Biochemical Diagnostic Strategies in the Evaluation of Short Stature: The Diagnosis of Insulin-Like Growth Factor Deficiency

1996 ◽  
Vol 46 (4-5) ◽  
pp. 170-173 ◽  
Author(s):  
Ron G. Rosenfeld
Keyword(s):  
Growth Factor ◽  
Short Stature ◽  
Insulin Like Growth Factor ◽  
Diagnostic Strategies ◽  
Factor Deficiency

The Role of Auxologic and Growth Factor Measurements in the Diagnosis of Growth Hormone Deficiency

PEDIATRICS ◽  
1998 ◽  
Vol 102 (Supplement_3) ◽  
pp. 524-526
Author(s):  
Raymond L. Hintz
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Growth Hormone Deficiency ◽  
Short Stature ◽  
The Body ◽  
Hormone Deficiency ◽  
Insulin Like Growth Factor ◽  
Growth Study ◽  
Short Children ◽  
National Cooperative

The use of auxologic measurements in the diagnosis of short stature in children has a long history in pediatric endocrinology, and they have even been used as the primary criteria in selecting children for growth hormone (GH) therapy. Certainly, an abnormality in the control of growth is more likely in short children than in children of normal stature. However, most studies have shown little or no value of auxologic criteria in differentiating short children who have classic growth hormone deficiency (GHD) from short children who do not. In National Cooperative Growth Study Substudy VI, in more than 6000 children being assessed for short stature, the overall mean height SD score was −2.5 ± 1.1 and the body mass index standard deviation score was −0.5 ± 1.4. However, there were no significant differences in these measures between the patients who were found subsequently to have GHD and those who were not. There also was no consistent difference in the growth rates between the patients with classic GHD and those short children without a diagnosis of GHD. This probably reflects the fact that we are dealing with a selected population of children who were referred for short stature and are further selecting those who are the shortest for additional investigation. Growth factor measurements have been somewhat more useful in selecting patients with GHD and have been proposed as primary diagnostic criteria. However, in National Cooperative Growth Study Substudy VI, only small differences in the levels of insulin-like growth factor I and insulin-like growth factor binding protein 3 were seen between the patients who were selected for GH treatment and those who were not. Many studies indicate that the primary value of growth factor measurements is to exclude patients who are unlikely to have GHD or to identify those patients in whom an expedited work-up should be performed. The diagnosis of GHD remains difficult and must be based on all of the data possible and the best judgment of an experienced clinician. Even under ideal circumstances, errors of both overdiagnosis and underdiagnosis of GHD still are likely.

Insulin-like growth factor ternary complex components as biomarkers for the diagnosis of short stature

2021 ◽  
Vol 185 (5) ◽  
pp. 629-635
Author(s):  
Aristeidis Giannakopoulos ◽  
Alexandra Efthymiadou ◽  
Dionisios Chrysis
Keyword(s):  
Growth Factor ◽  
Short Stature ◽  
Ternary Complex ◽  
Final Height ◽  
Hormone Deficiency ◽  
Receiver Operating Curve ◽  
Insulin Like Growth Factor ◽  
Igf I ◽  
Stimulation Tests ◽  
Igfbp 3

Objective The diagnosis of growth hormone deficiency (GHD) in children is not always straightforward because insulin-like growth factor 1 (IGF-I) or GH stimulation tests may not be able to discriminate GHD from constitutional delay of growth and puberty (CDGP) or other causes of short stature. Design Boys and girls (n = 429, 0.7–16 years) who attended our department for short stature participated in this study. They were followed up for an average period of 9 years. At the end of follow-up after reaching the final height, a definitive diagnosis was assigned, and all the components of ternary complex (IGF-I, IGF-binding protein-3 (IGFBP-3), acid-labile subunit (ALS), and IGF-I/IGFBP-3 ratio) were evaluated as biomarkers for the respective diagnosis. Results All the components of the ternary complex were tightly correlated with each other and were positively related to age. IGF-I, IGFBP-3, ALS, and IGF-I/IGFBP-3 ratio differed significantly between GHD and normal groups. IGF-I and ALS levels were lower in GHD compared to children with familial short stature, while IGF-I and IGF-I/IGFBP-3 ratio was significantly lower in GHD compared to children with CDGP. IGF-I and IGF-I/IGFBP-3 receiver operating curve cutoff points were unable to discriminate between GHD and normal groups or between GHD and CDGP groups. Conclusion Despite the tight correlation among all the components of the ternary complex, each one shows a statistically significant diagnosis-dependent alteration. There is a superiority of IGF-I, ALS, and IGF-I/IGFBP-3 ratio in the distinction between GHD and CDGP or between GHD and normal groups but without usable discriminating power, making auxology as the primary criterion for establishing the diagnosis.

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.

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