Diagnosis Of Growth Hormone Deficiency Research Articles

Comparison of growth hormone stimulation tests in prepubertal children with short stature according to response to growth hormone replacement.

Growth hormone (GH) stimulation tests are essential tools for diagnosing GH deficiency (GHD). We aimed to compare L-dopa, insulin, and arginine-induced stimulation tests based on response to GH replacement. We retrospectively collected data from a review of patients who underwent the GH stimulation test. A total of 138 patients diagnosed with idiopathic short stature were categorized into group I. The remaining 135 patients, who were diagnosed with GHD and treated for 1 year, were classified into 2 subgroups: group IIa, consisting of patients with an increase of at least 0.5 in height standard deviation score (SDS), and group IIb, patients with an increase of less than 0.5 in height SDS. At the initial visit, group IIa exhibited significantly lower insulin-like growth factor binding protein-3 (IGF-BP3) and higher body mass index (BMI) SDS compared to the other groups. Following 1 year of treatment, group IIb showed significantly lower height SDS, height SDS gain, growth velocity, predicted adult height SDS, weight SDS, and a higher insulin-like growth factor-1 SDS than group IIa. Bone age and IGF-BP3 were inversely associated, and BMI SDS and IGF-BP3 were positively associated with height SDS gain in GHD patients. The specificity and accuracy rates were 50.3% and 70.3% for the L-dopa-induced stimulation test, 72.3% and 86.6% for the insulin tolerance test (ITT), and 64.7% and 87.2% for the arginine-induced stimulation test (ArST). The ArST demonstrated lower specificity compared to the ITT. However, patients undergoing ArST experienced fewer side effects, suggesting that a careful selection of stimulation tests is crucial in diagnosing GHD.

Elucidating the relationship between blood glucose dynamics and growth hormone responses in glucagon stimulation tests among children with short stature

Introduction: The use of glucagon as a provocative agent for growth hormone (GH) assessment is a cornerstone in pediatric endocrinology. Glucagon's role as a GH secretagogue is integral to growth hormone stimulation tests (GHSTs), which diagnose suspected GH deficiency (GHD) in children. These tests are crucial for assessing the hypothalamic-pituitary-adrenal (HPA) axis's integrity. Despite its prevalent use, the exact mechanisms by which glucagon prompts GH release and the impact of ensuing blood glucose (BG) fluctuations are not fully understood. Objectives: This study aims to explore the relationship between GH and BG levels in children with short stature following glucagon administration. Patients and Methods: A retrospective cohort study involved 42 pediatric patients, aged 6 to 11, with short stature. We analyzed GH and BG levels before and after intramuscular glucagon Simulation test (GST). Blood samples were taken at baseline and multiple intervals post-injection. Results: The results revealed that the mean glucose peaked at 60 minutes and declined to a nadir at 120 minutes, which corresponded with a significant rise in GH levels. GH concentrations peaked at 120 minutes post-injection, with 31% of children showing peak GH levels of less than 7 μg/L. Notably, the study found an inverse correlation between BG and GH at peak glucose times, suggesting a complex interplay between glucose dynamics and GH response. Discussion: Our findings indicate a dynamic interrelation between BG and GH post-glucagon injection, challenging traditional interpretations of GST results. The study reinforces the notion that GHST results should be interpreted with consideration of patient-specific factors such as BMI to ensure accurate evaluation of GH reserve and subsequent clinical decision-making. Conclusion: The study corroborates the dynamic nature of GH and glucose responses following glucagon administration and highlights the need for personalized approaches in interpreting GHSTs. Further investigation is warranted to elucidate the mechanisms influencing this complex relationship, which is crucial for accurate diagnosis and management of GHD in children.

A 2024 Update on Growth Hormone Deficiency Syndrome in Adults: From Guidelines to Real Life.

Background: Adult growth hormone deficiency (GHD) has been recognized since the late 1980s. The clinical manifestations of adult GHD are often nonspecific, and diagnosis relies on GH stimulation tests, which are intricate, costly, time-consuming, and may carry the risk of adverse effects. Diagnosis is further complicated by factors like age, sex, and BMI, which affect GH response during testing. Therefore, GH replacement therapy remains challenging, requiring careful individualized evaluation of risks and benefits. The aim of this review is to provide an update on diagnosing and treating adult GHD, addressing current limitations and challenges based on recent studies. Methods: We conducted a comprehensive review of the literature regarding the diagnosis and management of adult GHD by searching PubMed and EMBASE. Only articles in English were included, and searches were conducted up to August 2024. Results: A review of guidelines and literature up to 2024 highlights the significant heterogeneity in the data and reveals various protocols for managing GHD, covering both diagnostic and therapeutic approaches. Conclusions: Despite diagnostic and treatment advances, managing adult GHD remains challenging due to variable presentation and the need for personalized GH therapy. Future efforts should aim to improve and standardize diagnostic and treatment protocols.

6743 Decline in IGF-1 after surgery of the nonfunctioning pituitary neuroendocrine tumor

Abstract Disclosure: J. Sugata: None. S. Fujio: None. R. Makino: None. T. Hanada: None. R. Hanaya: None. Background: Patients undergoing surgical treatment for nonfunctioning pituitary neuroendocrine tumors (PitNET) may experience impaired secretion of growth hormone (GH). The optimal timing for assessing GH secretory function postoperatively remains unclear. In our department, we typically conduct hormone-loading tests three months after surgery. However, even in some cases without a diagnosis of growth hormone deficiency (GHD) at that point, there might be a gradual decline in Insulin-like growth factor-1 (IGF-1). Methods: We studied patients who exhibited peak GH levels > 1.8ng/ml in an insulin tolerance test (ITT) three months after undergoing surgery for nonfunctioning PitNET. We evaluated the levels of IGF-1 during the last observation, excluding cases where reoperation or radiosurgery was performed. Results: We identified 67 cases (29 males, 38 females) meeting the study criteria, with a median age of 54 years. The median follow-up time spanned 6 years (range 1-13 years). The median standard deviation (SD) scores of IGF-1 three months after surgery were -0.96, with 14 cases (21%) below -2.0 SD. At the end of the follow-up period, the median SD scores of IGF-1 were -1.31. This was significantly lower than the three-month time point (p<0.01), and 21 cases (31%) recorded were below -2.0 SD. In 6 cases suspected of severe GHD due to subjective symptoms or decreased IGF-1, ITT, or GH-releasing peptide-2 were retested. Among these, 2 cases were diagnosed with severe GHD, while the remaining demonstrated normal secretion of GH despite the low concentration of IGF-1. The IGF-1 SD scores at the end of follow-up and the three-month time-point exhibited a significant correlation (R2=0.74, p<0.01). However, no correlation was found between IGF-1 scores and peak GH concentration, age, tumor size, pituitary apoplexy, or preoperative IGF-1 SD scores. Conclusions: IGF-1 exhibited a progressive decrease in the majority of cases without severe GHD, with some cases showing reductions greater than -2.0 SD. Our findings emphasize the importance of cases with long-term clinical follow-up low IGF-1 after PitNET surgery, even when GH secretion appears normal. Presentation: 6/1/2024

6471 Adult Height in Male Survivors of Childhood Cancer Treated with Aromatase Inhibitors and Growth Hormone

Abstract Disclosure: N.I. Pollock: None. M. Song: None. A. Wolf: None. Y. Li: None. C. Hawkes: None. N. Motamedi: None. M.R. Denburg: None. S. Mostoufi-Moab: None. Title: Adult Height in Male Survivors of Childhood Cancer Treated with Aromatase Inhibitors and Growth Hormone Objectives: Aromatase inhibitor (AI) therapy in combination with growth hormone (GH), or as monotherapy, may have a role in improving height outcomes in male pediatric patients with GH deficiency (GHD). The effectiveness of AI therapy in the childhood cancer survivors is not known. In this retrospective study, we assess adult height (AH) in childhood cancer survivors treated with AI combined with GH therapy compared to those treated with GH alone. Methods: This was a single center retrospective cohort study of male survivors of childhood cancer treated with GH for diagnosis of GHD between 2007 and 2023. We compared AH outcomes in males treated with GH alone or in combination with off-label use of AI. Demographic and clinical characteristics, including anthropometric measurements, endocrinopathies, and cancer history, were obtained from the medical record. AH was noted as height documented at fusion of growth plates or following 18 years of age. Differences in demographic, clinical, and treatment characteristics were assessed using univariate tests of association. Multivariable regression with stepwise selection was used to examine risk factors associated with AH. All statistical analyses were performed using Stata 18.0. Results: Ninety-two patients were included; 70 were treated with GH monotherapy and 22 with combination AI/GH. Median age at AI initiation was 13.6 years (IQR 12.3-14.3) versus 11.2 years (IQR 8.6-12.9) for GH (unpaired t-test p-value <0.01; 95% CI -4.01, -1.91). A greater proportion of patients in the AI/GH group had been treated with stem cell transplantation, abdominal radiation, total body irradiation, and cis-retinoic acid (Fisher’s exact p-value <0.01). There was no statistically significant difference in AH or AH Z-score between treatment groups, with the median AH Z-score in the AI/GH group -1.95 (IQR -3.11, -0.75) versus -1.39 (IQR -2.65, 0.11) in the GH group. In multivariable linear regression, history of radiation to the spine (β= -5.9, 95% CI -11.2, -0.6), height Z-score (β= 0.3, 95% CI 0.11, 0.46), BMI Z-score (β= 3.2, 95% CI 0.95, 5.5), and advanced bone age at GH or AI treatment initiation (β= -10.1, 95% CI -17.3, -2.9) were significantly associated with AH. Conclusions: Adjunctive treatment with AI and GH was not associated with increased AH outcomes in male survivors of childhood cancer compared to GH monotherapy. Future work is needed to determine optimal adjunctive medical therapy to maximize FAH impacted by cancer therapy for this patient population. Presentation: 6/3/2024

6369 Weiss-Kruszka Syndrome and Growth Hormone Deficiency, Adrenal Insufficiency, and Morbid Obesity

Abstract Disclosure: T. Falcon-Rodriguez: None. N. Solano: None. A. Diaz: None. Background: Weiss-Kruszka syndrome (WKSA) is a rare autosomal dominant genetic disorder caused by heterozygous loss-of-function variants in the ZNF462 gene. Individuals affected by this condition exhibit distinctive craniofacial features, ptosis, dysgenesis of the corpus callosum, hearing loss, intellectual disability, and hypotonia. There is one other case report that described a boy with empty sella syndrome with growth hormone deficiency and delayed puberty. Case Presentation: We present the case of a 15-year-old boy who initially came under the care of endocrinology at age 9 due to severe obesity and short stature. Past medical history included ADHD (for which he was on stimulants since age 5), microcephaly, VUR, asthma, and developmental delay. He grew along the 2nd percentile for height from the ages of 6 and 13, after which his growth velocity notably decelerated. His initial bone age at 9 years old was advanced by 3 years. His BMI had exceeded the 99th percentile since age 3. His family history was relevant for maternal type 1 diabetes mellitus, paternal height of 165 cm, and maternal height of 160 cm. Upon physical examination, notable findings included short stature, severe obesity, a low anterior hairline, arched eyebrows, upslanted palpebral fissures, low-set ears, a tubular and short nasal bridge, and an exaggerated cupid's bow. At age 9, the patient was diagnosed with growth hormone (GH) deficiency following a clonidine and glucagon stimulation test, with a GH peak of 1.9 ng/mL (normal >7 ng/mL). Additionally, he was diagnosed with adrenal insufficiency (cortisol peak of 5 ug/dL, after 250 mcg of cosyntropin). A brain/sella MRI revealed a hypoplastic pituitary gland. Subsequently, hydrocortisone replacement was initiated at a dose of 6 mg/m2/day, and GH treatment at a weekly dose of 0.3 mg/kg. Despite treatment with growth hormone and IGF-1 levels on the upper side of the normal range, his growth velocity did not improve significantly. He reached his peak adult height of 150 cm at age 15. His BMI had consistently been at the 99th percentile. According to his mother, he did not have issues with satiety, and his portion sizes were considered normal. He did not consume fast foods or sugary drinks, and his level of physical activity was suboptimal. Whole Exome Sequencing identified a heterozygous de novo pathogenic variant in the ZNF462 gene, specificallyc.2664 C>A, p.(C888*) (NM_021224.4), consistent with the diagnosis of Weiss-Kruszka syndrome (OMIM # 618619). Conclusion: We present, to our knowledge, the first report of morbid obesity and central adrenal insufficiency in a child with WSKA. GH deficiency had been previously reported in 1 patient with WSKA. The finding of a hypoplastic pituitary gland supports the diagnosis of GH deficiency and central adrenal insufficiency. Presentation: 6/3/2024

Establishment of IGF-1 and IGFBP-3 continuous reference percentiles from data of healthy children using three kinds of immunoassay systems

Background and aimsAppropriate continuous reference intervals (RIs) for serum insulin-like growth factor 1 (IGF-1) and insulin-like growth factor-binding protein 3 (IGFBP-3) are important for diagnosing growth hormone deficiency or excess. Material and methodsWe retrospectively reviewed serum IGF-1 and IGFBP-3 levels in Korean children aged 0–17 years who were diagnosed as healthy during a short stature workup in the outpatient clinics of three hospitals. IGF-1 and IGFBP-3 levels were measured using various immunoassays, including Liaison XL for IGF-1, an immunoradiometric assay (IRMA) for IGFBP-3 (n = 5522), and Immulite 2000 (n = 3036) and cobas e801 (n = 314). We established RIs from the 2.5th to 97.5th percentile RI curves using the lambda–mu–sigma (LMS) method for each sex group. ResultsPediatric serum continuous IGF-1 and IGFBP-3 reference percentiles by LMS method were found to be immunoassay method-dependent, but aligned relatively well with the manufacturers’ RIs. IGFBP-3 levels displayed notable discrepancies among the different immunoassay methods. ConclusionAge- and sex-specific pediatric LMS based continuous reference intervals are method dependent and they should be calculated for dynamic parameters that show variations throughout childhood.

Accuracy of arginine testing as first test for diagnosing growth hormone deficiency in children

Accuracy of arginine testing as first test for diagnosing growth hormone deficiency in children

Pituitary Gland Morphology: A Novel Diagnostic Marker for Differentiating Growth Hormone Deficiency from Idiopathic Short Stature in Children

Background: The primary causes of short stature (SS) are idiopathic short stature (ISS) and growth hormone deficiency (GHD). The diagnosis of GHD relies on growth hormone stimulation tests (GHSTs), while the diagnosis of ISS is achieved through exclusion. Objectives: Growth hormone (GH) and insulin-like growth factor-I are the best therapeutic drugs for treating GHD, but their suitability for ISS remains controversial. Therefore, distinguishing between these two causes of SS is crucial. Currently, the diagnosis of GHD depends on GHSTs, whereas the diagnosis of ISS is achieved through exclusion, which is an invasive process. Thus, developing a noninvasive and convenient method to differentiate between GHD and ISS would be of great importance. Patients and Methods: We enrolled patients aged 3 - 14 years who presented with SS and underwent GHSTs and pituitary gland (PG) magnetic resonance imaging (MRI) at our hospital from January 2020 to October 2022 for a cross-sectional study. A total of 205 patients were included, comprising 83 with ISS and 122 with GHD. The GHD patients were further divided into two groups based on the peak GH level in GHSTs. All patients underwent routine physical examinations, GHSTs, PG MRI, and X-rays of the left wrist. Two authors independently recorded the PG features (height, length, width, volume, pituitary stalk diameter, pituitary stalk length, and morphology). The PG morphology was categorized into three types: Convex, flat, and concave. Bone age was estimated from X-rays of the left wrist, which were reviewed by an experienced radiologist. Comparisons between the two groups were conducted using two independent samples t-tests or chi-square (χ²) tests. Results: There were no differences between the two groups regarding baseline clinical characteristics, except for the GH peak in GHSTs (P < 0.05). Pituitary stalk diameter, PG height, PG volume, and the dorsum sellae were significantly lower, while the tuberculum sellae was higher in the GHD group compared to the ISS group (all P < 0.05). The proportion of concave PG was higher, and the proportion of flat PG was lower in the GHD group (all P < 0.05). In subgroup analysis, PG height and PG volume were significantly lower in the absolute GHD (AGHD) group compared to the partial GHD (PGHD) group (all P < 0.05). Correlation analysis showed that PG height (r = 0.635, P < 0.01) and PG volume (r = 0.786, P < 0.01) were positively correlated with the GH peak level. Further analysis also demonstrated the differential diagnostic accuracy of PG height and PG volume, with high sensitivity (PG height: 66.3%; PG volume: 84.3%) and specificity (PG height: 85.2%; PG volume: 77.9%). Conclusion: pituitary gland height, PG volume, and the concave type of PG morphology may be very helpful in the differential diagnosis of GHD and ISS.

The role of IGF1 in determining body composition in children and adolescents with growth hormone deficiency and those with idiopathic short stature.

Treatment with recombinant human growth hormone (rhGH) increases insulin growth factor-1 (IGF1) levels, therefore, monitoring both IGF1 and growth constitutes an acceptable parameter of therapeutic safety and efficacy. We aimed to investigate the relationship between IGF1 level and body composition in children and adolescents undergoing rhGH therapy for growth hormone deficiency (GHD) and idiopathic short stature (ISS). This observational retrospective study included the bioimpedance analysis (BIA) reports (n = 305) of 135 pediatric patients (age 5-18 years), 64 with GHD and 71 with ISS, conducted as part of routine clinic visits. Sociodemographic and clinical data were extracted from medical records. Generalized estimating equations linear models were used to explore the contributing factors for body composition components of fat percentage (FATP), appendicular skeletal muscle mass (ASMM) z-score, and muscle-to-fat ratio (MFR) z-score while adjusting for cumulative doses of rhGH. Subjects with GHD exhibited higher body mass index z-scores (p < 0.001), higher FATP and truncal FATP scores, lower MFR z-score, and higher diastolic blood pressure percentiles than the ISS group (p = 0.010, p = 0.027, p = 0.050, and p = 0.050, respectively). Female sex (p < 0.001) and a GHD diagnosis (p < 0.001), were major contributors to higher FATP scores; female sex (p = 0.049) and ISS diagnosis (p = 0.005) were major contributors to higher MFR z-scores; and female sex (p < 0.001), older age (p < 0.001) and higher insulin-like growth factor 1 z-scores (p = 0.021) were major contributors to higher ASMM z-scores. Socioeconomic position and cumulative rhGH dose were not significant contributors to body composition parameters. Children with GHD, including those undergoing rhGH treatment, may be at risk for increased adiposity and associated metabolic implications. Sex- and age-adjusted IGF1 levels were related to muscle mass but not to adiposity. Hence, rhGH treatment aimed at increasing IGF1 levels may alleviate these effects by promoting muscle growth.

Program to optimise detecting growth hormone deficiency in children and increase adherence to replacement therapy

Background. The significance of this study lies in the fact that short stature is highly prevalent among children, affec­ting 1–5 % of the population and having diverse causes. The child’s growth potential in the long term is largely depends on the effectiveness of the diagnostic system and the level of adherence to the prescribed therapy. The purpose was to improve the diagnosis of growth hormone deficiency (GHD) in children and adherence to recombinant human growth hormone (rhGH) therapy based on information about the regional prevalence of the disease and barriers to adherence. Materials and methods. A follow-up study was conducted from 2012 to 2020 at the Odesa Regional Children’s Hospital. The cohort included 94 children with GHD. The prevalence was determined by calculating the ratio of the number of all detected GHD cases to the children population per 100,000. Adherence was measured using the Morisky Medication Adherence Scale. The statistical processing of the results was done using t-test and chi-square methods, and p-values less than 0.05 were considered statistically significant. Results. An assessment of GHD prevalence, the level of adherence and the frequency of continuity of rhGH therapy in children in the Odesa region at the end of 2014 revealed the incompleteness of regional diagnosis of the disease (in Odesa, 1 : 11,200; in the Odesa region, 1 : 10,800), as well as a low level of acceptable adhe­rence (in 57.4 %) and insufficient frequency of continuity of therapy (in 76.9 %). These data formed the basis of the regional program for optimizing the identification and management of GHD in children, which included organizational, medical and social measures. By the end of 2020, the prevalence of GHD in Odesa was 1 : 4,300, and in the Odesa region, 1 : 5,100. The rate of acceptable adherence to rhGH therapy increased to 80.0 %, and frequency of continuity of therapy to 91.1 %. Conclusions. The regional program designed to improve the detection and management of GHD in children has been found to improve the diagnosis of the disease, increase adhe­rence to rhGH therapy, and the frequency of continuity of treatment. High adherence to treatment is a bioethical issue because it signifies a good partnership between physicians, children, and parents and indicates respect for patient autonomy.

Transient Isolated, Idiopathic Growth Hormone Deficiency-A Self-Limiting Pediatric Disease with Male Predominance or a Diagnosis Based on Uncertain Criteria? Lesson from 20 Years' Real-World Experience with Retesting at One Center.

In the majority of children with growth hormone (GH) deficiency (GHD), normal GH secretion may occur before the attainment of final height. The aim of the study was to assess the incidence of persistent and transient GHD and the effectiveness of recombined human GH (rhGH) therapy in children with isolated, idiopathic GHD with respect to the moment of therapy withdrawal and according to different diagnostic criteria of GHD. The analysis included 260 patients (173 boys, 87 girls) with isolated, idiopathic GHD who had completed rhGH therapy and who had been reassessed for GH and IGF-1 secretion. The incidence of transient GHD with respect to different pre- and post-treatment criteria was compared together with the assessment of GH therapy effectiveness. The incidence of transient GHD, even with respect to pediatric criteria, was very high. Normal GH secretion occurred before the attainment of near-final height. Application of more restricted criteria decreased the number of children diagnosed with GHD but not the incidence of transient GHD among them. Poor response to GH therapy was observed mainly in the patients with normal IGF-1 before treatment, suggesting that their diagnosis of GHD may have been a false positive. Further efforts should be made to avoid the overdiagnosis GHD and the overtreatment of patients.

Consensus and controversies on the diagnosis of GH-deficiency in children and adults - A Delphi survey by the GH research society

Consensus and controversies on the diagnosis of GH-deficiency in children and adults - A Delphi survey by the GH research society

Metabolic Characteristics and Discriminative Diagnosis of Growth Hormone Deficiency and Idiopathic Short Stature in Preadolescents and Adolescents.

Growth hormone deficiency (GHD) and idiopathic short stature (ISS) are the most common types of short stature (SS), but little is known about their pathogenesis, and even less is known about the study of adolescent SS. In this study, nuclear magnetic resonance (NMR)-based metabolomic analysis combined with least absolute shrinkage and selection operator (LASSO) were performed to identify the biomarkers of different types of SS (including 94 preadolescent GHD (PAG), 61 preadolescent ISS (PAI), 43 adolescent GHD (ADG), and 19 adolescent ISS (ADI)), and the receiver operating characteristic curve (ROC) was further used to evaluate the predictive power of potential biomarkers. The results showed that fourteen, eleven, nine, and fifteen metabolites were identified as the potential biomarkers of PAG, PAI, ADG, and ADI compared with their corresponding controls, respectively. The disturbed metabolic pathways in preadolescent SS were mainly carbohydrate metabolism and lipid metabolism, while disorders of amino acid metabolism played an important role in adolescent SS. The combination of aspartate, ethanolamine, phosphocholine, and trimethylamine was screened out to identify PAI from PAG, and alanine, histidine, isobutyrate, methanol, and phosphocholine gave a high classification accuracy for ADI and ADC. The differences in metabolic characteristics between GHD and ISS in preadolescents and adolescents will contribute to the development of individualized clinical treatments in short stature.

Tackling access and payer barriers for growth hormone therapy in Saudi Arabia: a consensus statement for the Saudi Working Group for Pediatric Endocrinology.

Prompt diagnosis and early treatment are key goals to optimize the outcomes of children with growth hormone deficiency (GHD) and attain the genetically expected adult height. Nonetheless, several barriers can hinder prompt diagnosis and treatment of GHD, including payer-related issues. In Saudi Arabia, moderate-to-severe short stature was reported in 13.1 and 11.7 % of healthy boys and girls, respectively. Several access and payer barriers can face pediatric endocrinologists during the diagnosis and treatment of GHD in Saudi Arabia. Insurance coverage policies can restrict access to diagnostic tests for GHD and recombinant human growth hormone (rhGH) due to their high costs and lack of gold-standard criteria. Some insurance policies may limit the duration of treatment with rhGH or the amount of medication covered per month. This consensus article gathered the insights of pediatric endocrinologists from Saudi Arabia to reflect the access and payer barriers to the diagnostic tests and treatment options of children with short stature. We also discussed the current payer-related challenges endocrinologists face during the investigations of children with short stature. The consensus identified potential strategies to overcome these challenges and optimize patient management.

Very low serum IGF-1 levels are associated with vertebral fractures in adult males with beta-thalassemia major.

Patients with beta-thalassemia major (BTM) often develop several endocrine disorders due to chronic iron overload. They are also prone to osteoporosis and vertebral fractures. Plasmatic insulin-like growth factor-1 (IGF-1) levels are often low in subjects with BTM, which origin is multifactorial. The aim of this study was to evaluate a possible relationship between serum IGF-1 levels and the presence of osteoporosis and/or vertebral fractures. We retrospectively evaluated the occurrence of vertebral fractures in 30 adult male patients affected by BTM (mean age 43.3 ± 7.9years) with low serum IGF-1 (median value 52.4ng/ml, 38.5-83.4). Only 6 of them (20.0%) were diagnosed with GH deficiency (GHD) after GHRH/arginine stimulation test, while 23 (76.7%) had osteoporosis and 12 (40.0%) had known vertebral fractures. All patients except one also showed at least one endocrine disorder. Serum IGF-1 was significantly lower in BTM patients with vertebral fractures compared to patients without vertebral fractures (U = 41.0, p = 0.005) while it was not significantly different between patients with low bone mass compared to patients without low bone mass. The diagnosis of GHD was significantly associated with lower serum IGF-1 (p = 0.001) and vertebral fractures (p = 0.002) but not with low bone mass. After ROC analysis, we found that very low IGF-1 (≤ 50.0ng/dl) was associated with vertebral fractures (sensitivity 83.3%, specificity 75.0%) and was also predictive of GHD (sensitivity 75.0%, specificity 100.0%). Our study shows that, in male patients with BTM, serum IGF-1 ≤ 50.0ng/dl is a marker of vertebral fractures and it is predictive of a diagnosis of GHD.

Issues of prevalence, pathogenesis, clinical features, diagnosis and treatment of the associated course of non-alcoholic fatty liver disease and diagnosis of growth hormone deficiency: Brief overview of articles

Growth hormone deficiency (GHD) is associated with insulin resistance, visceral obesity, type 2 diabetes, dyslipidemia, and NAFLD. The diagnosis of GHD should be suspected in all patients with hypothalamic-pituitary axis disorders. If GHD is not adequately treated before or after transplantation, the presence of NAFLD can lead to rapid progression of NASH to cirrhosis. Future research should focus on developing early detection strategies as well as biochemical and imaging techniques to monitor patients with PG for progression of NAFLD and NASH. Randomized controlled trials should evaluate optimal treatment strategies in this cohort and balance the effects on NAFLD, glucose metabolism, and diabetes risk, as well as the long-term effects on fibrosis and cancer risk. The potential of GH therapy in patients with NAFLD without GH deficiency needs to be further studied with long-term follow-up. It is important to note that the standard treatment for these patients should be a multidisciplinary approach with close collaboration between hepatologists and endocrinologists, focused on the needs of the individual patient.

Evaluation of growth hormone deficiency in women with unexplained infertility

PurposeGrowth hormone (GH) has been recognized to play a regulatory role in female reproduction. It has been reported that infertile GH deficient patients regained fertility after GH replacement. The frequency of GH deficiency is not established in patients diagnosed with unexplained infertility. Here, we aim to present the prevalence of GH deficieny in this patient group. MethodsWe included patients diagnosed with unexplained infertility throughout 18 months. Insulin tolerance test (ITT) and glucagon stimulation tests (GST) were performed and insufficient response to both tests was required for the diagnosis of GH deficiency. ResultsTwenty-five patients were included in the study, the mean age was 27.4 ± 4.5 years and the median duration of infertility was 60 months (min:14, max:120). Two patients were GH deficient according to GST and 14 to ITT. Two patients (8%) showed lack of response on both tests and were diagnosed with GH deficiency. ConclusionThe rate of GH deficiency among women with unexplained infertility was 8% in this preliminary study. There is need for further studies with larger patient groups to verify the results.

Blood pressure response to clonidine in children with short stature is correlated with postural characteristics: a retrospective cross-sectional study

BackgroundClonidine stimulation test has been widely used in the diagnosis of growth hormone deficiency in children with short stature with a high level of reliability. However, it may cause hypotension, which usually appears as headache, dizziness, bradycardia, and even syncope. It is well known that elevating the beds to make patients’ feet above their cardiac level might relieve this discomfort. However, the real efficiency of this method remains to be proved while the best angle for the elevated bed is still unclear.MethodsA total of 1200 children with short stature were enrolled in this retrospective cross-sectional study. Age, gender, weight, and basic systolic and diastolic blood pressure were collected. Blood pressure at 1, 2, 3, and 4 h after stimulation tests were recorded. The participants were divided into 3 groups based on the angles of the elevated foot of their beds named 0°, 20°, and 40° groups.ResultsAt one hour after the commencement of the tests, participants lying on the elevated beds showed a higher mean increase on the change of pulse pressure. The difference in the angles of the elevated beds did not show statistical significance compared with those who did not elevate their beds (0.13 vs. 2.83, P = 0.001; 0.13 vs. 2.18, P = 0.005; 2.83 vs. 2.18, P = 0.369). When it came to 4 h after the tests began, participants whose beds were elevated at an angle around 20° had a significantly higher mean increase in the change of pulse pressure values compared with those whose beds were elevated at an angle around 40° (1.46 vs. -0.05, P = 0.042).ConclusionElevating the foot of the beds of the patients who are undergoing clonidine stimulation tests at an angle of 20°might be a good choice to alleviate the hypotension caused by the tests.

Postoperative Craniopharyngioma in a 10-Year-Old Girl Presenting with Central Precocious Puberty, Central Diabetes Insipidus, and Growth Hormone Deficiency

Background: Hypopituitarism is the most common endocrinology complication of postoperative craniopharyngioma. However, we found a 10-year-old girl with a history of postoperative craniopharyngioma presenting with central precocious puberty (CPP), central diabetes insipidus (CDI), and growth hormone deficiency (GHD).&#x0D; Case presentation: A 5-year-old girl experienced breast growth followed by menstruation six months later. The patient's weight was 19 kg (weight-for-age: P25-P50), height was 109 cm (height-for-age: P10-P25), and good nutritional status (Waterlow 90%). The stage of pubertal development was M2P2. There was a history of craniopharyngioma, and it was resected at the age of 2 years. After surgery, the patient developed CDI and has received desmopressin. No new tumour growth was found from evaluation with periodic MRIs every three years. After CPP was established, with increased serum levels of LH, FSH, and estradiol, GnRH agonist therapy was given at 100 mcg/kg BW every month. During five years of follow-up, the patient experienced clinical and laboratory improvement. However, the growth is only 3-4 cm/year (&lt;P3) with short stature (height-for-age: &lt;P3) and overweight. Low levels of IGF1 and GH were found in the stimulation test results, so the diagnosis of GHD was confirmed. The patient will receive growth hormone therapy and is expected to reach her potential genetic height (148.5 - 165.5 cm).&#x0D; Conclusion: Even though the craniopharyngioma tumour has been resected and no recurrence has occurred, it is crucial to evaluate the hormones produced by the pituitary thoroughly.