Growth hormone-releasing activity of growth hormone-releasing peptide-1 (a synthetic heptapeptide) in children and adolescents

1993 ◽  
Vol 129 (5) ◽  
pp. 424-426 ◽  
Author(s):  
Zvi Laron ◽  
Cyril Y Bowers ◽  
Daniel Hirsch ◽  
Antonio Selman Almonte ◽  
Moshe Pelz ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Children And Adolescents ◽  
Normal Values ◽  
Gh Deficiency ◽  
Clinical Applications ◽  
Hormone Deficiency ◽  
Pituitary Hormone ◽  
Pituitary Insufficiency ◽  
Healthy Children ◽  
Plasma Prolactin

The heptapeptide growth hormone-releasing peptide-1 (GHRP-1 ), one of a series of recently synthesized small growth hormone (GH)-releasing peptides, was administered as an iv bolus (1 μg/kg) to 15 (six prepubertal, nine pubertal) short but healthy children and adolescents and to eight juvenile patients with pituitary insufficiency (four with isolated growth hormone deficiency, two with multiple pituitary hormone deficiencies, one with partial GH deficiency and one with GH-releasing hormone (GHRH) deficiency). Eleven out of 23 subjects also underwent an iv GHRH (1–29) test (1 μg/kg). All the healthy children responded with a progressive rise in plasma human GH (hGH) peaking at 15–30 min, with a significantly higher rise (p<0.05) in the pubertal than prepubertal group. The hGH response to GHRH (1–29) in these children was similar or slightly higher. Six hypopituitary patients had no response to either GHRP-1 or GHRH; the patient with partial GH deficiency had a hGH peak of 6.5 μg/l (at 5 min) to GHRP-1 and 9.2 μg/l (at 1 5 min) to GHRH. One patient had no response of hGH to hypoglycemia, clonidine and GHRP-1, but the plasma hGH rose to 10 μg/l after GHRH. Following the GHRP-1 bolus there was a significant (p <0.01) rise in plasma free thyroxine and a decrease of thyrotropin (p <0.01), both in the limits of normal values. There was also a transitory rise of plasma cortisol (p <0.05). Plasma prolactin, luteinizing hormone and follicle-stimulating hormone did not change. It is concluded that GHRP-1 is a potent GH-releasing drug because it acts also when administered orally and has great pharmaceutical and clinical applications.

Growth hormone replacement for patients with adult onset growth hormone deficiency—what have we learned?

2004 ◽  
Vol 16 (4) ◽  
pp. 1-6
Author(s):  
Monique Piersanti
Keyword(s):  
Growth Hormone ◽  
Gh Deficiency ◽  
Hormone Replacement ◽  
Hormone Deficiency ◽  
Pituitary Hormone ◽  
Adult Onset ◽  
Gh Replacement ◽  
Term Benefit

Growth hormone (GH) deficiency is a condition recognized to occur in individuals who have had multiple pituitary hormone deficiencies as a result of pathological processes or neurosurgical interventions. The indications, benefits, and risks of GH replacement therapy will be reviewed with an emphasis on those patients who were adults with the deficiency first emerged. The results of this analysis indicate that, although a measurable improvement can be detected in the patient's quality of life, body composition, and some cardiovascular parameters, the larger questions of long-term benefit and patient selection currently remain unanswered.

Growth hormone and insulin-like growth factor regulate insulin-like growth factor-binding protein-1 in Laron type dwarfism, growth hormone deficiency and constitutional short stature

1992 ◽  
Vol 127 (4) ◽  
pp. 351-358 ◽  
Author(s):  
Zvi Laron ◽  
Anne-Maria Suikkari ◽  
Beatrice Klinger ◽  
Aviva Silbergeld ◽  
Athalia Pertzelan ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Growth Hormone Deficiency ◽  
Short Stature ◽  
Hormone Deficiency ◽  
Pituitary Hormone ◽  
Healthy Children ◽  
Insulin Like Growth Factor ◽  
Factor Binding ◽  
Igf I

Insulin-like growth factors (IGFs) mediate the effects of growth hormone (GH), and the insulin-like growth factor-binding proteins (IGFBPs) modulate the actions of IGFs in tissues. We studied the circulating levels of IGFBP-1 in 6 children and 9 adults with Laron type dwarfism (LTD), in 11 children and 21 adults with growth hormone deficiency (GHD), and in 8 children with constitutional short stature. Compared with the situation in healthy children, the basal serum IGFBP-1 concentration was 5.4-fold higher in LTD children, 4.1-fold higher in GHD children, and 3.8-fold higher in children with short stature (p<0.02 vs controls in all groups). In adult patients with multiple pituitary hormone deficiency (MPHD), the IGFBP-1 concentration was 2-fold elevated, but it was normal in adult LTD patients. Intravenous (N= 10) or subcutaneous (N=9) administration ofIGF-I (75 μg·kg−1 and 150 μg·kg−1, respectively) in LTD children resulted in a rapid 50–60% fall in serum insulin (p<0.02), a decline in blood glucose and a concomitant 40–60% rise of IGFBP-1 levels (p<0.05). Treatment for seven days with IGF-I (150 μg·kg−1·d−1) resulted in a decrease by 34% and 44% of serum IGFBP-1 level in two out of three children with LTD. After prolonged GH therapy, the IGFBP-1 level fell in GHD children by 29% (p<0.05), in GHD adults by 52% (p<0.02) and in children with constitutional short stature by 17% (p<0.02). IGFBP-1 and insulin concentrations were inversely related in patients with GHD (r= −0.66, p<0.001) or with LTD (r= −0.57, p<0.05). Our data suggest that: (a) increased IGFBP-1 concentration in LTD, GHD and constitutional short children may, at least in part, be accounted for by an IGF-I deficiency; (b) both the rise in IGF-I and a fall in insulin contributed to the rise in IGFBP-1 after acute IGF-I administration; (c) prolonged IGF-I or GH treatment causes a persistent decline in IGFBP-1 concentration. In conclusion, IGF-I and GH may regulate IGFBP-1 secretion either directly or via insulin.

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.

scholarly journals Clinical and genetic features of patients with multiple anterior pituitary hormone deficiency caused by mutations in the PROP1 gene; the efficacy of recombinant growth hormone therapy

2017 ◽  
Vol 63 (2) ◽  
pp. 72-81 ◽  
Author(s):  
Anna E. Gavrilova ◽  
Elena V. Nagaeva ◽  
Tatiana Yu. Shiryaeva ◽  
Olga Yu. Rebrova ◽  
Anatoly N. Tiulpakov ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Gh Deficiency ◽  
Final Height ◽  
Gene Mutations ◽  
Hormone Deficiency ◽  
Pituitary Hormone ◽  
Recombinant Growth Hormone ◽  
Secondary Hypothyroidism ◽  
Prop1 Gene ◽  
Secondary Hypogonadism

Rationale. One of the most common causes of multiple anterior pituitary hormone deficiency (MPHD) is genetic defects in the PROP1 gene. PROP1 deficiency leads to malfunction of somatotrophs, lactotrophs, thyrotrophs, corticotrophs, and gonadotrophs. Now, there is an opportunity to conduct large-scale population studies of patients with genetic MPHD, describe their clinical and genetic heterogeneity, and evaluate the efficacy of long-term therapy of these patients with a recombinant growth hormone (rGH). Aim. The study aim was to assess the spectrum of PROP1 gene mutations in the Russian population of MPHD patients, rate and expected age of hypopituitarism components, and efficacy of rGH therapy. Material and methods. We analyzed the data of 27 patients diagnosed with MPHD and genetically confirmed mutations in the PROP1 gene who were treated at the Institute of Pediatric Endocrinology of the Endocrinology Research Center (ERC) in 1978―2016. MPHD was diagnosed based on laboratory data and stimulatory tests characterizing the functional activity of the pituitary gland. The molecular genetic study was performed using high-performance parallel sequencing. We used a custom Ampliseq_HP primer panel developed at the Department of Hereditary Endocrinopathies of the ERC, which included coding regions of the following genes: ARNT2, GH1, GHRH, GHRHR, GHSR, GLI2, HESX1, LHX3, LHX4, OTX2, PAX6, POU1F1, PROP1, SHH, SOX2, and SOX3. All patients received rGH therapy at a growth-stimulating dose from the time of GH deficiency diagnosis until final height completion. We evaluated the efficacy of therapy by comparing the achieved final height with the genetically expected one. Results. Non-familial cases prevailed (N=23) in the study cohort of patients with MPHD caused by mutations in the PROP1 gene; only two patients were monochorionic twin sisters; the other two patients were siblings. An analysis of the distribution of PROP1 gene mutations revealed a hot-point mutation c.301_302delAG in 24 patients (89%, 95% CI 71%; 98%). A mutation in the c.150delA locus occurred in 11 patients (41%, 95% CI 22%; 61%). Two patients had other mutations (c.629delC and c.43_49delGGGCGAG). Total GH deficiency was detected in all patients. The rate of secondary hypothyroidism (SHT) in patients of the study sample was 78% (95% CI 58%; 91%) at the time of diagnosis of GH deficiency and 100% (95% CI 81%; 100%) at the time of final height. The rate of secondary hypogonadism (SHG) at the time of final height was 100% (95% CI 81%; 100%), and the rate of secondary hypocorticism (SHC) was 41% (95% CI 22%; 61%). The normal level of prolactin was detected in 83% (95% CI 65%; 94%) of patients. At the time of growth plate closure, patients receiving rGH therapy at the growth-stimulating dose achieved the genetically expected final height. Conclusion. According to our findings, the most common mutation in the PROP1 gene is a deletion of AG nucleotides in the 101 codon (c.301_302 delAG), which is found in 89% (95% CI 71%; 98) patients. Patients with MPHD caused by mutations in the PROP1 gene have total GH deficiency and are diagnosed with secondary hypothyroidism and secondary hypogonadism in 100% of cases. The possibility of delayed manifestation of hypopituitarism components requires regular screening of tropic hormone levels for the timely start of substitution therapy and prevention of life-threatening conditions. rGH therapy is highly effective for GH deficiency caused by PROP1 gene mutations and allows patients to achieve the genetically expected height in the case of early diagnosis of growth hormone deficiency.

scholarly journals Clinical and auxological characteristics of growth hormone deficiency in children of the southern region of Ukraine

2021 ◽  
Vol 25 (1) ◽  
pp. 40-44
Author(s):  
L. I. Senkivska ◽  
M. L. Aryayev
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Gh Deficiency ◽  
Bone Age ◽  
Hormone Deficiency ◽  
P Value ◽  
Organic Basis ◽  
Pituitary Hormone ◽  
Realistic Assessment ◽  
Stimulation Tests

Anotation. Regional clinical and auxological studies of growth hormone deficiency (GHD) in children contribute to a realistic assessment of the severity of the problem and prevent underdiagnostics of the disease. The aim of the study is to analyze the features of various forms of GHD in children of the Odessa region on the basis of the clinicians’ integrated assessment of history, physical examination, auxology, stature, growth velocity, bone age (BA), 2 growth hormone (GH) stimulation tests, insulin-like growth factor, magnetic resonance imaging in 92 children with GHD in the Odessa region. Parametric variables were assessed using criteria t-test and хі-square (χ2). The p value <0,05 was considered statistically significant. Decrease in SDS height from - 2,1 tо - 6,6 was found. Isolated GHD (IGHD) was diagnosed in 65,2% of diseases, multiple pituitary hormone deficiency (MPHD) in 34,8% cases. IGHD was more often idiopathic and MPHD was more often arose on an organic basis. Chronological age (CA), BA and height of children with MPHD were lower at the start of therapy compared with IGHD. Complete GH deficiency was more common in children with MPHD (62,7%), while partial GH deficiency was more common in children with IGHD (81,7%). Very low values of the coefficient CA/BA (less than 0,55) were significantly more often detected in children with MPHD compared with IGHD. The regional clinical and auxological characteristics of GHD in children in the Odessa region can be considered in further study of population aspects and patterns of growth.

scholarly journals Malignancy risk in adults with growth hormone deficiency undergoing long-term treatment with biosimilar somatropin (Omnitrope®): data from the PATRO Adults study

2020 ◽  
Vol 11 ◽  
pp. 204201882094337
Author(s):  
Paolo Beck-Peccoz ◽  
Charlotte Höybye ◽  
Robert D Murray ◽  
Suat Simsek ◽  
Markus Zabransky ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Gh Deficiency ◽  
Real Life ◽  
Hormone Deficiency ◽  
System Organ Class ◽  
Pituitary Hormone ◽  
Gh Treatment ◽  
Post Marketing Surveillance ◽  
Increased Risk ◽  
Long Term Treatment

Background: To assess the safety (particularly the occurrence of malignancies) of growth hormone (GH) replacement (Omnitrope®) in adults with GH deficiency, using data from the ongoing PATRO Adults post-marketing surveillance study. Methods: PATRO Adults is being conducted in hospitals and specialized endocrinology clinics across Europe. All enrolled patients who receive ⩾1 dose of Omnitrope® are included in the safety population. Malignancies are listed as adverse events under the MedDRA System Organ Class ‘neoplasms, benign, malignant and unspecified (including cysts and polyps)’. Results: As of July 2018, 1293 patients had been enrolled in the study and 983 (76.0%) remained active in the study. Approximately half [ n = 637 (49.3%)] of the patients were GH treatment-naïve on study entry. The majority of enrolled patients had multiple pituitary hormone deficiency ( n = 1128, 87.2%). A total of 41 on-study malignancies were reported in 33 patients (2.6%; incidence rate 7.94 per 1000 patient-years). The most common cancers were basal cell carcinoma ( n = 13), prostate ( n = 6), breast, kidney and malignant melanoma (each n = 3). Treatment with Omnitrope® was discontinued following diagnosis of malignancy in 16 patients. The tumors occurred after a mean of 79.4 months of recombinant hormone GH (rhGH) treatment overall. Conclusion: Based on this snapshot of data from PATRO Adults, Omnitrope® treatment is tolerated in adult patients with GH deficiency in a real-life clinical practice setting. Our results do not generally support a carcinogenic effect of rhGH in adults with GH deficiency, although an increased risk of second new malignancies in patients with previous cancer cannot be excluded based on the current dataset.

A novel diagnostic tool for the evaluation of hypothalamic-pituitary region and diagnosis of growth hormone deficiency: pons ratio

2020 ◽  
Vol 33 (6) ◽  
pp. 735-742
Author(s):  
Meliha Demiral ◽  
Mehmet Salih Karaca ◽  
Edip Unal ◽  
Birsen Baysal ◽  
Rıza Taner Baran ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Cost Benefit ◽  
Practical Method ◽  
Hormone Deficiency ◽  
Small Scale ◽  
Pituitary Hormone ◽  
Clinical Value ◽  
Pubertal Status ◽  
Sensitive Tool

AbstractBackgroundsLimitations in the evaluation of the pituitary size and changes according to pubertal status make its validity questionable. Recently, in a small-scale study, pons ratio (PR) has been suggested as a more sensitive tool for diagnosis and etiological evaluation of growth hormone deficiency (GHD). The aim of the study is to evaluate the diagnostic value of PR in the diagnosis of GHD.MethodsWe retrospectively evaluated the pituitary magnetic resonance imaging (MRI) of 133 patients with a diagnosis of GHD. Primary axis (PA) was assigned as a line crossing the mid-sagittal dorsum sella and fourth ventricle. PR was defined as the pons height above the PA divided by total pons height. The PR of patients with GHD was compared to subjects without GHD.ResultsStudy included 133 patients with GHD and 47 controls. In total, 121 (91%) patients had isolated GHD and 12 (9%) patients had multiple pituitary hormone deficiency. The PR of the patient group (mean: 0.32 ± 0.89; range: 0.14–0.63) was significantly higher than controls (mean: 0.26 ± 0.067; range 0.19–0.44) (p: 0.000). The optimal cut-off value of PR for GHD diagnosis was 0.27 (sensitivity 71% specificity 56%). There was a negative correlation between anterior pituitary height (APH)-SDS and PR (p: 0.002; r: −0.27). APH was increased, but PR remained unchanged in pubertal patients (p: 0.089).ConclusionsPR measurement is a noninvasive, practical method with a cost-benefit clinical value. As it is not affected by pubertal status, PR is potentially a more sensitive tool for evaluation of pituitary gland in GHD patients compared to APH.

scholarly journals Allelic Variants in Established Hypopituitarism Genes Expand Our Knowledge of the Phenotypic Spectrum

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1128
Author(s):  
Marilena Nakaguma ◽  
Nathalia Garcia Bianchi Pereira Ferreira ◽  
Anna Flavia Figueredo Benedetti ◽  
Mariana Cotarelli Madi ◽  
Juliana Moreira Silva ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Male Patient ◽  
Missense Variant ◽  
Hormone Deficiency ◽  
Pituitary Hormone ◽  
Incomplete Penetrance ◽  
Growth Hormone Gene ◽  
Posterior Lobe ◽  
Allelic Variants ◽  
Phenotypic Spectrum

We report four allelic variants (three novel) in three genes previously established as causal for hypopituitarism or related disorders. A novel homozygous variant in the growth hormone gene, GH1 c.171delT (p.Phe 57Leufs*43), was found in a male patient with severe isolated growth hormone deficiency (IGHD) born to consanguineous parents. A hemizygous SOX3 allelic variant (p.Met304Ile) was found in a male patient with IGHD and hypoplastic anterior pituitary. YASARA, a tool to evaluate protein stability, suggests that p.Met304Ile destabilizes the SOX3 protein (ΔΔG = 2.49 kcal/mol). A rare, heterozygous missense variant in the TALE homeobox protein gene, TGIF1 (c.268C>T:p.Arg90Cys) was found in a patient with combined pituitary hormone deficiency (CPHD), diabetes insipidus, and syndromic features of holoprosencephaly (HPE). This variant was previously reported in a patient with severe holoprosencephaly and shown to affect TGIF1 function. A novel heterozygous TGIF1 variant (c.82T>C:p.Ser28Pro) was identified in a patient with CPHD, pituitary aplasia and ectopic posterior lobe. Both TGIF1 variants have an autosomal dominant pattern of inheritance with incomplete penetrance. In conclusion, we have found allelic variants in three genes in hypopituitarism patients. We discuss these variants and associated patient phenotypes in relation to previously reported variants in these genes, expanding our knowledge of the phenotypic spectrum in patient populations.

scholarly journals Comparative study of glucagon and insulin tests for diagnostics of secondary adrenal insufficiency and growth hormone deficiency in children and adolescents

2021 ◽  
Vol 66 (6) ◽  
pp. 50-58
Author(s):  
A. V. Vitebskaya ◽  
E. A. Pisareva ◽  
A. V. Popovich
Keyword(s):  
Growth Hormone ◽  
Children And Adolescents ◽  
Growth Hormone Deficiency ◽  
Adrenal Insufficiency ◽  
Early Morning ◽  
Hormone Deficiency ◽  
Secondary Adrenal Insufficiency ◽  
Glucagon Test ◽  
Cortisol Levels ◽  
Glucagon And Insulin

BACKGROUND: Diagnostics of growth hormone deficiency (GHD) and secondary adrenal insufficiency (SAI) is based on estimation of peak GH and cortisol concentrations in provocation tests. Russian consensus on diagnostics and treatment of hypopituitarism in children and adolescences recommends to measure GH and cortisol concentrations in every time-point of insulin test (IT). Glucagon test (GT) is discussed in literature as alternative to IT.AIMS: To estimate the possibility to use provocation GT for diagnostics of SAI and GHD in children and adolescents.MATERIALS AND METHODS: We investigated blood and urine cortisol levels, IT, and GT in 20 patients 6.5–17.8 years (Me 13.0 (10.4; 15.3)) after surgery and/or radiology and/or chemical therapy of head and neck tumors; remission for 0.4–7.5 years (Ме 2.1 (1.5; 5.2)).RESULTS: With cut-off point 550 nmol/L sensitivity and specifity of IT was 100% and 60%, GT — 100% and 53% respectively. Minimal cortisol cut-off level for GT with sensitivity 100% was 500 nmol/L, maximal with specifity 100% — 400 nmol/L.Early morning cortisol levels did not exceed 250 nmol/l in 2 patients with SAI; and were above 500 nmol/l in 8 patients without SAI while primary or repeated examination.GHD was reviled by IT in all patients. Maximal GH concentrations in GT and IT did not differ significantly (p>0.05) but GT results of 4 patients exceeded or met cut-off for this test (7 ng/ml).GT was characterized by less severity compared with IT.CONCLUSIONS: For diagnostics of SAI by GT we can advise cut-off points of cortisol level 500 (sensitivity 100%, specifty 53%) and 400 nmol/L (sensitivity 80%, specifity 100%). Measuring of cortisol levels in 2–3 early morning blood samples allows to exclude or to suspect SAI in half of patients before tests. GH peaks in GT can exceed similarly data in IT that needs future investigation. 

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