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LEAP-2/ghrelin interplay in adult growth hormone deficiency: Cause or consequence? A pilot study.
Vergani, E, Bruno, C, Gavotti, C, Aversa, LS, Martire, M, Mancini, A, Currò, D
IUBMB life. 2021;(7):978-984
Abstract
Ghrelin and its endogenous antagonist liver-expressed antimicrobial peptide-2 (LEAP-2) are involved in GH secretion and glucose/lipids metabolism. LEAP-2 expression in conditions of metabolic impairment may be upregulated, usually pairing with a concomitant reduction in ghrelin secretion. Adult growth hormone deficiency (aGHD) is characterized by insulin resistance, weight gain, and increased fat mass. Therefore, the primary endpoint of this cross-sectional observational pilot study was to compare circulating LEAP-2 and ghrelin levels in aGHD and healthy controls. Thirty patients were included in the study. Group A included adult GHD: 15 patients, 8 females, and 7 males. Median and interquartile range age of the group was 53 (41-57) years, while BMI was 27.1 (25-35) kg/m2 . Group B was formed by 15 healthy controls (10 females and 5 males). Median and interquartile range age was 47 (36-57) years, while BMI 22.9 (20.8-33.1) kg/m2 . They were evaluated for serum glucose and insulin, HOMA-index, QUICKI-index, total/LDL/HDL cholesterol, triglycerides, IGF-1, ghrelin, and LEAP-2. Ghrelin levels in the aGHD group were significantly lower than in healthy controls. In contrast, LEAP-2 showed a trend toward higher levels, although the differences were not significant. However, the LEAP-2/Ghrelin ratio was significantly higher in aGHD. No significant correlations between ghrelin and LEAP-2 with BMI and HOMA index were found in aGHD population. However, a significant inverse correlation (r2 = 0.15, p = .047) between BMI and ghrelin was evidenced when considering the whole population. Taken together, these results may suggest a body adaptation to a metabolic scenario typical of aGHD. The decrease in ghrelin production could prevent further weight gain and fat mass increase, although losing its secretagogue effect.
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Ten years with biosimilar rhGH in clinical practice in Sweden - experience from the prospective PATRO children and adult studies.
Lundberg, E, Kriström, B, Zouater, H, Deleskog, A, Höybye, C
BMC endocrine disorders. 2020;(1):55
Abstract
BACKGROUND In 2007, Omnitrope® was the first biosimilar recombinant human growth hormone (rhGH) to be approved in Sweden for treatment in adults and children. Over 10 years' safety and effectiveness data for biosimilar rhGH can now be presented. METHODS PATRO Children and PATRO Adults are multicenter, longitudinal, observational, post-marketing surveillance studies. Eligible patients include children 0-18 years and adults receiving biosimilar rhGH treatment. Adverse events (AEs) are monitored for safety evaluation. Growth variables in children and metabolic data in adults are recorded for effectiveness evaluation. RESULTS As of January 2019, data from 136 children (48% male) were reported from Swedish centers. Mean age in rhGH treatment-naïve patients at study entry (n = 114) was 7.5 years, with mean 3.6 years treatment duration. No severe AEs of diabetes, impaired glucose tolerance, or malignancy were reported. The most frequently reported AE was nasopharyngitis (n = 16 patients). No clinically relevant anti-hGH or neutralizing antibodies were observed. The mean change from baseline in height standard deviation score (SDS) in naïve prepubertal GH deficiency patients was + 0.79 at 1 year, + 1.27 at 2 years, and + 1.55 at 3 years. Data from 293 adults (44% rhGH-naïve, 51% male) were included. Fatigue was the most frequently reported AE (n = 26 patients). The incidence of new neoplasms or existing neoplasm progression was 23.8 patients per 1000 patient-years. Type 2 diabetes mellitus was reported in four patients. At baseline in rhGH-naïve adults, mean (SD) body mass index (BMI) was 29.1 (5.6) kg/m2 and mean (SD) insulin-like growth factor (IGF)-I SDS was - 3.0 (1.4). Mean daily dose increased from 0.1 mg at baseline to 0.3 mg after 4 years. IGF-I SDS normalized during the first year of treatment. Mean BMI and glucose were unchanged over 4 years, while low-/high-density lipoprotein cholesterol ratio decreased. CONCLUSIONS For the first time, Swedish data from the PATRO Children and Adults studies are presented. The 10-year data suggest that biosimilar rhGH is well tolerated across pediatric and adult indications. Safety and effectiveness were similar to previous reports for other rhGH preparations. These results need to be confirmed in larger cohorts, highlighting the importance of long-term post-marketing studies.
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Human growth hormone level decreased in women aged <60 years but increased in men aged >50 years.
Wang, X, Wang, S, Wu, H, Jiang, M, Xue, H, Zhu, Y, Wang, C, Zha, X, Wen, Y
Medicine. 2020;(2):e18440
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Abstract
To investigate the relationship amongst human growth hormone (HGH), sex, and age groups.A cross-sectional study was conducted on a health check-up population from Wannan area of China from 2014 to 2016. The study involved 6843 individuals aged 23 to 85 years. Logistic regression analysis and smooth curve were applied to determine the relationship amongst age, sex, and HGH.The average level of HGH in the population was 0.37 ± 0.59 ng/mL. There were significant differences in sex, age, body mass index (BMI), triglycerides (TG), total cholesterol (TC), systolic blood pressure (SBP), diastolic blood pressure (DBP), and glucose (GLU) amongst different quartiles of HGH (P < .001). A U-shape relationship was established between HGH and age. After sex stratification, the results showed that the thresholds of age were 60 years in women, and 50 years in men, after adjusting for body mass index, triglycerides, total cholesterol, blood pressure, and blood glucose. Logistic regression showed that HGH level decreased in women aged <60 years (OR = 1.472, P < .001) and increased in men aged >50 years (OR = 0.711, P < .001). So the distributive characteristics of HGH concentration vary with sex and age group.
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Adherence to treatment in children with growth hormone deficiency, small for gestational age and Turner syndrome in Mexico: results of the Easypod™ connect observational study (ECOS).
Blanco-López, A, Antillón-Ferreira, C, Saavedra-Castillo, E, Barrientos-Pérez, M, Rivero-Escalante, H, Flores-Caloca, O, Calzada-León, R, Rosas-Guerra, CC, Koledova, E, Chiquete, E, et al
Journal of endocrinological investigation. 2020;(10):1447-1452
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BACKGROUND Assessing adherence to growth hormone (GH) is challenging. The Easypod™ connect device delivers pre-set doses of recombinant human GH (r-hGH) and stores a digital record of adherence that can be shared with healthcare provider. We assessed adherence to r-hGH delivered with Easypod™ according to the approved pediatric indications for r-hGH: growth hormone deficiency (GHD), born small for gestational age (SGA) who failed to show catch-up growth and Turner syndrome (TS). METHODS ECOS (NCT01555528) was a multicenter (24 countries), 5-year, longitudinal, observational study, which aimed to evaluate country-specific adherence to r-hGH therapy prescribed via the Easypod™ electronic injection device. The primary endpoint was yearly adherence. Secondary endpoints were height velocity, height velocity standard deviation scores (SDS), height, height SDS and IGF-1 concentrations. Clinical and auxological data were obtained from medical records and adherence from Easypod™ logs. RESULTS This study included 147 Easypod™-naïve Mexican children assessed during 3 years (mean age: 9.96 ± 3.41 years, 56.8% boys, mean height SDS at baseline: - 2.17 ± 0.97): 118 with GHD, 24 SGA and 5 with TS. A total of 105 (71.4%) patients were GH naïve. Overall median adherence was > 90% over the first year of treatment and > 80% at 3 years. Adherence was not different by r-hGH indication or between GH-naïve or experienced patients. At 1-year follow-up, mean change in height SDS was 0.57 ± 0.34, whereas mean height velocity SDS was 2.85 ± 2.51. In all, 84.7% patients had normal IGF-1 concentrations at 1-year follow-up. Adherence was associated with change in height SDS (r = 0.239, p = 0.005) and height velocity SDS (r = 0.194, p = 0.027). CONCLUSION Adherence rates with the Easypod™ device are high and maintained over time in GHD, SGA and TS Easypod™-naïve Mexican patients. High adherence is associated with better outcomes. Easypod™ assists physicians in monitoring adherence to r-hGH.
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ACROSTART: A retrospective study of the time to achieve hormonal control with lanreotide Autogel treatment in Spanish patients with acromegaly.
Álvarez-Escolá, C, Venegas-Moreno, EM, García-Arnés, JA, Blanco-Carrera, C, Marazuela-Azpiroz, M, Gálvez-Moreno, MÁ, Menéndez-Torre, E, Aller-Pardo, J, Salinas-Vert, I, Resmini, E, et al
Endocrinologia, diabetes y nutricion. 2019;(5):320-329
Abstract
OBJECTIVES The ACROSTART study was intended to determine the time to achieve normalization of GH and IGF-I levels in responding patients with acromegaly administered different dosage regimens of lanreotide Autogel (Somatuline® Autogel®). METHODS From March 2013 to October 2013, clinical data from 57 patients from 17 Spanish hospitals with active acromegaly treated with lanreotide for ≥4 months who achieved hormonal control (GH levels <2.5ng/ml and/or normalized IGF-I levels in ≥2 measurements) were analyzed. The primary objective was to determine the time from start of lanreotide treatment to hormonal normalization. RESULTS Median patient age was 64 years, 21 patients were male, 39 patients had undergone surgery, and 14 patients had received radiotherapy. Median hormonal values at start of lanreotide treatment were: GH, 2.6ng/ml; IGF-I, 1.6×ULN. The most common starting dose of lanreotide was 120mg (29 patients). The main initial regimens were 60mg/4 weeks (n=13), 90mg/4 weeks (n=6), 120mg/4 weeks (n=13), 120mg/6 weeks (n=6), and 120mg/8 weeks (n=9). An initial treatment regimen with a long interval (≥6 weeks) was administered in 25 patients. Mean duration of lanreotide treatment was 68 months (7-205). Median time to achieve hormonal control was 4.9 months. Injections were managed without healthcare assistance in 13 patients. Median number of visits to endocrinologists until hormonal control was achieved was 3. Fifty-one patients were "satisfied"/"very satisfied" with treatment and 49 patients did not miss any dose. CONCLUSIONS Real-life treatment with lanreotide Autogel resulted in early hormonal control in responding patients, with high treatment adherence and satisfaction despite disparity in starting doses and dosing intervals.
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Somatotropic Axis and Obesity: Is There Any Role for the Mediterranean Diet?
Muscogiuri, G, Barrea, L, Laudisio, D, Di Somma, C, Pugliese, G, Salzano, C, Colao, A, Savastano, S
Nutrients. 2019;(9)
Abstract
Obesity is associated with reduced spontaneous and stimulated growth hormone (GH) secretion and basal insulin-like growth factor I (IGF-1) levels-which in turn is associated with increased prevalence of cardiovascular risk factors. The aim of this study was to investigate: (1) the association of somatotropic axis with cardiometabolic status; (2) the association of somatotropic axis with the Mediterranean diet and nutritional pattern in people with obesity. Cross-sectional observational study was carried out in 200 adult women, aged 36.98 ± 11.10 years with severe obesity (body mass index-BMI of 45.19 ± 6.30 kg/m2). The adherence to the Mediterranean diet and the total calorie intake was assessed. Anthropometric measurements, body composition and biochemical profile were determined along with Growth Hormone (GH)/Insulin like Growth Factor 1 (IGF-1) axis and insulin resistance (homeostatic model assessment for insulin resistance-HoMA-IR). The enrolled subjects were compared after being divided according to GH peak response and according to IGF-1 standard deviation scores (SDS). Derangements of GH peak were detected in 61.5% of studied patients while IGF-1 deficiency was detected in 71% of the population. Both blunted GH peak response and IGF-1 SDS were indicators of derangements of somatotropic axis and were associated with comparable results in terms of cardiometabolic sequelae. Both GH peak and IGF-1 levels were inversely associated with anthropometric and metabolic parameters. The adherence to the Mediterranean diet predicts GH peak response. Fatty liver index (FLI), fat mass (FM) and phase angle (PhA) were predictive factors of GH peak response as well. In conclusion derangements of somatotropic axis is associated with a worse cardiometabolic profile in people with obesity. A high adherence to the Mediterranean diet-and in particular protein intake-was associated with a better GH status.
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Reduced Growth Hormone Secretion is Associated with Nonalcoholic Fatty Liver Disease in Obese Children.
Liang, S, Yu, Z, Song, X, Wang, Y, Li, M, Xue, J
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2018;(3):250-256
Abstract
The purpose of the study was to evaluate the relationship between arginine-levodopa-induced growth hormone (GH) secretion and nonalcoholic fatty liver disease (NAFLD) in obese children. This study includes a total of 84 obese and 43 normal weight children. The obese subjects are divided into two groups based on the presence or absence of NAFLD. Clinical examination, anthropometric and laboratory examinations, and liver ultrasonography are assessed for all participants. The obese group had significantly lower peak stimulated GH (p<0.001) and lower insulin-like growth factor 1 (IGF-1) (p<0.001) compared with the control group. Children with NAFLD had significantly lower peak stimulated GH (p<0.001) and lower IGF-1 (p=0.022) compared with non-NAFLD group. Results from logistic regression model showed that only peak GH after stimulation test was inversely associated with NAFLD (p=0.015), while body mass index (BMI) was positively associated with NAFLD (p=0.03). Among 84 obese children and adolescents, peak stimulated GH was negatively associated with alanine aminotransferase (r=-0.394, p<0.001), BMI (r=-0.571, p<0.001), systolic blood pressure (r=-0.223, p=0.041), diastolic blood pressure (r=-0.272, p=0.012), homeostasis model assessment of insulin resistance (r=-0.369, p=0.001), insulin (r=-0.382, p<0.001), and positively associated with high density lipoprotein cholesterol (r=0.275, p=0.011). Our study confirms a significant inverse relationship between NAFLD and GH response to standard stimulation testing in obese children without known hypothalamic/pituitary disease.
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Clinical assessment of a foam dressing containing growth factor-enhancing hydrated polyurethanes.
Mikosiński, J, Kotala, M, Stücker, M, Twardowska-Saucha, K, Bonnekoh, B, Pańczak, K, Aleksiejew-Kleszczyński, T, Dissemond, J, Eming, SA, Kaspar, D, et al
Journal of wound care. 2018;(9):608-618
Abstract
OBJECTIVE This study assesses a novel dressing concept in venous leg ulcer (VLU) patients. It is based on boosting endogenous growth factor activities synthesised by functional granulation tissue. METHODS Patients received treatment for eight weeks with a hydrated polyurethane-containing foam dressing plus concomitant compression therapy. Wound area reduction (WAR), percentage of wounds achieving a relative WAR of ≥40% and ≥60%, wound pain ratings for the last 24 hours and at dressing changes, EQ-5D Quality of Life questionnaire data, dressing handling and safety parameters were recorded. RESULTS There were 128 patients who received treatment and data for 123 wound treatment courses were documented. Wound area size decreased from 13.3±9.8cm2 to 10.5±12.2cm2 at week eight and median relative WAR was 48.8%. At week eight, a relative WAR ≥40% was reached by 54.5% of the wounds, 41.5% reached a relative WAR of ≥60% and complete healing was observed in 13.5% of wounds. Median wound pain ratings (last 24 hours before dressing change) declined significantly from 30 to 15.5 (100 visual analogue scale [VAS], p=0.0001) and pain at dressing changes from 30 to 12.5 (p≤0.0001). The EQ-5D VAS rating increased from 58.4±19.2mm to 63.1±19.1mm (p=0.0059). CONCLUSION This clinical assessment shows that the concept of boosting endogenous growth factors through hydrated polyurethanes has the potential to accelerate WAR in VLU patients while decreasing pain levels and improving quality of life parameters.
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Ten-year change in quality of life in adults on growth hormone replacement for growth hormone deficiency: an analysis of the hypopituitary control and complications study.
Mo, D, Blum, WF, Rosilio, M, Webb, SM, Qi, R, Strasburger, CJ
The Journal of clinical endocrinology and metabolism. 2014;(12):4581-8
Abstract
CONTEXT Previous studies showed improvement in impaired quality of life (QoL) in adult patients with growth hormone (GH) deficiency (GHD) who were treated with GH; improvement was sustained over a few years after GH therapy. OBJECTIVE To evaluate the QoL over 10 years. DESIGN This was a prospective observational study. SETTING The study was conducted in clinical practice. PATIENTS 1436 adult patients with adult-onset (AO) GHD (mean age [standard deviation (SD)]: 49.0 [12.2] years; 49% female) and 96 with childhood-onset (CO) GHD (31.3 [10.0] years; 60% female) (total N = 1532). INTERVENTION GH therapy. MAIN OUTCOME MEASURES QoL was measured by Questions on Life Satisfaction-Hypopituitarism (QLS-H) in countries where validated questionnaires and normative data for calculation of Z-scores were available. Change in QoL was tested by Student's t test and predicted by mixed-model repeated measures (MMRM) analysis. RESULTS At study entry, patients had diminished QoL Z-scores (mean [SD] AO, -1.55 [1.69]; CO -0.98 [1.32]). The largest QoL improvements were in the first year: mean (SD) increase 0.77 (1.37) for AO (P < .001) and 0.50 (1.37) for CO (P < .001). The initial improvement from study entry remained statistically significant throughout 10 years for AO and in years 1 to 4, 6, and 7 for CO (P < .05). MMRM analysis predicted a greater QoL improvement in those who were not depressed, lived in Europe, had poorer Z-scores at entry, had lower body mass index at entry, and had no impaired vision. CONCLUSION These data suggest that GH replacement provides sustained improvement in QLS-H scores toward normality for up to 10 years.