Macimorelin Acetate for the Diagnosis of Childhood-onset Growth Hormone Deficiency.
Ontology highlight
ABSTRACT:
SUBMITTER: Henry RK
PROVIDER: S-EPMC9835807 | biostudies-literature | 2022 Nov
REPOSITORIES: biostudies-literature
Publications
Macimorelin Acetate for the Diagnosis of Childhood-onset Growth Hormone Deficiency.
TouchREVIEWS in endocrinology 20220908 2
Growth hormone provocation testing forms the cornerstone of the diagnosis of childhood growth hormone deficiency in clinical practice. Despite the widespread use of these tests, various criticisms have been levelled against them, such as the labour-intensive nature of the tests, their potential for serious adverse effects and their questionable reproducibility. Macimorelin acetate, a ghrelin mimetic approved for the diagnosis of adult growth hormone deficiency, could serve an unmet need in the d ...[more]
Similar Datasets
Project description:BackgroundGene expression (GE) data have shown promise as a novel tool to aid in the diagnosis of childhood growth hormone deficiency (GHD) when comparing GHD children to normal children. The aim of this study was to assess the utility of GE data in the diagnosis of GHD in childhood and adolescence using non-GHD short stature children as a control group.MethodsGE data was obtained from patients undergoing growth hormone stimulation testing. Data were taken for the 271 genes whose expression was utilized in our previous study. The synthetic minority oversampling technique was used to balance the dataset and a random forest algorithm applied to predict GHD status.Results24 patients were recruited to the study and eight subsequently diagnosed with GHD. There were no significant differences in gender, age, auxology (height SDS, weight SDS, BMI SDS) or biochemistry (IGF-I SDS, IGFBP-3 SDS) between the GHD and non-GHD subjects. A random forest algorithm gave an AUC of 0.97 (95% CI 0.93 - 1.0) for the diagnosis of GHD.ConclusionThis study demonstrates highly accurate diagnosis of childhood GHD using a combination of GE data and random forest analysis.
| S-EPMC9973753 | biostudies-literature
Project description:ContextIn the absence of panhypopituitarism and low serum IGF-I levels, the diagnosis of adult GH deficiency (AGHD) requires confirmation with a GH stimulation test. Macimorelin is a novel, orally active ghrelin mimetic that stimulates GH secretion.ObjectiveThe objective of the study was to determine the diagnostic efficacy and safety of macimorelin in AGHD.DesignThis was a multicenter open-label study comparing the diagnostic accuracy of oral macimorelin with that of arginine+GHRH in AGHD patients and healthy, matched controls. After 43 AGHD patients and 10 controls were tested, the GHRH analog Geref Diagnostic [GHRH(1-29)NH2] became unavailable in the United States. The study was completed by testing 10 additional AGHD patients and 38 controls with macimorelin alone.Main outcome measurePeak GH area under the receiver operating characteristic curve after macimorelin was measured.ResultsFifty AGHD subjects and 48 controls were evaluated. Peak GH levels in AGHD patients and controls after macimorelin were 2.36 ± 5.69 and 17.71 ± 19.11 ng/mL, respectively (P < .0001). With macimorelin, the receiver operating characteristic analysis yielded an optimal GH cut point of 2.7 ng/mL, with 82% sensitivity, 92% specificity, and 13% misclassification rate. For subjects receiving both tests, macimorelin showed discrimination comparable with arginine+GHRH (area under the receiver operating characteristic curve 0.99 vs 0.94, respectively, P = .29). Obesity (body mass index > 30 kg/m(2)) was present in 58% of subjects, and peak GH levels were inversely associated with body mass index in controls (r = -0.37, P = .01). Using the separate cut points of 6.8 ng/mL for nonobese and 2.7 for obese subjects reduced the misclassification rate to 11%. Only 1 drug-related serious adverse event, an asymptomatic QT interval prolongation on the electrocardiogram, was reported.ConclusionOral macimorelin is safe, convenient, and effective in diagnosing AGHD with accuracy comparable with the arginine+GHRH test.
| S-EPMC4207947 | biostudies-literature
Project description:BackgroundChildhood-onset combined pituitary hormone deficiency (CPHD) has a wide spectrum of etiologies and genetic causes for congenital disease. We aimed to describe the clinical spectrum and genetic etiologies of CPHD in a single tertiary center and estimate the population-level incidence of congenital CPHD.MethodsThe retrospective clinical cohort comprised 124 CPHD patients (48 with congenital CPHD) treated at the Helsinki University Hospital (HUH) Children's Hospital between 1985 and 2018. Clinical data were collected from the patient charts. Whole exome sequencing was performed in 21 patients with congenital CPHD of unknown etiology.FindingsThe majority (61%;76/124) of the patients had acquired CPHD, most frequently due to craniopharyngiomas and gliomas. The estimated incidence of congenital CPHD was 1/16 000 (95%CI, 1/11 000-1/24 000). The clinical presentation of congenital CPHD in infancy included prolonged/severe neonatal hypoglycaemia, prolonged jaundice, and/or micropenis/bilateral cryptorchidism in 23 (66%) patients; despite these clinical cues, only 76% of them were referred to endocrine investigations during the first year of life. The median delay between the first violation of the growth screening rules and the initiation of GH Rx treatment among all congenital CPHD patients was 2·2 years, interquartile range 1·2-3·7 years. Seven patients harbored pathogenic variants in PROP1, SOX3, TBC1D32, OTX2, and SOX2, and one patient carried a likely pathogenic variant in SHH (c.676G>A, p.(Ala226Thr)).InterpretationOur study suggests that congenital CPHD can occur in 1/16 000 children, and that patients frequently exhibit neonatal cues of hypopituitarism and early height growth deflection. These results need to be corroborated in future studies and might inform clinical practice.FundingPäivikki and Sakari Sohlberg Foundation, Biomedicum Helsinki Foundation, and Emil Aaltonen Foundation research grants.
| S-EPMC9304914 | biostudies-literature
Project description:BackgroundDiscontinuing growth hormone (GH) treatment during the transition to adulthood has been associated with adverse health outcomes in patients with childhood-onset growth hormone deficiency (CO-GHD). This study investigated the metabolic changes associated with interrupting GH treatment in adolescents with CO-GHD during the transition period.MethodsThis study included 187 patients with CO-GHD who were confirmed to have adult GHD and were treated at six academic centers in Korea. Data on clinical parameters, including anthropometric measurements, metabolic profiles, and bone mineral density (BMD) at the end of childhood GH treatment, were collected at the time of re-evaluation for GHD and 1 year after treatment resumption.ResultsMost patients (n=182, 97.3%) had organic GHD. The median age at treatment discontinuation and re-evaluation was 15.6 and 18.7 years, respectively. The median duration of treatment interruption was 2.8 years. During treatment discontinuation, body mass index Z-scores and total cholesterol, low-density lipoprotein, and non-high-density lipoprotein (HDL) cholesterol levels increased, whereas fasting glucose levels decreased. One year after GH treatment resumption, fasting glucose levels, HDL cholesterol levels, and femoral neck BMD increased significantly. Longer GH interruption (>2 years, 60.4%) resulted in worse lipid profiles at re-evaluation. The duration of interruption was positively correlated with fasting glucose and non-HDL cholesterol levels after adjusting for covariates.ConclusionGH treatment interruption during the transition period resulted in worse metabolic parameters, and a longer interruption period was correlated with poorer outcomes. GH treatment should be resumed early in patients with CO-GHD during the transition period.
| S-EPMC9081298 | biostudies-literature
Project description:PurposeSurvivors of childhood leukemia are at risk of growth impairment due to intensive chemotherapy and radiation treatments. This study investigated the auxological and biochemical characteristics of childhood leukemia survivors diagnosed with growth hormone deficiency (GHD) and the changes in these parameters after 1 year of growth hormone (GH) treatment.MethodsA total of 24 children diagnosed with GHD after leukemia treatment was analyzed. Clinical and biochemical data were collected retrospectively at leukemia diagnosis, GHD diagnosis, and 1 year after GH treatment. Standard deviation score (SDS) was calculated based on the age- and gender-adjusted population.ResultsOf the 24 children included in this study, 19 received GH treatment. The median age at GHD diagnosis was 12.3 years, and the median delay in bone age was 1.46 years. Height SDS decreased from -0.69 at leukemia diagnosis to -2.58 at GHD diagnosis (P<0.001). The change in height SDS with and without GH for 1 year was 0.35 and -0.21, respectively (P=0.044). In regression analyses, higher height SDS at GHD diagnosis and a smaller decrease of the height SDS between leukemia and GHD diagnoses were positively correlated with height SDS after GH treatment.ConclusionGH treatment could be beneficial and safe for improving height in childhood leukemia survivors with GHD. Height SDS at GHD diagnosis and reduction of height SDS between leukemia and GHD diagnosis could be potential factors in predicting the therapeutic effects. Close auxological monitoring is recommended for any childhood leukemia survivors who experience posttreatment height decline.
| S-EPMC10329940 | biostudies-literature
Project description:The effect of gene expression data on diagnosis remains limited. Here, we show how diagnosis and classification of growth hormone deficiency (GHD) can be achieved from a single blood sample using a combination of transcriptomics and random forest analysis. Prepubertal treatment-naive children with GHD (n = 98) were enrolled from the PREDICT study, and controls (n = 26) were acquired from online data sets. Whole blood gene expression was correlated with peak growth hormone (GH) using rank regression and a random forest algorithm tested for prediction of the presence of GHD and in classification of GHD as severe (peak GH <4 μg/l) and nonsevere (peak ≥4 μg/l). Performance was assessed using area under the receiver operating characteristic curve (AUC-ROC). Rank regression identified 347 probe sets in which gene expression correlated with peak GH concentrations (r = ± 0.28, P < 0.01). These 347 probe sets yielded an AUC-ROC of 0.95 for prediction of GHD status versus controls and an AUC-ROC of 0.93 for prediction of GHD severity. This study demonstrates highly accurate diagnosis and disease classification for GHD using a combination of transcriptomics and random forest analysis. NCT00256126 and NCT00699855. Merck and the National Institute for Health Research (CL-2012-06-005).
| S-EPMC5928867 | biostudies-literature
Project description:BackgroundThe impact of growth hormone deficiency (GHD) on neurocognitive function is poorly understood in survivors of childhood acute lymphoblastic leukemia (ALL). This study examined the contribution of GHD to functional outcomes while adjusting for cranial radiation therapy (CRT).MethodsAdult survivors of ALL (N = 571; 49% female; mean age, 37.4 years; age range, 19.4-62.2 years) completed neurocognitive tests and self-reported neurocognitive symptoms, emotional distress, and quality of life. GHD was defined as a previous diagnosis of GHD or a plasma insulin-like growth factor1 level less than -2.0 standard deviations for sex and age at the time of neurocognitive testing. Hypothyroidism, hypogonadism, sex, age at diagnosis, CRT dose, and intrathecal and high-dose intravenous methotrexate were included as covariates in multivariable linear regression models.ResultsOf the 571 survivors, 298 (52%) had GHD, and those with GHD received higher doses of CRT (P = .002). Survivors who had GHD, irrespective of prior growth hormone treatment, demonstrated poorer vocabulary (z-score, -0.84 vs -0.61; P = .02), processing speed (z-score, -0.49 vs -0.30; P = .04), cognitive flexibility (z-score, -1.37 vs -0.94; P = .01), and verbal fluency (z-score, -0.74 vs -0.44; P = .001), and they self-reported more neurocognitive problems and poorer quality of life compared with survivors who did not have GHD. Multivariable and mediation models revealed that GHD was associated with small effects on quality of life (general health, P = .01; vitality, P = .01; mental health, P = .01); and CRT dose accounted for the lower neurocognitive outcomes.ConclusionsAdult survivors of childhood ALL who receive CRT are at risk for GHD, although poor neurocognitive outcomes are determined by CRT dose and not by the presence of GHD.
| S-EPMC6486430 | biostudies-literature
Project description:Understanding metabolite profiles may aid in providing a reference for individualized treatment using PEG-rhGH. Therefore, this study aimed to evaluate the clinical efficacy of PEG-rhGH in treating GHD patients by using a metabolomic approach. Fifty-seven pediatric participants treated with PEG-rhGH were enrolled (28 GHD patients with high clinical efficacy and 29 GHD patients with lower clinical efficacy). Serum samples from all patients were first collected at baseline for biochemical detection; then metabolite levels were measured using gas chromatography time-of-flight mass spectrometry. The candidates included heptadecanoic acid, stearic acid, 2-hydroxybutyric acid, myristic acid, palmitoleic acid, D-galactose, dodecanoic acid, and oleic acid. The related metabolic pathways involved fatty acid metabolism and energy metabolism. This study suggested that growth gains of PEG-rhGH treatment might be differentiated by altered serum levels of fatty acid. Collectively, the metabolomic study provides unique insights into the use of PEG-rhGH as a therapeutic strategy for individualized treatment.
| S-EPMC9092529 | biostudies-literature
Project description:BackgroundThe study aimed to compare the growth responses to 3 years of growth hormone (GH) treatment in children and adolescents with GH deficiency (GHD) according to idiopathic, organic, isolated (IGHD), and multiple pituitary hormone deficiency (MPHD).MethodsTotal 163 patients aged 2-18 years (100 males and 63 females; 131 idiopathic and 32 organic GHD; 129 IGHD and 34 MPHD) were included from data obtained from the LG Growth Study. Parameters of growth responses and biochemical results were compared during the 3-year GH treatment.ResultsThe baseline age, bone age (BA), height (Ht) standard deviation score (SDS), weight SDS, mid-parental Ht SDS, predicted adult Ht (PAH) SDS, and insulin like growth factor-1 (IGF-1) SDS were significantly higher in the organic GHD patients than in the idiopathic GHD patients, but peak GH on the GH-stimulation test, baseline GH dose, and mean 3-year-GH dosage were higher in the idiopathic GHD patients than in the organic GHD patients. The prevalence of MPHD was higher in the organic GHD patients than in the idiopathic GHD patients. Idiopathic MPHD subgroup showed the largest increase for the ΔHt SDS and ΔPAH SDS during GH treatment, and organic MPHD subgroup had the smallest mean increase after GH treatment, depending on ΔIGF-1 SDS and ΔIGF binding protein-3 (IGFBP-3) SDS. The growth velocity and the parental-adjusted Ht gain were greater in the idiopathic GHD patients than the organic GHD patients during the 3-year GH treatment, which may have been related to the different GH dose, ΔIGF-1 SDS, and ΔIGFBP-3 SDS between two groups. Multiple linear regression analysis revealed that baseline IGF-1 SDS, BA, and MPH SDS in idiopathic group and baseline HT SDS in organic group are the most predictable parameters for favorable 3-year-GH treatment.ConclusionThe 3-year-GH treatment was effective in both idiopathic and organic GHD patients regardless of the presence of MPHD or underlying causes, but their growth outcomes were not constant with each other. Close monitoring along with appropriate dosage of GH and annual growth responses, not specific at baseline, are more important in children and adolescents with GHD for long-term treatment.Trial registrationClinicalTrials.gov Identifier: NCT01604395.
| S-EPMC8938607 | biostudies-literature
Project description:BackgroundGrowth hormone deficiency (GHD) is a developmental disorder in children characterized by low growth hormone (GH), short stature and unfavorable lipid profiles. Familial hypercholesteremia (FH) is an inborn disorder of low-density lipoprotein cholesterol (LDL-C) metabolism which results in premature cardiovascular events. The co-occurrence of GHD and FH, which may aggravate the hypercholesteremic condition in the affected individuals, had rarely been discussed in previous publication.MethodsThis work reports two cases of GHD with FH, and explores the lipid profiles of GHD children and their therapeutic response to recombinant human growth hormone (rhGH). The diagnosis of GHD is based on low peak GH level (<7 ng/mL) in GH provocation test. FH is diagnosed by high LDL-C level (≥ 4 mmol/L) and confirmed genetic mutations in the LDL-C metabolic pathway. We also searched all previously published metabolic studies on GHD children as of December 31, 2020. Information on their LDL-C, duration and dose of rhGH treatment were retrieved and summarized.ResultsThe first case was a 5.3 year-old boy. His height was 103.6 cm (SDS = -2.29) and his peak GH in provocative test was 6.37 ng/mL. Additionally, his LDL-C was 4.80 mmol/L and he harbored a heterozygous mutation for the apolipoprotein B (APOB) gene (c.10579 C > T). The second case was a 9-year-old girl at the height of 117.3 cm (SDS = -2.91). Her GH peaked at 4.99 ng/mL in insulin-induced hypoglycemic test and 2.80 ng/mL in L-dopa test. Her LDL-C was 6.16 mmol/L, and she carried a mutated copy of the low-density lipoprotein receptor (LDLR) gene (c.809 G > A). Literature review indicated that GHD children suffered from higher baseline LDL-C, but it was significantly reduced after rhGH treatment.ConclusionsFH should be considered if a GHD child has remarkably elevated LDL-C that cannot be attributed to low GH level alone. Genetic mutations in the LDL-C metabolic pathway prevent the body from effectively metabolizing lipids, thereby resulting in early-onset hypercholesteremia and probably playing a negative role in children's growth.
| S-EPMC8249922 | biostudies-literature