Growth Hormone Values Research Articles

Automated 22-kD Growth Hormone–Specific Assay without Interference from Pegvisomant

Large variability exists among different growth hormone (GH) assays owing to differences in calibration, antibody specificity, isoform recognition, and interference from GH binding protein (GHBP). The GH receptor antagonist Pegvisomant presents a new challenge because Pegvisomant interferes with many GH assays. A recent consensus conference established criteria for standardization and evaluation of GH assays. Following consensus recommendations, we developed a new GH assay on an automated analyzer (IDS-iSYS, Immunodiagnostic Systems). A monoclonal antibody not cross-reacting with Pegvisomant was combined with a monoclonal antibody specific for 22-kD GH. Isoform specificity and interference from GHBP was tested and compared to that seen in 2 existing automated GH assays (Siemens Immulite, Diasorin Liaison). We also compared GH concentrations measured by the 3 assays for healthy volunteers and patients with acromegaly receiving different treatments. Using the iSYS assay, we also established nadir GH values during oral glucose load and analyzed changes in endogenous GH during Pegvisomant treatment. Analytical and functional sensitivities were 0.01 μg/L and 0.04 μg/L, with a dynamic range from 0.04 to 100 μg/L. Intraassay CVs were 2%-4%, whereas interassay CVs were 5%-7% at GH concentrations between 1.7 and 27.5 μg/L. The assay was specific for 22-kD GH and not affected by GHBP. The presence of Pegvisomant, which leads to a negative bias on the Immulite and dramatic overestimation of GH on the Liaison, had no impact on the iSYS GH assay. The new assay fulfils recent consensus recommendations and presents a useful new tool for reliable measurement of GH.

Cut-off values of serum growth hormone (GH) in pharmacological stimulation tests (PhT) evaluated in short-statured children using a chemiluminescent immunometric assay (ICMA) calibrated with the International Recombinant Human GH Standard 98/574

Hospital de Pediatr i a Prof. Dr. Juan P. Garrahan, Combate de los Pozos 1881, Ciudad Autonoma de Buenos Aires, CP 1245, Argentina, Phone: +54 11 43084300, Fax: +54 11 43086700, mE- ail: echaler@yahoo.com Juan M. Lazzati, Mercedes Maceiras, Marco A. Rivarola and Alicia Belgorosky: Hospital de Pediatr i a Prof. Dr. Juan P. Garrahan , Buenos Aires , Argentina Gabriela Ballerini, Mauro Frusti, Ignacio Bergada and Gabriela Ropelato: Hospital de Ni n os Ricardo Gutierrez , Buenos Aires , Argentina

Scoliosis in Prader–Willi syndrome: Effect of growth hormone therapy and value of paravertebral muscle volume by CT in predicting scoliosis progression

Growth hormone (GH) therapy is now widely given to Prader-Willi syndrome (PWS) patients to encourage growth in body height and to prevent obesity. Scoliosis, one of the complications in this syndrome, is thought to be accelerated in parallel with a rapid increase in body height, especially during adolescence. To determine whether GH therapy aggravates scoliosis and to identify any factor which might predict the progression of scoliosis, we studied 35 (22 males and 13 female) PWS patients between the ages of 2-16 years on GH therapy whose scoliosis was followed with spinal X-rays every 6 months. Thirteen (37.1%) of 35 patients had scoliosis with a Cobb angle of over 10°. Scoliosis was unchanged in five patients (14.3%), became worse in six (17.1%) and improved in two (5.7%). All 22 (62.9%) of 35 patients who did not have scoliosis did not develop scoliosis with GH therapy. Since abnormal paraspinal muscle development was thought to induce scoliosis, we measured cross-sectional areas of paraspinal muscles by using one slice CT scan at the level of the umbilicus at the level of L4. Since there was a delay in the increase in total paravertebral muscle area and prolonged asymmetry in patients with progressive scoliosis, both were thought to be useful predictors of progressive scoliosis in PWS patients with GH therapy.

Diagnosis of Growth Hormone Deficiency is Affected by Calibrators Used in GH Immunoassays

Growth hormone (GH) values vary among immunoassays depending on different factors, such as the assay method used, specificity of antibodies, matrix difference between standards and samples, and interference with endogenous GH binding proteins (GHBPs). We evaluated whether the use of different calibrators for GH measurement may affect GH values and, consequently, the formulation of GH deficiency (GHD) diagnosis in children. Twenty-three short children (5 F, 18 M; age 11.4±3.1 years), with the clinical characteristics of GHD (height: -2.3±0.5 SDS; height velocity -2.3±1.5 SDS; IGF-I -1.2±0.9 SDS), underwent GH stimulation tests to confirm the clinical diagnosis of GHD. Serum GH values were measured with Immulite 2000, using 2 different calibrators, IS 98/574, a recombinant 22 kDa molecule of more than 95% purity, and IS 80/505, of pituitary origin and resembling a variety of GH isoforms. We found blunted GH secretion in 20 subjects with the Immulite assay using the IS 98/574 GH as a calibrator, confirming the diagnosis of GHD. Subsequently, using IS 80/505 GH as a calibrator, in the same samples only 14 children showed reduced GH levels. The total cost for the first year of GH therapy of patients diagnosed with IS 98/574 as a calibrator was higher than that for patients diagnosed with IS 80/505 as a calibrator. These data confirm that GH values may depend on different calibrators used in the GH assay, affecting the formulation of GHD diagnosis and the consequent decision to start GH treatment.

Effects of Midazolam and Nitrous Oxide on Endocrine and Metabolic Measurements in Children

Objective: Pain, stress as well as drugs may affect metabolic and endocrine measurements, especially in stressed children. The aim was to study how release of glucose and stress hormones are affected when procedural sedation with nitrous oxide or midazolam are used for establishing intravenous access in obese and lean children. Methods: In a prospective, double-blind, randomized study 90 children, 60 obese and 30 growth-retarded (GR), aged 5–18 years, with reported anxiety or difficulties connected with i.v. access, were randomized to 1 of 3 groups: oral midazolam (0.3 mg/kg, max. 15 mg), 50% nitrous oxide (N₂O), and 10% N₂O. In addition, all children received anesthesia cream (EMLA®) locally 1 h before i.v. access. Blood samples were drawn at 4 time points during 30 min after establishing venous access and, when feasible, after 24 h. The 24-hour sample was regarded as obtained during unstressed condition. The effect of procedural sedation was analyzed. Children’s evaluations of pain (Numeric Rating Scale) and procedure (Likert Scale) were correlated with mean values of cortisol and glucose after i.v. access. For the metabolic and hormone control measurements, 60 children aged 4–18 years (40 obese and 20 GR) served as controls. These children underwent a 24-hour blood sampling and did not receive sedation. The control samples were drawn 10–12 h after i.v. access. Results: After midazolam, significantly lower cortisol levels were found compared to both 50% N₂O and 10% N₂O and to unstressed controls. The growth hormone levels decreased with time in the midazolam group compared to 50 and 10% N₂O, where the effect of time was reversed. Glucose levels among GR children increased from 0 to 30 min, whereas the opposite was found in obese children regardless of treatment. A post hoc analysis demonstrated significant correlations between children’s evaluations of the procedure and mean values of cortisol (r = –0.53), growth hormone (r = –0.52), and norepinephrine (r = –0.5) in children treated with a very low dose of N₂O (10%). Conclusions: When sedation is insufficient during i.v. access, and blood sampling pain and stress affect hormone values, treatment with N₂O or midazolam influence the glucose and stress hormone levels differently. These differences need to be accounted for when results are used for diagnosis and clinical decisions.

Sublingual apomorphine as a neuroendocrine probe

Subcutaneous apomorphine, a dopaminergic agonist, is used as a neuroendocrine probe for assessing central dopaminergic activity. The aim of our study was to test sublingual apomorphine for the same purpose. We administered sublingual apomorphine in a weight-dependent dose (0.033mg/kg) to 42 healthy men. Prolactin and growth hormone levels were measured before and after the administration at 15, 30, 45, 60, 75, 90, 120, 150 and 180min. Subjects filled in Zung's self-assessment scores of anxiety (SAS) and depression (SDS) questionnaires before and after the test. Areas under the curve for prolactin and growth hormone levels were calculated using the trapezoidal rule. All subjects showed decreased prolactin, and 40/42 subjects showed increased growth hormone, in response to sublingual apomorphine. Average peak value for prolactin was −4.6±1.8μg/l. Average peak value for growth hormone was 8.1±8.5ng/ml for the whole group, and 9.6±8.1ng/ml after exclusion of two negative growth hormone responders. Sublingual apomorphine produced no major side effects. Significant decreases in SAS (21.5±5.7 vs. 20.6±5.5) and SDS (9.7±7.8 vs. 7.8±6.8) scores were observed after the test. Sublingually administered apomorphine appears to be well tolerated and useful as a neuroendocrine marker of central dopaminergic activity.

Oral contraception enhances growth hormone responsiveness to hyper‐ and hypoglycaemia

Plasma glucose levels influence growth hormone concentrations. Oral contraceptives are known to affect circulating growth hormone levels and glucose metabolism. While growth hormone plays an important role in hypoglycaemia counter-regulation, it has been shown that oral contraceptives increase growth hormone concentrations. In this context, we tested if serum growth hormone concentrations display a differential response on glycaemic variations in healthy women using oral contraceptives and those not using contraceptives. Fifteen healthy women with oral contraceptive treatment and 10 without participated in a stepwise hyper- and hypoglycaemic glucose clamp procedure. Serum growth hormone concentrations were measured at euglycaemic baseline and subsequently at plasma glucose plateaus of 8.8, 6.8, 4.8 and 2.8 mmol/l. Growth hormone values were significantly higher in women using oral contraceptives throughout the experiments (P = 0.001). Hyperglycaemia decreased growth hormone concentrations in women using oral contraceptives (P = 0.009), but not in those who were not using oral contraceptives (P = 0.241). Hypoglycaemia significantly elevated growth hormone concentrations in women using oral contraceptives (P = 0.009), but not in those not using oral contraceptives (P = 0.094). Maximum growth hormone values were reached at the end of the hypoglycaemic plateau, with significantly higher concentrations in the group using oral contraceptives than in the group not using oral contraceptives (P = 0.016). Healthy women on oral contraceptive treatment display an increased responsiveness of growth hormone to hypoglycaemic, as well as hyperglycaemic conditions and generally higher serum growth hormone concentrations than women without oral contraceptives. Given the known boosting effects of growth hormone on hypoglycaemic hormonal counter-regulation, oral contraceptives may thus be a pharmacological candidate contributing to combat hypoglycaemia unawareness in women with diabetes in the future.

Effect of Arginine Infusion on Ghrelin Secretion in Growth Hormone-Sufficient and GH-Deficient Children

BackgroundThe physiological link between ghrelin and growth hormone (GH) has not yet been fully clarified. Furthermore, the existence of a negative feedback mechanism between growth hormone–insulin-like growth factor (GH–IGF)-I axis and ghrelin and the influence of amino acids on ghrelin secretion in children remain matters of debate.ObjectivesTo understand the regulation of ghrelin secretion and clarify the relationship between ghrelin and GH secretion in GH-deficient (GHD) and GH-sufficient (GHS) children.Patients and MethodsTen GHD (male/female [M/F], 6/4; age [mean ± SEM], 10.7 ± 0.9 years) and 10 GHS prepubertal children (M/F, 6/4; age [mean ± SEM], 10.3 ± 0.6 years), underwent an arginine (ARG) test (infusion, 0.5 g/kg, iv). Levels of GH, total ghrelin, and acylated ghrelin (AG) were assayed every 30 min from 0 to +120 min.ResultsPeak GH values were lower in GHD subjects than in GHS subjects (P < 0.0001). The baseline levels, peak levels, or area under the curves (AUC) for total ghrelin and AG were similar between GHD and GHS children. ARG infusion was followed by a slight to significant decrease in total ghrelin levels, but not AG levels, both in GHD and GHS subjects with a nadir at +30 min. No correlation was seen between GH, total ghrelin, or AG response and ARG infusion.ConclusionsTotal ghrelin and AG levels seemed unaffected by GH status in prepubertal children. ARG infusion was unable to blunt ghrelin secretion irrespective of GH status in childhood. Moreover, since ARG influences GH secretion via modulation of somatostatin release, ghrelin secretion seems to be partially refractory to somatostatin action.

Discordant growth hormone and IGF-1 levels post pituitary surgery in patients with acromegaly naïve to medical therapy and radiation: what to follow, GH or IGF-1 values?

New criteria that define acromegaly remission are more stringent: normal (age/sex-adjusted) insulin-like growth factor type 1 (IGF-1), growth hormone (GH) random (GHr) <1 μg/L, and a GH nadir (GHn) during oral glucose tolerance test (OGTT) of <0.4 μg/L. Discordance between GH and IGF-1 values is often attributed to somatostatin receptor ligands (SRLs) or radiation. The purpose of this study was to evaluate rates of discordant IGF-1 and GH levels in patients with GH secreting adenomas (after pituitary surgery), who were naïve to any other treatment. We retrospectively analyzed data over a 5 year time period (2006-2010), in post-surgery acromegaly patients who had elevated IGF-1 but normal GH levels (per the new cure criteria). Symptoms of acromegaly were scored according to a 4-point scale. Fifty-four patients had post-operative GHr and IGF-1 measurements, 28 patients had GHn during OGTT, and 16 patients had 5-point 2-h GH day curve tests. Thirteen of 54 (24%) patients were found to have intermittent persistent discordant values; high IGF-1 and normal GH at final evaluation (77% of these patients were women). Patients had a median number of IGF-1 evaluations of 7.5 (range: 2-15) over a median of 22 months (range: 3-47 months). Mean elevated IGF-1 in the discordant population was 1.25 × upper limit of normal (ULN) ± 0.17 (range: 1.01-1.6 × ULN). Twelve of the 13 (92%) patients had macroadenomas; 10 of the 13 (69%) patients had mammosomatotroph, mixed lacto/somatotroph tumors or prolactin staining. No patient in the discordant population was on estrogen replacement therapy or had overt cardiac disease. When the relatively asymptomatic discordant population was compared with 35 patients from the concordant population (six were excluded because of preoperative medical treatment for acromegaly), no significant difference between age, gender distribution, body mass index (BMI), presence of diabetes mellitus (DM) or glucose intolerance and adrenal insufficiency between groups was noted. In our study of postoperative patients with acromegaly naïve to both SRLs and radiation, using new GH cut-off levels, 24% had intermittent or persistent discordant values. Our results highlight that relying on IGF-1 or GH measurements alone is not adequate for assessing disease control in surgically treated acromegaly patients. Management of such patients needs to be individualized and long-term studies evaluating morbidity and mortality incorporated into treatment decisions. Further studies with larger patient populations and longer follow-up are required to determine the long-term implications of discordant GH and IGF-1 value patterns.

Comparison of oral glucose tolerance test (OGTT) 100 g with OGTT 75 g for evaluation of acromegalic patients and the impact of gender on test reproducibility

Growth hormone (GH) measurements during an oral glucose tolerance test (OGTT) are essential for the diagnosis and follow-up management of acromegaly. However, both 100 g glucose (OGTT(100) ) and 75 g glucose (OGTT(75) ) test variants are in clinical use. Whether the tests are interchangeable concerning GH nadir and test interpretation is unclear. Furthermore, information on test reproducibility and the impact of gender is scarce. To compare both tests in acromegalic patients and to evaluate test reproducibility with respect to gender. OGTT(100) and OGTT(75) were performed on two consecutive days in 54 acromegalic patients (46·9 ± 1·8 years, 30 women). OGTT(75) was repeated on three different occasions in 11 healthy men and 13 healthy women at different phases of the menstrual cycle. GH nadirs were comparable between tests [2·40 ± 0·52 (OGTT(100) ) and 2·46 ± 0·54 μg/l (OGTT(75) ); P = 0·356]. There were no differences at any time point in the mean values of GH, serum glucose or insulin between the two test variants. Test interpretation was highly consistent between the OGTT(100) and OGTT(75) [area under the receiver operated curve (ROC) = 0·995]. In men, GH, insulin and glucose measurements during OGTT(75) were highly reproducible. In women, however, basal and GH nadirs were significantly higher midcycle (P < 0·05). In acromegalic patients, there is no difference in GH nadirs and test interpretation after the ingestion of 100 g or 75 g glucose. The OGTT(75) is highly reproducible in men, but in women, it should be performed preferably in the early follicular phase.

Comparison of octreotide LAR and lanreotide autogel as post-operative medical treatment in acromegaly

Long-acting somatostatin analogs are frequently used as adjuvant treatment of acromegaly patients after noncurative surgery. This sudy aims to compare the efficacy of octreotide long-acting release (OCT) and lanreotide Autogel (LAN) in acromegaly patients. Sixty-eight patients not cured by transsphenoidal endoscopic or microscopic pituitary surgery between 2003 and 2009 were retrospectively analyzed (25 men; 43 women; mean age 41.1 ± 10.9 years [range 18–65 years]). The patients were assigned randomly to OCT (n = 36) and LAN (n = 32) groups. Evaluations included insulin-like growth factor I (IGF-I) and growth hormone (GH) after oral glucose tolerance test (OGTT) 3, 6, 12 and 18 months after starting medical treatment; pituitary magnetic resonance imaging was performed before treatment and after 3 and 12 months. Patients achieving IGF-I levels within the age and gender normal range and GH level <1 μg/l following OGTT were considered a ‘biochemical cure’. Mean IGF-I and GH values and tumor volumes (cm3) in the LAN and OCT groups were similar in the post-operative period before initiation of medical treatment. A statistically significant decrease in GH and IGF-I levels was obtained for both treatment groups at each follow-up visit compared to the previous value. Tumor shrinkage after 12 months of treatment was statistically significant in both groups but the percentage tumor shrinkage (28.5% vs. 34.9%, P = 0.166) and rate of patients achieving biochemical cure (63.9 and 78.1%, P = 0.454) were similar between OCT and LAN groups, respectively. OCT and LAN treatment options have similar efficacy for ensuring biochemical cure and tumor shrinkage in acromegaly patients who had noncurative surgery.

Growth hormone and outcome in patients with intracerebral hemorrhage: a pilot study

Background: Endocrine alterations of the hypothalamic-pituitary-axis are one of the first measurable physiological changes in cerebral insults. During acute stress, human growth hormone (GH) is stimulated and has shown to have a prognostic value in various diseases. Within this pilot study, we evaluated the prognostic value of GH in patients with acute intracerebral hemorrhage (ICH).Methods: In a prospective observational study in 40 consecutive patients with ICH, GH was measured on admission. The prognostic value of GH to predict 30-day mortality and 90-day functional outcome was assessed. Favorable functional outcome was defined as Barthel Index score >85 points and Modified Rankin Scale <3 points.Results: GH levels were increased in patients who died within 30 days as compared to survivors (0.45 (IQR 0.20–1.51) vs. 1.51 (IQR 0.91–4.08) p = 0.03), and in patients with an unfavorable functional outcome as compared to patients with a favorable functional outcome after 90 days 0.28 (IQR 0.16–0.61) vs. 0.78 (IQR 0.31–1.99) p = 0.03). For mortality prediction, receiver-operating-characteristics revealed an area under the curve (AUC) on admission for GH of 0.78 (95% CI 0.60–0.96), which was in the range of the Glasgow Coma Score (GCS) (AUC 0.82 (95% CI 0.59–1.00) p = 0.80). For functional outcome prediction, GH had an AUC of 0.71 (95% CI 0.54–0.87), which was statistically not different from the GCS (AUC 0.81 (95% CI 0.68–0.94) p = 0.36).Conclusions: In our small cohort of patients with acute ICH, elevated GH level were associated with increased mortality and worse outcome. If confirmed in a larger study, GH levels may be used as an additional prognostic factor in ICH patients. (ClincalTrials.gov number NCT00390962).

Neuroendocrine Assessment of Serotonergic, Dopaminergic, and Noradrenergic Functions in Alcohol‐Dependent Individuals

Alcohol dependence has been associated with reduced function of serotonin, dopamine as well as noradrenaline activities in several neuroendocrine studies. To our knowledge, there is, however, no study investigating all these 3 systems with the use of neuroendocrine methods in one and the same alcohol-dependent individual. Alcohol-dependent individuals (n = 42) and controls (n = 28) participated in the neuroendocrine test series. Central serotonergic neurotransmission was assessed by the prolactin (PRL) response to citalopram (CIT). The postsynaptic DRD2 function was measured by the growth hormone (GH) response to apomorphine (APO) and the postsynaptic α2-adrenoceptor function by GH response to clonidine (CLON). In the alcohol-dependent individuals, the PRL concentrations were significantly lower at the time points 240 minutes and 300 minutes after CIT administration and mean delta PRL value was significantly reduced by 45% in comparison with controls. There were no significant differences in APO-GH and CLON-GH concentrations at any time points or in mean delta GH values between the groups. An impaired monoaminergic profile, including all 3 systems, was significantly more frequent in alcohol-dependent individuals than controls (43% vs. 6% respectively). The monoaminergic dysfunction was restricted to an impairment of the serotonergic system, suggesting that this system is especially vulnerable to long-term and excessive alcohol consumption. Moreover, impaired monoaminergic profiles, including low responses in 2 or 3 systems, were more frequently observed in alcohol-dependent individuals than in controls. Such impaired profiles may be of clinical importance, but further studies are needed.

Pharmacodynamic effects of intravenous alcohol on hepatic and gonadal hormones: influence of age and sex.

Growth hormone (GH)-insulin-like growth factor-1 (IGF-1) axis and gonadal hormones demonstrate extensively associated regulation; however, little is known about the effects of acute alcohol exposure on these hormones. This study examined the effects of intravenous alcohol on the GH-IGF-1 axis and gonadal hormone concentrations, and the influence of age and sex on their regulation. Forty-eight healthy volunteers (24 men and 24 women each in the 21 to 25 and 55 to 65 year age groups) underwent a 2-session single-blinded study. Subjects received in randomized counter-balanced order, alcohol infusions, individually computed based on a physiologically based pharmacokinetic model, to maintain a steady-state ("clamped") exposure of 50 mg% or saline for 3 hours in separate sessions. Blood samples collected at baseline and postinfusion in each session were assayed for levels of GH, IGF-1, free testosterone, and estradiol. Acute alcohol administration resulted in changes in gonadal hormones that differed by sex. Change in free testosterone showed a significant treatment × baseline interaction (p < 0.001), indicating that alcohol-induced suppression of testosterone occurred predominantly in men. On the other hand, change in estradiol showed a significant treatment × sex interaction (p = 0.028), indicating that alcohol-induced increases in estradiol occurred predominantly in women. There was a trend for alcohol-induced decreases in IGF-1 levels. Change in GH showed a significant main effect of baseline (p < 0.001) and a trend for treatment by baseline interaction, suggesting an alcohol-induced decrease in individuals with high baseline GH values. There was also a significant main effect of sex (p = 0.046) indicating that men had greater changes in GH across treatment compared with women. Alcohol induced a complex pattern of hormonal responses that varied between younger and older men and women. Some of the observed sex-based differences may help improve our understanding of the greater susceptibility to alcohol-related hepatic damage seen in women.

The clinical value of growth hormone for the patients who were failed in previous IVE-ET

Objective To study the application value of growth hormone in the renewal cycle for those patients who were failed in the first IVE-ET treatment.Methods 68 patients who were failed in the previous IVE-ET treatment were divided into two groups and were given long term down-regulating protocol in the first cycle and current cycle.The study group consisted of cases with using GH (4U/d)from the day of down-regulating till the day before embryo transfer and control group consisted of those without using GH.Results The rate of pregnancy of study group and control group was 26.77% and 0, while the rate of quality embryos was 46.26% and 33.58%, respectively.There was significant difference between the two groups( X2 = 3.97,4.86, P 0.05 ).Conclusion In the second cycle,growth hormone could improve the clinical pregnancy rate and the rate of quality embryos for those patients who were failed in the first IVE-ET treatment. Key words: IVF-ET Growth; Hormone

Influence of Body Mass Index on Growth Hormone Responses to Classic Provocative Tests in Children with Short Stature

Background: The diagnosis of growth hormone (GH) deficiency is based on a reduced peak GH response to provocative tests. However, the provocative tests are poorly reproducible and GH secretion is regulated by physiological parameters, such as body weight and puberty. The aim of this study was to assess the influence of body mass index (BMI) on GH response to provocative testing and to analyze the reproducibility of GH stimulation test. Methods: Clinical data were collected retrospectively by chart review from the Pediatric Endocrine Unit at the Ajou University Hospital. A total of 187 subjects with short stature who completed a GH stimulation testing between 2003 and 2009 were included in the study. Results: Of the 187 subjects, 66 (35.3%) had GH deficiency, while 121 (64.7%) were categorized as having idiopathic short stature. Reliability was calculated for 48 patients with idiopathic short stature who underwent the GH stimulation test twice. A GH response ≧10 ng/ml after retesting was found in 39 patients (81.3%) and a GH response <10 ng/ml was found in 9 patients (18.7%). In a stepwise multivariate analysis, BMI was a significantly independent predictor of peak GH. Elevated BMI was negatively associated with peak plasma GH levels. Conclusions: The lack of reliability of GH values in response to pharmacological stimuli should be taken into account in the diagnosis of GH deficiency. Also, higher BMI is associated with lower GH secretion. BMI should be measured and GH results appropriately interpreted for all subjects undergoing GH stimulation testing.

Human growth hormone (GH) immunoassay: standardization and clinical implications

The poor comparability of growth hormone (GH) results obtained using commercially available methods, is partly due to standard preparations used in calibration. The system relies on the use of the International Reference Preparation (IRP) international standard (IS) 80/505, of human pituitary origin, containing all GH isoforms. Recently, a 22K recombinant GH isoform IRP IS 98/574 was commercialized. Our aim was to evaluate the influence of both calibrators on GH results. GH concentration in 97 serum samples from children undergoing a growth hormone releasing hormone+arginine stimulation test was measured using Siemens IMMULITE electro-chemiluminescence method, calibrated with both IS 80/505 and IS 98/574 (GRH Growth hormone-Recombinant 98/574-kit). Comparison of our results obtained with the two sets of calibrators showed good correlation, although we found higher percentage variation (var%) than that stated by Siemens. The mean var% value was confirmed when all results were sub-divided into subgroups based on both high and low GH concentrations. Since the GH assay is influenced by a variety of binding proteins, isoforms and conversion factors, standardization of the assay is strongly required. In Italy, the Agenzia Italiana del Farmaco 39 note provides GH laboratory values which are useful for therapy. On the basis of our results, we therefore propose to adjourn these GH values in order to ensure better management of patients with GH-related disorders.

Anterior pituitary axis hormones and outcome in acute ischaemic stroke

Early and accurate prediction of outcome in acute stroke is important and influences risk-optimized therapeutic strategies. Endocrine alterations of the hypothalamic-pituitary axis are amongst the first measurable alterations after cerebral ischaemia. We therefore evaluated the prognostic value of cortisol, triiodothyronine (T3), free thyroxine (fT4), thyroid-stimulating hormone (TSH) and growth hormone (GH) in patients with an acute ischaemic stroke. In an observational study including 281 patients with ischaemic stroke, anterior pituitary axis hormones (i.e. cortisol, T3, fT4, TSH and GH) were simultaneously assessed to determine their value to predict functional outcome and mortality within 90 days and 1 year. In receiver operating characteristic curve analysis, the prognostic accuracy of cortisol was higher compared to all measured hormones and was in the range of the National Institutes of Health Stroke Scale (NIHSS). Cortisol was an independent prognostic marker of functional outcome and death [odds ratio (OR) 1.0 (1.0-1.01) and 1.62 (1.37-1.92), respectively, P<0.0002 for both, adjusted for age and the NIHSS] in patients with ischaemic stroke, but added no significant additional predictive value to the clinical NIHSS score. Cortisol is an independent prognostic marker for death and functional outcome within 90 days and 1 year in patients with ischaemic stroke. By contrast, other anterior pituitary axis hormones such as peripheral thyroid hormones and GH are only of minor value to predict outcome in stroke.

Correlation between blood growth hormone profile and reproduction performance in Arabic rams

The aim of this study was to evaluate the seasonal variations of growth hormone concentration in serum and its association with semen characteristics and testosterone level in Arabic rams. The study was carried out with six adult Arabic rams aged 2 to 3 years old. The experiments showed a seasonal variation in growth hormone level. The concentration of growth hormone in breeding season was significantly higher than that in the non-breeding season. In both breeding and non-breeding seasons, there was a positive correlation between serum growth hormone concentration and spermatozoa quality parameters include motility, concentration and viability as well as testosterone concentration. Controversy, a negative correlation was revealed between growth hormone value and abnormal sperm percent in both seasons. Thus, seasonal variation of growth hormone concentration was accompanied with marked alterations in semen characteristics and testosterone level. It can be concluded that one reason for low concentration of testosterone and poor semen quality in the non-breeding season can likely be due to low concentration of blood growth hormone.

Serum IGF-1 concentrations in a sample of patients with traumatic brain injury as a diagnostic marker of growth hormone secretory response to glucagon stimulation testing

The diagnosis of growth hormone deficiency (GHD) in adults is established through growth hormone (GH) stimulation testing, which is often complex, expensive, time-consuming and may be associated with adverse side effects. The decision to perform GH provocative testing is influenced by clinical findings, medical history and biochemical evidence. We report in this study our experience using the glucagon stimulation test (GST) in assessing GHD in adult patients with traumatic brain injury (TBI) as it relates to baseline serum insulin-like growth factor-1 (IGF-1) concentrations. A receiver operating characteristic (ROC) curve analysis was performed to determine the optimal IGF-1 cut-off for diagnosis of GHD at different potential diagnostic GST cut-off values (<3, <5, & <10 μg/l). One hundred and thirty-eight patients (98 men and 40 women) with a documented history of moderate to severe TBI were assessed for GHD using serum IGF-1 concentrations and the GST. IGF-1 values were compared with peak GH values obtained following the GST. An IGF-1 cut-off value of 175 μg/l minimized the misclassification of GHD patients and GH-sufficient patients and provided a sensitivity of 83% and specificity of 40%, as well as a negative predictive power of 90% considering a criterion for peak GH response of <3 μg/l. Our current findings are consistent with previous work assessing peak GH response using the insulin tolerance test (ITT) in a non-TBI sample, suggesting that diagnostic accuracy may be optimized if the GST is used when obtained serum IGF-1 concentrations are below 175 μg/l. While the decision to perform provocative testing to assess GHD in adult patients should be based on the clinician's clinical impression, the findings from this retrospective study can provide useful clinical information and serve as a guide.