Correlation Between the Responses to Growth Hormone (GH) Treatment During Childhood and Adulthood in a Monocentric Cohort of GH-Deficient Patients

2018 ◽  
Vol 50 (06) ◽  
pp. 462-468
Author(s):  
Sarah Thilmany ◽  
Leila Mchirgui ◽  
Chloé Brunelle ◽  
Véronique Beauloye ◽  
Dominique Maiter ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Velocity ◽  
Significant Positive Correlation ◽  
Growth Parameters ◽  
Hormone Deficiency ◽  
First Year ◽  
Z Score ◽  
Gh Treatment ◽  
Positive Correlation ◽  
Igf I

AbstractOur aim was to analyze a cohort of patients with childhood-onset growth hormone deficiency (GHD) to evaluate if there is some correlation between the response to GH treatment during childhood and adulthood, respectively. This was an observational retrospective monocentric cohort study of 47 patients treated with GH during childhood and adulthood. Changes in growth parameters during childhood were compared with the increase of IGF-I z-score and other indexes of GH response (body composition, lipid profile) after 1 year of treatment in adulthood. The only significant positive correlation was observed between final growth velocity during the last year of childhood GH treatment and increase in IGF-I z-score in GH-treated adults (r=0.592, p=< 0.01). No correlation was observed between growth-promoting effects of GH as child and metabolic changes induced by GH as adult. We also observed a negative correlation between weight at the end of childhood GH treatment and the IGF-I response during first year of treatment in adults (r=− 0.335, p <0.05). No significant positive correlation could be observed between the main parameters that evaluate response to GH treatment in children and adults. However, the final growth velocity, which may be considered as one of the main criteria of end of GH treatment in children, was identified as parameter that could predict future response to GH treatment in adulthood.

Impact of Overweight on Effectiveness of Treatment with Human Growth Hormone in Growth Hormone Deficient Children: Analysis of German KIGS Data

2011 ◽  
Vol 119 (09) ◽  
pp. 544-548 ◽  
Author(s):  
T. Reinehr ◽  
S. Bechtold-Dalla Pozza ◽  
M. Bettendorf ◽  
H.-G. Doerr ◽  
B. Gohlke ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Velocity ◽  
Normal Weight ◽  
First Year ◽  
Overweight Children ◽  
Gh Treatment ◽  
Prepubertal Children ◽  
Significant Difference ◽  
Igf I ◽  
Group A

AbstractWe hypothesized that overweight children with growth hormone deficiency (GHD) demonstrate a lower response to growth hormone (GH) as a result of a misclassification since obesity is associated with lower GH peaks in stimulation tests.Anthropometric data, response, and responsiveness to GH in the first year of treatment were compared in 1.712 prepubertal children with GHD from the German KIGS database according to BMI (underweight=group A, normal weight=group B, overweight=group C) (median age: group A, B, C: 7.3, 7.28, and 8.4 years).Maximum GH levels to tests (median: group A, B, C: 5.8, 5.8, and 4.0 µg/ml) were significantly lower in group C. IGF-I SDS levels were not different between the groups. Growth velocity in the first year of GH treatment was significantly lower in the underweight cohort (median: group A, B, C: 8.2, 8.8, and 9.0 cm/yr), while the gain in height was not different between groups. The difference between observed and predicted growth velocity expressed as Studentized residuals was not significantly different between groups. Separating the 164 overweight children into obese children (BMI>97th centile; n=71) and moderate overweight children (BMI>90th to 97th centile, n=93) demonstrated no significant difference in any parameter.Overweight prepubertal children with idiopathic GHD demonstrated similar levels of responsiveness to GH treatment compared to normal weight children. Furthermore, the IGF-I levels were low in overweight children. Therefore, a misclassification of GHD in overweight prepubertal children within the KIGS database seems unlikely. The first year growth prediction models can be applied to overweight and obese GHD children.

scholarly journals Is a Two-Year Growth Response to Growth Hormone Treatment a Better Predictor of Poor Adult Height Outcome Than a First-Year Growth Response in Prepubertal Children With Growth Hormone Deficiency?

2021 ◽  
Vol 12 ◽  
Author(s):  
Saartje Straetemans ◽  
Raoul Rooman ◽  
Jean De Schepper
Keyword(s):  
Growth Hormone ◽  
Growth Response ◽  
Adult Height ◽  
Poor Response ◽  
Hormone Treatment ◽  
Hormone Deficiency ◽  
First Year ◽  
Gh Treatment ◽  
Height Gain ◽  
Design And Methods

ObjectiveThe first year response to growth hormone (GH) treatment is related to the total height gain in GH treated children, but an individual poor first year response is a weak predictor of a poor total GH effect in GH deficient (GHD) children. We investigated whether an underwhelming growth response after 2 years might be a better predictor of poor adult height (AH) outcome after GH treatment in GHD children.Design and methodsHeight data of GHD children treated with GH for at least 4 consecutive years of which at least two prepubertal and who attained (near) (n)AH were retrieved from the Belgian Register for GH treated children (n = 110, 63% boys). In ROC analyses, the change in height (ΔHt) SDS after the first and second GH treatment years were tested as predictors of poor AH outcome defined as: (1) nAH SDS &lt;−2.0, or (2) nAH SDS minus mid-parental height SDS &lt;−1.3, or (3) total ΔHt SDS &lt;1.0. The cut-offs for ΔHt SDS and its sensitivity at a 95% specificity level to detect poor AH outcome were determined.ResultsEleven percent of the cohort had a total ΔHt SDS &lt;1.0. ROC curve testing of first and second years ΔHt SDS as a predictor for total ΔHt SDS &lt;1.0 had an AUC &gt;70%. First-year ΔHt SDS &lt;0.41 correctly identified 42% of the patients with poor AH outcome at a 95% specificity level, resulting in respectively 5/12 (4.6%) correctly identified poor final responders and 5/98 (4.5%) misclassified good final responders (ratio 1.0). ΔHt SDS after 2 prepubertal years had a cut-off level of 0.65 and a sensitivity of 50% at a 95% specificity level, resulting in respectively 6/12 (5.5%) correctly identified poor final responders and 5/98 (4.5%) misclassified good final responders (ratio 1.2).ConclusionIn GHD children the growth response after 2 prepubertal years of GH treatment did not meaningfully improve the prediction of poor AH outcome after GH treatment compared to first-year growth response parameters. Therefore, the decision to re-evaluate the diagnosis or adapt the GH dose in case of poor response after 1 year should not be postponed for another year.

scholarly journals Once-Weekly Somapacitan vs Daily GH in Children With GH Deficiency: Results From a Randomized Phase 2 Trial

2020 ◽  
Vol 105 (4) ◽  
pp. e1847-e1861 ◽  
Author(s):  
Lars Sävendahl ◽  
Tadej Battelino ◽  
Meryl Brod ◽  
Michael Højby Rasmussen ◽  
Reiko Horikawa ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Hormone Deficiency ◽  
Height Velocity ◽  
Phase 2 ◽  
Gh Treatment ◽  
Double Blind ◽  
Daily Growth ◽  
Phase 2 Trial ◽  
Igf I ◽  
Treatment Naïve

Abstract Context Daily growth hormone (GH) injections can be burdensome for patients and carers. Somapacitan is a long-acting, reversible albumin-binding GH derivative in development for once-weekly administration in patients with growth hormone deficiency (GHD). Objective The objective of this study is to evaluate the efficacy, safety, and tolerability of once-weekly somapacitan vs once-daily GH. Design REAL 3 is a multicenter, randomized, controlled, double-blind (somapacitan doses), phase 2 study with a 26-week main and 26-week extension phase (NCT02616562). Setting This study took place at 29 sites in 11 countries. Patients Fifty-nine GH treatment-naive prepubertal children with GHD were randomly assigned; 58 completed the trial. Interventions Interventions comprised 3 somapacitan doses (0.04 [n = 16], 0.08 [n = 15], or 0.16 mg/kg/wk [n = 14]) and daily GH (0.034 mg/kg/d [n = 14]), administered subcutaneously. Main Outcome Measures The primary end point was height velocity (HV) at week 26. Secondary efficacy end points included HV SD score (SDS) and insulin-like growth factor-I (IGF-I) SDS. Results At week 26, mean (SD) annualized HV for the somapacitan groups was 8.0 (2.0), 10.9 (1.9), and 12.9 (3.5) cm/year, respectively, vs 11.4 (3.3) cm/year for daily GH; estimated treatment difference (somapacitan 0.16 mg/kg/week—daily GH): 1.7 [95% CI –0.2 to 3.6] cm/year. HV was sustained at week 52, and significantly greater with somapacitan 0.16 mg/kg/week vs daily GH. Mean (SD) change from baseline in HV SDS at week 52 was 4.72 (2.79), 6.14 (3.36), and 8.60 (3.15) for the somapacitan groups, respectively, vs 7.41 (4.08) for daily GH. Model-derived mean (SD) IGF-I SDS for the somapacitan groups was −1.62 (0.86), −1.09 (0.78), and 0.31 (1.06), respectively, vs −0.40 (1.50) observed for daily GH. Safety and tolerability were consistent with the profile of daily GH. Conclusions In children with GHD, once-weekly somapacitan 0.16 mg/kg/week provided the closest efficacy match with similar safety and tolerability to daily GH after 26 and 52 weeks of treatment. A short visual summary of our work is available (1).

scholarly journals Growth hormone secretion in response to glucagon stimulation test in healthy middle-aged men

2009 ◽  
Vol 53 (7) ◽  
pp. 853-858 ◽  
Author(s):  
Eduardo Micmacher ◽  
Roberto P. Assumpção ◽  
Renato G. Redorat ◽  
Luciana D. Spina ◽  
Ivan C. Cruz ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Tolerance Test ◽  
Stimulation Test ◽  
Hormone Deficiency ◽  
Glucagon Stimulation Test ◽  
Healthy Men ◽  
Positive Correlation ◽  
Igf I

OBJECTIVE: To investigate the growth hormone (GH) response to glucagon stimulation test (GST) in a population of healthy men over 50 years old in comparison to insulin tolerance test (ITT), analysis of the spontaneous 24-hour GH profile and insulin-like growth factor 1 (IGF-I). METHODS: 27 healthy men aged between 51 and 65 years were tested. RESULTS: Using non-parametric correlation analysis, a positive correlation between GH peak after GST and mean IGF-I (r = 0.528; p = 0.005) was found, as well with GH peak in 24-hour profile (r = 0.494; p = 0.009). No correlation was found comparing GH peak after ITT with the same parameters. Ten subjects presented GH peak of less than 3.0 μg/L after GST, none confirmed in ITT. CONCLUSIONS: GH peak response to GST was lower than ITT, but it showed a positive correlation with mean IGF-I and also with GH peak in 24-hour profile. However, GST should not be used to differentiate organic growth hormone deficiency (GDH) from the expected decline on GH secretion due to aging.

scholarly journals Impact of the underlying etiology of growth hormone deficiency on serum IGF-I SDS levels during GH treatment in children

2017 ◽  
Vol 177 (3) ◽  
pp. 267-276 ◽  
Author(s):  
Juliane Léger ◽  
Damir Mohamed ◽  
Sophie Dos Santos ◽  
Myriam Ben Azoun ◽  
Delphine Zénaty ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Gh Deficiency ◽  
Care Center ◽  
Treatment Compliance ◽  
Hormone Deficiency ◽  
Pediatric Care ◽  
Pituitary Hormone ◽  
Gh Treatment ◽  
Pubertal Stage ◽  
Igf I

ContextRegular monitoring of serum IGF-I levels during growth hormone (GH) therapy has been recommended, for assessing treatment compliance and safety.ObjectiveTo investigate serum IGF-I SDS levels during GH treatment in children with GH deficiency, and to identify potential determinants of these levels.Design, patients and methodsThis observational cohort study included all patients (n = 308) with childhood-onset non-acquired or acquired GH deficiency (GHD) included in the database of a single academic pediatric care center over a period of 10 years for whom at least one serum IGF-I SDS determination during GH treatment was available. These determinations had to have been carried out centrally, with the same immunoradiometric assay. Serum IGF-I SDS levels were determined as a function of sex, age and pubertal stage, according to our published normative data.ResultsOver a median of 4.0 (2–5.8) years of GH treatment per patient, 995 serum IGF-I SDS determinations were recorded. In addition to BMI SDS, height SDS and GH dose (P < 0.01), etiological group (P < 0.01) had a significant effect on serum IGF-I SDS levels, with patients suffering from acquired GHD having higher serum IGF-I SDS levels than those with non-acquired GHD, whereas sex, age, pubertal stage, treatment duration, hormonal status (isolated GHD (IGHD) vs multiple pituitary hormone deficiency (MPHD)) and initial severity of GHD, had no effect.ConclusionsThese original findings have important clinical implications for long-term management and highlight the need for careful and appropriate monitoring of serum IGF-I SDS and GH dose, particularly in patients with acquired GHD, to prevent the unnecessary impact of potential comorbid conditions.

Clinical utility of insulin-like growth factor binding protein-3 in the evaluation and treatment of short children with suspected growth hormone deficiency

1994 ◽  
Vol 131 (1) ◽  
pp. 27-32 ◽  
Author(s):  
Yukihiro Hasegawa ◽  
Tomonobu Hasegawa ◽  
Taiji Aso ◽  
Shinobu Kotoh ◽  
Osamu Nose ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Hormone Deficiency ◽  
Insulin Like Growth Factor ◽  
Normal Children ◽  
Gh Treatment ◽  
Factor Binding ◽  
Short Children ◽  
Igf I ◽  
Igfbp 3

Hasegawa Y, Hasegawa T, Aso T, Kotoh S, Nose 0, Ohyama Y, Araki K, Tanaka T, Saisyo S, Yokoya S, Nishi Y, Miyamoto S, Sasaki N, Kurimoto F, Stene M, Tsuchiya Y, Clinical utility of insulin-like growth factor binding protein-3 in the evaluation and treatment of short children with suspected growth hormone deficiency. Eur J Endocrinol 1994;131:27–32. ISSN 0804–4643 We have shown previously that serum insulin-like growth factor binding protein-3 (IGFBP-3) levels have good predictive value for complete, but not partial, growth hormone deficiency (GHD). In this study, we compare IGFBP-3 levels in short children previously divided into groups on the basis of their post-stimulation GH levels. Complete GHD (N = 59) included those children with peak poststimulation GH < 5 μg/l. The partial GHD group (N = 49) had post-stimulation GH peaks of > 5 μg/l but < 10 μg/l. The normal children with short stature (N = 103) had post-stimulation GH peaks > 10 μg/l. Partial GHD and normal children with short stature also were divided into either low IGF-I or normal IGF-I subgroups. The clinical sensitivity of IGFBP-3 for complete GHD was 92%, whereas its sensitivity for partial GHD was 39%. For partial GHD, among those with low IGF-I (N = 19) 68% were also low for IGFBP-3, while 80% of those with normal IGF-I (N = 30) were also normal for IGFBP-3. The clinical specificity of IGFBP-3 for normal children with short stature was 69%. For these groups, among those with low IGF-I (N = 22) 73% also were low for IGFBP-3, while 80% of those with normal IGF-I (N = 81) also were normal for IGFBP-3. In addition, we tested whether IGFBP-3 can predict the response to GH treatment in prepubertal children by comparing pretreatment IGFBP-3 with the height gain achieved by 1 year of GH treatment. The incremental growth velocity during treatment correlated significantly with the pretreatment IGFBP-3 sd score (N = 46 r = –0.80, p < 0.005). The baseline IGFBP-3 sd score for all subjects correlated (N = 171, r = 0.51 p < 0.0001) with height. These data suggest that IGFBP-3 may reflect GH secretion status in most children being evaluated for GHD and that a low pretreatment IGFBP-3 sd score predicts improved growth during the first year of GH treatment. Yukihiro Hasegawa, Division of Endocrinology and Metabolism, Tokyo Metropolitan Kiyose Children's Hospital, 1-3-1 Umezono, Kiyose, Tokyo 204, Japan

scholarly journals Once-Weekly Somapacitan Versus Daily Growth Hormone in Growth Hormone Deficiency: 2-Year Efficacy Results From REAL 3, a Randomized Phase 2 Trial

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A680-A680
Author(s):  
Lars S Sävendahl ◽  
Tadej Battelino ◽  
Michael Højby Rasmussen ◽  
Reiko Horikawa ◽  
Paul Saenger
Keyword(s):  
Growth Hormone ◽  
Standard Deviation ◽  
Height Velocity ◽  
First Year ◽  
Phase 2 ◽  
Efficacy And Safety ◽  
Gh Treatment ◽  
Treatment Groups ◽  
Igf I ◽  
Second Year

Abstract Current treatment for growth hormone (GH) deficiency (GHD) requires daily injections, which can be burdensome for the patients/caregivers. Once-weekly somapacitan is a long-acting GH derivative currently in phase 3 for use in children with GHD and phase 2 for short children born small for gestational age. A phase 2, multinational, randomized, open-label, controlled trial (NCT02616562) investigated the efficacy and safety of somapacitan in children compared with daily GH (Norditropin®). GH-treatment-naïve prepubertal children with GHD received 0.04 (n=16), 0.08 (n=15) or 0.16 mg/kg/week (n=14) subcutaneous (s.c.) somapacitan, or s.c. daily GH 0.034 mg/kg/day (0.24 mg/kg/week; n=14) for 52 weeks, followed by a 104-week safety extension. In the extension phase, all patients on somapacitan received 0.16 mg/kg/week; daily GH dose remained unaltered. The 52-week efficacy and safety results have been reported previously. We report here the efficacy results after 104 weeks of GH treatment. At week 104, mean (standard deviation [SD]) height velocity (HV) in the first year of the safety extension was: 10.6 (1.4), 10.0 (1.6) and 9.2 (1.7) cm/year for 0.04/0.16 mg/kg/week (n=13), 0.08/0.16 mg/kg/week (n=15) and 0.16/0.16 mg/kg/week (n=14) somapacitan, respectively, versus 9.0 (2.3) cm/year for daily GH (n=11). Mean (SD) change from baseline in HV standard deviation score (SDS) was 8.04 (2.52), 6.21 (2.90) and 6.40 (3.04) for somapacitan, respectively, versus 6.58 (3.15) for daily GH. Compared with week 52, mean HV and HV SDS at week 104 were increased in children in the somapacitan 0.04/0.16 mg/kg/week and 0.08/0.16 mg/kg/week treatment groups. Height SDS values improved during the second year of treatment with somapacitan and daily GH, with the greatest change from baseline in the somapacitan 0.16/0.16 mg/kg/week treatment group. The mean (SD) change in height SDS from baseline to week 104 was 1.73 (0.76), 1.87 (0.81) and 2.18 (1.18) for somapacitan, respectively, versus 1.72 (0.65) for daily GH. The observed mean (SD) change in insulin-like growth factor-I (IGF-I) SDS from baseline was similar between the somapacitan 0.08/0.16 and 0.16/0.16 mg/kg/week treatment groups (3.15 [1.17] and 3.21 [1.12], respectively), and slightly higher compared with IGF-I SDS in the 0.04/0.16 mg/kg/week group (2.99 [1.05]) and the daily GH group (3.06 [1.26]). Mean IGF-I SDS values remained below the upper limit (+2) of the normal range for all treatment groups throughout the 104-week trial duration. Somapacitan was well tolerated at all doses investigated, with no new safety or local tolerability issues identified during the 104 weeks of treatment. In conclusion, at week 104, height-based outcomes were similar between somapacitan 0.16/0.16 mg/kg/week and daily GH, with comparable mean change in IGF-I SDS. Furthermore, the key improvements observed in the first year were maintained in the second year of the study.

scholarly journals Mini Review/Commentary: Growth Hormone Treatment in Children with Type 1 Diabetes

2019 ◽  
Vol 20 (3) ◽  
pp. 772
Author(s):  
Walter Bonfig ◽  
Reinhard Holl
Keyword(s):  
Growth Hormone ◽  
Type 1 Diabetes ◽  
Hormone Treatment ◽  
Hormone Deficiency ◽  
Gh Treatment ◽  
Complex Interactions ◽  
Igf I ◽  
Gh Excess ◽  
Gh Resistance

In the state of insulin deficiency, the growth hormone—insulin-like growth factor-I (GH–IGF-I) axis is altered due to hepatic GH resistance, which leads to GH hypersecretion and low circulating IGF-I concentration. On the other hand, both growth hormone deficiency (GHD) and GH excess have significant influence on carbohydrate metabolism. These complex interactions are challenging in diagnosing GHD in subjects with type 1 diabetes mellitus (T1DM) and in treating subjects with T1DM with GH. So far, there is only limited clinical experience in GH treatment in patients with T1DM, but recently first reports on metabolic safety and efficacy of GH treatment in subjects with T1DM have been published.

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

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Edoardo Vergani ◽  
Diego Currò ◽  
Simone Comi ◽  
Claudia D’Abate ◽  
Maria Vittoria Notari ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Significant Positive Correlation ◽  
Dynamic Test ◽  
Hormone Deficiency ◽  
Homa Index ◽  
Lipocalin 2 ◽  
Positive Correlation ◽  
End Point

Abstract 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 &lt; 30 kg/m2 or 4 and 9 μg/L when BMI was &gt; 30 kg/m2. Partial GHD was defined with dynamic test using GHRH, with a peak GH response &lt; 9 μg/L when BMI was &lt; 30 kg/m2 or &lt; 4 μg/L when BMI was &gt; 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.

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