Effect of the Concentration Levels of Growth Hormone and Insulin-like Growth Factor I on the Polymorphisms of the Il12p40 Gene in Lung Cancer Patients.

The prevalence of lung cancer as one of the most common cancers with the highest mortality rate is one of the most important health problems in humans across the world. Molecular research can provide valuable information about genetic changes associated with the pathogenesis of the disease that may be used to improve prognosis and treatment. The current study aimed to examine the genotyping utility of the Il12p40 (IL-12B) gene (rs3212227, A>C) polymorphisms and detect its relationship with the concentration levels of HGH and IGF-1 for the non-small cell lung carcinoma (NSCLC). This study investigated 67 cases with NSCLC (60 males and 7 females) and 28 healthy individuals as controls. The serum level of HGH and IGF-1 was determined using an enzyme-linked immunosorbent assay. Genotyping of the IL-12B gene polymorphisms (rs3212227, A>C) was carried out by polymerase chain reaction-restriction fragment length polymorphism. The serum levels of the HGH and IGF-1 were estimated, and the results of the IL-12B genotyping showed an increased risk of NSCLC. The homozygous wild (AA) genotype of the IL-12 gene showed that the risk of NSCLC was higher than that of the heterozygous (AC) and homozygous genotypes (CC). Moreover, a significant elevation was found in the serum levels of the HGH in the NSCLC patients, compared to the control group. The result showed that the IL-12 gene polymorphism was implicated in the pathogenesis of the NSCLC and directed several metabolic changes.

Research Note: Development of a sandwich ELISA for determining plasma growth hormone concentrations in goose.

Growth hormone (GH) is required for normal postnatal development in poultry; however, no immunoassay exists to assess its levels in geese plasma, hindering the study of endocrine regulation in this species. We developed a sandwich ELISA to determine the GH concentrations in the plasma of geese. Recombinant goose GH was produced using a eukaryotic expression system and purified for use as the reference standard in ELISA and the antigen for producing the polyclonal antibodies in rabbits. Rabbit anti-goose GH polyclonal antibody was used to coat the wells of the ELISA plate, and its biotinylated form served as the detection antibody. An avidin-conjugated horseradish peroxidase was used to bind the detection antibody and catalyze the chromogenic reaction of 3,3,5,5-tetramethylbenzidine and H2O2. A sigmoidal curve was fitted to the optical density and the log of the standard GH concentration using the four-parameter logistic model. The sensitivity of the assay was less than 0.156 ng/mL. The intra- and interassay coefficients of variation were less than 9 and 13%, respectively. The response curve of the serially diluted plasma samples from geese exhibited a good parallel relationship with that observed for the reference standards. The assay effectively detected differences in GH concentrations in plasma samples from geese at various physiological stages; thus, it will be useful for future study of their growth and metabolism.

Predicting Subtype of Growth Hormone Pituitary Adenoma based on Magnetic Resonance Imaging Characteristics.

PURPOSE: This study aimed to investigate the value of magnetic resonance (MR) characteristics in differentiating the subtypes of growth hormone pituitary adenomas. MATERIALS AND METHODS: The clinical and MR imaging data of 70 patients with growth hormone pituitary adenoma confirmed by surgery and pathology were retrospectively analyzed. The tumors were divided into dense granular (DG; 36 cases) and sparse granular subtypes (SG; 34 cases). The tumors' MR features were analyzed, including the mean and maximum diameters, T2 signal intensity, T2 relative signal intensity (rSI), homogeneity, enhancement degree, and invasiveness (Knosp grade). Mann-Whitney U test and χ2 test were used to analyze MR characteristics between the 2 groups. The independent predictors and predictive probabilities of tumor subtypes were obtained via a logistic regression model, and the efficacy was compared by receiver operating characteristic curve. RESULTS: The mean and maximum diameters of growth hormone adenoma in DG and SG were 1.77 versus 2.45 and 1.95 versus 3.00 cm (median, P < 0.05), respectively. There was a significant difference between the 2 groups in T2 signal intensity and rSI (P values were 0.02 and 0.001, respectively). Most DG adenomas (86.1%) appeared as hypointense on T2 images, and 38.2% of SG adenomas were hyperintense. There was no significant difference in tumor homogeneity (P = 0.622). A significant difference was found in the Knosp grade between the 2 subtypes (P = 0.004). In addition, the enhancement degree of SG adenomas was significantly higher than that of DG adenomas (P = 0.001). Logistic regression analysis showed that high T2 rSI value and marked contrast enhancement were independent predictors of the 2 subtypes, and the odds ratios were 4.811 and 4.649, respectively. The multivariate logistic model obtained relatively high predicting efficacy, and the area under the curve, sensitivity, and specificity were 0.765, 0.882, and 0.500, respectively. CONCLUSIONS: There are significant differences in tumor size, T2 signal intensity, T2 rSI, enhancement degree, and invasiveness between DG and SG adenomas. The logistic model based on the marked contrast enhancement and high T2 rSI value has an important value in predicting the subtype of growth hormone adenoma.

Malnutrition in children associated with low growth hormone (Gh) Levels.

OBJECTIVE: This study aimed to compare serum levels of Growth Hormone in children with malnutrition and good nutritional status. METHOD: This cross-sectional study included 41 participants consisting of 31 malnourished, 10 well-nourished children aged between 36 and 60 months. Demographic data of participants were obtained utilizing a questionnaire. Nutritional status was determined by calculating the Z-score of body weight for age, height for age, and body weight for height indices using the WHO classification. GH levels were determined by the Enzyme-Linked Immunosorbent Assay (ELISA) method. RESULT: Median serum GH levels in malnourished children were found to be lower i.e. 1.25ng/mL (minimum-maximum: 0.10-6.19ng/mL) compared to well-nourished children 11.01ng/mL (1.72-15.64ng/mL). CONCLUSION: Serum GH levels can be used as indicators to assess nutritional status.

Acute hypoglycemia and risk of cardiac arrhythmias in insulin-treated type 2 diabetes and controls.

OBJECTIVE: Hypoglycemia is associated with an increased risk of cardiovascular disease including cardiac arrhythmias. We investigated the effect of hypoglycemia in the setting of acute glycemic fluctuations on cardiac rhythm and cardiac repolarization in insulin-treated patients with type 2 diabetes compared with matched controls without diabetes. DESIGN: A non-randomized, mechanistic intervention study. METHODS: Insulin-treated patients with type 2 diabetes (n = 21, age (mean ± s.d.): 62.8 ± 6.5 years, BMI: 29.0 ± 4.2 kg/m2, HbA1c: 6.8 ± 0.5% (51.0 ± 5.4 mmol/mol)) and matched controls (n = 21, age: 62.2 ± 8.3 years, BMI 29.2 ± 3.5 kg/m2, HbA1c: 5.3 ± 0.3% (34.3 ± 3.3 mmol/mol)) underwent a sequential hyperglycemic and hypoglycemic clamp with three steady-states of plasma glucose: (i) fasting plasma glucose, (ii) hyperglycemia (fasting plasma glucose +10 mmol/L) and (iii) hyperinsulinemic hypoglycemia (plasma glucose < 3.0 mmol/L). Participants underwent continuous ECG monitoring and blood samples for counterregulatory hormones and plasma potassium were obtained. RESULTS: Both groups experienced progressively increasing heart rate corrected QT (Fridericia's formula) interval prolongations during hypoglycemia ((∆mean (95% CI): 31 ms (16, 45) and 39 ms (24, 53) in the group of patients with type 2 diabetes and controls, respectively) with similar increases from baseline at the end of the hypoglycemic phase (P = 0.43). The incidence of ventricular premature beats increased significantly in both groups during hypoglycemia (P = 0.033 and P < 0.0001, respectively). One patient with type 2 diabetes developed atrial fibrillation during recovery from hypoglycemia. CONCLUSIONS: In insulin-treated patients with type 2 diabetes and controls without diabetes, hypoglycemia causes clinically significant and similar increases in cardiac repolarization that might increase vulnerability for serious cardiac arrhythmias and sudden cardiac death.

Lack of Brain Insulin Receptor Substrate-1 Causes Growth Retardation, With Decreased Expression of Growth Hormone-Releasing Hormone in the Hypothalamus.

Insulin receptor substrate-1 (Irs1) is one of the major substrates for insulin receptor and insulin-like growth factor-1 (IGF-1) receptor tyrosine kinases. Systemic Irs1-deficient mice show growth retardation, with resistance to insulin and IGF-1, although the underlying mechanisms remain poorly understood. For this study, we generated mice with brain-specific deletion of Irs1 (NIrs1KO mice). The NIrs1KO mice exhibited lower body weights, shorter bodies and bone lengths, and decreased bone density. Moreover, the NIrs1KO mice exhibited increased insulin sensitivity and glucose utilization in the skeletal muscle. Although the ability of the pituitary to secrete growth hormone (GH) remained intact, the amount of hypothalamic growth hormone-releasing hormone (GHRH) was significantly decreased and, accordingly, the pituitary GH mRNA expression levels were impaired in these mice. Plasma GH and IGF-1 levels were also lower in the NIrs1KO mice. The expression levels of GHRH protein in the median eminence, where Irs1 antibody staining is observed, were markedly decreased in the NIrs1KO mice. In vitro, neurite elongation after IGF-1 stimulation was significantly impaired by Irs1 downregulation in the cultured N-38 hypothalamic neurons. In conclusion, brain Irs1 plays important roles in the regulation of neurite outgrowth of GHRH neurons, somatic growth, and glucose homeostasis.

Evaluation of sex hormone profile and semen parameters in acromegalic male patients.

OBJECTIVE: To investigate the changes in semen quality and bioavailable testosterone concentrations in acromegalic male patients according to their disease activity and compare them with patients with non-functional pituitary adenoma (NFA) and healthy controls (HC). METHODS: Twenty-four acromegalic patients with active disease, 22 acromegalic patients in remission, 10 HCs, and 10 patients with NFA were included. RESULTS: Total and calculated bioavailable testosterone concentrations were lower in patients with pituitary disease. Patients with acromegaly had more severely impaired total testosterone levels and semen parameters in comparison to HCs and patients with NFA. The degree of impairment was more prominent in acromegalic patients with active disease than acromegalic patients in remission. Acromegalic patients in remission had residual impairments in both semen quality and testosterone concentrations. Patients with NFA had the lowest concentrations of calculated bioavailable testosterone, followed by acromegalic patients with active disease and acromegalic patients in remission. Increasing growth hormone (GH) levels were found to be associated with both more severely impaired semen quality and androgen concentrations. CONCLUSION: Growth hormone hypersecretion can disturb reproductive biology and thereof semen quality. The reduction in semen quality and androgen levels may not fully recover upon disease control. Clinicians should be aware of the increased risk of impaired semen parameters and reduced total/bioavailable levels in acromegalic patients, especially in the setting of active disease.

Prevalence of growth hormone deficiency in patients with unexplained chronic fatigue after undergoing bone marrow transplantation in adulthood.

PURPOSE: Many patients who undergo bone marrow transplantation (BMT) in adulthood experience unexplained chronic fatigue which can have a major impact on their health-related quality of life (QoL). Pre-BMT treatment regimens increase the risk of developing acquired growth hormone deficiency (GHD), which results in a clinical syndrome with decreased energy and has additionally been linked to metabolic syndrome. METHODS: Using the gold-standard insulin hypoglycemic test (IHT), we evaluated the prevalence of GHD in 18 post-BMT adult patients with unexplained chronic fatigue, as well as the correlation between peak serum GH response and QoL scores, the metabolic syndrome, and insulin resistance. Peak serum GH cut-point less than 3.0 ug/L was used for the diagnosis of severe GHD. The Fatigue Severity Scale and Quality of Life in Adult GHD Assessment questionnaires were used to quantify fatigue symptoms. RESULTS: The prevalence of severe GHD within this sample of 18 patients was 50%. A trend between lower peak serum GH response and higher fatigue and QoL-AGHDA scores was observed. CONCLUSIONS: GHD may represent a remediable contributor to post-BMT chronic fatigue in adults, further studies are needed to evaluate the potential role of screening and GH replacement therapy in this vulnerable patient population. IMPLICATIONS FOR CANCER SURVIVORS: GHD may be a treatable explanation for disabling post-BMT fatigue pending results of intervention studies.

Clinicopathological Features of Growth Hormone-producing Pituitary Adenomas and Correlation With Preoperative Laboratory Findings.

BACKGROUND/AIM: The histopathological variability of each type of pituitary adenoma (PA) that causes growth hormone (GH) excess influences the phenotype, radiological characteristics and therapy response of acromegaly patients. We correlated the immunohistochemical (IHC) features of GH-secreting PAs with their clinical, laboratory and imaging data. PATIENTS AND METHODS: We included 32 patients with documented acromegaly; tumour specimens were histologically and IHC examined: anterior pituitary hormones, pituitary-specific transcription factor-1 (PIT-1), Ki-67 labelling index were evaluated. RESULTS: Macroadenomas represented 93.75%. Post-surgery disease control negatively correlated with the maximum initial tumour diameter (p=0.04). Ki-67 did not predict remission. No correlation was found between GH serum levels and IHC expression (p=0.45). PIT-1 was positive in all specimens, two had a weak expression. Four were considered PIT-1 positive plurihormonal adenomas and several had unusual IHC combinations. CONCLUSION: PIT-1 accurately classifies GH-secreting PAs. The IHC classification as well as radiological dimensions and extent influence disease control, probably being the best prognosis factors.

Ghrelin-induced Food Intake, but not GH Secretion, Requires the Expression of the GH Receptor in the Brain of Male Mice.

Ghrelin stimulates both GH secretion and food intake. The orexigenic action of ghrelin is mainly mediated by neurons that coexpress agouti-related protein (AgRP) and neuropeptide Y (NPY) in the arcuate nucleus of the hypothalamus (ARH). GH also stimulates food intake and, importantly, ARHAgRP/NPY neurons express GH receptor (GHR). Thus, ghrelin-induced GH secretion may contribute to the orexigenic effect of ghrelin. Here, we investigated the response to ghrelin in male mice carrying GHR ablation specifically in neurons (brain GHR knockout [KO] mice) or exclusively in ARHAgRP/NPY neurons (AgRP GHR KO mice). Although brain GHR KO mice showed normal ghrelin-induced increase in plasma GH levels, these mutants lacked the expected orexigenic response to ghrelin. Additionally, brain GHR KO mice displayed reduced hypothalamic levels of Npy and Ghsr mRNA and did not elicit ghrelin-induced c-Fos expression in the ARH. Furthermore, brain GHR KO mice exhibited a prominent reduction in AgRP fiber density in the ARH and paraventricular nucleus of the hypothalamus (PVH). In contrast, AgRP GHR KO mice showed no changes in the hypothalamic Npy and Ghsr mRNAs and conserved ghrelin-induced food intake and c-Fos expression in the ARH. AgRP GHR KO mice displayed a reduced AgRP fiber density (~16%) in the PVH, but this reduction was less than that observed in brain GHR KO mice (~61%). Our findings indicate that GHR signaling in the brain is required for the orexigenic effect of ghrelin, independently of GH action on ARHAgRP/NPY neurons.

Concentrations of Ca, Mg, P, Prostaglandin E2 in Bones and Parathyroid Hormone; 1,25-dihydroxyvitamin D3; 17-ß-estradiol; Testosterone and Somatotropin in Plasma of Aging Rats Subjected to Physical Training in Cold Water.

Exposure to low temperatures can be considered a stressor, which when applied for a specific time can lead to adaptive reactions. In our study we hypothesized that cold, when applied to the entire body, may be a factor that positively modifies the aging process of bones by improving the mechanisms related to the body's mineral balance. Taking the above into account, the aim of the study was to determine the concentration of calcium (Ca), magnesium (Mg), and phosphorus (P) in bones, and to examine bone density and concentrations of the key hormones for bone metabolism, namely parathyroid hormone (PTH), somatotropin (GH), 1,25-dihydroxyvitamin D3, 17-ß estradiol, testosterone (T) in plasma, and prostaglandin E2 (PGE2) in the bone of aging rats subjected to physical training in cold water. The animals in the experiment were subjected to a series of swimming sessions for nine weeks. Study group animals (male and female respectively) performed swimming training in cold water at 5 ± 2 °C and in water with thermal comfort temperature (36 ± 2 °C). Control animals were kept in a sedentary condition. Immersion in cold water affects bone mineral metabolism in aging rats by changing the concentration of Ca, Mg, and P in the bone, altering bone mineral density and the concentration of key hormones involved in the regulation of bone mineral metabolism. The effect of cold-water immersion may be gender-dependent. In females, it decreases Ca and Mg content in bones while increasing bone density and 17-ß estradiol and 1,25-dihydroxyvitamin D3 levels, and with a longer perspective in aging animals may be positive not only for bone health but also other estrogen-dependent tissues. In males, cold water swimming decreased PTH and PGE2 which resulted in a decrease in phosphorus content in bones (with no effect on bone density), an increase in 1,25-dihydroxyvitamin D3, and increase in T and GH, and may have positive consequences especially in bones and muscle tissue for the prevention of elderly sarcopenia.

The 24-hour average concentration of cortisol is elevated in obese African-American youth with type 2 diabetes.

INTRODUCTION: 24-h average (IC) plasma concentrations of cortisol and growth hormone are lower in obese youth and adults without Type 2 diabetes (T2D) compared to lean subjects. Here we examined IC-cortisol and IC-growth hormone levels in obese youth with and without T2D. METHODS: We pooled ½-hourly samples from 20 to 24-hour sampling to create an IC for cortisol, cortisone, C-peptide, insulin, growth hormone and cortisol-binding-globulin in obese African-American youth with (n = 8) and without T2D (N = 9). Analytes were assayed by standard methods. RESULTS: The groups were similar in age and sex, all participants had BMI% ≥94. T2D patients had slightly lower BMI z-score (2.25 ±â€¯0.36 versus 2.58 ±â€¯0.16, p = 0.0429). IC-cortisol (5.70 ±â€¯1.8 µg/dl vs 4.18 ±â€¯1.07 µg/dl, p = 0.0481) was higher and IC-C-peptide (2.33 ±â€¯0.89 ng/ml vs 4.36 ±â€¯1.12 ng/ml, p = 0.001) lower in T2D. There were no differences in cortisone/cortisol or for other analytes between groups. IC-cortisol was correlated with IC-cortisone (r = 0.46, p = 0.0471) but not with ICs of insulin, C-peptide, cortisol-binding-globulin, or growth hormone. CONCLUSIONS: IC-cortisol levels are higher and IC-C-peptide lower in obese African-American youth with T2D. Higher levels of IC-cortisol in obese youth with T2D may indicate a change in hypothalamic-pituitary-adrenal regulation which may exacerbate hyperglycemia and other metabolic complications of obesity.

The effects of 14-week betaine supplementation on endocrine markers, body composition and anthropometrics in professional youth soccer players: a double blind, randomized, placebo-controlled trial.

OBJECTIVE: Betaine supplementation may enhance body composition outcomes when supplemented chronically during an exercise program. The purpose of this study was to evaluate the effect of betaine supplementation on development-related hormones, body composition, and anthropometrics in professional youth soccer players during a competitive season. METHODS: Twenty-nine players (age, 15.45 ± 0.25 years) were matched based upon position and then randomly assigned to a betaine group (2 g/day; n = 14, BG) or placebo group (PG, n = 15). All subjects participated in team practices, conditioning, and games. If a subject did not participate in a game, a conditioning protocol was used to ensure workload was standardized throughout the 14-week season. Growth hormone (GH), insulin-like growth factor-1 (IGF-1), testosterone, cortisol, height, weight, and body composition were assessed at pre-season (P1), mid-season (P2) and post-season (P3). Anthropometric variables were also measured following a one-year follow-up (F). RESULTS: Significant (p < 0.05) group x time interactions were found for testosterone and testosterone to cortisol ratio (T/C). Both variables were greater in BG at P2 and P3 compared to P1, however, the testosterone was less in the PG at P3 compared to P2. There was no significant group by time interactions for GH, IGF-1, lean body mass, or body fat. There was a significant (p < 0.05) group x time interaction in height and weight at F, with the greater increases in BG compared to PG. CONCLUSION: Betaine supplementation increased testosterone levels and T/C ratio in youth professional soccer players during a competitive season. Betaine supplementation had no negative effects on growth (height and weight) and may attenuate reductions in testosterone due to intense training during puberty.

The Effect of 6 Months' Treatment With Pasireotide LAR on Glucose Metabolism in Patients With Resistant Acromegaly in Real-World Clinical Settings.

Objective: The aim of the study was to evaluate glucose metabolism, as measured by glycated hemoglobin (HbA1c) levels and the need for antidiabetic medical treatment, in patients with acromegaly resistant to first-generation somatostatin receptors ligands (SRLs) treated with pasireotide long-acting release (LAR) in real-world clinical practice. Biochemical control of acromegaly, as measured by growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels, was also assessed. Study Design: Two-center retrospective cohort of consecutive patients with acromegaly treated with first-generation SRLs at maximum doses, who had not achieved biochemical disease control. After SRLs were discontinued, patients were given pasireotide LAR 40 mg i.m. every 28 days. The dose was increased to 60 mg i.m. in patients for whom adequate control was not achieved after 3 months. Patients were given dietary and lifestyle advice, and antihyperglycemic treatment was modified as needed. Main Outcome Measures: Biochemical disease control parameters (GH and IGF-1 concentration), as well as HbA1c level at baseline and after 6 months. Results: In total, 39 patients with acromegaly were enrolled. GH concentration decreased (Δme =-1.56 µg/L, range -21.38-3.62, p <0.001) during 6 months of pasireotide LAR treatment. A worsening of metabolic status was observed, with an increase of median HbA1c (Δme =0.40%, range -0.20%-2.30%, p <0.001), and antihyperglycemic treatment intensification in 23 (59.0%) patients. The median decline in IGF-1 concentration was: -283.0 µg/L, range -682.7-171.6, p <0.001. IGF-1 reached the age- and gender-specific upper level of normal in 23 (59%) patients. Conclusions: Pasireotide LAR is an effective therapeutic option in patients with acromegaly refractory to first-generation SRLs. However, this therapy may result in pasireotide LAR-associated hyperglycemia, which requires early and aggressive antidiabetic medical therapy to prevent glucose homeostasis alterations.

In ovo green light photostimulation during the late incubation stage affects somatotropic axis activity.

Targeted green light photostimulation during the last stage of broiler incubation increases expression of the somatotropic axis. The purpose of this study was to further shorten the in ovo green light photostimulation and determine the critical age for photostimulation in broilers embryos, as a future strategy for broiler incubation. Fertile broilers eggs (n = 420) were divided into 5 treatment groups. The first group was incubated under standard conditions (in the dark) as the negative control group. The second was incubated under intermittent monochromatic green light using light-emitting diode lamps with an intensity of 0.1 W/m2 at shell level from embryonic day (ED) 0 of incubation until hatch, as a positive control. The third, fourth, and fifth groups were incubated under intermittent monochromatic green light from ED 15, 16, and 18 of incubation, respectively, until hatch. All treatment groups showed elevated somatotropic axis expression compared with the negative control, with the group incubated under monochromatic green light from ED 18 until hatch showing results closest to the positive control. This suggests that broiler embryos can be exposed to in ovo green light photostimulation from a late stage of incubation (when transferring the eggs to the hatchery) and exhibit essentially the same outcome as obtained by photostimulation during the entire incubation period.

Association between triglyceride glucose index and peak growth hormone in children with short stature.

Growth hormone (GH) secretion is related to many factors, such as weight and puberty, and the reproducibility of GH provocation tests is very poor. This study aimed to evaluate whether the triglyceride (TyG) index was associated with peak GH in children with short stature. This study included 1095 children with short stature divided into two groups based on peak GH level in GH provocation tests [GH deficiency (GHD) group = 733 children; non-GHD group = 362 children]. We found that the TyG index was significantly higher in the GHD group than in the non-GHD group (P < 0.001). A nonlinear relationship was detected between the TyG index and peak GH, whose point was 7.8. A significant negative association between the TyG index and peak GH was observed when the TyG index was greater than 7.8 (ß - 2.61, 95% CI - 3.98, - 1.24; P < 0.001), whereas, the relationship between the TyG index and peak GH was not significant when the TyG index was lower than 7.8 (ß 0.25, 95% CI - 1.68, 2.17; P = 0.799). There is a nonlinear relationship between the TyG index and peak GH, and a higher TyG index is associated with decreased peak GH in children with short stature.

Laron syndrome - A historical perspective.

Laron Syndrome (LS) [OMIm#262500], or primary GH insensitivity, was first described in 1966 in consanguineous Jewish families from Yemen. LS is characterized by a typical phenotype that includes dwarfism, obesity and hypogenitalism. The disease is caused by deletions or mutations of the GH-receptor gene, causing high serum GH and low IGF-I serum levels. We studied 75 patients from childhood to adult age. After early hypoglycemia due to the progressive obesity, patients tend to develop glucose intolerance and diabetes. The treatment is by recombinant IGF-I, which improves the height and restores some of the metabolic parameters. An unexpected finding was that patients homozygous for GH-R defects are protected from malignancy lifelong, not so heterozygotes or double heterozygote subjects. We estimate that there are at least 500 patients worldwide, unfortunately only few treated.

"Non-Classical" Indication for Provocative Testing of Growth Hormone: A Retrospective Cohort Study in Adult Patients Under Replacement Therapy.

BACKGROUND: Adult growth hormone deficiency (GHD) is considered a rare condition. Current guidelines state that GH provocative test is indicated in patients affected by organic hypothalamic/ pituitary disease or with a history of head injury, irradiation, hemorrhage or hypothalamic disease with multiple pituitary deficiencies. Nevertheless, the clinical picture related to GHD may be subtle. OBJECTIVE: We have retrospectively evaluated the indication to GHRH+arginine test in our monocentric cohort of patients treated with hrGH in order to assess whether other conditions had been considered as a rationale for provocative testing. METHODS: Ninety-six patients (51 females and 45 males), aged 19-67 years were included. The GHRH+arginine test had been performed in 29 patients with organic hypothalamic/pituitary disease and in 4 patients for Childhood onset-GHD (CoGHD). In other patients, the diagnosis was suspected for "non classical" reasons in the clinical picture suspected for GHD. RESULTS: Classical indications included previously known primary empty sella (n=15), pituitary surgery (n=14), pituitary cyst (n=1), non-secreting pituitary tumors (n=3) but more than half of the patients (57.3%) had been studied for "non classical" indications: metabolic syndrome (n=25), asthenia (n=13), heart failure (n=4), osteoporosis (n=6), unexplained hypoglycaemia (n=1) and infertility (n=6). The latter represented a significant percentage in the male subgroup under 45 ys. IGF-1 levels were lower than 50th percentile in 63% of patients. Finally, among non-classical reasons, organic pituitary disease was discovered in 22 patients. CONCLUSION: Idiopathic GHD may be unrecognized due to its subtle manifestations and that an extended use of dynamic GH tests may reveal such conditions. A potential field of investigation could be to identify subsets of patients with clinical conditions caused or worsened by underlying unrecognized GHD.

Exercise-induced GH secretion is related to puberty.

PURPOSE: Exercise represents a physiological stimulus that initiates the coordinated responses of hypothalamic-pituitary axis and sympathetic nervous system. Aims of the study were: 1) to analyze the response of GH, cortisol and prolactin to acute exercise in healthy children with normal GH response to stimulation tests 2) to evaluate the reliability of physical exercise as a screening test for GH secretion. METHODS: Forty-four children (mean age 9.35 ± 2.69 years, range 4-13.7) underwent standardized Bruce's test on treadmill. Twenty-nine children were pre-pubertal (nine females and 20 males) and 15 children were pubertal (ten females and five males). RESULTS: Exercise elicited a peak secretion of all the analyzed hormones. GH showed the highest mean percentage increase (558%), followed by prolactin (178%) and cortisol (23%). In 19/44 children (43.2%), GH peak did not reach the cut-off level of 8 ng/ml, considered as the normal GH response to stimulation tests. Despite a wide inter-individual variability, both GH peak and GH increase from baseline were higher in pubertal children than in pre-pubertal ones (GH peak: 13.49 ± 10.28 ng/ml versus 6.6 ± 4.09 ng/ml-p < 0.001; GH increase: 12.02 ± 10.30 ng/ml versus 5.28 ± 3.97 ng/ml-p < 0.001). The impact of puberty on both GH peak and GH increase was independent of sex, age, BMI SDS and VO2max. No differences related to sex or pubertal status were found in cortisol and prolactin responses. CONCLUSION: Exercise-induced GH secretion should not be considered a valuable screening tool in the diagnostic work-up of GH deficiency, due to the wide inter-individual variability in GH response. As described for standard GH stimulation tests, puberty represents the key factor that enhances GH secretion in healthy children.

Mice with an RGS-insensitive Gαi2 protein show growth hormone axis dysfunction.

Mice carrying an RGS-insensitive Gαi2 mutation display growth retardation early after birth. Although the growth hormone (GH)-axis is a key endocrine modulator of postnatal growth, its functional state in these mice has not been characterized. The present study was undertaken to address this issue. Results revealed that pituitary mRNA levels for GH, prolactin (PRL), somatostatin (SST), GH-releasing-hormone receptor (GHRH-R) and GH secretagogue receptor (GHS-R) were decreased in mutants compared to controls. These changes were reflected by a significant decrease in plasma levels of GH, IGF-1 and IGF-binding protein-3 (IGFBP-3). Mutants were also less responsive to GHRH and ghrelin (GhL) on GH stimulation of release from pituitary primary cell cultures. In contrast, they were more sensitive to the inhibitory effect of SST. These data provide the first evidence for an alteration of the functional state of the GH-axis in Gαi2G184S mice that likely contributes to their growth retardation.