Human Growth Hormone Deficiency Research Articles

Soluble Expression, One-Step Purification and Characterization of Recombinant Human Growth Hormone Fused with ompA3 in Escherichia coli.

Human growth hormone (hGH) is the first recombinant protein approved for the treatment of human growth hormone deficiency. However, expression in inclusion bodies and low expression levels are enormous challenges for heterologous expression of hGH in Escherichia coli. To increase the soluble expression of recombinant hGH with correct folding in E. coli. We constructed a new recombinant expression plasmid containing the coding sequence of the outer membrane protein A (ompA3) which was used for the expression in Transetta (DE3) E. coli. In order to simplify the purification process and cleavage of recombinant proteins, the fusion sequence should contain hexahistidine-tag (His6) and enterokinase recognition sites (D4K). The effect of different expression conditions on recombinant hGH expression was optimized in flask cultivations. Furthermore, the periplasmic solution containing soluble hGH was purified by Ni-NTA affinity chromatography. Circular dichroism (CD), western blot and mass spectrometry analyses were used to characterize the protein. Moreover, the growth-promoting effect of the purified hGH was also evaluated by cell proliferation assay. High-level expression (800 μg/mL) was achieved by induction with 0.5 mM IPTG at 30°C for 10 hours. The purity of hGH was over 90%. The immunological activity, secondary structure and molecular weight of the purified hGH were consistent with native hGH. The purified hGH was found to promote the growth of MC3T3-E1 cells, and was found to show the highest activity at a concentration of 100 ng/mL. Our research provides a feasible and convenient method for the soluble expression of recombinant hGH in E. coli, and may lay a foundation for the production and application of hGH in the industry.

SUN-038 Role Of The Satb 1 Gene In Growth Across Species: Findings In A Cohort Of Patients With Short Stature And In A Knockout Zebrafish Model

Background: Short stature is a common pediatric disorder, affecting 3% of the population; however, the identification of its cause is limited by its largely variable clinical presentation and genetic heterogeneity. Identification of novel genetic causes of short stature is of great importance to customize the therapeutic approach of this entity. The especial AT-rich sequence binding protein1 gene (SATB1) encodes a chromatin organizer with important roles in cell growth and immunosuppression. SATB1 is highly expressed in the pituitary gland, where it regulates the differentiation of PIT1 positive cells. Indeed, the conditional knockout of Satb1 in the mouse pituitary decreases growth hormone expression, leading to reduced growth. Aim: To investigate the putative role of SATB1 in growth in a cohort of individuals with short stature and in a zebrafish knockout (KO) model. Methods: We obtained germline DNA samples from a cohort of 287 Brazilian patients diagnosed with short stature (height <2 SDS for age and sex), including 52 patients small for gestational age (SGA), 5 cases with growth hormone deficiency (GHD), 10 cases with syndromic short stature and 220 cases with idiopathic short stature. All cases were screened for SATB1 copy number variations (CNVs) using droplet digital PCR, and 190 cases were screened for mutations via Sanger sequencing. In silico predictions were retrieved from the Varsome browser. All variants were annotated to RefSeq NM_002971.5. Using CRISPR-Cas9, we generated two lines of zebrafish satb1 bearing frameshift mutations; both lines were crossed to obtain full KOs. Growth was monitored from 3 to 12 weeks post-fertilization (wpf) and expression of pituitary hormones was analyzed at 6 wpf by quantitative PCR. Results: No variants predicted as damaging were found in the short stature cohort. Nevertheless, variants of uncertain significance (VUS, mostly intronic) were found in 11% of our cohort, in which 57% of the individuals that carry a VUS presented familial short stature while 43% were non-familial. Interestingly, the variant c.515+112G>A was identified in 3/33 (9.1%) of SGA patients, but only in 2/143 (1.4%) of ISS patients. No CNVs were observed. In the zebrafish model, satb1 knockout led to significantly smaller size at 3 wpf, compared with heterozygous and wild type controls (median standard length: 6.6, 7.4, and 7.8 cm, and mean weight: 2.7, 4.3, and 4.6 mg, respectively, P<0.05 for all comparisons). At 6 wpf, we identified a trend for lower gh1 expression in the KOs vs. heterozygous zebrafish (relative quantification: 0.68 vs. 1.79, P=0.06). Conclusion: Our results support a role for SATB1 in regulating growth hormone production across species. Although loss of SATB1 function could theoretically lead to growth hormone deficiency in humans, defects in this gene do not seem to play a crucial role in the height of individuals with short stature.

Incretin Hormones, Thyroid Stimulating Hormone and Human Growth Hormone Responses During Ogtt in Newly Diagnosed T2DM Patients

Several research groups have reported variable results about incretin effects of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1(GLP-1), altered thyroid stimulating hormone (TSH) status, human growth hormone (hGH) deficiency and perturbed cytokines balances in type 2 diabetes mellitus (T2DM).The present case-control prospective interventional study was conducted investigating responses of incretin hormones (GIP, GLP-1), TSH and hGH to oral glucose tolerance test (OGTT) in newly diagnosed Bangladeshi T2DM patient. Blood samples were collected from 36 OGTT positive newly diagnosed T2DM patients as cases and 30 normal adults as controls at '0' minute (fasting) and at 2 hours after OGTT. Laboratory investigations were done and special parameters in serum, i.e. hGH, TSH, Insulin, GIP and GLP-1 were analyzed using enzyme immunoassay (EIA) kits. Statistical analyses were made by Student's 't' test using SPSS programm. T2DM patients (cases) had FBG and BG2Hr levels much higher than controls (p&lt;0.001). No significant differences were observed between controls and cases for F-TSH (p=0.927), TSH2HrA (p=0.413), F-hGH (p=0.532) and hGH2HrA (p=0.773) levels. It was observed that F-GIP (p=0.309) and F-GLP-1 (p=0.984) levels were similar between cases and controls. Interestingly, control subjects responded to OGTT by increasing GIP2HA and GLP-1, 2HR levels about 3 times compared to F-GIP and F-GLP-1 (p&lt;0.001). In cases, F-GIP and F-GLP-1 levels were also raised responding to OGTT but by about 1.5 times only compared to F-GIP and F-GLP-1 (p&lt;0.025). Although no significant differences were observed for F-TSH, TSH2HrA, F-hGH and hGH2HrA between cases and controls, F-GIP and F-GLP-1 levels were raised responding to OGTT in cases by about 1.5 times only compared to about 3.0 times in controls subjects. But responses of GIP and GLP-1 to glucose load were lower leading to reduced insulin levels in these T2DM patients reported earlier. Further studies with a larger sample size including cytokines are warranted.&#x0D; Bangladesh J Med Biochem 2018; 11(1): 9-16

Growth Hormone Deficiency Is Frequent After Recent Stroke.

Introduction: The incidence of pituitary dysfunction after severe ischemic stroke is unknown, however given the increasing attention to pituitary dysfunction after neurological injuries such as traumatic brain injury, this may represent a novel area of research in stroke.Methods: We perform an arginine and human growth hormone releasing hormone challenge on ischemic stroke patients within a week of symptom onset.Results: Over the study period, 13 patients were successfully tested within a week of stroke (baseline NIHSS 10, range 7–16). Overall, 9(69%) patients had a poor response, with 7(54%) of these patients meeting the criteria for had human growth hormone deficiency. Other measures of pituitary function were within normal ranges.Conclusion: After major ischemic stroke, low GH levels are common and may play a role in stroke recovery.

Growth hormone modulates in vitro endothelial cell migration and formation of capillary-like structures.

The generation of new blood vessels is a complex process mediated by a variety of growth factors, and the growth hormone (GH) has been shown to act as a proangiogenic factor. In fact, human GH deficiency or excess are associated with endothelial dysfunction. Moreover, mouse models have revealed the action of GH in both tissue repair and in the microvascular circulation of normal tissues. In this study, we investigated the in vitro effects of GH on endothelial cells. Using a murine endothelioma cell line (tEnd.1), we demonstrated that GH has a mitogenic effect. The hormone also affected the endothelial cellular morphology and augmented the deposition of the extracellular matrix molecules, laminin, and fibronectin, on tEnd.1 surface. GH could stimulate tEnd.1 cell fugetaxis, in transwell chambers migration assay, and increased the formation of capillary-like structures in Matrigel®-coated plates. Given the important role of angiogenesis during tissue injury, for example, at ischemic lesions, these findings shed light on therapeutic angiogenesis, particularly in pathologies where the cardiovascular system has been compromised.

One year pituitary function follow-up in survivors of severe brain injury presenting at a regional neurosurgical centre

Introduction 5% of traumatic brain injuries are severe (NICE) 30% develop hypopituitarism 3 t0 12 months later i.e. Human growth hormone deficiency (the most common ) Hypocortisolism / Hypothyroidism /Hypogonadism Diabetes Insipidus Currently there are no UK guidelines to advise on the follow up of such patients Patients Individuals with severe head injury admitted to Hurstwood Park Neurosurgical Centre between 1st January 2010—31st December 2012 Severe head injury defined as GCS of 8 and below

Bone and hypopituitarism: not only a mass issue

Bone and hypopituitarism: not only a mass issue

Sheehan Syndrome in Costa Rica: Clinical Experience With 60 Cases

To describe the clinical and hormonal characteristics of patients with Sheehan syndrome. We performed a 20-year cohort study (1969 to 1989) of patients with Sheehan syndrome who were cared for in the endocrinology unit of the México Hospital in San José, Costa Rica. Medical history, physical examination findings, and laboratory test results were documented and reviewed. Sixty patients with a diagnosis of Sheehan syndrome were identified. Mean age at diagnosis was 45.8 ± 10.6 years. The average time between the previous obstetric event and Sheehan syndrome diagnosis was 13 years. Thirteen patients (22%) had a home birth. The median parity was 7. The most frequent obstetric antecedents were history of obstetric hemorrhage in 49 (82%), shock in 28 (47%), blood transfusion in 26 (43%), and peripartum hysterectomy in 4 (7%). The most common symptoms included asthenia and adynamia in 51 (85%), amenorrhea in 44 (73%), loss of axillary or pubic hair in 40 (67%), and agalactia in 40 (67%). The most common findings on physical examination were absence of axillary hair in 56 (93%) and pubic hair in 56 (93%), dry skin in 49 (82%), and pallor in 42 (70%). When a combined pituitary test was performed, 38 of 38 patients (100%) had human growth hormone deficiency, 29 of 30 patients (97%) had adrenal insufficiency, 8 of 10 patients (80%) had hypothyroidism, 8 of 12 patients (67%) had hypogonadism, and 9 of 13 patients (69%) had prolactin deficiency. Despite early onset of symptoms, Sheehan syndrome was diagnosed relatively late in these 60 patients. Hemorrhage during the last delivery, especially if severe and/or associated with shock or transfusion, was the most important obstetric antecedent event. Absence of amenorrhea or presence of postpartum lactation did not exclude the diagnosis. Abnormal responses of human growth hormone to insulin tolerance testing and of prolactin to thyrotropin-releasing hormone confirm the diagnosis. Identification of patients affected with Sheehan syndrome is critical to avoid delays in diagnosis and treatment. Appropriate replacement therapy is capable of yielding complete remission of symptoms.

Human growth hormone and the development of osteochondritis dissecans lesions

No single etiology regarding the cause of osteochondritis dissecans (OCD) lesions is unanimously accepted. This report documents a novel case of multiple OCD lesions affecting the left knee and a solitary defect of the right elbow in a patient with acquired human growth hormone (hGH) deficiency and supplementation. hGH deficiency and hormone replacement may be related to the development of OCD lesions.

Fungal exposure endocrinopathy in sinusitis with growth hormone deficiency: Dennis-Robertson syndrome

A retrospective study was carried out on 79 patients with a history of mold exposure, fatigue, and chronic rhinosinusitis (CRS) to determine whether there is a causal relationship between fungal exposure and chronic sinusitis, fatigue, and anterior hypopituitarism, especially growth hormone deficiency (GHD). Of the patients, 94% had a history of CRS, endoscopically and/or computed tomography (CT) confirmed; 100% had chronic fatigue and 100% had either significant history of indoor mold exposure and/or positive mold plate testing as measured by settle plates, with an average colony count of 21 (0-4 normal). A total of 62 had positive mold plate testing and 17 had positive history of mold exposure. Of 75, 73 (97.3%) had positive serum immunoglobulin G (IgG)-specific antibodies to fungal antigens. Out of 8, 7 were positive for urinary trichothecenes. Resting levels of insulin-like growth factor 1 (IGF-1) averaged 123 ng/mL (range 43-285, normal 88-249 ng/mL). Despite normal resting levels of IGF-1, significant deficiency of serum human growth hormone (GH) was confirmed by insulin tolerance test (ITT) in 40 of 50 tested. In all, 51% (40/79) were GH deficient. Primary or secondary hypothyroidism in T3 and/or T4 was seen in 81% (64/79) patients; 75% (59/79) had adrenocorticotrophic hormone (ACTH) deficiency. Fungal exposure endocrinopathy likely represents the major cause of GHD, affecting approximately 4.8 million people compared to approximately known 60,000 cases from all other causes. A literature review indicates a possible mechanism of GHD in fungal exposure is that the fungal glucan receptors in the lenticulostellate cells of the anterior pituitary bind to fungal cells wall glucans and activate the innate immune system, which activates macrophages that destroy the fungus and lenticulostellate tissue. Treatment of patients included normal saline nasal irrigations, antifungal and antibiotic nasal sprays, appropriate use of oral antibiotics and antifungals, facial steamer with CitriDrops. Thymate and/or Intramax vitamin supplements, hormone replacement, and reduction of indoor mold levels. Resolution of rhinosinusitis was seen in 93% (41 of 45) of the patients who achieved a mold count by settling plates of 0-4 colonies. Thirty patients were unable to lower their mold counts below four colonies and had various degrees of mucosal disease and fatigue remaining. Fatigue was improved in all 37 patients who received GH and cortisol and/or thyroid hormone, which were deficient. Fatigue was partially relieved in 7 of the 37 who did not achieve mold counts of fewer than four colonies.

A New 6-bp SOX-3 Polyalanine Tract Deletion Does Not Segregate with Mental Retardation

SOX-3 is a transcription factor expressed throughout the developing central nervous system and is involved in maintenance of pluripotency in self-renewing stem cells, specification events, lineage progression, and terminal differentiation. An association between growth hormone deficiency, mental retardation, and Sox-3 mutations in humans was previously reported. The occurrence of abnormalities affecting the polyalanine tract of the Sox-3 gene was determined in a group of 77 unrelated mentally retarded patients without a definite genetic diagnosis and in 84 control subjects. A new SOX-3 polyalanine tract deletion was identified in a mentally impaired boy, in his mother (homozygous), and in 2 healthy brothers of the proband. This new mutation does not segregate with mental retardation.

Physiological effects of human growth hormone produced after hydrodynamic gene transfer of a plasmid vector containing the human ubiquitin promotor.

Human growth hormone (hGH) deficiency causes retarded growth and abnormalities in body fat distribution and abundance, muscle growth, and bone mineralization. While injection of recombinant hGH may reverse or ameliorate symptoms of deficiency, therapy aiming at in vivo synthesis of hGH is still of considerable clinical interest. Hydrodynamic injection of a simple plasmid vector containing a human ubiquitin promotor and the hGH gene were found to result in high and prolonged expression. Synthesis of hGH was achieved both in NOD/SCID mice and in three different inbred strains of immune competent mice. Although hGH antibodies were produced in immunocompetent mice, physiological effects of the protein were documented by increase in body weight, increased serum levels of insulin-like growth factor I and relative increased weight of the internal organs. Nonviral gene therapy may be regarded as a potential future way of reconstituting hGH expression in deficient individuals.

Obesity in children and adolescents worldwide: current views and future directions--Working Group Report of the First World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition.

Obesity in children and adolescents worldwide: current views and future directions--Working Group Report of the First World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition.

Systemic ghrelin levels in subjects with growth hormone deficiency are not modified by one year of growth hormone replacement therapy.

Ghrelin stimulates growth hormone (GH) secretion both in vivo and in vitro. Ghrelin is mainly produced in and released from the stomach but it is probably also produced in the hypothalamic arcuate nucleus. Whether pituitary GH release is under the control of ghrelin from the stomach and/or from the arcuate nucleus is not known. Moreover, no data on the feedback of GH on systemic ghrelin concentrations are available. It has recently been suggested that ghrelin may induce obesity. In this study, we addressed the following two questions: a) are circulating ghrelin levels increased in human GH deficiency (GHD), and b) does GH treatment modify ghrelin levels in human GHD? The study group consisted of 23 patients with GHD. Eighteen had developed adult-onset GHD and five had developed GHD in their childhood (childhood-onset GHD). Ghrelin was measured with a commercially available radioimmunoassay. All measurements were performed twice, first at baseline, before the start of GH replacement therapy, and then again after one year of therapy. GH doses were adjusted every 3 months, targeting serum total IGF-I levels within the normal gender- and age-related reference values for the healthy population. Maintenance doses were continued once the target serum total IGF-I levels were reached. The sum of skinfolds and body water increased significantly, body fat mass and percentage body fat decreased significantly and body mass index and waist-hip ratio were not significantly changed by one year of GH replacement therapy. Before the start of GH replacement therapy, mean value and range for fasting ghrelin in the studied GHD subjects tended to be lower in comparison with healthy subjects in the control group although the difference did not reach significance (GHD ghrelin mean 67.8 pmol/l, range 37.6-116.3 pmol/l; control mean 83.8 pmol/l, range 35.4-132 pmol/l; P=0.11). One year of GH replacement therapy did not modify circulating ghrelin levels (ghrelin before GH therapy: 67.8 pmol/l, range 37.6-116.3 pmol/l; after GH therapy: 65.3 pmol/l, range 35.8-112.6; P=0.56). We did not observe elevated ghrelin levels in adult GHD subjects and GH replacement therapy did not modify circulating ghrelin levels, despite significant decreases in body fat mass and percentage body fat. It is conceivable that the lack of ghrelin modifications after long-term GH therapy was due to the reduction of adiposity and insulin on one hand, and increased GH secretion on the other. However, it is still possible that systemic ghrelin is involved in the development of obesity, both in normal and GHD subjects.

Genentech jury deadlocks on patent suit

A nine-member federal jury deadlocked last week on whether to convict pioneering biotechnology firm Genentech of infringing a University of California patent for human growth hormone DNA. After more than a week of deliberation, the jury voted 8 to 1 in favor of the university—a unanimous verdict was needed to convict. The suit alleged that 20 years ago, Genentech stole genetic material from UC San Francisco labs and used it to develop its successful drug Protropin, which treats human growth hormone deficiency in children. A conviction conceivably could have cost Genentech up to $1.2 billion, nearly seven times its profit in 1998. The jury did reject Genentech's claim that the UC human growth hormone DNA patent was In a statement, James E. Hoist, the University of California's general counsel and vice president for legal affairs, said: We are gratified that the jury rejected the claim that the...patent for human growth hormone is invalid. Hoist ...

Comparison of Bone Changes between Hypophysectomized Rats and Mini Rats.

Growth hormone (GH) plays an important role in longitudinal bone growth, and hypophysectomized rats have generally been used as a model for GH deficiency in humans. Recently, researchers have bred Mini rats, a Wistar-derived transgenic rat strain harboring a rat GH antisense gene and showing lower plasma GH levels than Wistar rats. In a previous study, Mini rats showed a smaller femur size with lower mineral density and a reduction of the metaphyseal and diaphyseal bone mass. In the present study, Wistar rats were hypophysectomized (HX) and treated with GH, and then their bones were examined and compared with vehicle-treated intact age-matched Wistar rats and Mini rats. GH-treated (HX+GH) rats exhibited an increase in the mineral density of the tibia and increases in the length and mineral content of the femur and tibia. These changes in the HX+GH rats were attributable to an increase in the longitudinal growth and periosteal bone formation of the femur and tibia. When Mini rats and HX rats were compared with Wistar rats, both animals showed similar reductions in the bone length, mineral content, and mineral density of the femur, but the Mini rats showed a greater longitudinal growth rate, cancellous bone mass, and mineralizing surface than the HX rats, as well as less remarkable changes in body weight, relative organ weights, and hematological and blood chemical parameters. Therefore, Mini rats are considered to be a useful model for clarifying features of GH deficiency and examining effects of various treatments on the bone without any specific surgery or drug-administration.

Effects of growth hormone and insulin-like growth factor I on T- and B-lymphocytes and immune function.

The concept of a neuro-endocrine-immune axis was proposed more than 50 years ago. Growth hormone (GH), a central component of this axis has many functions at both a molecular and cellular level, including thymocyte proliferation, stimulation of the cytotoxic activity of natural killer cells and induction of lymphocyte proliferation. Binding of GH to its receptors on lymphocytes stimulates the production of insulin-like growth factor I (IGF-I), which mediates the effects of GH on cell proliferation. Other effects of GH on the immune system appear to be direct, such as priming monocytes for enhanced production of hydrogen peroxide in response to phorbol esters, and stimulating neutrophils to secrete superoxide anions associated with enhanced phagocytic activity. Many of the effects of GH are shared by IGF-I. Despite these observations, and the fact that GH is produced and secreted in immunological tissues such as the thymus and spleen, immune deficiency is not characteristic of GH deficiency in humans. The question remains as to whether GH and IGF-I could be used as immunotherapy. Currently, both agents have been used in adults to diminish wasting due to acquired immunodeficiency syndrome, and GH has been shown to stimulate CD8+ cell counts. However, they had little impact on CD4+ cell counts, which may be due to IGF-I and GH resistance in these individuals. The use of GH and IGF-I as immunotherapies merits further study.

Logarithmic quantitation model using serum ferritin to estimate iron overload in secondary haemochromatosis.

Nineteen children and adolescents receiving repeated transfusions and subcutaneous desferrioxamine treatment were investigated in an attempt to quantitate iron overload non-invasively. Before patients were started on desferrioxamine individual relationships were correlated for 12 to 36 months between transfused iron, absorbed iron estimated gastrointestinally, and increasing serum ferritin concentrations. Patients with inflammation, increased liver enzymes, or haemolysis were excluded from analysis. The relationship between the variables could be described by a logarithmic regression curve (y = transfused iron [plus eventually gastrointestinally absorbed iron] = iron overload = a+b log [x = serum ferritin]) for each individual patient. All patients showed close correlation (R2) between x and y (median R2 of 0.909, 0.98, and 0.92 in thalassaemia, aplastic anaemia, and sickle cell anaemia patients, respectively). When started on desferrioxamine, current serum ferritin concentrations were used to derive the iron overload from each individual regression curve. The derived estimated iron overload ranged from 0.6 g to 31 g. Left ventricular dilatation was observed in three patients with beta thalassaemia and in one patient with aplastic anaemia with median iron overload of 20.7 (14.1-31.3) g and 24.0 g respectively. Hypothyroidism was found in four patients with beta thalassaemia and one patient with aplastic anaemia with iron overload between 14.7 (6.8 and 26.1) g and 15.1 g respectively. Human growth hormone deficiency was detected in three patients with beta thalassaemia with an iron overload of 4.2 (3.5-6.8) g; all three patients had excellent desferrioxamine compliance.

Genetic basis of endocrine disease. 6. Molecular basis of familial human growth hormone deficiency.

T HE GENE encoding GH-N (GHl) and those genes encoding chorionic somatomammotropin (CSH1,2) hormones reside in a 50,000 base-pair (50 kb) gene cluster on human chromosome 17 (Fig. 1) (1). The GH2 gene also resides in this cluster and encodes a protein (GH-V) that is expressed in the placenta rather than in the pituitary and differs from the primary sequence of GH-N by 13 amino acids. The CSH1,2 genes encode proteins of identical sequences, whereas the CSH pseudogene (CSHPl) encodes a protein differing by 13 amino acids and contains a mutation that should alter its pattern of messenger RNA (mRNA) splicing and thus the primary sequence of the resulting protein (1, 2). The extensive homology (92-98%) between the immediate flanking, intervening, and coding sequences of these 5 genes suggests that this multigene family arose through a series of gene duplication events (1, 3, 4). These duplications are thought to have arisen from successive unequal recombinations between Alu family repeats. This method of gene amplification is analogous to the Alu-Alu recombinations that cause deletions of the human @globin and low density lipoprotein receptor genes (5, 6). Expression of the GHl gene is controlled by cis and truns factors. The former include the CAT and TATA promoter components located 85 and 30 bp, respectively, upstream from the GHl gene’s origin of transcription. In addition, there are cis sequences that bind the Pit-I transacting factor. Thus, Pit-l factor binds to and activates the promoters of the GHl and PRL genes and also affects differentiation of thyrotropes (7). The frequency of GH deficiency is estimated to range from l/4,000-l/10,000 in various studies (8-11). Most cases are sporadic and are assumed to arise from cerebral insults or defects that include cerebral edema, chromosome anomalies, histiocytosis, infections, radiation, septo-optic dysplasia, trauma, or tumors affecting the hypothalamus or pituitary (1). Magnetic resonance exams detect hypothalamic or pituitary anomalies in about 12% of patients who have isolated GH deficiency (IGHD) (12).

Genetic basis of endocrine disease. 6. Molecular basis of familial human growth hormone deficiency

Genetic basis of endocrine disease. 6. Molecular basis of familial human growth hormone deficiency