Serum Levels of Ghrelin, Leptin, IGF-I, IGFBP-3, Insulin, Thyroid Hormones and Cortisol in Prepubertal Children with Iron Deficiency

Stimulation of pituitary GH secretion with administered GHRH can be effective therapy for those GH deficient (GHD) patients whose disorder results from insufficient endogenous GHRH secretion. We have previously shown that most such patients also respond acutely to the GH-releasing peptides (GHRP’s), which have a different mechanism of action from GHRH, with release of GH. In this study we tested whether the GH response to a newer GHRP, GHRP-2, would be sustained over time. Six prepubertal children with GHD and growth failure received stepwise increasing sc doses of GHRP-2, at 0.3, 1.0, and 3.0 μg/kg/day, in successive 2-month treatment periods, with monitoring of overnight 12 h episodic GH secretion and toxicity measures at the end of each period. During a fourth 2-month period, they received 3 μg/kg GHRP-2 together with 3 μg/kg sc GHRH. Serum levels of IGF-I and IGFBP-3 were also measured, and stadiometer height measurements were recorded. GHRP-2 administration produced a dosewise increase in overnight GH secretion. GH profiles showed that the effect of GHRP-2 injections was relatively brief, with little effect upon GH secretion later in the night. Serum levels of IGF-I and of IGFBP-3 did not increase. Growth velocity was higher during GHRP-2 treatment than during pretreatment and post-treatment evaluations. There were no side effects or toxicities observed. Thus GHRP-2 is well tolerated and is able to stimulate GH secretion. Formulations or routes of administration that allow for a longer duration of action will likely be needed to use GHRP-2 in therapy.

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Free Insulin-Like Growth Factor I Serum Levels in 1430 Healthy Children and Adults, and Its Diagnostic Value in Patients Suspected of Growth Hormone Deficiency1

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.82.8.4137 ◽

1997 ◽

Vol 82 (8) ◽

pp. 2497-2502 ◽

Cited By ~ 1

Author(s):

Anders Juul ◽

Kirsten Holm ◽

Knud W. Kastrup ◽

Søren A. Pedersen ◽

Kim Fleischer Michaelsen ◽

...

Keyword(s):

Growth Factor ◽

Serum Levels ◽

Diagnostic Value ◽

Healthy Children ◽

Provocative Test ◽

Prepubertal Children ◽

Factor I ◽

Igf I ◽

Igfbp 3

Serum levels of total insulin-like growth factor I (IGF-I) and IGF-binding protein-3 (IGFBP-3) reflect endogenous GH secretion in healthy children, which makes them good diagnostic markers for screening of GH deficiency (GHD) in short children, although some controversy still exists. Only a minor fraction of the total IGF-I circulates in its free form, which is believed to be the biologically active form. However, our knowledge of the clinical or physiological value of determination of free IGF-I in serum is limited at present. In adults, the diagnostic value of total IGF-I and IGFBP-3 determinations in patients suspected of GHD has only been reported in a few studies, whereas no previous reports on the diagnostic value of free IGF-I levels in adults suspected of GHD exist. Serum levels of free IGF-I were determined in 1430 healthy children, adolescents, and adults by a newly developed, commercially available immunoradiometric assay (Diagnostic Systems Laboratories) to establish valid normative data for this analysis. We studied the diagnostic value of free IGF-I in relation to total IGF-I and IGFBP-3 determinations in adults who were suspected of GHD. A GH provocative test, using oral clonidine, was performed in 108 adult patients who had previously been treated with GH in childhood. In healthy subjects, free IGF-I levels increased during childhood, with the highest mean values during puberty. After puberty, a subsequent decline in serum levels of free IGF-I was apparent. We found unmeasurable free IGF-I values in 34 of the prepubertal children (3.3%). All individuals over 8 yr of age had measurable free IGF-I levels that amounted to approximately 1% of the total IGF-I concentrations. Free IGF-I levels were below −2 sd in 56 of 79 GHD patients (sensitivity, 71%) and above −2 sd in 24 of 29 patients with a normal GH response (specificity, 83%). Multiple linear regression analysis demonstrated that free IGF-I was significantly dependent on peak GH levels, duration of the disease, and number of other pituitary axes affected. We conclude that free IGF-I serum levels increase during childhood with a peak in puberty, whereafter free IGF-I levels return to prepubertal levels. Three percent of healthy prepubertal children had unmeasurable free IGF-I levels using this assay. We found that determination of the free IGF-I serum concentration may predict the outcome of a GH provocative test in adults suspected of GHD, but that a single determination of free IGF-I offered no significant advantage compared to determination of total IGF-I or IGFBP-3 serum levels.

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Serum levels of free insulin-like growth factor (IGF)-I and IGF-binding protein-1 in prepubertal children with idiopathic short stature

Clinical Endocrinology ◽

10.1046/j.1365-2265.2000.01145.x ◽

2000 ◽

Vol 53 (6) ◽

pp. 683-688 ◽

Cited By ~ 10

Author(s):

Tomohiro Kamoda ◽

Hisako Saitoh ◽

Takeki Hirano ◽

Akira Matsui

Keyword(s):

Growth Factor ◽

Short Stature ◽

Serum Levels ◽

Idiopathic Short Stature ◽

Insulin Like Growth Factor ◽

Prepubertal Children ◽

Free Insulin ◽

Igf I ◽

Igf Binding ◽

Igf Binding Protein

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Serum levels of insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) in healthy infants, children, and adolescents: the relation to IGF-I, IGF-II, IGFBP-1, IGFBP-2, age, sex, body mass index, and pubertal maturation.

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.80.8.7543116 ◽

1995 ◽

Vol 80 (8) ◽

pp. 2534-2542 ◽

Cited By ~ 9

Author(s):

A Juul ◽

P Dalgaard ◽

W F Blum ◽

P Bang ◽

K Hall ◽

...

Keyword(s):

Body Mass Index ◽

Growth Factor ◽

Children And Adolescents ◽

Body Mass ◽

Serum Levels ◽

Healthy Infants ◽

Igf I ◽

Igf Binding ◽

Igf Binding Protein ◽

Igfbp 3

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Relationship of insulin-like growth factor (IGF) binding protein-3 (IGFBP-3) gene polymorphism with the susceptibility to development of prostate cancer and influence on serum levels of IGF-I, and IGFBP-3

Growth Hormone & IGF Research ◽

10.1016/j.ghir.2011.03.008 ◽

2011 ◽

Vol 21 (3) ◽

pp. 146-154 ◽

Cited By ~ 12

Author(s):

Mohammad Reza Safarinejad ◽

Nayyer Shafiei ◽

Shiva Safarinejad

Keyword(s):

Prostate Cancer ◽

Growth Factor ◽

Gene Polymorphism ◽

Serum Levels ◽

Insulin Like Growth Factor ◽

Igf I ◽

Igf Binding ◽

Igf Binding Protein ◽

Relationship Of ◽

Igfbp 3

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Influence of peritoneal loss of GHBP, IGF-I and IGFBP-3 on serum levels in children with ESRD

Nephrology Dialysis Transplantation ◽

10.1093/ndt/14.1.257 ◽

1999 ◽

Vol 14 (1) ◽

pp. 257-258 ◽

Cited By ~ 2

Author(s):

H van der Kamp

Keyword(s):

Serum Levels ◽

Igf I ◽

Igfbp 3

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Serum levels of insulin-like growth factors (IGF-I and IGF-II) and their binding protein (IGFBP-3) are not elevated in pancreatic cancer

International Journal of Gastrointestinal Cancer ◽

10.1007/bf02787466 ◽

1997 ◽

Vol 22 (2) ◽

pp. 95-100

Author(s):

James D. Evans ◽

Margaret C. Eggo ◽

Ian A. Donovan ◽

Simon R. Bramhall ◽

John P. Neoptolemos

Keyword(s):

Pancreatic Cancer ◽

Growth Factors ◽

Binding Protein ◽

Serum Levels ◽

Igf I ◽

Igfbp 3 ◽

Insulin Like Growth Factors

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Abnormal Sex Chromosome Constitution and Longitudinal Growth: Serum Levels of Insulin-Like Growth Factor (IGF)-I, IGF Binding Protein-3, Luteinizing Hormone, and Testosterone in 109 Males with 47,XXY, 47,XYY, or Sex-Determining Region of the Y Chromosome (SRY)-Positive 46,XX Karyotypes

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2007-1426 ◽

2008 ◽

Vol 93 (1) ◽

pp. 169-176 ◽

Cited By ~ 47

Author(s):

Lise Aksglaede ◽

Niels E. Skakkebaek ◽

Anders Juul

Keyword(s):

Sex Chromosome ◽

Serum Levels ◽

Reproductive Hormones ◽

Chromosome Constitution ◽

Sitting Height ◽

Igf I ◽

Igf Binding ◽

Xx Males ◽

Igf Binding Protein ◽

Igfbp 3

Abstract Context: Growth is a highly complex process regulated by the interaction between sex steroids and the GH IGF-axis. However, other factors such as sex chromosome-related genes play independent roles. Aim: The aim of the study was to evaluate the role of abnormal chromosome constitution for longitudinal growth in relation to reproductive hormones, IGF-I, and IGF binding protein (IGFBP)-3. Setting: The study was conducted at an outpatient clinic, Copenhagen University Hospital. Participants: Participants included 86 47,XXY males, 14 46,XX-males, and nine 47,XYY. Main Outcome Measures: Standing and sitting height, serum levels of reproductive hormones, IGF-I, and IGFBP-3 were measured. Results: In boys with 47,XXY and 47,XYY karyotypes, growth was accelerated already in childhood, compared with healthy boys. 46,XX-males were significantly shorter than healthy boys but matched the stature of healthy girls. In 47,XXY sitting height to height ratios were lower than expected, whereas body proportions in 46,XX-males and 47,XYY were normal. In all subjects serum levels of IGF-I and IGFBP-3 were within normal limits. The boys with 46,XX and 47,XXY karyotypes presented with low normal testosterone and elevated LH levels after puberty, whereas the sex hormone secretion of the 47,XYY boys remained normal. Conclusion: We found accelerated growth in early childhood in boys with 47,XXY and 47,XYY karyotypes, whereas 46,XX-males were shorter than controls. These abnormal growth patterns were not reflected in circulating levels of IGF-I and IGFBP-3. The boys with 46,XX and 47,XXY karyotypes developed hypogonadism in puberty, but androgen secretion in 47,XYY boys remained normal. The abnormal stature of these patients may be a result of abnormal gene expression due to the underlying chromosome aberration resulting in excessive expression of growth-related genes.

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Abnormality of growth hormone and insulin-like growth factor I axis in advanced cancer patients

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.19671 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 19671-19671

Author(s):

T. Takahata ◽

M. Munakata ◽

Y. Sakata ◽

K. Nakagawa ◽

T. Mukaiyama ◽

...

Keyword(s):

Growth Hormone ◽

Growth Factor ◽

Thyroid Hormones ◽

Cancer Patients ◽

Performance Status ◽

Insulin Like Growth Factor ◽

Igf I ◽

Cancer Anorexia ◽

Cachexia Syndrome ◽

Igfbp 3

19671 Background: Pituitary and thyroid hormones are known to be altered in anorexia nervosa, but few hormonal studies have been performed in cancer anorexia-cachexia syndrome. This study focused on growth hormone (GH) and Insulin-like Growth Factor (IGF)-I axis in cancer patients. Methods: To investigate the relationship among performance status (PS), nutritional and hormonal status, blood sampling was performed to measure GH, IGF-I, IGF-binding protein 3(IGFBP-3), T3, T4, complete blood counts and blood chemistry profiles for 15 cancer patients in each of PS0–1, PS2, PS3 and PS4 after the informed consent was obtained. Results: A total of 58 patients were evaluated including 15 patients in PS0–1, PS2 and PS3 and 13 in PS4. Hemoglobin and albumin levels went down along with progression of PS. GH level was high and T3 was low in poor PS. T4 and IGFBP-3 were lower in PS4 than those of other PS. There is a tendency of low IGF-I and thyroid hormones and high GH levels in poor PS as compared with those of good PS (p=0.0064 for IGF-I, p<0.001 for T3, and T4, not significant for GH analyzed by ANOVA). Conclusions: Abnormal GH - IGF-I axis was more pronounced in poor PS. It is conceivable that normalization of this abnormality can improve cancer anorexia-cachexia syndrome and new drug development for such normalizing agents is warranted. No significant financial relationships to disclose.

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