Cases Of Growth Hormone Deficiency Research Articles

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.

Therapeutic efficacy of recombinant human growth hormone in children with different etiologies of dwarfism from a pharmacoeconomic point of view.

Treatment outcomes for different causes of childhood dwarfism vary widely, and there are no studies on the economic burden of treatment in relation to outcomes. This paper compared the efficacy and healthcare costs per unit height of recombinant human growth hormone (rhGH) for the treatment of growth hormone deficiency (GHD) and idiopathic short stature (ISS) with a view to providing a more cost-effective treatment option for children. We retrospectively analyzed 117 cases (66 cases of GHD and 51 cases of ISS) of short-stature children who first visited Weifang People's Hospital between 2019.1 and 2022.1 and were treated with rhGH for 1 to 3 years to track the treatment effect and statistically analyzed by using paired t tests, non-parametric tests, and chi-square tests, to evaluate the efficacy of rhGH treatment for GHD and ISS children and the medicinal cost. The annual growth velocity (GV) of children with GHD and ISS increased the fastest during 3 to 6 months after treatment and then gradually slowed down. The GV of the GHD group was higher than that of the ISS group from 0 to 36 months after treatment (P < .05 at 3, 6, 9, and 12 months); the height standard deviation scores (HtSDS) of the children in the GHD and ISS groups increased gradually with the increase of the treatment time, and the changes in the height standard deviation scores (ΔHtSDS) of the GHD group were more significant than those of the ISS group (P < .05 at 3, 6, 9, and 12 months). (2) The medical costs in the pubertal group for a 1-cm increase in height were higher than those of children in the pre-pubertal group at the same stage (3 to 24 months P < .05). The longer the treatment time within the same group, the higher the medical cost of increasing 1cm height. RhGH is effective in treating children with dwarfism to promote height growth, and the effect on children with GHD is better than that of children with ISS; the earlier the treatment time, the lower the medical cost and the higher the comprehensive benefit.

Beyond the bias! Sex distribution in paediatric growth hormone deficiency reexamined.

Various biases pertaining to stature account for a male sex predominance in growth hormone deficiency (GHD) cases diagnosed by endocrinology clinics. This manuscript will assess the sex distribution when biases are minimised. Retrospective chart review was conducted on patients diagnosed with GHD between 3 and 16 years of age. The sex distribution of cases was ascertained according to: (1) peak GH (pGH) by groups; based on growth hormone provocative testing, (2) pituitary gland imaging results, and (3) isolated GHD (IGHD) versus multiple pituitary hormone deficiencies (MPHD). The relative frequency of each sex was compared according to these subgroups with significance evaluated at α = .05 level. Of the 5880 clinic referrals for short stature, there were 3709 boys (63%) and 2171 girls (37%). Of these, 20% of boys (n = 745) and 15.3% of girls (n = 332) underwent provocative testing for GHD. Of those tested, 39.2% of boys (n = 292) and 32.2% of girls (n = 107) were diagnosed with GHD, all p < .001. There was a male predominance in GHD cases based on pGH or GHD severity. Though not significant, girls were more likely than boys to have MPHD (p = .056), even across pGH groups (p = .06). Both boys and girls had a similar distribution of imaging abnormalities. Stratifying by sex, we found similar percentages of pituitary imaging abnormalities (including tumours) and the number of pituitary hormone deficiencies in boys and girls as the cause of GHD. For these classifications, we did not find the historically reported male sex predominance.

FRI598 Evolving Growth Hormone Deficiency: A Proof Of Concept

Abstract Disclosure: S. Chimatapu: None. S. Sethuram: None. J. Samuels: None. M. Savage: None. R. Rapaport: None. Introduction: Most cases of growth hormone deficiency (GHD) in pediatric patients are idiopathic, isolated and acquired. All acquired conditions commence with a period during which the diagnosis maybe unapparent. We document here evidence for evolution of GHD in a group of adolescent males who tested sufficient on initial GH stimulation test (GST) but tested deficient upon reevaluation. The rationale for repeat GST was ongoing growth failure. Hypothesis: We hypothesize that GHD in some individuals evolves with time and can be diagnosed by repeat testing (EGHD). We also postulate that their response to GH therapy is similar to other patients with GHD. Methods: We performed an IRB-approved retrospective chart review of children who presented for short stature (height less &amp;lt; 2SD for mean or &amp;lt; 2SD for mid-parental height) to pediatric endocrinology at Kravis Children’s Hospital at Mount Sinai, New York and who had 2 GST. GST were performed using two different stimuli (arginine and glucagon) and highly sensitive assay serum GH measurements were processed by the same laboratory, Esoterix. No patient had obesity, chronic illnesses, or any genetic conditions affecting growth. Data were collected from electronic medical records and analyzed using SPSS v28.0 once at least half the population studied reached adult height. We defined adult height as bone age ≥ 16 years and growth velocity ≤ 2 cm/year. Results: Of 42 charts analyzed, all male, 25 had EGHD. Their average GH peak on initial GST was 15.48 ± 4.92 ng/ml, mean age 10.07 ± 2.65 years, mean height -1.68 ± 0.56 SD , IGF-1 -1.00 ± 0.88 SD. After 2.23 ± 1.22 years, at 12.04 ± 2.41years, height decreased to -1.82 ± 0.63 SD and IGF-1 was -1.08 ± 0.84 SD. At repeat GST, GH peak was 7.59 ± 2.12 ng/mL and 28% were in puberty. All patients had MRI before starting GH therapy; 40% had small anterior pituitary glands. 12 males who reached adult height had a height of -1.88 ± 0.64 SD, IGF-1 of -1.15 ± 0.81 SD, with 42% pubertal and peak GH of 7.33 ± 2.47 ng/mL at repeat GST. They had a mean height gain of 1.83 ± 0.56 SD(p&amp;lt;0.005), with an adult height of 0.09 ± 0.70 SD after 4.64 ± 1.4years of treatment. They were 2.10 ± 4.20 cm taller than their mid-parental target heights. Discussion/Conclusions: We provide proof of concept for the diagnosis of EGHD. The diagnosis could be established by repeat GST in children with ongoing growth deceleration despite pubertal progression and a non-diagnostic initial GST. Our patients who reached adult height had a height gain consistent with that reported by KIGS for patients with growth hormone deficiency (1.7SD; Cutfield,1999) and indeed better than patients with ISS (0.7SD; Maghnie,2022). Presentation: Friday, June 16, 2023

FRI340 Growth Hormone Deficiency Post Carbon Monoxide Poisoning

Abstract Disclosure: A.Y. Ghamlouche: None. O. Alzohaili: None. A.H. Elkadry: None. Carbon monoxide (CO) is the poisonous byproduct of combustion of fossil fuels, that is odorless and tasteless. In toxic levels CO leads to the impaired functioning of red blood cell’s ability to transport oxygen to tissues.1 Following CO toxicity, white matter demyelination and necrosis of the Globus pallidus that further results in other neurologic disorders, is common.2 A novel and underrecognized consequence of CO poisoning is growth hormone deficiency (GHD). GHD is the most common pituitary hormone deficiency following a traumatic brain injury.3 Four cases of GHD were described following an event of CO poisoning. Recommended GHD diagnosis criteria of less than 5.0 ng/mL was used with these patients. The Insulin Tolerance Test (ITT) and Glucagon stimulation test (GST) were administered. All patients had no causes of GHD in their medical history prior to their encounters with CO poisoning. A 44-year-old male with exposure in 2020, came for an evaluation in January of 2022 complaining of memory impairment, brain fog, mental fatigue, cognitive decline, anxiety, poor libido, and neuropathy. showed a GH peak of 1.1 ng/mL during the ITT a peak of 1.0 ng/mL during the GST. A 51-year-old male with exposure in 2016, came for an evaluation in December of 2020 complaining of memory impairment, blurry vision, fatigue, physical weakness, mood changes, and stuttered speech. Results showed a GH peak of 4.4 ng/mL during ITT and a GH peak of 0.157 ng/mL during the GST.A 43-year-old female with exposure in 2017, came for an evaluation in January of 2022 complaining of memory loss, attention issues, anxiety, depression, fatigue, weight gain and neuropathy. Results showed a GH peak of 1.7 ng/mL during ITT and a GH peak of 2.6 ng/mL during the GST. A 42-year-old male with exposure in 2018, came for an evaluation in November of 2019 complaining of memory impairment, headaches, tremors, fatigue, anxiety, depression, declining cognition, insomnia, poor libido, lack of concentration, and poor vision. Results showed a GH peak of 3.6 ng/mL during ITT and a GH peak of 0.109 ng/mL during the GST. All 4 patients were started on GH replacement therapy following their tests. All patients responded well, and showed significant improvements in quality of life. A possible connection can be drawn between pituitary gland damage and hypoxia from CO poisoning.

Challenges in Treating Childhood Infratentorial Ependymoma: A Low- and Middle-Income Country Experience

Patients and physicians in low and middle-income countries (LMICs) face challenges due to limited expertise and suboptimal access to appropriate diagnostic and treatment modalities. We report our experience in treating posterior fossa ependymoma (PFE) at MAHAK, a charity organization in Iran. The radiation oncology department is the only one exclusively dedicated to childhood cancer in the whole country. Pediatric patients with PFE and referred to MAHAK between November 2008 and January 2016 were identified. Details on investigations and management done before referral were collected. Management at MAHAK and patients outcome were analyzed. Out of 80 patients diagnosed as having ependymoma, 54 with PFE were identified. Fortythree received adjuvant radiotherapy and 11 patients were irradiated initially after recurrence. At a median follow-up of 5.1 years (range 0.3-9.7), the latter group had the worst outcome with a 5year overall survival (OS) of 27% (95% CI: 7-54). Patients who started radiotherapy within 77 days after initial surgery had a better outcome compared to those who started later (5-year OS: 74% vs 32%, p=0.05). Compliance with follow-up recommendations was poor. Only 22% of the patients had at least two IQ test assessments and 50% showed some decline over time. Three cases of growth hormone deficiency were detected but no one received replacement therapy. Access to pediatric neurosurgery, anesthesia, and timely radiotherapy are among the most challenging obstacles to be overcome in LMICs. Our series confirms that chemotherapy is not an appropriate option for delaying radiotherapy, especially in young children. The importance of long-term follow-up should be acknowledged by the parents and medical team.

Abstract #1180419: A rare case of Central Hypogonadism and Growth Hormone Deficiency in a patient with Sturge-Weber Syndrome

Sturge-Weber Syndrome (SWS) is a rare non-hereditary disorder characterized by capillary-venous malformations affecting brain and eyes leading to complications such as epilepsy, hemiparesis, intellectual disabilities, glaucoma and visual field defects. SWS may also lead to neuroendocrine disorders and cases of growth hormone deficiency as well as central hypothyroidism have been reported. One study found an 18 fold increase in GH deficiency in this population. This report describes a rare case of a patient with SWS who was found to have growth hormone deficiency and central hypogonadism without evidence of structural pituitary abnormality.

Contribution of Ghrelin to the Pathogenesis of Growth Hormone Deficiency.

In this review we described the interactions between ghrelin and the growth hormone (GH)-insulin-like growth factor 1 (IGF-1) axis in children and adults with growth hormone deficiency (GHD). A possible involvement of these interactions in the pathogenesis of unexplained cases of GHD was suggested. Current research provides more and more details to the knowledge on the circadian rhythm of ghrelin. We gathered reports on the decreasing effect of Helicobacter pylori-related chronic gastritis on the number of ghrelin immunopositive cells and the consequent decrease in ghrelin serum concentration. The gastrointestinal tract microflora modification of the ghrelin action, by the mechanism of molecular mimicry, was also stressed. Moreover, the mutual relationships between ghrelin and the TSH-FT4/FT3 axis in growth and metabolic processes are described. It is to be recalled that FT4 and FT3 exert a permissive impact on IGF-1 action and, in turn, GH, in reaction mediated by IGF-1, enhances the monodeiodination of FT4 to FT3. Finally, we discussed the latest attempts to use the GH secretagogue receptor (GHS-R) analogues for possible diagnostic and therapeutic purposes.

BASELINE CHARACTERISTICS OF PATIENTS WITH GROWTH HORMONE DEFICIENCY

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

A case report of glucose transporter 1 deficiency syndrome with growth hormone deficiency diagnosed before starting ketogenic diet

BackgroundGrowth failure and growth hormone deficiency (GHD) have been reported as one accessory feature of GLUT1 deficiency syndrome (GLUT1DS), considered so far as a long-term adverse effects of ketogenic diet which is used to treat this condition.Case presentationWe report the case of a 10-year-old Caucasian boy referred for short stature (height − 2.56 SDS) and delayed growth (growth velocity − 4.33 SDS) who was diagnosed with GHD and started treatment with recombinant human growth hormone (rhGH). Because of his history of seizures with infantile onset, deceleration of head growth with microcephaly, ataxia, and moderate intellectual disability, a lumbar puncture was performed, which revealed a low CSF glucose concentration with a very low CSF-to-blood glucose ratio (< 0.4), and genetic tests detected a SLC2A1 gene exon 1 deletion confirming a diagnosis of GLUT1DS. Ketogenic diet was started. After 5.5 years of rhGH treatment his height was normalized (− 1.15 SDS). No side effects were reported during treatment, particularly on glycemic metabolism.ConclusionsThis is the first case of GHD in a Caucasian boy with GLUT1DS diagnosed before starting ketogenic diet, with a good response to rhGH treatment and absence of side effects. We speculate that GHD may represent a poorly recognized clinical feature of GLUT1DS rather than a complication due to ketogenic diet. Under-diagnosis may derive from the fact that growth failure is usually ascribed to ketogenic diet and therefore not further investigated. Pediatric neurologists need to be alerted to the possible presence of GHD in patients with GLUT1DS with slow growth, while pediatric endocrinologist need to refer GHD patients with additional features (motor and cognitive developmental delay, seizures with infantile onset, deceleration of head growth with acquired microcephaly, movement disorder with ataxia, dystonia, and spasticity) that may suggest GLUT1DS.

Clinical features of anterior pituitary hypofunction

Objective To investigate the common etiology, clinical manifestations and abnormal hormone levels of anterior pituitary hypofunction (APH). Methods A retrospective analysis was performed on 140 patients diagnosed with APH at Department of Endocrine & Metabolic Diseases, Fujian Provincial Hospital from January 2013 to January 2017. Basic clinical data were collected to analyze the common causes of APH, main clinical manifestations and laboratory examination results of the patients. Results Among all 140 patients, 30 (21.4%) were pituitary adenoma patients, 28 (20.0%) were postoperative pituitary adenoma patients, 18 (12.9%) suffered from pituitary hypofunction caused by craniocerebral radiotherapy, 16 (11.4%) developed pituitary stalk interruption syndrome, and 15 (10.7%) had with Sheehan syndrome. There were 67 (94.4%) cases of growth hormone deficiency (growth hormone function measured in only 71 of 140 subjects), 114 (81.4%) cases of gonadal hormone deficiency, 113 (80.7%) cases of thyroid hormone deficiency and 107 (76.4%) cases of adrenocortical hypofunction. Fatigue in 40 (28.6%) cases and delayed growth in 13 (9.3%) cases were the most common complaints, headache in 11 (7.9%) and visual impairment in 10 (7.1%) were the most common symptoms. In male patients, hormonal abnormalities included growth hormone deficiency (94.6%, 53/56), gonadal hormone deficiency (85.0%, 68/80), thyroid hormone deficiency (81.3%, 65/80), and adrenocortical hormone deficiency (78.8%, 63/80). In femal patients, hormonal abnormalities included growth hormone deficiency (93.3%, 14/15), thyroid hormone deficiency (80.0%, 48/60), gonadal hormone deficiency (76.7%, 46/60), and adrenocortical hormone deficiency (73.3%, 44/60). Conclusions The most common reason leading to APH is pituitary adenoma, followed by pituitary adenoma after surgery. The most common complaint is fatigue. The most important hormone abnormalities are? growth hormone and gonadal hormone. There are differences in hormone abnormality caused by APH in different genders. Key words: Hypopituitarism; Clinical features; Pituitary hormones; Etiology

SUN-286 Growth Hormone Deficiency and Gingival Fibromatosis Due to Missense Mutation of KCNQ1

Background: Multiple genes have been implicated in the genetic etiology of growth hormone deficiency (GHD) including genes that contribute to hypothalamus and pituitary development. Mutations of these genes can be associated with additional pituitary hormone deficiencies and developmental abnormalities. KCNQ1 gene encodes the alpha subunit of the voltage-gated ion channel Kv7.1, which has been previously implicated in cardiac arrhythmia syndromes. In 2017, two missense mutations, c.347G>T p.(Arg116Leu) or c.1106C>T p.(Pro369Leu), in KCNQ1 were reported for the first time in three unrelated families causing GHD and maternally inherited gingival fibromatosis (GF) (1). Members of these families displayed variable phenotypes including GHD, multiple pituitary hormone deficiencies, small pituitary on MRI, GF, craniofacial dysmorphic features, and short QT syndrome. Many had hypogonadotropic hypogonadism. Clinical Case: 9 year old male was referred to pediatric endocrinology for short stature and slow growth. He maintained height around 6%ile (Z=-1.55) until the age of 9 years with subsequent slowing to 0.95%ile (Z=-2.34). He had history of significant gingival hyperplasia requiring 5 surgical interventions in the past. He has done well developmentally. No history of cardiac arrhythmia. Physical exam showed coarse facial features and normal pre-pubertal genitalia. Family history was negative for short stature, arrhythmia, gingival hyperplasia, or coarse facial features. Studies showed delayed bone age of 6 years, low IGF-1 of 57 ng/ml, max growth hormone level of only 3 ng/ml on Arginine-Glucagon tolerance test, and normal other pituitary hormones. EKG and MRI of brain and pituitary were normal. Given his coarse facial features and gingival problem, he had a detailed work up for lysosomal storage disorders with negative results. Whole exome sequencing showed a missense variant in the maternal KCNQ1 gene denoted as c.1106C>T p.(Pro369Leu). Neither of his parents were found to have this KCNQ1 variant. He was started on growth hormone therapy with appropriate catchup growth. He was noticed 9 months later to have pubertal changes with testicular volume of 4-5 ml, LH 1.1 mIU/ml, and testosterone level of 98 ng/dl. Conclusion: To our knowledge, this is the first case of GHD and GF due to KCNQ1 mutation to be reported in the United States. Our patient had many unique features in contrast to previous report including lack of identified parental mutation, lack of clinical features in the family and early puberty indicating that there is still more to learn about clinical spectrum of KCNQ1 mutations in children. Reference: (1) Two missense mutations in KCNQ1 cause pituitary hormone deficiency and maternally inherited gingival fibromatosis. J.Tommiska et al, Nat Commun. 2017 Nov 3;8(1):1289.

Growth hormone of dried blood spot for the diagnosis of growth hormone deficiency

The diagnosis of growth hormone deficiency (GHD) is difficult to determine, and could be associated with severe complications, especially in the neonatal period. The stimulation test of growth hormone (GH) secretion is considered the gold standard for diagnosis, but it has methodological complications and is associated with adverse effects. Neonates present physiological increased secretion of GH, representing a diagnostic window. To evaluate if the dried blood spot on filter paper obtained in the neonatal period, as part of a neonatal screening for con genital hypothyroidism and phenylketonuria, allows differentiating patients with GHD from those who do not have it. Study of cases and controls by measuring the GH concen tration in dried blood spot on filter paper obtained in the neonatal period, comparing controls with GHD with cases with discarded deficiency. The sample was extracted from the filter paper, obtaining two 0.125 inch discs per each patient from the center of the blood spot on the paper, for a highly sen sitive ELISA assay for human GH based on the use of polyclonal antibodies against 22 kDa recom binant human GH. Seven cases of GHD and ten controls were obtained. The median GH concentration of the dried blood spot in the cases is 2.0 ng/ml (Interquartile range 3.6 ng/ml) and 2.05 ng/ml (Interquartile range 2.0 ng/ml) in the controls, Mann-Whitney U test 30.5 (p = 0.68). The two cases with multiple pituitary-hormone deficiency (MPHD) present concentrations lower than 1 ng/ml. The dried blood spot sample did not differentiate GHD patients from control cases, although MPHD cases present much lower concentrations compared to isolated growth hor mone deficiency (IGHD).

Causes and Follow-Up of Central Diabetes Insipidus in Children.

Objective To identify the causes of central diabetes insipidus (CDI) by evaluating the values of magnetic resonance imaging (MRI) in the diagnosis of pediatric CDI, providing evidence for the clinical diagnosis and treatment of CDI. Methods Seventy-nine patients with CDI (CDI group) hospitalized from July 2012 to March 2017 and 43 healthy children (control group) were enrolled in this study. All cases underwent MRI examination including T1-weighted three-dimensional magnetization-prepared rapid gradient-echo (T1WI-3D-MP RAGE) imaging sequences. The pituitary volume, the signal intensity of posterior pituitary, and the morphology of pituitary stalk were measured between two groups. The medical history, urine testing, imaging of hypothalamic-pituitary region, and hormone levels were also recorded. Results Age and gender were matched between the CDI and control groups. The height and BMI in the CDI group were less and the urine volume in 24 h was higher than those in the control group. The signal intensity of the posterior pituitary was higher in the control group, whereas the pituitary volume was smaller in the CDI group. In the CDI group, 44 cases presented with morphological changes of the pituitary stalk. Clinical symptoms mainly included polydipsia, polyuria, short stature, and vomiting. All patients were confirmed by water deprivation vasopressin test. Forty-four CDI children were associated with hypopituitarism, including 33 cases of PSIS with multiple pituitary hormone deficiencies (MPHD) and 11 cases of growth hormone deficiency (IGHD). The pituitary volume in the cases of pituitary stalk interruption syndrome (PSIS) with MPHD was smaller than that in the IGHD patients. Conclusions The signal intensity ratio of the posterior lobe, pituitary volume, and the morphology of pituitary stalk on T1WI-3D-MP RAGE image contribute to the diagnosis of CDI.

Analysis of the value and correlation of IGF-1 with GH and IGFBP-3 in the diagnosis of dwarfism.

Correlation between the value of insulin-like growth factor-1 (IGF-1) in the diagnosis of dwarfism and the levels of growth hormone (GH) and insulin-like growth factor binding protein-3 (IGFBP-3) was investigated. From April 2014 to June 2017, 122 children with dwarfism who were treated in The Affiliated Wuxi No. 2 People's Hospital of Nanjing Medical University and The First Affiliated Hospital of Xinxiang Medical University were selected as the experimental group, and 51 normal children as the control group. The basic information was recorded in detail; serum GH and IGFBP-3 levels were measured using an arginine stimulation test and an insulin hypoglycemia stimulation test, respectively. According to the peak of GH in the experimental group, there were 65 cases of growth hormone deficiency (GHD) and 57 cases of idiopathic short stature (ISS). The expression levels of IGF-1 of the serum in the experimental and control group were detected by chemiluminescence immunoassay (CLIA). The correlation between IGF-1 and GH, IGF-1 and IGFBP-3 was analyzed. The expression level of serum IGF-1 in GHD group was significantly lower than that in the ISS group (P<0.05). The expression level of serum IGF-1 in GHD group was significantly lower than that in the control group (P<0.05). The expression level of serum IGF-1 in ISS group was significantly lower than that in the control group (P<0.05). The results of partial correlation studies showed that IGF-1 is positively correlated with GH and IGFBP-3. Detection of GH and IGFBP-3 are important for the early diagnosis and comprehensive evaluation of children with dwarfism, and also in the detection of IGF-1 can reflect the therapeutic effect of dwarfism on recombinant human growth hormone (rhGH) treatment, which is worthy of application in clinics.

A case of growth hormone deficiency combined with neurofibromatosis Type 1 and its gene analysis

Neurofibromatosis Type 1 (NF1) is an autosomal dominant genetic disorder caused by NF1 gene mutations. Café au lait spots, neurofibromatosis, Lisch nodules, axillary freckling, dermal neurofibromas and skeletal dysplasia are the most common manifestations for this disease. A 11-year-old boy visited Third Xiangya Hospital, Central South University due to growth-retardation. He was eventually diagnosed as NF1 with growth hormone deficiency. A novel heterozygous splicing mutation c.6579+2 T>C (IVS 34+2 T>C) of NF1 gene was identified in the patient and his mother. Considering NF1 may present with short stature due to growth hormone deficiency, all children with short stature combined with café au lait spots should be screened for NF1, which may assist the clinical diagnosis and the genetic counseling.

Pons ratio as a potential diagnostic biomarker for the detection of growth hormone deficiency in children.

Pituitary insufficiency (PI) needs further research to optimize treatment. Growth hormone deficiency (GHD) is a subtype of PI. The purpose of the present study is to investigate the possible relationship between GHD and the anatomical position of the pons as revealed by magnetic resonance imaging (MRI) in the pediatric age group. In the current study, we developed a novel and simple index using MRI that could provide an alternative to other indexes in the classical literature. Brain MRI and clinical data of 48 children with suspected PI (22 females, 26 males; mean age 11.6 ± 2.2 years) were examined retrospectively. To estimate the location of the pons, the ratio of pons height over the axis between the dorsum sellae and the fourth ventricular hill in the sagittal plane (A) to the total height of the pons (B) was calculated (A/B). It was termed the pons ratio (PR). The PRs of children with or without a diagnosis of GHD were then compared statistically. Fifteen children were diagnosed with GHD and treated with growth hormone (GH), whereas the remaining 33 were reported normal. The mean PRs of the children diagnosed with GHD and given GH treatment (0.31 ± 0.07, range: 0.18-0.42) differed significantly from those without PI (0.26 ± 0.06, range: 0.17-0.44; P = 0.018). There appears to be an association between GHD and decreased PR in children receiving GH treatment. Spatial measurements of posterior fossa in radiological examinations may provide additional information that is helpful in the diagnosis of suspected cases of GHD.

Effects of recombinant human growth hormone in the treatment of dwarfism and relationship between IGF-1, IGFBP-3 and thyroid hormone.

The effects of recombinant human growth hormone (rhGH) in the treatment of dwarfism and the relationship between insulin-like growth factor (IGF)-1, IGF-binding protein (IGFBP)-3 and thyroid hormone were examined in the present study. For this purpose, 66 patients diagnosed with dwarfism were selected retrospectively, with 36 cases of growth hormone deficiency (GHD) and 30 cases of idiopathic short stature (ISS). The therapeutic dose of GHD 0.10 IU/kg·day and ISS 0.15 IU/kg·day were injected subcutaneously every night before sleep until adulthood. The average follow-up was 5 years, and the results were evaluated and measured every 3 months, including height, BA, secondary test of growth hormone (GH peak), IGF-1, IGFBP-3 and thyroid hormone (FT3, FT4 and TSH). After treatment, the height, BA, GH peak, IGF-A and IGFBP-3 of the GHD group were all increased, and the differences were statistically significant (P<0.05), while FT3, FT4 and TSH had no significant change (P<0.05). The height and BA increased and the differences were statistically significant (P<0.05). The indexes of the ISS group were not statistically significant (P>0.05). The results of the Pearson-related analysis suggested that GH peak of the GHD group, IGF-1 and IGFBP-3 were positively associated with height (P<0.05), and had no relationship with BA (P<0.05). None of the above indexes of the ISS group had an obvious correlation with height and BA (P>0.05). rhGH was effective for GHD and ISS, with the GHD effect being positively associated with the GH peak, IGF-1 and IGFBP-3. ISS had no obvious relationship with GH peak, IGF-1 and IGFBP-3 although other influencing factors may be involved.

Evaluation of Asymmetric Dimethylarginine (ADMA) Levels in Children with Growth Hormone Deficiency

Ob­jec­ti­ve: To investigate serum asymmetric dimethylarginine (ADMA) levels in children with isolated growth hormone deficiency (GHD) and to determine the effect of GH replacement therapy on these levels.Methods: 31 patients diagnosed with isolated GHD and 29 age-and sex-matched healthy children were enrolled in the study. Height, weight and waist circumference were measured in all subjects. Fasting serum insulin-like growth factor-1 (IGF-1), IGF binding protein-3, glucose, insulin and lipid levels were evaluated. Serum ADMA levels were assessed using the enzyme-linked immunosorbent assay technique. The same evaluations were repeated on the 3rd and 6th months of treatment in 28 of the GHD cases.Results: There were no significant differences in ADMA levels between the patient and control groups [0.513±0.130 (0.291-0.820) µmol/L vs. 0.573±0.199 (0.241-1.049) µmol/L]. There was a positive correlation between serum ADMA and HbA1c levels in the control group. In the GHD cases, ADMA levels negatively correlated with high-density lipoprotein levels and positively correlated with low-density lipoprotein levels. There was also a significant increase in ADMA levels in patients receiving GH therapy compared to pre-treatment levels [serum ADMA level, 1.075±0.133 (0.796-1.303) µmol/L at the 3rd month and 0.923±0.121 (0.695-1.159) µmol/L at the 6th month of treatment]. There was a negative correlation between ADMA levels and homeostasis model assessment of insulin resistance values at the 6th month evaluation. There were no relationships between ADMA levels and age, sex, or pubertal state either before or during the treatment.Conclusion: Serum ADMA levels were found to be similar in patients with GHD and in healthy children. However, serum ADMA levels showed a significant increase in GHD patients following GH replacement therapy.

Growth Hormone Deficiency and Lysinuric Protein Intolerance: Case Report and Review of the Literature.

Lysinuric protein intolerance (LPI; MIM# 222700) is a rare metabolic disorder caused by a defective cationic amino acids (CAA) membrane transport leading to decreased circulating plasma CAA levels and resulting in dysfunction of the urea cycle. Short stature is commonly observed in children with LPI and has been associated with protein malnutrition. A correlation between LPI and growth hormone deficiency (GHD) has also been postulated because of the known interaction between the AA arginine, ornithine, and lysine and growth hormone (GH) secretion. Our report describes a case of GHD in an LPI patient, who has not presented a significant increase in growth velocity with recombinant-human GH (rhGH) therapy, suggesting some possible pathogenic mechanisms of growth failure. The proband was a 6-year-old boy, diagnosed as suffering from LPI, erythrophagocytosis (HP) in bone marrow, and short stature. Two GH provocative tests revealed GHD. The patient started rhGH therapy and a controlled-protein diet initially with supplementation of oral arginine and then of citrulline. At 3-year follow-up, no significant increase in growth velocity and in insulin-like growth factor-1 (IGF-1) levels was observed. Inadequate nutrition and low plasmatic levels of arginine, ornithine, lysine, and HP may have contributed to his poor growth. Our case suggests that growth failure in patients with GHD and LPI treated with rhGH could have a complex and multifactorial pathogenesis. Persistently low plasmatic levels of lysine, arginine, and ornithine, associated with dietary protein and caloric restriction and systemic inflammation, could determine a defect in coupling GH to IGF-1 production explaining why GH replacement therapy is not able to significantly improve growth impairment. We hypothesize that a better understanding of growth failure pathophysiology in these patients could lead to the development of more rational strategies to treat short stature in patients with LPI.