smartphones and collected into the data center through a cloud server.Results: Although cumulative adherence rates remained higher than 95% throughout the observation period, five (12.2%) patients had low adherence (< 85%). Subsequently, subgroup and logistic regression analyses for exploring factors affecting adherence revealed that self-selection of GH device and irregular injection schedule (ie, frequent injections after midnight) significantly affected adherence rate (p=0.034 and 0.048, respectively). In addition, higher rates of irregular injections significantly affected low adherence (median[range], 11.26[0.79 ~ 30.50]% vs 0.26[0.00 ~ 33.33]%, p = 0.029).Discussion: Our study indicated that injection log analysis using an electronic GH device could detect irregular injection schedules due to a night owl or disturbance in lifetime rhythm affecting low adherence and had significant potential to encourage collaborative monitoring of adherence with healthcare providers and patients themselves/caregivers, along with growing autonomy and shared decision-making. Our study suggests the significance of narrative and personal approaches to adherence of patients with GHT and the usefulness of digital devices for such an approach and for removing various barriers to patient autonomy, leading to improvement and maintenance of adherence.Keywords: GH therapy, digital health technology, shared decision- making, patient autonomy

Introduction: Prader-Willi syndrome (PWS) is a complex disorder resulting from the failure of expression of paternal alleles in the PWS region of chromosome 15. The PWS phenotype resembles that observed in the classic non-PWS GH deficiency (GHD), including short stature, excessive fat mass, and reduced muscle mass. To date, a small number of studies on the long-term effects of GH treatment are available in adult subjects with PWS. Methods: In this longitudinal study, 12 obese subjects with PWS (GHD/non-GHD 6/6) were treated for a median of 17 years, with a median GH dose of 0.35 mg/day. The median age was 27.1 years. Anthropometric, body composition, hormonal, biochemical, and blood pressure variables were analyzed in all subjects. Results: Waist circumference was significantly lower at the end of the treatment period (p-value=0.0449), while body mass index (BMI) did not differ significantly. Compared to the baseline, a highly significant reduction of Fat Mass % (FM%) was observed (p-value=0.0005). IGF-I SDS values significantly increased during GH therapy (p-value=0.0005). A slight impairment of glucose homeostasis was observed after GH therapy, with an increase in the median fasting glucose levels, while insulin, HOMA-IR, and HbA1c values remained unchanged. Considering GH secretory status, both subjects with and without GHD showed a significant increase in IGF-I SDS and a reduction of FM% after GH therapy (p-value=0.0313 for all). Discussion: Our results indicate that long-term GH treatment has beneficial effects on body composition and body fat distribution in adults with PWS associated with obesity. However, the increase in glucose values during GH therapy should be considered, and continuous surveillance of glucose metabolism is mandatory during long-term GH therapy, especially in subjects with obesity. [ABSTRACT FROM AUTHOR]

Background: The link between the effects of recombinant human growth hormone (rhGH) therapy in patients with growth hormone deficiency (GHD) and Chiari malformation type I (CM-1) is controversial. Summary: We report the case of a patient with an unusual association of GHD due to ectopic posterior pituitary and CM-1. Our patient developed a headache and worsening of CM-1 after the initiation of rhGH therapy. Following an atlo-occipital decompression surgery, the patient was able to resume therapy with a marked growth improvement. Based on this observation, we provide a systematic review of the current literature about these two pathologies. Key Messages: A careful follow-up of all patients with CM-1 treated with GH is mandatory, paying particular attention to the appearance of any neurological signs and symptoms. [ABSTRACT FROM AUTHOR]

IntroductionPrader-Willi syndrome (PWS) is a complex disorder resulting from the failure of expression of paternal alleles in the PWS region of chromosome 15. The PWS phenotype resembles that observed in the classic non-PWS GH deficiency (GHD), including short stature, excessive fat mass, and reduced muscle mass. To date, a small number of studies on the long-term effects of GH treatment are available in adult subjects with PWS.MethodsIn this longitudinal study, 12 obese subjects with PWS (GHD/non-GHD 6/6) were treated for a median of 17 years, with a median GH dose of 0.35 mg/day. The median age was 27.1 years. Anthropometric, body composition, hormonal, biochemical, and blood pressure variables were analyzed in all subjects.ResultsWaist circumference was significantly lower at the end of the treatment period (p-value=0.0449), while body mass index (BMI) did not differ significantly. Compared to the baseline, a highly significant reduction of Fat Mass % (FM%) was observed (p-value=0.0005). IGF-I SDS values significantly increased during GH therapy (p-value=0.0005). A slight impairment of glucose homeostasis was observed after GH therapy, with an increase in the median fasting glucose levels, while insulin, HOMA-IR, and HbA1c values remained unchanged. Considering GH secretory status, both subjects with and without GHD showed a significant increase in IGF-I SDS and a reduction of FM% after GH therapy (p-value= 0.0313 for all).DiscussionOur results indicate that long-term GH treatment has beneficial effects on body composition and body fat distribution in adults with PWS associated with obesity. However, the increase in glucose values during GH therapy should be considered, and continuous surveillance of glucose metabolism is mandatory during long-term GH therapy, especially in subjects with obesity.

Type 1 insulin-like growth factor receptor (IGF1R) plays an important role in normal fetal and postnatal growth. Over 30 pathogenic variants of IGF1R have been identified in patients with short stature. Yet, 20 years after the first report, a variety of phenotypes remain poorly defined. We analyzed the genetic and clinical data and responses to GH therapy in 11 patients using results from questionnaires. Eight of the 11 patients have already been reported in previous articles, and all of the identified mutations were heterozygous. The patients exhibited various phenotypes. At least two patients did not meet the criteria for GH treatment for small for gestational age (SGA) short stature, and two more patients showed lower serum IGF1 levels. Nine of the 11 patients had thin upper lips. Five patients with heterozygous IGF1R treated with GH exhibited similar height gains to those reported in previous Japanese studies on SGA short stature, which also led to extremely high serum IGF1 levels. Patients with short stature due to IGF1R mutations exhibit various phenotypes. Their presentation at diagnosis may be indistinguishable from common short stature. More specific clinical scoring that considers elevated IGF1 levels after GH treatment is needed to better detect IGF1R mutations. [ABSTRACT FROM AUTHOR]

Context: Nationwide data on children diagnosed with craniopharyngioma (CP) are not available in Italy. Objective: This work aimed to identify patients' characteristics, type of surgical approach, complications and recurrences, number of pituitary deficits, and number of patients starting growth hormone (GH) treatment. Methods: A retrospective multicenter collection took place of 145 patients aged 0 to 18 years who underwent surgery for CP between 2000 and 2018, and followed up in 17 Italian centers of pediatric endocrinology. Results: Age at diagnosis was 8.4 ± 4.1 years. Duration of symptoms was 10.8 ± 12.5 months and headache was most frequent (54%), followed by impaired growth (48%) and visual disturbances (44%). Most lesions were suprasellar (85%), and histology was adamantinomatous in all cases but two. Surgical approach was transcranial (TC) in 67.5% of cases and transsphenoidal (TS) in 31.%. The TC approach was prevalent in all age groups. Postsurgery complications occurred in 53% of cases, with water-electrolyte disturbances most frequent. Radiotherapy was used in 39% of cases. All patients but one presented with at least one hormone pituitary deficiency, with thyrotropin deficiency most frequent (98.3%), followed by adrenocorticotropin (96.8%), arginine vasopressin (91.1%), and GH (77.4%). Body mass index (BMI) significantly increased over time. A hypothalamic disturbance was present in 55% of cases. GH therapy was started during follow-up in 112 patients at a mean age of 10.6 years, and 54 developed a recurrence or regrowth of the residual lesion. Conclusion: CP is often diagnosed late in Italy, with TC more frequent than the TS surgical approach. Postsurgery complications were not rare, and hypopituitarism developed almost in all cases. BMI shows a tendency to increase overtime. [ABSTRACT FROM AUTHOR]

Growth hormone (GH) therapy dates back to 1958 and, though has shown an excellent safety profile in the short-term, has never ceased to raise concern about potential long-term side effects. In the last decade, a number of observational studies in different cohorts of young adult patients treated with GH during childhood have yielded conflicting results. The attention has mainly focused on three major potential risks associated with GH therapy: cancer, cardio and cerebrovascular diseases and diabetes. This review intends to provide a detailed overview of the main studies reporting long-term safety in subjects treated with rhGH therapy during childhood, highlighting the evidence for or against the risk of cancer, cardio and cerebrovascular diseases and diabetes. [ABSTRACT FROM AUTHOR]

Growth hormone (GH) therapy dates back to 1958 and, though has shown an excellent safety profile in the short-term, has never ceased to raise concern about potential long-term side effects. In the last decade, a number of observational studies in different cohorts of young adult patients treated with GH during childhood have yielded conflicting results. The attention has mainly focused on three major potential risks associated with GH therapy: cancer, cardio and cerebrovascular diseases and diabetes. This review intends to provide a detailed overview of the main studies reporting long-term safety in subjects treated with rhGH therapy during childhood, highlighting the evidence for or against the risk of cancer, cardio and cerebrovascular diseases and diabetes.

Thyroid nodules in children are less common than in adults but they are approximately two- to three-fold more likely to be malignant in children. Among thyroid nodular diseases, Plummer's adenoma occurs very rarely in pediatrics, and currently, there is no literature providing evidence of this diagnosis in patients with Prader-Willi syndrome (PWS). We report the case of a 9-year-old Caucasian boy affected by PWS presenting with a rapidly growing palpable mass in the thyroid lodge associated with subclinical hyperthyroidism. Laboratory and other examinations (thyroid ultrasound, fine-needle aspiration of the nodule, and scintigraphy) were strongly suggestive for Plummer's adenoma; therefore, the patient underwent left hemithyroidectomy surgery, and anatomo-pathological examination confirmed the diagnosis. Our case describes the first evidence of an isolated follicular adenoma in children with PWS. Surgery is the only therapeutic option in younger children. Further evidence is needed to assess the possible correlation between these two conditions and the existence of potential risk factors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declared that they were an editorial board member of Frontiers at the time of submission. This had no impact on the peer review process and final decision., (© 2024 Corica, Toscano, Moleti, Pepe, Campenni, Fadda, Dionigi, Romeo, Aversa and Wasniewska.)

Short stature with IGF-1 receptor (IGF1R) gene alteration is known as small-for-gestational-age (SGA) short stature with elevated serum IGF1 levels. Its prevalence and clinical characteristics remain unclear. No adapted treatment is available for short stature related to IGF1R gene alteration in Japan, and genetic testing is not yet widely accessible. We investigated short stature with IGF1R gene alterations and analyzed the clinical data of 13 patients using the results of questionnaires issued to the Japanese Society for Pediatric Endocrinology. Four cases were caused by a deletion of chromosome 15q26.3, and eight were caused by heterozygous pathogenic variants in the IGF1R gene. Cases with deletions showed a more severe degree of growth impairment (-4.5 ± 0.43 SD) than those caused by pathological variants (-2.71 ± 0.15 SD) and were accompanied by neurodevelopmental delay. However, cases caused by pathological variants lacked distinctive features. Only three of the 12 cases demonstrated serum IGF1 values exceeding +2 SD, and the other three had values below 0 SD. Four patients did not meet the criteria for SGA at birth. Six patients received GH therapy for SGA short stature and showed improvement in growth rate without any side effects or elevated serum IGF1 levels during treatment. Elevated IGF1 levels (over +2 SD) after GH treatment should be considered a suspicious finding. Owing to the lack of distinctive features, there was a possibility of undiagnosed cases of this condition. Promoting genetic testing and clinical trials on GH administration for this condition is recommended.

Objective:IGF1 concentration is the most widely used parameter for the monitoring and therapeutic adaptation of recombinant human growth hormone (rGH) treatment. However, more than half the variation of the therapeutic response is accounted for by variability in the serum concentrations of IGF1 and IGFBP3. We therefore compared the use of IGF1/IGFBP3 molar ratio with that of IGF1 concentration alone.Methods:We selected 92 children on rGH for this study and assigned them to three groups on the basis of growth deficiency etiology: small for gestational age (SGA), GH deficiency (GHD) and Prader-Willi syndrome (PWS). Plasma IGF1 and IGFBP3 concentrations and their molar ratio were determined.Results:Before rGH treatment, mean IGF1/IGFBP3 molar ratio in the SGA, GHD and PWS groups was 0.14±0.04, 0.07±0.01 and 0.12±0.02, respectively. After the initiation of rGH treatment, these averages were 0.19±0.07, 0.20±0.08 and 0.19±0.09, within the normal range for most children, even at puberty and despite some significant increases in serum IGF1 levels.Conclusion:We consider IGF1/IGFBP3 molar ratio to be a useful additional parameter for assessing therapeutic safety in patients on rGH, and for maintaning the values within the normal range for age and pubertal stage.

ABSTRACT Background Dubowitz syndrome (DS) is a complex and rare condition characterized by postnatal growth retardation, microcephaly, short stature, mild developmental delay, facial dysmorphism, skin eruption and bone marrow failure. Though approximately 200 cases have been described so far, no specific genetic analysis, laboratory tests or radiological exams are available to confirm the diagnosis which is still based on clinical and facial features. Although short stature is a major feature of the syndrome, no endocrine alterations have been reported so far and scant data are available about the efficacy and safety of GH treatment in these patients. Methods A 13‐year‐old male patient was referred to our attention for short stature. Endocrinological evaluation including GH axis, adrenal and gonadal functions were assessed. aCGH was performed. Results 14q terminal microdeletion associated with Dubowitz phenotype was found. Endocrinological investigations revealed the presence of hypopituitarism which showed a satisfactory response to short‐term growth hormone therapy. The subject also started glucocorticoid replacement therapy. Disorders in pubertal progression and gonadal function were noted. Conclusions Dubowitz syndrome (DS) includes different clinical findings variably occurring. Subjects with a Dubowitz phenotype should be carefully monitored for endocrinological anomalies. The prompt recognition of potential life‐threatening endocrinological condition for example adrenal insufficiency is mandatory in order to start an adequate and early treatment.

Background: Dubowitz syndrome (DS) is a complex and rare condition characterized by postnatal growth retardation, microcephaly, short stature, mild developmental delay, facial dysmorphism, skin eruption and bone marrow failure. Though approximately 200 cases have been described so far, no specific genetic analysis, laboratory tests or radiological exams are available to confirm the diagnosis which is still based on clinical and facial features. Although short stature is a major feature of the syndrome, no endocrine alterations have been reported so far and scant data are available about the efficacy and safety of GH treatment in these patients. Methods: A 13‐year‐old male patient was referred to our attention for short stature. Endocrinological evaluation including GH axis, adrenal and gonadal functions were assessed. aCGH was performed. Results: 14q terminal microdeletion associated with Dubowitz phenotype was found. Endocrinological investigations revealed the presence of hypopituitarism which showed a satisfactory response to short‐term growth hormone therapy. The subject also started glucocorticoid replacement therapy. Disorders in pubertal progression and gonadal function were noted. Conclusions: Dubowitz syndrome (DS) includes different clinical findings variably occurring. Subjects with a Dubowitz phenotype should be carefully monitored for endocrinological anomalies. The prompt recognition of potential life‐threatening endocrinological condition for example adrenal insufficiency is mandatory in order to start an adequate and early treatment. [ABSTRACT FROM AUTHOR]

We described a three-year-old girl whose Chiari type 1 malformation associated with mosaic Turner syndrome disappeared after GH therapy. She was diagnosed with mosaic Turner syndrome at the age of 1 yr and 7 mo by a chromosomal analysis (G-band) for short stature and was treated with GH. Sagittal T1-weighted magnetic resonance imaging (MRI) performed before the start of GH demonstrated herniation of the cerebellar tonsils 7 mm below the foramen magnum into the cervical spinal cord. After the initiation of GH therapy, the growth in height was favorable and improved from 70.6 cm (-3.5 SD) to 92 cm (-1.5 SD) in 2 yr. An MRI examination 19 mo later showed the disappearance of Chiari type 1 malformation. GH therapy either exacerbates or ameliorates Chiari type 1 malformations associated with GH deficiency (GHD). Since Turner syndrome uses more GH than GHD, careful follow-up is required if the disease is associated with Chiari type 1 malformation. [ABSTRACT FROM AUTHOR]

This present study aimed to quantify serum lipid levels [Total cholesterol (TC), Triglyceride (TG), Low Density Lipoprotein --cholesterol (LDL-c), Very Low Density Lipoprotein --cholesterol( VLDL-c), High Density Lipoprotein--cholesterol (HDL--c) ] quantified before and after 6 months of treatment in Iraqi children with HGH deficiency This study was conducted at the National Center for Diabetes Treatment and Research of the Mustansiriya University in Baghdad and for the period from, (October 2016 to July 2017). The study included 200 samples divided into two groups. The patient group included 100 children with short stature including 52 males and 48 females with their age ranged from 5 to 12 years . For comparison, 100 samples (50 females and 50 males) of healthy children corresponding to patients with sex, age were selected as control group. The results of the study showed Serum (TC), (TG), (LDL-C) and (VLDL) levels had a highly significantly increased in children GHD group when compared with controls group (P<0.001). Regarding serum (HDL-C) levels there was a highly significantly decreased in children GHD group when compared with healthy children (P<0.001) before treatment, and after 6 months of treatment a decrease in fat levels was observed in patients [ (TC), (TG) and (LDL-C), (VLDL), very significantly (p <0.001), while their HDL-C level was higher than before treatment . To distinguish between GHD patients and the control group, the Receiver Operator Curve (ROC) analysis showed a descending order of significance for the indicators that showed significant differences before treatment. The serum level of LDL-C was 0.77, followed by (TG) (0.637 ),(VLDL-C) (0.637),( TC) (0.626), and ( HDL-C) (0.614) respectively [this means that all variables managed to occupy a significant region of ROC It was concluded from this study that there was a significant increase (P <0.001) in serum TG, TC, LDL-C and VLDL-C, while the level of HDL-C in the blood decreased significantly in GHD children compared with healthy children. After 6 months of treatment rhGH has improved the lipid profile of children with growth hormone deficiency. [ABSTRACT FROM AUTHOR]

In Japan, anabolic steroid hormone (ASH) treatment for Turner syndrome (TS) to promote growth had been provided before GH therapy for TS was approved. ASH effectively improved the adult height (AH) of TS patients without spontaneous puberty but decreased the AH of TS patients with spontaneous puberty. Although GH therapy for TS was approved in 1991, the approved dosage remained 0.5 IU/kg/wk for GH-deficient TS patients and improved AH by approximately 7 cm. However, AH did not reach -2 standard deviations in healthy girls. In 1999, the requirement of GH deficiency was removed and a dose of 1.0 IU/kg/wk was approved. Although an increase in AH was expected, no reports showed significant improvements in AH at a high dose of GH. GH + ASH combination therapy was reevaluated and recommended for TS patients with gonadal failure and an extremely short stature or those who respond poorly to GH therapy. Although early estrogen replacement therapy is recommended to improve psychological quality of life and prevent osteoporosis, it lowered AH even at a low dose of ethinyl estradiol (25 ng/kg/d). The initiation of ethynyl estradiol at an extremely low dose (1-5 ng/kg/d) at a relatively young age successfully improved AH. [ABSTRACT FROM AUTHOR]

Growth hormone (GH), also known as human growth hormone or somatotropin, is a peptide hormone produced by the anterior lobe of the pituitary gland. Stimulates the growth of all body tissues, including bones. Aim of study: In the present study, we have examined the effect of growth hormone on serum bone turnover markers with respect to children with growth hormone deficiency. These markers can be used as predictors for the growth response to growth hormone treatment before and after 6 months of therapy. Patients and methods: The study included (200) samples divided into two groups. The patient group included 100 samples (52 males and 48 females) of children with growth hormone deficiency Informed consent was obtained from parents, For the purpose of comparison, 100 samples (50 females and 50 males) of healthy children corresponding to patients with sex, age, nutritional behavior, and geographical area, were selected as control group Informed consent was obtained from parents,The study also included age groups for both sexes between (5-12) years and for both infected samples and control group, This study was conducted at the National Center for Diabetes Treatment and Research of the Mustansiriya University in Baghdad and for the period from, (October 2016 to July 2017) Results: Regarding serum (Ca+2) levels there was a highly significantly decreased in children GHD group when compared with healthy children (P<0.001) before treatment, Regarding serum (V.D3) levels there was a highly significantly decreased in children GHD group when compared with healthy children (P<0.001) before treatment, and after 6 months of treatment the results of the study showed that serum (V.D) level had a highly significantly increased in children GHD group compared to before treatment (P <0.001). Levels of Serum phosphorus (PO4-2) and serum alkaline phosphatase (ALP) have also slightly reduced in children with growth hormone deficiency when compared with healthy children. Measuring the serum levels of parathyroid hormone (PTH) is another parameter to be considered in this study the two-sample t test has demonstrated that there is no significant difference between healthy children and those with growth hormone deficiency with respect to parathyroid hormone at baseline. Conclusion: It was concluded from this study that there was a disparate influence of growth hormone on serum bone turnover markers . We can clearly observe the significant influence of growth hormone on vitamin D3 levels in short-term treatment of children with growth hormone deficiency. Serum calcium was the second affected bone marker in this study, where a slight increase in serum calcium level was observed. Although this increment has shown to be ineffective, however we believe that the elevated levels of vitamin D3 is most likely the driven force of calcium absorption that responsible of reducing calcium levels in the blood. Vitamin D3 has known as the key player to improve the absorption of calcium and also involved in maintaining bone mineral homeostasis in addition to regulating renal calcium excretion 42. Parathyroid hormone has also recognized as an important element adjusting calcium and phosphate homeostasis 43, however it is hard to claim this hypothesis in the present study. Levels of Serum phosphorus and serum alkaline phosphatase have also slightly reduced as a response of growth hormone therapy in children with growth hormone deficiency. Even though this decrement in levels seems to be ineffective, however it could be attributed to the short treatment plan and more research is required for longer time period. [ABSTRACT FROM AUTHOR]

Objective: IGF1 concentration is the most widely used parameter for the monitoring and therapeutic adaptation of recombinant human growth hormone (rGH) treatment. However, more than half the variation of the therapeutic response is accounted for by variability in the serum concentrations of IGF1 and IGFBP3. We therefore compared the use of IGF1/IGFBP3 molar ratio with that of IGF1 concentration alone. Methods: We selected 92 children on rGH for this study and assigned them to three groups on the basis of growth deficiency etiology: small for gestational age (SGA), GH deficiency (GHD) and Prader-Willi syndrome (PWS). Plasma IGF1 and IGFBP3 concentrations and their molar ratio were determined. Results: Before rGH treatment, mean IGF1/IGFBP3 molar ratio in the SGA, GHD and PWS groups was 0.14±0.04, 0.07±0.01 and 0.12±0.02, respectively. After the initiation of rGH treatment, these averages were 0.19±0.07, 0.20±0.08 and 0.19±0.09, within the normal range for most children, even at puberty and despite some significant increases in serum IGF1 levels. Conclusion: We consider IGF1/IGFBP3 molar ratio to be a useful additional parameter for assessing therapeutic safety in patients on rGH, and for maintaning the values within the normal range for age and pubertal stage. [ABSTRACT FROM AUTHOR]

Background: Bartter syndrome is a group of rare autosomal-recessive renal disorders characterized by hypokalemic hypochloremic metabolic alkalosis associated with severe growth failure; the exact causes for growth retardation are unclear. GH deficiency (GHD) has been reported in a few cases of Bartter syndrome. The aim of our study was to determine the prevalence of GHD in children with antenatal Bartter syndrome and to assess their response to GH therapy. Methods: Ten patients aged 1.5–14.5 years and diagnosed with antenatal Bartter syndrome were enrolled. Seven children with short stature underwent GH stimulation tests. Results: Common presenting symptoms were failure to thrive and polyuria. The mean patient height at study entry was −2.7 standard deviation (SD) (range 0.89 to −5.95) and mean weight (SD) was −1.7 (range 1.89 to −4.11). A decline in height and weight (SD) was observed over the years. GHD was diagnosed in four children and GH therapy was started in all of them. Two patients responded very well and gained >1 SD in height, one patient stopped therapy due to non-adherence and one had a poor response. Conclusions: In addition to other important causes for poor growth in antenatal Bartter syndrome, our findings suggest that GHD should also be considered as a cause of growth retardation and therefore, clinical assessment of the GH axis is recommended. GH therapy has a role in the treatment of growth failure in some individuals with Bartter syndrome. [ABSTRACT FROM AUTHOR]

Graziano Grugni,1,2 Alessandro Sartorio,1,2 Antonino Crinò3 1Division of Auxology, 2Experimental Laboratory for Auxo-endocrinological Research, San Giuseppe Hospital, Istituto Auxologico Italiano, Verbania, 3Autoimmune Endocrine Diseases Unit, Bambino Gesù Children’s Hospital, Rome, Italy Abstract: Prader–Willi syndrome (PWS) is characterized by a dysregulation of growth hormone (GH)/insulin-like growth factor I axis, as the consequence of a complex hypothalamic involvement. PWS’ clinical picture seems to resemble the classic non-PWS GH deficiency (GHD), including short stature, excessive body fat, decreased muscle mass, and impaired quality of life. GH therapy is able to ameliorate the phenotypic appearance of the syndrome, as well as to improve body composition, physical strength, and cognitive level. In this regard, however, some pathophysiologic and clinical questions still remain, representing a challenge to give the most appropriate care to PWS patients. Data about the prevalence of GHD in PWS children are not unequivocal, ranging from 40% to 100%. In this context, to establish whether the presence (or not) of GHD may have a different effect on clinical course during GH therapy may be helpful. In addition, the comparison of GH effects in PWS children diagnosed as small for gestational age with those obtained in subjects born appropriate for gestational age is of potential interest for future trials. Emerging information seems to demonstrate the maintenance of beneficial effects of GH therapy in PWS subjects after adolescent years. Thus, GH retesting after achievement of final height should be taken into consideration for all PWS patients. However, it is noteworthy that GH administration exerts positive effects both in PWS adults with and without GHD. Another critical issue is to clarify whether the genotype–phenotype correlations may be relevant to specific outcome measures related to GH therapy. Moreover, progress of our understanding of the role of GH replacement and concomitant therapies on bone characteristics of PWS is required. Finally, a long-term surveillance of benefits and risks of GH therapy is strongly recommended for PWS population, since most of the current studies are uncontrolled and of short duration. Keywords: PWS, GH deficiency, GH therapy, transition phase

A 5-years-old girl was diagnosed with Turner syndrome (TS) during a diagnostic work-up for short stature and dysmorphic features. Chromosome analysis revealed rare X-chromosomal abnormalities 46 Xt (13:X) (p12:q24). GH therapy was started at the age of 5.5 years, and continued for 7 years with a fixed dose of 0.33 mg/kg/week, until adult height (AH) achievement. Six-monthly assessment of height standard deviation score and height velocity was performed under therapy, evaluating a prepubertal height gain of 31.7 cm and pubertal height gain of 20 cm. She achieved an AH of 159.3 cm, better than her target height (156.8 cm). In addition, she underwent spontaneous puberty at the age of 9.6 years, completed with menarche at 11.6 years and followed by regular menstrual cycles. During GH treatment, IGF-1, insulin and glucose blood levels remained within a normal range. The early onset of GH therapy may have allowed such a successful height outcome, with the achievement of full stature recovery during childhood and puberty in this TS case. The rare karyotype of our patient may also positively influenced her height final result.

Background: The short stature homeobox-containing (SHOX) gene strongly affects height. Therefore, a better understanding of SHOX haploinsufficiency could be advantageous to early diagnosis and treatment. We investigated the rate of SHOX haploinsufficiency in patients of short stature and documented their anthropometric measurements. Methods: Between 2010 and 2017, we evaluated 86 patients (70 females, 16 males; age 4.3–18 years) with clinical diagnoses of short stature and Madelung deformity (MD). Clinical abnormalities are presented for patients with MD with and without SHOX haploinsufficiency as determined by fluorescence in situ hybridisation (FISH). Results: According to our inclusion criteria, 78 of 86 patients (70 females, 16 males) had short stature (height <−2.5 standard deviation [SD]) and a family history suggestive of short stature. Eight patients had short stature, a family history suggestive of short stature and MD. MD was obvious in eight children in radiographic examinations. Although five of these had no deletion of SHOX, three had deletion of this gene. The deletion detection rate was 37.5% in the individuals with short stature and MD, i.e. Leri-Weill dyschondrosteosis syndrome (LWS), whilst no deletions were detected in the individuals with only short stature. One individual responded well to growth hormone (GH) treatment for the first 2 years but then developed an intolerance with persistently elevated insulin-like growth factor-1 (IGF-1) levels. Conclusions: As we likely missed cases due to our methodology, the routine analysis for SHOX screening should be firstly multiplex ligation-dependent probe amplification (MLPA). The incidence of MD may have been higher in the cohort if X-rays were performed in all individuals. GH treatment was not well tolerated in one case due to persistently elevated IGF-1 levels, and long-term evaluations of patients with SHOX deficiency are required. [ABSTRACT FROM AUTHOR]

We describe the case of a short-statured 12-yr-old boy who developed a Chiari type 1 malformation associated with central sleep apnea after administration of high-dose GH therapy, which he had been receiving since the age of 10 yr and 4 mo. He responded well to GH therapy, and his height increased by 18.8 cm in 2 yr. At 12 yr and 4 mo of age, his mother reported that he had developed sleep apnea during the previous year and it had worsened over a month prior to presentation at our hospital. Otolaryngological examination did not reveal tonsillar or adenoidal hypertrophy. Polysomnography demonstrated severe central sleep apnea with an apnea-hypopnea index of 46.5/h. Sagittal T1-weighted magnetic resonance imaging (MRI) demonstrated herniation of the cerebellar tonsils 15 mm below the foramen magnum into the cervical spinal cord. Continuous positive airway pressure therapy initiated prior to performing neurosurgery was ineffective. Following uncomplicated foramen magnum decompression, his breathing pattern during sleep returned to normal. Sagittal MRI examination should be considered in patients who develop sleep apnea during/following administration of GH therapy. [ABSTRACT FROM AUTHOR]

Introduction. The diagnosis of growth hormone (GH) deficiency is based on the results of GH stimulation tests. Growth hormone therapy in children with normal GH secretion is a matter of discussion. Recently, GH deficiency has been defined as a secondary insulin-like growth factor-I (IGF-I) deficiency. Objective. The aim of the study was to assess GH therapy efficacy in short children with respect to GH peak in stimulation tests and IGF-I secretion before treatment. Material and methods. The retrospective analysis comprised 182 children with partial GH deficiency (GH peak in stimulation tests 5-10 ng/ml), qualified to pGHD Group, and 75 children with normal GH peak in stimulation tests (>10 ng/ml), qualified to normGH Group. According to IGF-I secretion, expressed as IGF-I SDS for age and sex, the patients were qualified to the following subgroups: pGHD-1 and normGH-1 - IGF-I SDS <-2.0; pGHD-2 and normGH-2 - IGF-I SDS between -2.0 and -1.0; pGHD-3 and normGH-3 - IGF-I SDS =-1.0. The increase of the final height SDS with respect to the height SDS before treatment (DHSDS) was calculated as the main index of the GH therapy effectiveness. Results. The best DHSDS was in pGHD-1 (1.65±0.89) and normGH-1 (1.86±0.93), the worse in normGH-3 (0.99±0.71), with insignificant differences between pGHD-1 and normGH-1, pGHD-2 and normGH-2, as well as pGHD-3 and normGH-3. Conclusions. The effectiveness of the GH therapy was the best in the patients with the most severe IGF-I deficiency but almost independent from either decreased or normal GH secretion in stimulation tests before treatment. [ABSTRACT FROM AUTHOR]

Prader–Willi syndrome (PWS) results from under-expression of the paternally-derived chromosomal region 15q11-13. Growth failure is a recognized feature of PWS, and both quantitative and qualitative defects of the GH/IGF-I axis revealing GH deficiency (GHD) have been demonstrated in most children with PWS. In PWS adults, criteria for GHD are biochemically fulfilled in 8–38% of the studied cohorts. Published data support benefits of early institution of GH therapy (GHT) in PWS children, with positive effects on statural growth, body composition, metabolic homeostasis, and neurocognitive function. Like in pediatric PWS, GHT also yields beneficial effects on lean and body fat, exercise capacity, and quality of life of PWS adults. Although GHT has been generally administered safely in PWS children and adults, careful surveillance of risks is mandatory during prolonged GH replacement for all PWS individuals. [ABSTRACT FROM AUTHOR]

Objective: Seamless transition of endocrine patients from the paediatric to adult setting is still suboptimal, especially in patients with complex disorders, i.e., small for gestational age, Turner or Prader–Willi syndromes; Childhood Cancer Survivors, and those with childhood-onset growth hormone deficiency. Methods: An expert panel meeting comprised of European paediatric and adult endocrinologists was convened to explore the current gaps in managing the healthcare of patients with endocrine diseases during transition from paediatric to adult care settings. Results: While a consensus was reached that a team approach is best, discussions revealed that a ‘one size fits all’ model for transition is largely unsuccessful in these patients. They need more tailored care during adolescence to prevent complications like failure to achieve target adult height, reduced bone mineral density, morbid obesity, metabolic perturbations (obesity and body composition), inappropriate/inadequate puberty, compromised fertility, diminished quality of life and failure to adapt to the demands of adult life. Sometimes it is difficult for young people to detach emotionally from their paediatric endocrinologist and/or the abrupt change from an environment of parental responsibility to one of autonomy. Discussions about impending transition and healthcare autonomy should begin in early adolescence and continue throughout young adulthood to ensure seamless continuum of care and optimal treatment outcomes. Conclusions: Even amongst a group of healthcare professionals with a great interest in improving transition services for patients with endocrine diseases, there is still much work to be done to improve the quality of healthcare for transition patients.

Background: Long-term growth hormone (GH) treatments in short children born small for gestational age (SGA) restore lipid metabolism, but also increase insulin resistance. The aim of this study was to evaluate the influence of long-term GH therapy on lipid and glucose metabolism as well as its dose dependency in short Japanese children born SGA. Methods: Eighty Japanese children with a short stature who were born SGA participated in this study; 65 were treated with fixed GH doses of 0.033 (low) or 0.067 (high) mg/kg/day for 260 weeks; 15 were untreated controls in the first year and were randomized to one of the two treatment groups at week 52. Serum cholesterol, glucose and insulin levels were regularly measured. An oral glucose tolerance test (OGTT) was conducted annually. Results: The mean age at the start of GH therapy was approximately 5.3 years. Serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in the high dose group significantly decreased over time during GH therapy. In both dose groups for TC, and in the high dose group for LDL-C, the higher the baseline values, the greater the decrease after 260 weeks. The rate of the decrease observed after 260 weeks in patients with high LDL-C levels was greater in the high dose group. Based on the results of OGTT, no patient was classified as being diabetic; however, annual increases were observed in post-OGTT insulin levels. After 260 weeks, the homeostasis model assessment as an index of insulin resistance (HOMA-IR) increased, suggesting that insulin resistance developed over time with the GH treatment, while 36.6 % of the subjects entered puberty. Conclusions: Long-term continuous GH treatment for children born SGA may have a potentially beneficial effect on several parameters in lipid metabolism and does not adversely affect glucose metabolism. [ABSTRACT FROM AUTHOR]

Background and Aims: Prader-Willi syndrome (PWS) is characterized by a high incidence of altered glucose metabolism (AGM). However, epidemiological data on impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) are still discordant.Methods and Results: We performed a multicenter study based on 274 PWS patients [144 females, aged 20.3 ± 10.4 yrs (range: 8.1-50.1 years)] evaluating the prevalence for AGM in the entire group, and according to age (children <10 yrs; adolescents 10-18 yrs, and adults >18 yrs), Body Mass Index (BMI = kg/m(2)), gender, genotypes (deletion or uniparental disomy for chromosome 15), and GH therapy (GHT) (untreated, previously or currently treated). Altogether, AGM was detected in 67 (24.4%) of patients (0.7% IFG, 10.2% IGT, 13.5% T2DM). The prevalence of AGM was correlated to age (p = 0.001), BMI (p = 0.001) and HOMA-IR (p = 0.001). However, gender, genotype, and GHT did not influence AGM development in univariate analysis. These data were confirmed as positive predictors when inserted in a multivariate analysis model.Conclusion: This study is the first report on the prevalence of AGM in a large population of PWS. Overall, PWS subjects show a high prevalence of AGM that appears more common in obese and adult subjects. Our data confirm the main role of obesity on the individual metabolic risk clustering in PWS, and thus reinforce the concept that improvement in weight control remains the most important goal of any PWS treatment program. [ABSTRACT FROM AUTHOR]

Noonan-like syndrome with loose anagen hair (NS/LAH; OMIM 607721) is caused by a heterozygous c.4A>G mutation in SHOC2. Most cases exhibit both growth hormone deficiency (GHD) and growth hormone insensitivity (GHI) and thus require a high dose of growth hormone (GH) therapy (e.g., 35-40 µg/kg/day). We report on a genetically diagnosed NS/LAH patient manifesting severe short stature (−3.85 SDs) with low serum level of IGF1, 30 ng/ml. The peak levels of GH stimulation tests were within the normal range, and GHI was not observed in the IGF1 generation test. However, with low-dose GH therapy (25 µg/kg/day) for two years, IGF1 level and height were remarkably improved (IGF1: 117 ng/ml, height SDs: −2.20 SDs). Further, catch-up of motor development and improvement of the proportion of extending limbs to trunk were observed (the Developmental Quotient score increased from 68 to 98 points, and the relative sitting height ratio decreased from 0.62 to 0.57). Our results suggest that endocrinological causes for short stature are variable in NS/LAH and that GH therapy should be considered as a possible treatment for delayed development in NS/LAH. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Objective: To ascertain the impact of pituitary size as judged by Magnetic Resonance Imaging (MRI), on response to Growth Hormone (GH) therapy in GH deficient children. Methods: Thirty nine children (9.1 ± 2.7 y, 22 boys) with non-acquired GH deficiency (21 Isolated GH deficiency and 18 Combined pituitary hormone deficiency) were consecutively recruited and followed up for one year. Clinical, radiological (bone age and MRI) and biochemical parameters were studied. Results: Children with hypoplastic pituitary (pituitary height < 3 mm) had more severe height deficit (height for age Z-score −6.0 vs. −5.0) and retardation of skeletal maturation (bone age chronological age ratio of 0.59 vs. 0.48) at baseline as compared to children with normal pituitary heights ( p < 0.05 for both). After one year of GH therapy, height for age Z scores and percentage change in height for age Z scores were significantly higher in children with hypoplastic pituitaries (13.8 ± 3.6 and 28.7 % vs. 11.2 ± 4.1 and 21.4 %). Significant co-relation was observed between pituitary height and height for age Z-scores at baseline ( r = 0.39, p < 0.05). The predicted adult height using Tanner Whitehouse-2 equations improved from 140.8 to 152.3 cm in children with hypoplastic pituitary when compared to an increase from 145.8 to 153.5 cm observed in children with normal pituitary height ( p < 0.05). Conclusions: Indian growth hormone deficient children with hypoplastic pituitary respond better to therapy with GH in short term. [ABSTRACT FROM AUTHOR]

Growth hormone (GH) deficiency (GHD) is currently defined as secondary IGF-I deficiency. In the patients with normal GH secretion, significant increase of IGF-I during generation test excludes primary IGF-I deficiency, however is not an approved indication for GH therapy. The aim of the study was to assess GH therapy effectiveness in children with IGF-I deficiency which turned to be out non-primary, despite normal GH secretion. Patients and methods. Analysis comprised 42 patients with spontaneous (after falling asleep) and stimulated GH peak >10.0 ng/ml, and IGF-ISDS for age and sex <-1.0, in whom IGF-I concentrations increased significantly during generation test, suggesting that IGF-I deficiency is non-primary (npIGFD Group). All patients were subjected to GH therapy. First-year response to treatment: height velocity (HV) increase and IGF-I SDS increase were assessed in all of them, final height (FH) - in 28 patients. The therapy efficacy was compared with 110 children with isolated, partial GHD (pGHD Group), including 42 treated up to FH. Results. In npIGFD Group, height SDS before treatment (H0SDS) was -2.87±0.72, in 1st year of treatment HV increased from 3.8±0.9 to 9.4±1.9 cm/year, IGF-I SDS increased from -2.19±0.78 to 0.34±1.07, FHSDS was -1.14±0.82. In pGHD Group, H0SDS was -2,79±0.59, HV increased from 3.8±1.4 to 9.8±2.1 cm/year, IGF-ISDS increased from -1.76±0.88 to 0.52±0.87, FH SDS was -1.20±0.80. The differences in all the analysed indices of GH therapy effectiveness between the Groups were insignificant. Conclusions. Children with short stature, normal spontaneous and stimulated GH secretion and non-primary IGF-I deficiency may benefit during GH therapy similarly to children with partial GHD. It seems worth considering not diagnose idiopathic short stature in such patients. [ABSTRACT FROM AUTHOR]

In children with childhood-onset growth hormone deficiency, replacement GH therapy is effective in normalising height during childhood and achieving adult height within the genetic target range. GH has further beneficial effects on body composition and metabolism through adult life. The transition phase, defined as the period from mid to late teens until 6–7 years after the achievement of final height, represents a crucial time for reassessing children’s GH secretion and deciding whether GH therapy should be continued throughout life. Evidence-based guidelines for diagnosis and treatment of GHD children during transition are lacking. The aim of this review is to critically review the up-to-date evidence on the best management of transition patients in order to ensure the correct definitive diagnosis and establish the appropriate therapeutic regimen.

Our study aimed to evaluate clinical, endocrine and genetic aspects in three patients with Noonan syndrome and to establish genotype - phenotype correlations. Noonan syndrome is a frequent autosomal dominant disorder, characterized by distinctive facial features, short stature, congenital heart defects, unusual chest shape, broad/ webbed neck, cryptorchidism and developmental delay. GH therapy initiated early adds 1 SD to final adult height. We have identified common features that are very suggestive for the diagnosis, as well as the changing of facial aspect in time. In case 2 we recorded a milder phenotype than expected for KRAS mutations. In case 3 we identified new features (severe scoliosis and ventricular septal defect) as well as more severe clinical features than expected for SOS 1 mutations. We have detected particular patterns of growth in our patients before and after GH therapy. Unlike literature data, our PTPN11 mutation positive child reacted very well to GH, whereas our KRAS mutation positive case started to gain Ht only after 3 years of GH therapy. We have recorded hypertrophic scars either as a new feature of NS, or as a possible adverse event of GH therapy. GH therapy was successful in our patients, without classical adverse events recorded. Somatotropic axis dysfunction is discussed. [ABSTRACT FROM AUTHOR]