Peak GH Response Research Articles

Effect of GH Deficiency Caused by Nonfunctioning Pituitary Masses on Serum C-reactive Protein Levels.

GH supplementation for GH deficiency (GHD) has been reported to decrease high-sensitivity C-reactive protein (hs-CRP), an inflammatory marker; however, the association between GHD and hs-CRP remains unclear. We aimed to clarify the impact of impaired GH secretion due to pituitary masses on hs-CRP levels. We retrospectively examined the association between GH secretion, assessed using GH-releasing peptide-2, and serum hs-CRP levels before and a year after the pituitary surgery in patients with nonfunctioning pituitary neuroendocrine tumor or Rathke cleft cyst. Among 171 patients, 55 (32%) presented with severe GHD (peak GH response to GH-releasing peptide-2 < 9 ng/mL). Serum hs-CRP levels were significantly higher in patients with severe GHD than in those without (P < .001) and significantly correlated with the peak GH (r = -0.50, P < .001). Multiple regression analyses showed that the peak GH significantly and negatively predicted hs-CRP levels (β = -0.345; 95% CI, -0.533 to -0.158) and the lowest quartile of the peak GH (<5.04 ng/mL) were significantly associated with increase in hs-CRP levels (exp [β] = 1.840; 95% CI, 1.209 to 2.801), after controlling for other anterior hormones and metabolic parameters. Postoperative change in the peak GH (N = 60) significantly predicted change in hs-CRP levels (β = -0.391; 95% CI, -0.675 to -0.108), independent of alterations in other anterior hormones and metabolic parameters. The inverse association between GH secretion and hs-CRP levels highlights the protective role of GH in the increase in hs-CRP.

ODP323 Increased Serum High-Sensitivity C-Reactive Protein Levels in Adult Growth Hormone Deficient Patients with Non-Functioning Pituitary Tumors

Abstract Background Growth hormone (GH) deficiency, a common endocrine deficit in non-functioning pituitary tumors, causes visceral obesity and fatty liver and increases cardiovascular event risks. High-sensitivity C-reactive protein (hs-CRP) has been used as a useful marker to estimate cardiovascular event risks. Because GH supplementation therapy was reported to decrease serum hs-CRP levels in GH deficient patients, inflammatory processes might be activated in GH deficient state, however, the underlying mechanism has been still unknown. Patients and Methods We retrospectively reviewed charts of 134 patients with non-functioning pituitary adenoma and Rathke's cysts who underwent preoperative GH-releasing peptide-2 (GHRP-2) tests and investigated the association between serum hs-CRP levels and background characteristics. Patients who had a history of pituitary surgery, severe renal insufficiency or active inflammatory diseases or received GH supplementation therapy were excluded. GH secretion was determined by GHRP-2 tests. Results Among 134 patients (94 NFPA and 40 Rathke's cysts), 46 (34%) presented severe GH deficiency, as diagnosed using GHRP-2 tests. Serum hs-CRP levels were significantly higher in the patients with severe GH deficiency than in those without severe GH deficiency (723 [299-1285] vs 278 [124-561] ng/mL, P &amp;lt; 0. 001). Serum hs-CRP levels were significantly higher in men (P = 0. 003) and in patients with diabetes mellitus (P = 0. 040) and were significantly correlated with age (r s = 0.19, P = 0. 039), body mass index (r s = 0.37, P &amp;lt; 0. 001), serum levels ofgamma-glutamyl transpeptidase(r s = 0.28, P = 0. 001), creatinine (r s = 0.30, P &amp;lt; 0. 001), low-density lipoprotein cholesterol (r s = 0.21, P = 0. 013), triglyceride (r s = 0.38, P &amp;lt; 0. 001) and free thyroxine (r s = -0.30, P= 0. 001), blood hemoglobin A1c levels (r s = 0.20, P = 0. 018), peak GH response to GHRP-2 (r s = -0.47, P &amp;lt; 0. 001) and IGF-1 SD score (r s = -0.18, P = 0. 040). In the multiple regression analysis, peak GH response to GHRP-2 was a significant variable for determining serum hs-CRP levels (β = -0.340, P = 0. 003) after adjustment with age, sex, BMI, smoking, alcohol consumption, hypertension, diabetes mellitus, serum levels ofgamma-glutamyl transpeptidase, creatinine,triglyceride and free thyroxine and adrenal function. Conclusion We observed a significant association between GH deficiency and increased serum hs-CRP levels independent to BMI and liver dysfunction. GH deficient state might cause inflammation independent to development of visceral obesity and fatty liver. Presentation: No date and time listed

Association between overweight and growth hormone secretion in patients with non-functioning pituitary tumors.

IntroductionGrowth hormone (GH) deficiency (GHD) is often complicated by non-functioning pituitary tumors (NFPTs); however, its prevalence remains unclear because preoperative screening for GHD with provocative tests is not recommended. Accordingly, we attempted to clarify the characteristics of GHD in unoperated patients with NFPT.Materials and methodsWe retrospectively reviewed adult patients with non-functioning pituitary adenoma (NFPA) and Rathke’s cyst who underwent preoperative GH-releasing peptide-2 (GHRP-2) tests from January 2013 to December 2016. We investigated the association between peak GH response to GHRP-2 and background characteristics.ResultsAmong 104 patients (85 NFPA and 19 Rathke’s cysts), 45 (43%) presented severe GHD, as diagnosed using GHRP-2 tests. Body mass index (β = -0.210, P = 0.007), free thyroxine (β = 0.440, P < 0.001), and tumor height (β = -0.254, P < 0.001) were significant variables for determining the peak GH response to GHRP-2 in multiple regression analyses. Overweight (odds ratio, 3.86; 95% confidence interval, 1.02–14.66) was significantly associated with severe GHD after adjustment for age, sex, creatinine, free thyroxine, tumor height and clinical diagnosis. The regression slopes between tumor height and peak GH response to GHRP-2 significantly differed between overweight patients and non-overweight individuals, as determined by analysis of covariance (P = 0.040). In the 48 patients who underwent postoperative GHRP-2 tests, severe postoperative GHD was significantly more common in overweight patients than non-overweight individuals (100% vs. 48%, P < 0.001).ConclusionWe observed a negative synergistic effect between overweight and tumor size on GH secretion in patients with NFPTs, indicating that GH provocation tests for diagnosing underestimated GHD could be considered in overweight unoperated patients with large NFPTs.

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

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. 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. 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. 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. GHD may be a treatable explanation for disabling post-BMT fatigue pending results of intervention studies.

The Arginine Stimulation Test Allows Rapid Diagnosis of Central Diabetes Insipidus in Children

Introduction: Water deprivation testing (H2O-dep) is usually required to distinguish between diabetes insipidus (DI) and primary polydipsia (PP) in children with polydipsia-polyuria syndrome (PP-S). The H2O-dep is challenging for children and their families. The prolonged fasting may provoke hypoglycemia and dehydration, particularly in younger children. Serum concentrations of copeptin (COP) (a surrogate marker of AVP, which is easier to measure by a robust assay), are known to increase in adults and children undergoing IV arginine (ARG) stimulation testing (ASTT). Objective: To test the hypothesis that COP levels during ASTT would differentiate between DI and PP. Methods: Serum COP responses to ARG were measured in 13 healthy short children being tested for GH deficiency (controls); and in 4 patients with PP-S. Arginine-HCl (500 mg/Kg) was infused IV from 0 to 30 min, with blood sampling at 0, 15, 30, 45, 60 min; seven of 13 controls also received clonidine PO (150 mcg/m2) at 0 min. COP was measured with a 2-site immunometric assay (BRAHMS Platform, Quest Diagnostics). Results: A-Controls. As the COP values at each time point were similar in the ARG and ARG-Clonidine controls, the data from both groups were combined. COP peaked at 45-60 min post ARG in the 13 controls. COP (Mean+SD; pMol/l)) increased from 9.7+4.3, (range 3-17) to a peak of 12.4+5.0 (range 6-21) at 60 min; Δ% increase 47+50 % (range 0-133). The peak COP values on ASTT showed no correlation with subjects’ age or peak GH response. Results B: Subjects with PP-S: On the basis of H2O-dep, MRI findings, and long-term response to desmopressin therapy, 3 of 4 children were diagnosed with central DI, and 1 with PP. Abbreviations: S[Osm], U[Osm]= serum, urine osmolality (mOsm/Kg); values obtained at the end of the H2O Dep: Subject 1. 3 y-old male, diagnosed with PP. After H2O-dep S[Osm] / U[Osm] 286 / 615. On ASTT COP (base vs. peak) 15 vs.116 pMol/l. Subject 2. 8 y-old male, diagnosed with central DI with Langerhans cell histiocytosis (LCH). MRI: absent bright spot. After H2O-dep S[Osm] / U[Osm] 318/202; On ASTT COP (base vs. peak) 2 vs. 2 pMol/l. Subject 3. 2 y-old male. diagnosed with central DI, possible LCH; MRI: absent bright spot. No H2O-dep; On ASTT COP (base vs. peak) 3 vs 3 pMol/l. Subject 4. Male, 3 y-old. Diagnosed with partial DI with LCH. MRI: absent bright spot. After H2O-dep S[Osm] / U[Osm] 297/569. On ASTT COP (base vs. peak) 5 vs. 6 pMol/l. Comment: In all DI patients, COP concentrations remained flat in the ASTT, at 2-3 pmol/L in 2 subjects with complete DI, and 5-6 pmol/L in 1 subject with partial DI. The latter response overlapped with that of 1 of 13 control subjects. Conclusions: These preliminary data support the hypothesis that ASTT is an easy, minimally invasive test, valuable for differentiating the etiology of PP-S in children. However, patients with partial DI may have low-normal COP responses at ASTT that overlap with values in normal children.

Clinical and Biochemical Phenotype of Indian Children with Different Types of Idiopathic Growth Hormone Deficiency and their Association with Pituitary Height on MRI.

Background and Objectives:Differentiation of growth hormone deficiency (GHD) into various types has been made based on peak stimulated growth hormone levels and other hormone axis involvement. The data regarding how this classification is associated with variation in clinical and biochemical phenotype and how these findings associate with pituitary morphology remains sparse, especially in the Indian population. Therefore, we aimed to ascertain the differences in the pattern of auxological, clinical features including pituitary hypoplasia, and endocrinological profile among patients with severe GHD, partial GHD, and MPHD in the Indian population and to evaluate the association of pituitary height with various clinical and hormonal parameters.Materials and Methods:We conducted a cross-sectional study in 100 patients with idiopathic GHD. Patients were grouped into severe GHD, partial GHD, and MPHD to observe the differences in clinical, biochemical, and MRI findings. The pituitary height findings were correlated clinical and biochemical presentation.Results:MPHD subjects had a significantly higher frequency of breech delivery, neonatal jaundice, neonatal hypoglycemia, and micropenis. A significant difference was observed in the chronological age, bone age retardation (CA-BA), height SDS, weight SDS, peak GH response, IGF-1, IGF-1 SDS, and prevalence of pituitary hypoplasia, pituitary height, and pituitary height SDS among these three groups. In the composite population of GHD, pituitary height SDS was correlated with peak GH, basal IGF-I SDS, and body height SDS.Conclusion:The clinical and biochemical phenotype differs significantly among the various types of GHD. Pituitary height correlates with these findings and is helpful in further assessment of these patients.

Can plasma antioxidants prevent DNA damage in oxidative stress condition induced by growth hormone deficiency? A pilot study.

Adult growth hormone deficiency (GHD), a condition characterized by increased oxidative stress, is related to augmented cardiovascular, metabolic and oncological risk. A case-control observational study has been performed to evaluate DNA oxidative damage analysing the production of thymidine-glycol in lymphocytes and its correlation with plasma antioxidant levels, evaluated as Total Antioxidant Capacity (TAC). GHD was diagnosed using GHRH 50μg iv+arginine 0,5 g/Kg test, with peak GH response <9 μg/L when BMI was <30 kg/m2 or <4 μg/L when BMI was >30 kg/m2. Three groups were identified: total GHD (n = 16), partial GHD (n = 11), and controls (n = 12). Thymidine-glycol, TAC and IGF-1 have been determined respectively in lymphocytes, plasma and serum samples. When considering thymidine-glycol, we found a significant difference between total vs partial GHD and controls. Unexpectedly thymidine-glycol was lower in total GHD, also accompanied with a significant increase in plasmatic TAC. Our results showed that in adult GHD condition, the production of antioxidant species, in response to increased oxidative stress, could exert a protective effect on thymidine-glycol formation, and consequently on DNA intracellular damages. This pilot study could be inserted in the complex scenario of oxidative damage of GHD, a subtle, yet poorly defined condition, worthy of further insights.

Corroboration of Height Velocity Prediction Markers for rhGH With an Oral GH Secretagogue Treatment in Children With GHD.

ContextRecombinant human growth hormone (rhGH) is approved for treatment of pediatric growth hormone deficiency (GHD), with greatest growth responses observed in those with severe GHD. Orally administered GH secretagogues (GHS) may be useful treatment in patients with moderate GHD. Distinguishing children with severe vs moderate GHD could identify children who would be better treated with rhGH or GHS.ObjectivesEvaluate baseline insulin-like growth factor-I (IGF-I) and stimulated peak GH response as predictors of 12-month height velocity (HV) in children with GHD.DesignData on children with GHD were analyzed in a legacy data base (GeNeSIS data).Participants514 naïve to rhGH-treatment, prepubertal children with idiopathic isolated GHD for whom stimulated GH, baseline serum IGF-I, and first-year HV during rhGH treatment data are available.Outcome MeasuresChildren with severe or moderate GHD were categorized based on GH and IGF-I data and evaluated based on baseline auxologic and hormone profiles and first-year growth response to rhGH.ResultsCohorts of severe and moderate GHD were 81/514 (15.8%) and 433/514 (84.2%). Cohorts differed significantly with regard to indicators of GHD [eg, baseline height SD score (SDS), height SDS minus target height SDS, HV, HV SDS, and change in height SDS during rhGH treatment]. Multiple regression analysis showed IGF-I and stimulated GH were significant predictors of HV independent of other known variables. Expected first-year HV in moderate GHD was 8.3 cm/y.ConclusionsThe combination of peak GH to GH stimulation testing and baseline IGF-I concentration are predictive enrichment markers for annualized HV responses to rhGH therapy.

Immune dyscrasia in adult growth hormone deficiency: Evaluation of hemolytic complement activity (CH50) and IgG subclasses

CH50 is a screening assay for the activation of the classical complement pathway, the immunoglobulins-mediated one, activated in several inflammatory diseases. Adult growth hormone deficiency (aGHD) is recognized as a chronic inflammatory condition, although poorly evaluated under the profile of inflammatory biomarkers. The aim of this case-control observational study is to analyze CH50 and immunoglobulins G (IgG) subclasses production in aGHD, comparing this condition to healthy controls.38 subjects were included and divided as follows: aGHD (n = 18, 6 females and 12 males); healthy controls (n = 20, 10 females and 10 males). GHD was diagnosed with dynamic test using Growth Hormone-Releasing Hormone (GHRH 50 μg i.v. + arginine 0,5 g/Kg), with a peak GH response < 9 μg/L when BMI was <30 kg/m2 or < 4 μg/L when BMI was >30 kg/m2. The two groups were evaluated for hormonal and metabolic parameters, CH50 and IgG subtypes.IgG1 and IgG2 were significantly higher in controls than in aGHD, while IgG3 and IgG4 showed a trend to higher levels in controls, although not significant. Furthermore, CH50 levels were significantly higher in aGHD.These data substantiate the hypothesis of a dyscrasia in IgG subclasses production in aGHD. As IgG levels decrease, CH50 levels do not.

Evaluation of oxidative stress effects on different macromolecules in adult growth hormone deficiency.

Adult growth hormone deficiency (GHD) is being increasingly recognized to cause premature mortality exacerbated by oxidative stress. A case-control observational study has been performed with the primary objective of evaluating new parameters of oxidative stress and macromolecular damage in adult GHD subjects: serum nitrotryptophan; Total Antioxidant Capacity expressed as LAG time; urinary hexanoil-lysine; urinary dityrosine and urinary 8-OH-deoxyguanosine. GHD was diagnosed using Growth Hormone-Releasing Hormone 50μg iv+arginine 0,5 g/Kg test, with a peak GH response <9 μg /L when BMI was <30 kg/m2 or <4 μg/L when BMI was >30 kg/m2. Patients affected by adult GHD were divided into three groups, total GHD (n = 26), partial GHD (n = 25), and controls (n = 29). Total Antioxidant Capacity, metabolic and hormonal parameters have been determined in separate plasma samples; nitrotryptophan in serum samples; hexanoil-lysine, dityrosine, 8-OH-deoxyguanosine in urine samples. Assessment of hexanoil-lysine exhibited a trend to increase in comparing total GHD vs partial and controls, although not significant. Values of 8-OH-deoxyguanosine did not significantly differ among the three groups. Significant lower levels of dityrosine in partial GHD vs total and controls were found. No significant difference in nitrotriptophan serum levels was found, while significantly greater values of Total Antioxidant Capacity were showed in total and partial GHD vs controls. Thus, our result confirm that oxidative stress is increased both in partial and total adult GHD. The lack of compensation by antioxidants in total GHD may be connected to the complications associated to this rare disorder.

MON-280 Plasmatic Lipocalin-2 Levels in Chronic Low-Grade Inflammation Syndromes: Comparison Between Metabolic Syndrome, Total and Partial Growth Hormone Deficiency

Lipocalin-2 (LCN2) is a secreted glycoprotein, member of the lipocalin superfamily and mediator of several chronic inflammatory processes. Metabolic syndrome (METs) and total growth hormone deficiency (GHD) are known as chronic inflammatory conditions (1,2). While discrepant results have been found in literature on LCN2 plasmatic levels in metabolic syndrome, no studies have been performed in GHD. Partial growth hormone deficiency (pGHD) either is associated with cardiovascular risk (3). Therefore, the primary end-point of this observational cross-sectional study was to compare LCN2 in these clinical settings, trying to assess its possible role as a biomarker in these diseases, whether the secondary end-point was to evaluate the impact of BMI and indexes of insulin sensitivity/resistance on this protein plasmatic levels. 74 patients were included in the study. They were divided as follows: Group A, METs (18 patients, 13 females and 5 males, mean±SEM age 45.1±4.11 ys, BMI 31.22±1.73 kg/m2); Group B, GHD (18 patients, 8 F and 10 M, mean±SEM age 52.44±2.61 ys, BMI 30.49±1.87 kg/m2); Group C, Partial GHD (19 patients, 13 F and 6 M, mean±SEM age 48.63±2.19 ys, BMI 29.11±1.85 kg/m2); Group D, Controls (19 patients, 13 F and 6 M, mean±SEM age 40.26±2.87 ys, BMI 23.25±0.95 kg/m2). The diagnosis of metabolic syndrome was made according to NCEP ATPIII criteria (2005 revision). GHD was diagnosed with dynamic test using Growth Hormone-Releasing Hormone (GHRH 50 μg i.v. + arginine 0,5 g/Kg), with a peak GH response between 9 and 16 μg/L when BMI was < 30 kg/m2 or 4 and 9 μg/L when BMI was > 30 kg/m2. Partial GHD was defined with dynamic test using GHRH, with a peak GH response < 9 μg/L when BMI was < 30 kg/m2 or < 4 μg/L when BMI was > 30 kg/m2.They were evaluated for: serum glucose and insulin, HOMA-index, QUICKI-index, Total/LDL/HDL cholesterol, triglycerides, IGF-1 and LCN2 (measured using ELISA kit DuoSet LCN2/NGAL, R&D systems).LCN2 plasmatic levels were significantly increased in METs, while no difference with control group was found in total and partial GHD. LCN2 levels were not influenced by BMI and HOMA-index. A significant positive correlation between LCN2 and HOMA-index was found in controls, while a trend-like, yet not significant, positive correlation was evidenced in partial GHD. No correlations between these parameters were identified in METs and GHD groups. Our data support the hypothesis that LCN2 plasmatic levels increase in metabolic syndrome. As previously shown (4), different inflammatory patterns characterize the two pathological conditions. However, the correlation between HOMA index and LCN2 suggest a possible modulatory action of LCN2 on insulin resistance in normal subjects and partial GHD ones. (1): Esser et al, Diab Res Clin Prac, 105(2):141–50, 2014.(2): Caicedo et al, Int J Mol Sci, 19(1), 2018.(3): Colao et al, JCEM, 91(6):2191–200, 2006.(4): Mancini et al, Endocrine, 59(1):130–136, 2018.

The Cut-off Limits of Growth Hormone Response to the Insulin Tolerance Test Related to Body Mass Index for the Diagnosis of Adult Growth Hormone Deficiency

Introduction: The diagnosis of growth hormone deficiency (GHD) in adults is based on a reduced GH response to provocative tests, such as the insulin tolerance test (ITT) and the GH-releasing hormone (GHRH) + arginine (ARG) test. However, the cut-off limits of peak GH response in lean subjects are not reliable in obese patients; this is noteworthy since adult GHD is often associated with obesity. To date, there are no ITT cut-offs related to body mass index (BMI). Objective: We aimed to evaluate the diagnostic cut-offs of GH response to the ITT in the function of BMI. Methods: The GH response to the ITT was studied in 106 patients with a history of hypothalamic-pituitary disease, a mean age of 48.2 ± 12.4 years, and a mean BMI of 26.8 ± 6.1 kg/m²). Patients were divided into lean, overweight, and obese groups according to their BMI. The lack of GH response to GHRH + ARG test was considered the gold standard for the diagnosis of GHD. The best GH cut-off in the ITT, defined as the one with the best sensitivity (SE) and specificity (SP), was identified using receiver-operating characteristics curve (ROC) analysis. Results: The best GH cut-off in the ITT was 3.5 μg/L in lean subjects (SE 82.1%; SP 85.7%), 1.3 μg/L in overweight subjects (SE 74.1%; SP 85.7%), and 2.2 μg/L in obese subjects (SE 90.0%; SP 50.0%). The diagnostic accuracy was 97.2, 76.5, and 76.7%, respectively. Conclusions: Our data show that the ITT represents a reliable diagnostic tool for the diagnosis of adult GHD in lean subjects if an appropriate cut-off limit is assumed. Overweight and obesity strongly reduce the GH response to the ITT, GH BMI-related cut-off limits, and the diagnostic reliability of the test.

Disparate Effect of Aromatization on the Central Regulation of GH Secretion by Estrogens in Men and Postmenopausal Women.

Estrogen receptor antagonism by tamoxifen inhibits GH secretion in both men and postmenopausal women, suggesting that estrogen, albeit at low concentration, stimulates GH secretion. However, systemic estrogen replacement in postmenopausal women does not enhance GH secretion. To clarify the role of estrogen in mediating GH secretion, we investigated the effect of estrogen deprivation by using aromatase inhibitors. To determine whether estrogens mediate GH secretion in men and postmenopausal women. The effects of letrozole, an aromatase inhibitor, and tamoxifen were compared in an open-label crossover study. Eight men and 14 women received tamoxifen (20 mg/d) and letrozole (2.5 mg/d) for 2 weeks each. The primary endpoints were GH response to arginine stimulation and gonadal steroid levels. In men, letrozole significantly (P < 0.05) reduced the peak GH response to arginine (mean ± SEM; Δ -49.4% ± 18.1%). Tamoxifen also reduced the mean peak GH, but this did not reach statistical significance. In postmenopausal women, letrozole did not affect peak GH, whereas tamoxifen significantly (P < 0.05) reduced peak GH (Δ -47.3% ± 10%). In men, letrozole reduced circulating estradiol (from 43.1 ± 2.8 to 12.7 ± 1.3 pmol/L; P < 0.001), whereas in women estradiol was undetectable (<11 pmol/L) at baseline and throughout letrozole therapy. Because estrogen deprivation reduced circulating GH, we conclude that estrogens regulate GH secretion in men. In postmenopausal women, the neutral effect of aromatase inhibition is likely explained by pre-existing estrogen deficiency. The inhibition of GH secretion by tamoxifen in menopause suggests a non-estrogen receptor-mediated mechanism of action. In contrast to men, estrogen is unlikely to mediate GH secretion in postmenopausal women.

Relevance of Pituitary Gland Magnetic Resonance Imaging Results with Clinical and Laboratory Findings in Growth Hormone Deficiency.

BackgroundThe present study investigated the relationship between detection of organic pathologies with magnetic resonance imaging of the pituitary gland, clinical and laboratory findings, and treatment response.Material/MethodsThe study included a total of 183 patients who had isolated growth hormone deficiency, received at least 1 year of treatment, returned regularly for follow-ups, and whose pituitary magnetic resonance images were available. The patients were divided into 2 groups: those with and without pathological evidence with magnetic resonance imaging. Clinical and laboratory features and treatment responses were compared between patients with and without pathological evidence with magnetic resonance imaging.ResultsOf the 183 patients, 105 were females and 78 were males, and 114 patients (62.2%) were prepubertal and 69 patients (37.8%) were pubertal. Their mean age was 10.01±3.25 years (1–17.6 years). Pituitary images of 153 (83.6%) patients were normal. Of the patients with detected pathologies (16.4%), 19 (10,4%) had pituitary hypoplasia, 5 (2.7%) had partial empty sella, 3 (1.7%) had ectopic neurohypophysis and 3 (1.7%) had empty sella, pineal, and arachnoid cyst. A statistically significant increase was observed in the height increase rate after treatment compared to before treatment in both groups (p<0.001). However, the group with pathology had a statistically significant (p=0. 007) post-treatment increase height rate. Although in the group with pathology there was a lower L-DOPA and clonidine peak GH response, there was not any statistically significant difference between the 2 groups (p=0.051, p=0.113). Pituitary gland length was also shorter in the group with pathology compared to the group without pathology (P<0.001).ConclusionsMagnetic resonance imaging is a useful tool in assessing GH deficiency pathogenesis and in predicting treatment response.

Reduced peak stimulated growth hormone is associated with hyperuricemia in obese children and adolescents

The purpose of the study is to investigate whether reduced peak GH response to arginine-levodopa test is associated with hyperuricemia in obese children and adolescents. The study population consisted of a total sample of 78 obese and 30 normal-weight children and adolescents without known hypopituitarism. All participants underwent clinical examination and GH stimulation testing. IGF-1, lipid profile and other metabolic markers were assessed. The obese subjects were then divided into two groups according to the serum levels of uric acid. Results show that obese subjects had significantly lower peak GH, lower IGF-1 and similar height SDS than those in the control group. Children with hyperuricemia had significantly lower peak stimulated GH compared with non-hyperuricemia obese subjects. Results from logistic regression model showed that peak GH were negatively associated with hyperuricemia after controlling for age, gender, tanner stage, BMI SDS, IGF-1, blood pressure, HOMA-IR, lipids status. These data indicate that lower peak GH is positively associated with hyperuricemia in obese children and adolescents without known hypothalamic/pituitary disease after controlling BMI and insulin resistance, as well as other cardiometabolic risk factors.

Gender has to be taken into account in diagnosing adult growth hormone deficiency by the GHRH plus arginine test

ObjectiveData on the effect of gender on the interpretation of the GHRH plus arginine stimulation test (GHRH+ARG test) is controversial. We validated the GHRH+ARG stimulation test in control subjects and patients with organic or idiopathic pituitary disease and a suspicion of adult growth hormone deficiency (AGHD) using the Immulite 2000 XPi GH assay. DesignWe studied 126 apparently healthy adults (median age 38.8years) and 34 patients with a suspicion of AGHD (median age 42.2years). Identification of AGHD with the GHRH+ARG test was investigated with commonly accepted BMI-related consensus cut-off limits for peak GH concentrations. Serum samples collected during the GHRH+ARG test were analysed for GH in 2014–2015. Serum IGF-1 concentrations were studied as a reference. ResultsIn 14 of 65 (22%) control males the GH peak value was below the BMI-related cut-off limits for GH sufficiency indicating a false diagnosis of AGHD. All control females had a normal GHRH+ARG response. Median peak GH response was significantly (p<0.001) higher in female (39.3μg/L) than in male controls (21μg/L). According to consensus cut-offs all but one young female patient had a deficient response compatible with a diagnosis of AGHD. ConclusionsThe GH response to stimulation by GHRH+ARG is gender-dependent, being lower in healthy males than in females. Gender should be considered when defining cut-off limits for peak GH concentrations in the GHRH+ARG test. The presently used BMI-related cut-off levels will lead to a significant misclassification of males as GH deficient.

Cut-off limits of the peak GH response to stimulation tests for the diagnosis of GH deficiency in children and adolescents: study in patients with organic GHD.

The diagnosis of GH deficiency (GHD) in children and adolescents is established when GH concentrations fail to reach an arbitrary cut-off level after at least two provocative tests. The objective of the study was to define the optimal GH cut-offs to provocative tests in children and adolescents. Retrospective study in 372 subjects who underwent evaluation of GH secretion. GH and IGF-I were measured by chemiluminescence assay in all samples. Receiver operating characteristic (ROC) analysis was used to evaluate the optimal GH cut-offs and the diagnostic accuracy of provocative tests. Seventy four patients with organic GHD (GH peak <10μg/L after two provocative tests) and 298 control subjects (GH response >10μg/L to at least one test) were included in the study. The provocative tests used were arginine, insulin tolerance test (ITT) and clonidine. Diagnostic criteria based on cut-offs identified by ROC analysis (best pair of values for sensitivity and specificity) were evaluated for each test individually and for each test combined with IGF-I SDS. The optimal GH cut-off for arginine resulted 6.5μg/L, 5.1μg/L for ITT and 6.8μg/L for clonidine. IGF-I SDS has low accuracy in diagnosing GHD (AUC=0.85). The combination of the results of provocative tests with IGF-I concentrations increased the specificity. The results of the ROC analysis showed that the cut-off limits which discriminate between normal and GHD are lower than those commonly employed. IGF-I is characterized by low diagnostic accuracy.

Can a glucagon stimulation test characterized by lower GH cut-off value be used for the diagnosis of growth hormone deficiency in adults?

The aim of this study was to assess diagnostic values of insulin tolerance test (ITT), glucagon stimulation test (GST), and insulin like growth factor-I (IGF-I) level, to find optimal GH cut-off values for GST, and to evaluate efficiencies of patient age, gender, body-mass index (BMI), and additional pituitary hormone deficiencies (PHDs) in the diagnosis of growth hormone deficiency (GHD). This retrospective study involved 216 patients with a pituitary disease and 26 healthy controls. Age, gender, BMI, medical histories, and hormonal data including baseline and stimulated hormone values were evaluated. Three cut-off values for peak GH responses to stimulation tests were evaluated: (a) 3.00µg/L on ITT, (b) 3.00µg/L on GST, and (c) 1.07µg/L on GST. According to the ITT, GST with 3.00µg/L cut-off, and GST with 1.07µg/L cut-off, GHD was present in 86.1, 74.5, and 54.2% patients, respectively. Patient age, BMI, and number of PHDs, but not gender, were found to be correlated with IGF-I and peak GH concentrations. All patients with an IGF-I concentration ≤95ng/ml or ≥3 PHD had GHD. None of the patients with adequate GH response to the GST with 1.07µg/L cut-off, but blunted responses to ITT and GST with 3.00µg/L cut-off, had ≥3 PHDs. 12 out of 26 (46.2%) healthy subjects failed the GST with 3.00µg/L cut-off, but not with 1.07µg/L cut-off. Patient age, IGF-I, BMI, and number of PHDs are efficient factors associated with the diagnosis of GHD. A 4h GST with a diagnostic GH threshold of 1.07µg/L seems to be a good diagnostic method for GHD.

Early retesting by GHRH+arginine test shows normal GH response in most children with idiopathic GH deficiency.

Most children with idiopathic isolated GH deficiency (IGHD) normalize GH response to stimulation tests when retested at the completion of growth. The objective of this study was to test the effectiveness of early retesting in challenging the diagnosis of idiopathic IGHD and critically review the diagnostic workup leading to this diagnosis in children with short stature. We cross-sectionally retested 38 children with idiopathic IGHD and still on GH treatment. The initial diagnosis of idiopathic IGHD was based on subnormal GH responses to two stimulation tests and normal brain imaging or minor/nonspecific findings at magnetic resonance. The GH response normalization at retesting was considered as the main outcome measure. Clinical features of children who were falsely classified as idiopathic IGHD based on first GH testing were retrospectively analyzed. GH secretion was normal in 36/38 children (95%). Two children showed slightly reduced peak GH responses and normal IGF-I levels. Fourteen children underwent GH retesting before puberty, 24 children during puberty. The diagnostic process should be improved to minimize the rate of false positive at GH testing and, in case of unsatisfactory response to GH treatment, the diagnosis of isolated idiopathic GHD should be challenged with early retesting.

PO-0072 A Boy With Decelerated Linear Growth With Normal Growth Hormone (gh) – Insulin-like Growth Factor–i (igf-i) Axis Had An Exceptional Response To Gh Therapy

<h3></h3> Y M is a boy who presented at the age of 5.5 years with slow growth He had a birth weight = 3.1 kg and length = 49.5 cm. Infantile and early neonatal periods are uneventful. He had normal development and appropriate nutritional history. No family history of endocrinopathy and/ or short stature was reported. His measurements were: weight= 16.9 kg, Height = 104 cm (HtSDS = -1.8), growth velocity (GV = 1 cm/y) and BMI= 16 and mid-parental height (MPHt) SDS = -0.6. He had no dysmorphic features, skeletal anomalies, goitre or pigmentation. The rest of the examination was unrevealing. Investigations showed normal CBC, ESR, and liver and renal and thyroid functions. Sweat chloride test, and tissue trans-glutaminase concentrations were normal. His IGF-I level = 70 (IGF-I SDS = -1) and his bone age = 3 years. The peak GH response to clonidine stimulation test = 10 ng/dl. Brain MRI showed normal pituitary gland. Because of the decelerated growth and marginally low IGF-I a trial of GH therapy was started (0.035 mg/kg/day s.c. HS). A rapid catch-up of growth occured during the first 3 years of treatment that was maintained at a slower pace during the following 5 years. Testicular enlargement started at 11 years and at 12 years his HtSDS = 0.8 and bone age = 12.5 years. His predicted adult height = 181 cm. <h3>Conclusion</h3> Prolonged GH treatment of this boy (normal GH-IGF-I axis) with GH unexpectedly resulted in a HTSDS which surpassed his MPHtSDS by 1.4 SD.