Measurement Of Growth Hormone 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.

Growth hormone variants: a potential avenue for a better diagnostic characterization of growth hormone deficiency in children.

Human GH (hGH) is a heterogeneous protein hormone consisting of several isoforms. This heterogeneity is the consequence of multiple hGH genes, mRNA splicing, post-translational modifications, and peripheral metabolism, and it represents one important reason for the disparity among GH assay results from different laboratories. However, other factors are involved: a) interference from endogenous GH binding proteins; b) different specificities of anti- GH (monoclonal and polyclonal) antibodies; c) different matrix effects among the calibrators; d) the use of different calibrators. The measurement of GH levels in response to provocative testing is an essential part of the diagnosis of GH deficiency. For this purpose, an accurate, reproducible and universally valid GH measurement would be highly desirable, but, despite a huge number of efforts in clinical biochemistry, this goal remains elusive.

465P - The Preclinical Pharmacological Profile of Anamorelin/Ono-7643, A New Ghrelin Receptor Agonist for the Treatment of Cancer Cachexia

ABSTRACT Introduction Ghrelin is the only known circulating orexigenic hormone which acts as the endogenous ligand for the ghrelin receptor (GRLN), and is considered a potential agent to treat cancer cachexia/anorexia. The aim of this study was to evaluate the in vitro and in vivo pharmacological activities of Anamorelin/ONO-7643 (ANA), a new synthetic ghrelin receptor agonist, on food intake (FI), body weight (BW) and GH in rats. Material and methods HEK293 cells expressing human recombinant ghrelin receptor were utilized in a Fluorescent Imaging Plate Reader (FLIPR), along with Fluo-8 dye to signal intracellular calcium. Ghrelin and ANA were incubated (0.001-1000 nM) to generate a concentration-response increase of Ca++. Binding experiments were also performed by using [125I]Ghrelin. In vivo experiments were performed on male SD rats after oral treatment of ANA or vehicle. FI and BW were measured daily from Day 1 up to Day 7 of once-daily treatment. In other experiments, blood samples were collected at different time interval up to 6 hours post single dose for GH measurements. Results Ghrelin and ANA showed a significant agonist activity on the ghrelin receptor in the FLIPR assay, with EC50 values of 0.67 nM and 0.74 nM, respectively. No significant antagonist activity was observed with ANA up to 1000 nM. In binding experiments, the affinity of ghrelin and ANA for ghrelin receptors were evaluated and resulted in a Ki of0.58 nM and 0.70 nM, respectively. In the in vivo experiments, ANA (3, 10, 30 mg/kg p.o.) significantly (p Conclusions Anamorelin is a potent ghrelin agonist endowed with significant orexigenic activity demonstrating both an increase of FI and BW after subchronic treatment in rats. Plasma GH levels were increased after a single administration of ANA. These results support the continued investigation of Anamorelin as a potential treatment of cancer cachexia/anorexia. Disclosure C. Pietra: Employee of Helsinn SA. Y. Takeda: Ono employee. N. Tazawa-Ogata: ONO employee. M. Minami: ONO Employee. E. Duus: Helsinn Therapeutics employee. R. Northrup: Helsinntheraputics employee. All other authors have declared no conflicts of interest.

Measurement of free GH and bioactive IGF-I in non-diabetic haemodialysis patients treated with GH for 7 days

End-stage renal failure (ESRF) patients demonstrate augmented growth hormone (GH) secretion, but normal insulin-like growth factor-I (IGF-I) concentrations, indicating a state of GH resistance. To test this hypothesis, we compared the IGF-I response with exogenous GH in haemodialysis patients and healthy controls, with special focus on free GH and bioactive IGF-I. Ultrafiltered free GH and total GH were measured in serum collected hourly for 24 h at baseline and after 7 days of recombinant human (rh) GH (50 µg/kg/day) treatment in 11 non-diabetic haemodialysis patients and 10 matched controls. Serum levels of bioactive IGF-I (determined by cell-based IGF-I receptor activation assay), total IGF-I and the GH-binding protein (GHBP) were assayed twice daily. At baseline, patients showed elevated total GH (24 ± 5 versus 9 ± 1 µg/L × h, P < 0.02), free GH (21 ± 5 versus 7 ± 1 µg/L × h, P < 0.02), reduced GHBP (1.5 ± 0.3 versus 2.5 ± 0.2 nmol/L, P < 0.01), high-normal total IGF-I (173 ± 18 versus 135 ± 14 µg/L, P = 0.12) and subnormal bioactive IGF-I (2.1 ± 0.3 versus 2.8 ± 0.2 µg/L, P < 0.05) when compared with controls. After 7 days of rhGH treatment, there was a greater GH increase in the non-diabetic haemodialysis patients than in controls (total GH: 293 ± 33 versus 166 ± 13 µg/L × h, P < 0.001; free GH: 284 ± 40 versus 126 ± 15 µg/L × h, P < 0.001). GHB remained unaffected and total IGF-I increased to the same extent in patients and controls (701 ± 87 versus 572 ± 33 µg/L, P = 0.17), whereas bioactive IGF-I tended to be lower in patients (5.37 ± 0.55 versus 6.63 ± 0.25 µg/L, P < 0.10). When adjusting for the actual increments in plasma GH, the ability of exogenous GH to stimulate bioactive IGF-I levels was reduced by ~50% in ESRF (P < 0.02), whereas the response of total IGF-I remained normal (74%; P= 0.18) The study demonstrates that ESRF is associated with markedly elevated serum levels of free GH. Furthermore changes in bioactive, but not immunoreactive, IGF-I indicated that the hepatic sensitivity to GH was reduced by 50% in ESRF patients. Clearly, the physiological importance of our observations awaits further studies, but they suggest that changes in total IGF-I may not necessarily reflect changes in the endogenous activity of IGF-I in ESRF patients on GH treatment.

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.

Detailed studies of growth hormone secretion in cystinosis patients

Cystinosis is an autosomal recessive disorder characterized by intralysosomal cystine accumulation. Growth retardation is more pronounced in cystinosis than in other chronic kidney diseases and is mostly not corrected by cysteamine. Growth was evaluated in nine cystinosis patients, all treated with cysteamine, both after cysteamine and recombinant human growth hormone (rhGH) therapy initiation. Growth hormone (GH) secretion was studied by nocturnal GH measurements in four of nine patients and by glucagon test in four of nine patients. RhGH was administered to seven of nine patients. At rhGH initiation, height was below -2 SDS in five of seven patients, final height was above -2 SDS in six of seven. In two patients not treated with rhGH, final height remained below -4 SDS despite cysteamine treatment being started at the age of 6.1 and 8.1 years, respectively. Nocturnal GH secretion was normal in all patients. Glucagon tests revealed GH deficiency in one patient; two of four patients had abnormal GH peak timing. We present the first reported case of GH deficiency in cystinosis. Although no overt GH deficiency was detected in other patients, abnormal GH peak timing can indicate a subclinical GH secretion problem. RhGH significantly improved growth in cystinosis patients and should be initiated early in life.

The Ability of β-Cells to Compensate for Insulin Resistance is Restored with a Reduction in Excess Growth Hormone in Korean Acromegalic Patients

The aim of this study was to assess the prevalence of diabetes and to study the effects of excess growth hormone (GH) on insulin sensitivity and β-cell function in Korean acromegalic patients. One hundred and eighty-four acromegalic patients were analyzed to assess the prevalence of diabetes, and 52 naïve acromegalic patients were enrolled in order to analyze insulin sensitivity and insulin secretion. Patients underwent a 75 g oral glucose tolerance test with measurements of GH, glucose, insulin, and C-peptide levels. The insulin sensitivity index and β-cell function index were calculated and compared according to glucose status. Changes in the insulin sensitivity index and β-cell function index were evaluated one to two months after surgery. Of the 184 patients, 17.4% were in the normal glucose tolerance (NGT) group, 45.1% were in the pre-diabetic group and 37.5% were in the diabetic group. The insulin sensitivity index (ISI0,120) was significantly higher and the HOMA-IR was lower in the NGT compared to the diabetic group (P = 0.001 and P = 0.037, respectively). The ISI0,120 and disposition index were significantly improved after tumor resection. Our findings suggest that both insulin sensitivity and β-cell function are improved by tumor resection in acromegalic patients.

Diagnosing Growth Hormone Deficiency in Adults

Adult growth hormone (GH) deficiency is a recognised syndrome associated with adverse phenotypic, metabolic, and quality-of-life features which improve in many patients when GH is substituted. The appropriate selection of patients at risk of growth hormone deficiency (GHD) is the crucial first step in arriving at a correct diagnosis. Although multiple diagnostic modalities are available including a 24-hour serum GH profile, stimulated GH levels, and insulin-like growth factor-1 (IGF-1) levels, the use of dynamic tests for GH reserves is required in most cases. This paper discusses the utility and drawbacks of the various testing modalities with reference to international guidelines. Regardless of the test chosen, clinical pitfalls including age and obesity must be taken into account. In addition, there is considerable analytical variation in the biochemical measurements of GH and IGF-1 which must be considered before making a diagnosis of GHD in adulthood.

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.

Growth Hormone Deficiency in Children and Adolescents with Cerebral Palsy: Relation to Gross Motor Function and Degree of Spasticity

Children with Cerebral Palsy (CP) often have poor linear growth during childhood with short final height. Thus, we aimed to assess serum growth hormone (GH), insulin like growth factor-1 (IGF-1) and insulin like growth factor binding protein-3 (IGFBP-3) levels among CP patients and their relation to each of gross motor function and degree of spasticity. Fifty CP children and adolescents were studied in comparison to 50 healthy age-, sex- and pubertal stage-matched children and adolescents. All subjects were subjected to clinical evaluation, Intelligence Quotient (IQ) assessment and measurement of serum GH, IGF-1 and IGFBP-3. All auxological and hormonal parameters were significantly lower among cases. Fifty two% of cases were GH-deficient and 62% had reduced IGF-land IGFBP-3 levels. Gross Motor Function Measure- 88 (GMFM-88) score correlated negatively with each of basal (r = -0.71, p = 0.02) and peak stimulated GH (r =-0.88, p = <0.001); IGF-1 (r = -0.64, p = 0.04) and IGFBP-3 (r = -0.69, p = 0.031). There were significant negative correlations between the degree of spasticity assessed by Modified Ashworth Scale and each of basal (r = -0.61, p = 0.032) and peak stimulated GH (r = -0.78, p = 0.01); IGF-1 (r = -0.65, p = 0.041) and IGFBP-3 (r = -0.62, p = 0.035). Growth Hormone Deficiency (GHD) is prevalent in children with CP and could be one of the causes of their short stature.

Acromegaly: recent progress in diagnostics and treatment

Acromegaly is a serious disease with different complications leads to reduced life expectancy and increase mortality. Only early diagnosis and modern methods of management of disease lead to remission. According to consensus on criteria for cure of acromegaly (2010) the measurement of GH and age-matched total IGF-I concentrations are the most important biochemical variables for the diagnosis of acromegaly and for monitoring progression or treatment response. The optimal disease control is now defined as IGF-I level in the age – adjusted normal range, random GH levels less than 1,0 µg/liter and nadir GH level during OGTT less than 0,4 µg/liter. MRI with use a contract substance is the best method of adenoma visualization. The trassphenoidal surgery with new technologies (endoscope, intraoperative blood sampling, neuronavigation, intraoperative MRI), radiosurgery, modern medical treatment (multiligand long-acting somatostatin analogs, GH receptor antagonist) are effective modalities for treatment of acromegaly, which elaborated last decades.

Pregnancy-induced increase in circulating IGF-I is associated with progression of diabetic retinopathy in women with type 1 diabetes

Objective To evaluate the influence of Insulin-like Growth factor-I (IGF-I) and Placental Growth Hormone (GH) on progression of diabetic retinopathy during pregnancy in women with type 1 diabetes. Design Observational study of 88 consecutive pregnant women with type 1 diabetes for median 16.5 years (range 1–36) and HbA 1c 6.6% (5.2–10.5) in early pregnancy. At 8, 14, 21, 27 and 33 weeks blood samples were drawn for measurement of IGF-I, placental GH and Hemoglobin A 1c (HbA 1c) and blood pressure was recorded. Fundus photography was performed at 8 and 27 weeks. Diabetic retinopathy was classified in five stages. Progression was defined as deterioration of at least one stage of diabetic retinopathy and/or development of macular edema on at least one eye. Results Placental GH and IGF-I levels increased throughout pregnancy and new onset or progression of diabetic retinopathy occurred in 22 (25%). A steeper increase in women with progression of diabetic retinopathy resulted in higher IGF-I levels at 27 weeks ( p = 0.01) and 16% higher IGF-I levels throughout pregnancy ( p = 0.02) compared with women without progression while similar levels of placental GH ( p = 0.58) and HbA 1c ( p = 0.85) were observed throughout pregnancy. In a multivariate logistic regression analysis, progression of diabetic retinopathy was associated with higher IGF-I levels at 33 weeks (odds ratio 2.0 [95% confidence interval 1.1–3.6], p = 0.02) and higher systolic blood pressure at 8 weeks (1.9 [1.1–3.2], p = 0.02) independent of placental GH and HbA 1c levels. Conclusions Pregnancy-induced increase in IGF-I levels is associated with progression of diabetic retinopathy in women with type 1 diabetes.

Frequency of acromegaly in adults with diabetes or glucose intolerance and estimated prevalence in the general population

The objective of this study was to evaluate the frequency of acromegaly in adults with diabetes mellitus (DM) or glucose intolerance (GI) and to estimate its prevalence in the general population. A total of 2,270 patients with DM or GI and age from 20 to 70years were studied. Patients with known pituitary disease and pregnant women were excluded. Serum IGF-1 was measured in all subjects and, if elevated, a new measurement was obtained together with the measurement of GH in the oral glucose tolerance test (OGTT). Patients with persistently elevated IGF-1 and inadequate suppression of GH were submitted to magnetic resonance imaging (MRI). Acromegaly was not suspected by the assistant physician in any of the patients. Six patients had persistently elevated IGF-1 and inadequate suppression of GH in the OGTT (without other conditions associated with GH or IGF-1 elevation). Pituitary adenoma was detected by MRI in three patients, and two subjects presented an acromegalic phenotype. Two patients were submitted to transsphenoidal surgery, with immunohistochemistry confirming immunoreactivity for GH. Another patient was treated with octreotide LAR which resulted in the normalization of IGF-1 and GH. Considering a prevalence of DM or GI of 20% in adults and the occurrence of these co-morbidities in 55% of patients with acromegaly, the frequency of 3/2,270 found in this study permits to estimate 480 cases/1,000,000 adults. The present results suggest that the prevalence of acromegaly is underestimated and further studies are needed to evaluate the cost-effectiveness of biochemical screening in certain groups of patients.

Clinical and biochemical characteristics of acromegalic patients with different abnormalities in glucose metabolism

To determine the prevalence of diabetes, glucose intolerance and impaired fasting glucose in Mexican patients with acromegaly and establish associations with clinical, anthropometric and biochemical variables. 257 patients with acromegaly were evaluated by a 75g-oral glucose tolerance test with measurements of both GH and glucose (0, 30, 60, 90 120min) as well as baseline IGF-1. Normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and diabetes (DM) were defined based on the 2003 ADA criteria. NGT, IFG, IGT and DM were found in 27.6, 8.9, 31.6 and 31.9% of the subjects, respectively; 42 of the DM patients were unaware of the diagnosis. Patients with diabetes were older than subjects in the other 3 categories (P=0.001), and the proportion of women was significantly higher in the DM (74%) and IGT (68%) groups than in the NGT group (52%) (P=0.004). Odds ratio for the development of DM was 3.29 (95% CI 3.28-3.3). GH and IGF-1 levels were comparable among the different groups. In a multivariable analysis DM was significantly associated with age, presence of a macroadenoma, disease duration and a basal GH>30μg/dl. DM and probably IGT are more prevalent in acromegaly than in the general Mexican population. DM was more frequent in females of all ages, in subjects with severely elevated GH concentrations, in patients with macroadenomas, and long-standing disease duration. The odds ratio for DM in our subjects with acromegaly is more than 3times higher than in the general population.

The growth hormone/insulin‐like growth factor‐I system in chronic heart failure and its interaction with adiponectin

The growth hormone/insulin‐like growth factor‐I system in chronic heart failure and its interaction with adiponectin

Measurement of basal GH in the diagnosis of acromegaly

Measurement of basal GH in the diagnosis of acromegaly

Rheumatoid arthritis masquerading as acromegaly recurrence: report of two cases

Acromegaly is a chronic endocrinopathy characterized by hypersecretion of growth hormone (GH) and consequently of insulin-like growth factor-1 (IGF-1). The arthropathy in acromegaly is the most frequent and important cause of morbidity and functional disability in acromegaly. Rheumatoid arthritis (RA) is a rarely reported clinical situation in patients with acromegalic. We herein report 57- and 45-year-old two women, who complained bilateral, symmetric pain, swelling and morning stiffness in the joints of hands after optimal acromegaly treatment resembling acromegaly arthropathy. There was not arthralgia in other joints of the patients. Laboratory and radiological evaluations were carried out. After excluding the acromegaly activation and arthropathy by GH and IGF-1 measurement, according to clinical presentation, laboratory and radiological assessments, patients were diagnosed as RA.

Nadir growth hormone after oral glucose overload in obese subjects

The nadir growth hormone (n-GH) in the oral glucose tolerance test (OGTT) is the gold standard for the demonstration of secretory autonomy of this hormone and a laboratory parameter necessary for the diagnosis of acromegaly (1,2). Although measurement of GH after oral glucose overload is not recommended during treatment with somatostatin analogs or GH receptor antagonists (3), normalization of n-GH continues to be necessary for the definition of “control” after surgical treatment of acromegaly (3). Nadir GH levels vary according to the assay used (4-7) and are influenced by gender, age and body mass index [BMI (4-6,8)]. The inverse correlation with BMI observed in normal subjects (4,6,8) and acromegalic patients (9) indicates the need for adjusting the n-GH cut-off as a function of BMI (4,6,8). We have previously defined n-GH reference values in subjects with a BMI ≤ 27 kg/m2 (5). The possibility that the current reference values are inadequate (overestimated) for obese subjects led to the elaboration of the present study, for which the objective was to evaluate the n-GH in the OGTT in subjects with a BMI ≥ 30 kg/m2. A total of 200 volunteers (120 women and 80 men) ranging in age from 18 to 70 years (median of 44 years), matched with 200 subjects from the previous study (5), who had a BMI ≥ 30 kg/m2 (median of 34.8 kg/m2) were studied. The selection criteria, protocol and statistical analysis are described in detail in the previous study (5). Briefly, apparently healthy subjects (excluding pregnant women) without associated diseases who were not using medications that might interfere with GH levels and who presented no abnormalities upon minimum laboratory assessment (glycemia, blood count, albumin, creatinine, TSH, GOT, GPT and bilirubin) were selected. The study was approved by the Ethics Committee of Santa Casa de Belo Horizonte. The GH Immulite kit (Diagnostic Products Corporation, Los Angeles, CA) was used for the measurement of GH since it is the kit most widely used in Brazil. In addition, the kit meets the requirements of calibrated standards against > 95% pure preparations of GH 22 kDa (10), its specificity for the 22 and 20 kDa isoforms is known (4), and its intraand interassay sensitivity and variability have been previously established (5,11). The cut-off was defined as the 97.5th percentile of the values found. The Spearman correlation test was used to analyze the correlation between n-GH and age, BMI. The nonparametric Kruskal-Wallis test and the parametric Shapiro-Wilk test were used to compare GH values obtained between groups. P values 35 years (n = 80), with higher values in the former (n-GH cut-off: 0.42 μg/L versus 0.3 μg/L, p < 0.05). There was an inverse correlation between n-GH levels and 1 Programa de Pos-graduacao, Santa Casa de Belo Horizonte, MG, Brazil 2 Faculdade de Medicina do Vale do Aco, Ipatinga, MG, Brazil

OR7,38 Measurement of free GH and bioactive IGF-I in non-diabetic hemodialysis patients treated with rh-GH for 7 days

OR7,38 Measurement of free GH and bioactive IGF-I in non-diabetic hemodialysis patients treated with rh-GH for 7 days