High Serum Levels of Growth Hormone (GH) and Insulin-Like Growth Factor-I (IGF-I) during High-Dose GH Treatment in Short Children Born Small for Gestational Age

Dijk, Marije van; Mulder, Paul; Houdijk, Mieke; Mulder, Jaap C.; Noordam, C.; Odink, Roelof J.; Rongen-Westerlaken, C; Voorhoeve, P G; Waelkens, J. J. J.; Stokvis-Brantsma, Jet; Hokken-Koelega, Anita

doi:10.1210/jc.2005-1663

Cited by 44 publications

(30 citation statements)

References 37 publications

(53 reference statements)

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“…During combined treatment, mean and maximum GH levels were lower in our study group compared with levels in prepubertal SGA children treated with GH only (38). Moreover, maximum GH levels in children treated with GnRHa and 2 mg GH/m 2 per day were similar to maximum GH levels in prepubertal children treated with 1 mg GH/m 2 per day.…”

Section: Start Of Gnrha Treatment (Nz41)supporting

confidence: 46%

“…GH and IGF1 levels increased significantly in both GH dosage groups, but to significantly higher levels in the 2 mg GH/m 2 per day group. Dose-dependent rises have been described in prepubertal short children born SGA, GH-deficient adolescents, and girls with Turner syndrome (38,43,44). The percentage of children with IGF1 SDS above 2 SDS was not significantly different between the groups.…”

Section: Start Of Gnrha Treatment (Nz41)mentioning

confidence: 93%

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Randomized GH trial with two different dosages in combination with a GnRH analogue in short small for gestational age children: effects on metabolic profile and serum GH, IGF1, and IGFBP3 levels

Kaay¹,

Bakker²,

Hulst³

et al. 2010

European Journal of Endocrinology

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Background: GnRH analogue (GnRHa) combined with GH treatment has been proposed to increase adult height. Effect on metabolic profile and GH, IGF1, and IGFBP3 levels in short small for gestational age (SGA) children is unknown. Objective: To assess fat mass and lean body mass SDS, percentage trunk fat, blood pressure (BP), insulin sensitivity (Si), b-cell function (disposition index, DI), lipid profile, and GH, IGF1, and IGFBP3 levels during 2 years of combined treatment. Subjects: Forty-one pubertal short SGA children with a mean (GS.D.) age of 12.1 (G1.0) years. Design: Children received 3.75 mg of leuprolide acetate depot subcutaneously every 4 weeks, and they were randomly assigned to receive 1 mg (group A) or 2 mg (group B) of GH/m 2 per day. Results: Percentage trunk fat increased in both groups, but to a lower extent in group B. Lean body mass SDS increased only in group B. Changes in BP, Si, DI, and lipids were similar in both groups. Si significantly decreased, but DI remained unchanged. Lipids remained normal. GH and IGF1 levels were significantly higher in group B. Conclusion: Our study is the first to report that 2 years of combined treatment with a GnRHa and either 1 or 2 mg GH/m 2 per day does not adversely affect body composition and metabolic profile of short SGA children who come under medical attention at the onset of puberty. There was a dose-dependent effect on fat mass SDS height , percentage trunk fat, lean body mass SDS height , and GH and IGF1 levels in favor of treatment with GnRHa and the higher GH dose of 2 mg/m 2 per day.

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Section: Start Of Gnrha Treatment (Nz41)supporting

confidence: 46%

Section: Start Of Gnrha Treatment (Nz41)mentioning

confidence: 93%

Randomized GH trial with two different dosages in combination with a GnRH analogue in short small for gestational age children: effects on metabolic profile and serum GH, IGF1, and IGFBP3 levels

Kaay¹,

Bakker²,

Hulst³

et al. 2010

European Journal of Endocrinology

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“…In recent years, SGA children have been treated with recombinant human GH, and some of them needed an increased GH dose for their poor response. van Dijk M. et al reported children with higher GH and IGF-I levels in combination with a poorer growth response, who may have had IGF-IR gene anomalies [28]. Further studies investigating the possibility and frequency of IGF-IR mutations among familial short-stature, SGA children are desired.…”

Section: Prevalence Of Igf-ir Gene Anomaly In Short-stature Individualsmentioning

confidence: 99%

Familial short stature with IGF-I receptor gene anomaly [Review]

2012

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Abstract. Type I insulin-like growth factor receptor (IGF-IR) is widely expressed across many cell types in fetal and postnatal tissues. The activation of this receptor after the binding of secreted IGF-I and IGF-II promotes cell differentiation and proliferation. IGF-IR has an important role in normal fetal and postnatal growth and development. IGF-IR gene anomalies presenting with intrauterine and postnatal growth retardation have recently been reported in some families. Familial short stature with IGF-IR gene anomaly is considered rare, and the clinical condition and features remain unknown. IGF-IR gene anomaly such as heterozygous IGF-IR mutation or haploinsufficiency of the IGF-IR gene should be investigated in those patients presenting with 1) low birth weight and birth height (< -1.5 SD), 2) a familial history of low birth weight, 3) a normal or increased IGF-I level, 4) a normal or increased GH response to the GH stimulation test, and/or 5) less response to GH treatment than common small for gestational age (SGA) short-stature patients. In this review, we provide an overview of current knowledge of familial short stature with IGF-IR gene anomaly.Key words: Insulin-like growth factor (IGF), IGF-I receptor, Intrauterine and postnatal growth retardation, Short stature Type I insulin-like growth factor receptor (IGF-IR) is widely expressed across many cell types in fetal and postnatal tissues. The activation of this receptor after the binding of the secreted growth factor ligands IGF-I and IGF-II elicits a repertoire of cellular responses, including the proliferation and protection of cells from programmed cell death or apoptosis [1,2]. This signaling results in fetal somatic growth, whereas this postnatal somatic growth is achieved through the synergistic interaction of the growth hormone (GH) and IGFs. IGF-IR has an important role in normal fetal and postnatal growth and development [3,4].Intrauterine growth retardation is a common condition in newborns, in which fetal events constrain birth size, and 10-20% of children born small for their gestational age (SGA) remain short into adulthood. The birth weight of IGF-IR knockout mice is 45% of normal, but they die within minutes of birth due to respiratory failure [3,4]. Thus, it has been assumed that mutations in the IGF-IR gene are probably not a common cause of intrauterine growth retardation (IUGR) in humans [5]. However, recently heterozygous IGF-IR mutations presenting with intrauterine and postnatal growth retardation have been observed in10 families [6][7][8][9][10][11][12][13], including a patient we had previously reported [9]. In this review, we describe current knowledge of familial short stature with IGF-IR gene anomaly. IGFs knock-out miceThe first paper from Liu JP, Baker J and colleagues revealed the essential role of IGFs in promoting fetal and postnatal growth by presenting the phenotype of igf1 - /-, igf2-/-, igf1r -/-, igf2r-/-[3, 4]. Mice lacking either the igf1 or igf2 genes exhibited intrauterine growth retardation, with weights approxi...

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“…Two children had the same mother but different fathers. Inclusion criteria for the children have previously been described (16). In short, the children were included when prepubertal, with a birth length or birth weight SD score (SDS) and actual height SDS below Ϫ2, without signs of catch-up growth in height and without growth failure caused by other disorders.…”

Section: Methodsmentioning

confidence: 99%

Cardiovascular Risk Factors in Parents of Short Children Born Small for Gestational Age

et al. 2008

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Small for gestational age (SGA) children have a higher prevalence of cardiovascular risk factors at a young age. It is not known whether this increased risk is caused by their size at birth, a familial predisposition for cardiovascular disease or smallness at birth or a combination of these factors. The cardiovascular risk profile of parents of SGA children is unknown. We compared anthropometry, blood pressure, fasting serum lipid, glucose, and insulin levels of 482 parents (mean age 41 y) and 286 short SGA children with age-and sex-matched references. We also investigated whether these parameters correlated between parents and their offspring. Mothers had higher systolic blood pressure, fathers had a higher body mass index and parents had more frequently high fasting glucose levels than age-and sex-matched references. Children had significantly higher systolic and diastolic blood pressure than sexand height-matched references. Twenty-four percent (mothers) and 10% (fathers) were born SGA but they did not have more cardiovascular risk factors than those born appropriate for gestational age. Cardiovascular risk factors did not correlate between parents and children. In conclusion, parents of short SGA children have a modest increase in some cardiovascular risk factors but risk factors did not correlate between parents and children. E pidemiologic studies reported an inverse association between birth weight and risk for cardiovascular disease (CVD) in adult life (1-3). In addition, some studies described a relation between birth weight of offspring and subsequent cardiovascular mortality of the parents (4,5). The exact mechanism behind these associations and the relative roles of environmental and genetic factors has not yet been elucidated. A familial component has been proposed (4,5), but others could not find a family history of CVD as explanation for the higher prevalence of cardiovascular risk factors in subjects born with a lower birth weight (6). Clustering of cardiovascular risk factors within families has also been described irrespective of birth weight (7,8), whereas there is a relation between birth weight of parents and offspring (9,10).Short small for gestational age (SGA) children constitute a special group within the group of low birth weight children because they did not reach a normal height. An increased prevalence of cardiovascular risk factors in short SGA children has been described (11,12). Some parents of short SGA children were born SGA themselves (13,14). It is unknown whether an increased risk for CVD in a short SGA child can be predicted by the presence of risk factors in his/her parents. We hypothesized that parents of short SGA children have an increased risk for CVD. In addition, we hypothesized that a relative high percentage of parents was born SGA themselves and that anthropometric data and cardiovascular risk factors correlate between parents and children. We, therefore evaluated in parents of short SGA children anthropometry, blood pressure, fasting serum lipids, glucos...

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High Serum Levels of Growth Hormone (GH) and Insulin-Like Growth Factor-I (IGF-I) during High-Dose GH Treatment in Short Children Born Small for Gestational Age

Abstract: Our study shows that high-dose GH treatment in short SGA children results in high serum GH and IGF-I levels in most children. We recommend monitoring IGF-I levels during GH therapy to ensure that these remain within the normal range.

Cited by 44 publications

References 37 publications

Randomized GH trial with two different dosages in combination with a GnRH analogue in short small for gestational age children: effects on metabolic profile and serum GH, IGF1, and IGFBP3 levels

Randomized GH trial with two different dosages in combination with a GnRH analogue in short small for gestational age children: effects on metabolic profile and serum GH, IGF1, and IGFBP3 levels

Familial short stature with IGF-I receptor gene anomaly [Review]

Cardiovascular Risk Factors in Parents of Short Children Born Small for Gestational Age

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