scholarly journals Amino-Terminal Propeptide of C-Type Natriuretic Peptide and Linear Growth in Children: Effects of Puberty, Testosterone, and Growth Hormone

2007 ◽  
Vol 92 (11) ◽  
pp. 4294-4298 ◽  
Author(s):  
Robert C. Olney ◽  
Timothy C. R. Prickett ◽  
Timothy G. Yandle ◽  
Eric A. Espiner ◽  
Joan C. Han ◽  
...  
Keyword(s):  
Short Stature ◽  
Growth Plate ◽  
Natriuretic Peptide ◽  
Linear Growth ◽  
Gh Deficiency ◽  
Gh Treatment ◽  
Amino Terminal ◽  
Pubertal Growth ◽  
Potential Biomarker ◽  
Growth Promoting

Abstract Context: C-type natriuretic peptide (CNP), a paracrine factor of the growth plate, plays a key role in stimulating bone growth. The amino-terminal propeptide of CNP (NTproCNP) is produced in equimolar amounts with CNP and is measurable in plasma, providing a potential biomarker for growth plate activity and, hence, linear growth. Objective: We explored the effects of puberty, testosterone, and GH treatment on NTproCNP levels in normal and short-statured children. Design: This was a retrospective analysis of samples obtained during previous studies. Setting: The study was conducted at a pediatric clinical research center. Subjects: Children with short stature due to GH deficiency, idiopathic short stature (ISS), or constitutional delay of growth and maturation (CDGM) were studied (n = 37). A cohort of normal-statured adolescent boys was also studied (n = 23). Interventions: Children with GH deficiency and ISS were studied before and during testosterone and/or GH treatment. Boys with CDGM and healthy controls were studied once. Main Outcome Measures: The main outcomes were NTproCNP levels before and during growth-promoting therapy and during pubertal growth. Results: Children with short stature due to GH deficiency, ISS, or CDGM had comparable baseline levels of NTproCNP, and levels increased markedly in response to GH or testosterone treatment. In boys with CDGM, levels were comparable with height-matched controls but were less than those from age-matched controls. In healthy boys, NTproCNP appears to peak with the pubertal growth spurt. Conclusions: NTproCNP levels increase during growth-promoting therapy and are increased during puberty in boys. This novel biomarker of growth may have clinical utility in the evaluation of children with short stature and for monitoring growth-promoting therapy.

scholarly journals Resistance to GHRH but Not to PTH in a 15-Year-Old Boy With Pseudohypoparathyroidism 1A

2019 ◽  
Vol 3 (7) ◽  
pp. 1383-1389 ◽  
Author(s):  
Martin Munteanu ◽  
Cordula Kiewert ◽  
Nora Matar ◽  
Berthold P Hauffa ◽  
Nicole Unger ◽  
...  
Keyword(s):  
Short Stature ◽  
Growth Plate ◽  
Gh Deficiency ◽  
Final Height ◽  
Standard Deviation Score ◽  
Clinical Signs ◽  
Bone Age ◽  
Heterozygous Mutation ◽  
Gh Treatment ◽  
Recombinant Growth Hormone

Abstract Pseudohypoparathyroidism 1A (PHP1A) consists of signs of Albright hereditary osteodystrophy (AHO) and multiple, variable hormonal resistances. Elevated PTH levels are the biochemical hallmark of the disease. Short stature in PHP1A may be caused by a form of accelerated chondrocyte differentiation leading to premature growth plate closure, possibly in combination with GH deficiency in some patients. Treatment of short stature with recombinant growth hormone (rhGH) in pediatric patients may improve final height if started during childhood. The 10 11/12-year-old boy with clinical signs of AHO presented for evaluation of short stature [height standard deviation score (SDS) −2.72]. Clinically his mother was affected by AHO as well. A heterozygous mutation c.505G>A (p.E169K) in exon 6 of the GNAS gene confirmed a diagnosis of PHP1A in the boy. However, hormonal assessment was unremarkable except for low serum IGF-1 (SDS −2.67). On follow-up, GH deficiency due to GHRH resistance was suspected and confirmed by clonidine and arginine stimulation tests. Treatment with rhGH (0.035 mg/kg) for 2 years resulted in catch-up growth (height SDS −1.52). At age 15 years the PTH levels and bone age of the patient remain within the normal range. In patients with PHP1A, short stature is caused by the effects of Gs-α deficiency on the growth plate. However, resistance to GHRH and the resulting GH deficiency might also contribute. Recombinant GH treatment increases growth in these patients. Diagnostic workup for GH deficiency as a factor contributing to short stature is recommended even in the absence of other hormonal resistances.

scholarly journals Pharmacodynamic responses of plasma and tissue C-type natriuretic peptide to GH: correlation with linear growth in GH-deficient rats

2011 ◽  
Vol 212 (2) ◽  
pp. 217-225 ◽  
Author(s):  
T C R Prickett ◽  
J C Bothwell ◽  
T G Yandle ◽  
A M Richards ◽  
E A Espiner
Keyword(s):  
Natriuretic Peptide ◽  
Linear Growth ◽  
Plasma Concentrations ◽  
Kidney Tissue ◽  
Tail Length ◽  
Saline Control ◽  
Growth Disorders ◽  
Tissue Concentrations ◽  
Amino Terminal ◽  
Endochondral Growth

Studies from genetic modification and spontaneous mutations show that C-type natriuretic peptide (CNP) signalling plays an essential part in postnatal endochondral growth, but measurement of CNP proteins and changes in their abundance in tissues and plasma during normal growth has not been reported. Using rodent pups with GH deficiency, we now describe the pharmacodynamic response of CNP and rat amino-terminal proCNP (NTproCNP) in plasma and tissues, and relate these to changes in linear growth (nose–tail length, tibial length and tibial growth plate width) during the course of 1 week of GH or saline (control) administration. Compared with saline, significant increases in plasma and tissue CNP forms were observed after 24 h in GH-treated pups and before any detectable change in linear growth. Whereas CNP abundance was increased in most tissues (muscle, heart and liver) by GH, enrichment was the greatest in extracts from growth plates and kidney. Plasma and tissue concentrations in GH-treated pups were sustained or further increased at 1 week when strong positive associations were found between plasma NTproCNP and linear growth or tissue concentrations. High content of NTproCNP in kidney tissue strongly correlated with plasma concentrations, which is consistent with previous data showing renal extraction of the peptide. In showing a prompt and significant increase in CNP in tissues driving normal endochondral growth, these findings provide further rationale for CNP agonists in the treatment of growth disorders resistant to current therapies and support the use of CNP concentrations as biomarkers of linear growth.

Russian national consensus. Diagnostics and treatment of hypopituitarism in children and adolescences

2019 ◽  
Vol 64 (6) ◽  
pp. 402-411
Author(s):  
Elena V. Nagaeva ◽  
Tatiana Y. Shiryaeva ◽  
Valentina A. Peterkova ◽  
Olga B. Bezlepkina ◽  
Anatoly N. Tiulpakov ◽  
...  
Keyword(s):  
Short Stature ◽  
Growth Velocity ◽  
Gh Deficiency ◽  
Final Height ◽  
Pituitary Hormone ◽  
Complete Disappearance ◽  
Gh Treatment ◽  
Central Hypothyroidism ◽  
Igf I ◽  
National Consensus

The materials of the National Consensus reflect the modern domestic and international experience on this issue. Before conducting a specialized endocrinological examination of a short child, all other causes of short stature should be excluded: severe somatic diseases in a state of decompensation that can affect growth velocity, congenital systemic skeletal diseases, syndromic short stature (all girls with growth retardation require a mandatory study of karyotype, depending on the presence or absence of phenotypic signs of Turner syndrome), endocrine diseases in decompensation. A specialized examination of the state of GH-IGF-I axis is carried out when the proportionally folded child has pronounced short stature: if the child’s height is < –2.0 SDS, if the difference between the child’s height SDS and child’s midparental height SDS exceeds 1.5 SDS and/or a low growth velocity. The consensus reflects clear criteria for the diagnosis of GH-deficiency, central hypothyroidism, central hypocorticosolism, central hypogonadism, diabetes insipidus, hypoprolactinemia, and also the criteria for their compensation. The dose of somatropin with GH-deficiency in children and adolescents is 0.025–0.033 mg/kg/day. With total somatotropic insufficiency, especially in young children, it is advisable to start therapy with somatropin from lower doses: 25–50% of the substitution, gradually increasing it within 3–6 months to optimal. In children with a growth deficit when entering puberty, the dose may be increased to 0.045–0.05 mg/kg/day. With the development of side effects, the dose of somatropin can be reduced (by 30–50%), or temporarily canceled (depending on the severity of the clinical picture) until the complete disappearance of undesirable symptoms. With swelling of the optic nerve, treatment is temporarily stopped until the picture of the fundus of the eye fully normalizes. If therapy has been temporarily discontinued, treatment is resumed in smaller doses (50% of the initial) with a gradual (within 1–3 months) return to the optimum. GH treatment at pediatric doses not continue beyond attainment of a growth velocity below 2–2.5 cm/year, closure of the epiphyseal growth zones, or earlier, when: the achievement of genetically predicted height, but not more than 170 cm in girls, 180 cm in boys, the patient’s desire and his parents / legal representatives satisfied with the achieved result of the final height. Re-evaluation of the somatotropic axis is carried out after reaching the adult height, after 1–3 months GH therapy will be discontinued. Patients with isolated GH-deficiency or patients with 1 (besides GH) pituitary hormone deficiencies in the presence of a normal IGF-1 level (against the background of somatropin withdrawal) and not having molecular genetic confirmation of the diagnosis need re- evaluation. Patients with two or more (besides GH) pituitary hormone deficiencies, acquired hypothalamic-pituitary lesions due to operations on the pituitary and irradiation of the hypothalamic-pituitary area (if the IGF-1 level is low against somatropin withdrawal), specific pituitary/ hypothalamic structural defect on MRI, gene defects of the GH-IGF-I system do not need re- evaluation. If GH deficiency is confirmed, treatment with somatropin is resumed at metabolic doses of 0.01—0.003 mg/kg/day under the control of the IGF-I level in the blood (measurement 1 time in 6 months), the indicator should not exceed the upper limit of the reference value for the corresponding age and floor.

Plasma Amino-Terminal Pro C-Type Natriuretic Peptide in the Neonate: Relation to Gestational Age and Postnatal Linear Growth

2008 ◽  
Vol 93 (1) ◽  
pp. 225-232 ◽  
Author(s):  
Timothy C. R. Prickett ◽  
Bronwyn Dixon ◽  
Chris Frampton ◽  
Timothy G. Yandle ◽  
A. Mark Richards ◽  
...  
Keyword(s):  
Bone Turnover ◽  
Natriuretic Peptide ◽  
Gestational Age ◽  
Growth Velocity ◽  
Linear Growth ◽  
Postnatal Life ◽  
Strongly Correlated ◽  
Amino Terminal ◽  
Cord Plasma ◽  
Markers Of Bone Turnover

Abstract Context: C-type natriuretic peptide (CNP) plays an essential role in endochondral bone growth. Insight into CNP’s paracrine actions is possible using plasma measurements of the amino-terminal pro C-type natriuretic peptide (NTproCNP). Whether correlations of NTproCNP with linear growth, as found in children and lambs, apply in neonates is unknown. Objectives: Our objective was to determine the effects of prematurity, gender, and antenatal steroids on plasma NTproCNP at birth, and serial changes in hormone concentrations, linear growth, and markers of bone turnover in the first month of postnatal life. Design and Setting: This is a prospective study of newborn infants admitted to an intensive care unit. Subjects: A total of 48 infants (four gestation groups) were enrolled. Umbilical cord samples were also obtained from 39 healthy term infants. Main Outcome Measures: Plasma NTproCNP and CNP were measured in cord plasma. In enrolled neonates, serial measurements of hormone concentrations and markers of bone turnover were related to tibial growth velocity as measured by knemometry. Results: Cord plasma NTproCNP was inversely related to gestational age (r = −0.35; P = 0.003) and was higher in males (P &lt; 0.001). Plasma NTproCNP (P = 0.016) and CNP (P &lt; 0.001) increased within the first week of life, the increase relating inversely to gestational age (r = −0.64; P &lt; 0.001). Plasma NTproCNP at 1 wk was strongly correlated with linear growth velocity (r = 0.49; P &lt; 0.001), and also at 2–4 wk, the relation being stronger than observed between bone turnover markers and growth velocity. Conclusions: In neonates with diverse disorders affecting growth and nutrition, plasma NTproCNP was strongly correlated with linear growth during the first 4 wk of postnatal life and may prove to be a novel marker of growth plate activity in neonates.

scholarly journals Growth and Adult Height in GH-Treated Children with Nonacquired GH Deficiency and Idiopathic Short Stature: The Influence of Pituitary Magnetic Resonance Imaging Findings

2001 ◽  
Vol 86 (10) ◽  
pp. 4649-4654 ◽  
Author(s):  
Régis Coutant ◽  
Stéphanie Rouleau ◽  
François Despert ◽  
Nathalie Magontier ◽  
Didier Loisel ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Short Stature ◽  
Gh Deficiency ◽  
Final Height ◽  
Idiopathic Short Stature ◽  
Imaging Findings ◽  
Resonance Imaging ◽  
Gh Treatment ◽  
Catch Up

We analyzed the final height of 146 short children with either nonacquired GH deficiency or idiopathic short stature. Our purpose was 1) to assess growth according to the pituitary magnetic resonance imaging findings in the 63 GH-treated children with GH deficiency and 2) to compare the growth of the GH-deficient patients with normal magnetic resonance imaging (n = 48) to that of 32 treated and 51 untreated children with idiopathic short stature (GH peak to provocative tests &gt;10 μg/liter). The mean GH dose was 0.44 IU/kg·wk (0.15 mg/kg·wk), given for a mean duration of 4.6 yr. Among the GH-deficient children, 15 had hypothalamic-pituitary abnormalities (stalk agenesis), all with total GH deficiency (GH peak&lt;5 μg/liter). They were significantly shorter and younger at the time of diagnosis than those with normal magnetic resonance imaging, had better catch-up growth (+2.7 ± 0.9 vs.+ 1.3 ± 0.8 sd score; P &lt; 0.01), and reached greater final height (−1.1 ± 1.0 vs.− 1.7 ± 1.0 sd score; P &lt; 0.05). Among patients with normal magnetic resonance imaging, there was no difference in catch-up growth and final height between partial and total GH deficiencies. GH-deficient subjects with normal magnetic resonance imaging and treated and untreated patients with idiopathic short stature had comparable auxological characteristics, age at evaluation, and target height. Although they had different catch-up growth (+1.3 ± 0.8,+ 0.9 ± 0.6, and +0.7 ± 0.9 sd score, respectively; P &lt; 0.01, by ANOVA), these patients reached a similar final height (−1.7 ± 1.0, −2.1 ± 0.8, and −2.1 ± 1.0 sd score, respectively; P = 0.13). Pituitary magnetic resonance imaging findings show the heterogeneity within the group of nonacquired GH deficiency and help to predict the response to GH treatment in these patients. The similarities in growth between the GH-deficient children with normal magnetic resonance imaging and those with idiopathic short stature suggest that the short stature in the former subjects is at least partly due to factors other than GH deficiency.

scholarly journals Safety Outcomes During Pediatric GH Therapy: Final Results From the Prospective GeNeSIS Observational Program

2018 ◽  
Vol 104 (2) ◽  
pp. 379-389 ◽  
Author(s):  
Christopher J Child ◽  
Alan G Zimmermann ◽  
George P Chrousos ◽  
Elisabeth Cummings ◽  
Cheri L Deal ◽  
...  
Keyword(s):  
Risk Factors ◽  
General Population ◽  
Short Stature ◽  
Gh Deficiency ◽  
Growth Disorders ◽  
Primary Cancer ◽  
Gh Therapy ◽  
Gh Treatment ◽  
Safety Outcomes

Abstract Context Safety concerns have been raised regarding premature mortality, diabetes, neoplasia, and cerebrovascular disease in association with GH therapy. Objective To assess incidence of key safety outcomes. Design Prospective, multinational, observational study (1999 to 2015). Setting A total of 22,311 GH-treated children from 827 investigative sites in 30 countries. Patients Children with growth disorders. Interventions GH treatment. Main outcome measures Standardized mortality ratio (SMR) and standardized incidence ratio (SIR) with 95% CIs for mortality, diabetes, and primary cancer using general population registries. Results Predominant short stature diagnoses were GH deficiency (63%), idiopathic short stature (13%), and Turner syndrome (8%), with mean ± SD follow-up of 4.2 ± 3.2 years (∼92,000 person-years [PY]). Forty-two deaths occurred in patients with follow-up, with an SMR (95% CI) of 0.61 (0.44, 0.82); the SMR was elevated for patients with cancer-related organic GH deficiency [5.87 (3.21, 9.85)]. Based on 18 cases, type 2 diabetes mellitus (T2DM) risk was elevated [SIR: 3.77 (2.24, 5.96)], but 72% had risk factors. In patients without cancer history, 14 primary cancers were observed [SIR: 0.71 (0.39, 1.20)]. Second neoplasms occurred in 31 of 622 cancer survivors [5.0%; 10.7 (7.5, 15.2) cases/1000 PY] and intracranial tumor recurrences in 67 of 823 tumor survivors [8.1%; 16.9 (13.3, 21.5) cases/1000 PY]. All three hemorrhagic stroke cases had risk factors. Conclusions GeNeSIS (Genetics and Neuroendocrinology of Short Stature International Study) data support the favorable safety profile of pediatric GH treatment. Overall risk of death or primary cancer was not elevated in GH-treated children, and no hemorrhagic strokes occurred in patients without risk factors. T2DM incidence was elevated compared with the general population, but most cases had diabetes risk factors.

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