IGF-1 Levels in Down Syndrome
Letizia Ragusa, Proto, Alberti, Corrado Romano, Rossodivita and Colabucci
The authors examined IgF-1 plasma levels in 113 patients with Down Syndrome (DS) (68 males and 45 females, aged 1-23.66 years), all without severe congenital malformations, malnutrition, coeliac disease, alterations in thyroid or adrenal function, or taking any medication which might affect the study. The authors used a radioimmunoassay (RIA) method with plasma previously treated by acid-ethanol extraction and correlated the IgF-1 plasma levels with age and BMI (Body Mass Index) using multiple regression analysis. The BMI was higher in Down syndrome compared with normal subjects (NS), both in males (p=0.000006) and females (p= 0.034829). The two groups showed a positive correlation of IgF-1 levels with age. However, no correlation was found between IgF-1 levels and BMI.
Ragusa L, Proto C, Alberti A, Romano C, Rossodivita A, Colabucci F. IGF-1 Levels in Down Syndrome. Down Syndrome Research and Practice. 1998;5(3);123-125.
* From a paper presented at the 6th World Congress on Down Syndrome, Madrid,
Spain, October 1997.
Growth Retardation (GR) is one of the main features in Down syndrome (Jones,
1988) and becomes manifest from the age of 6 months, when growth hormone
(GH) usually starts acting (Anneren,
Growth hormone controls the production of Insulin-like Growth Factors (IgFs),
of which two main forms have been identified in human plasma: the active
form (SmC/IgF-1) and the neutral form (IgF-2). These IgFs are bound to specific
proteins in blood and no free forms are known. They stabilise the serum
concentration and delay the half-life of somatomedins. IgF-1 has a molecular
weight of 7649 daltons and is encoded by a single gene localised in the
long arm of chromosome 12. The IgF binding protein complex can be separated
after acid treatment (Furlanetto, RW 1977).
IgF-1 levels are influenced by age and diet. They are low in children with
protein malnutrition, hypothyroidism, coeliac disease and anorexia nervosa
1985). Depressed IgF-1 concentrations have been found in cirrhosis of
the liver and other hepato-cellular diseases.
In patients with end-stage renal failure, serum somatomedin concentrations
have been reported as low, normal or elevated, depending on the assay technique
used (Takano, 1979).
Sara found that while foetal somatomedins, determined by radio-immune assay
(RIA), were scarcely detectable in the first Down syndrome foetus examined
a significant amount was observed in the youngest age group examined (Sara,
1981). This increase remained constant throught life (Sara,
1983). Normal brain receptors for Insulin, IgF-1 and IgF-2 have been
found in foetuses with Down syndrome (Sara,
1984). Anneren et al (1990) found normal values of RIA IgF-2, but low
levels of RIA IgF-1, and they hypothesised a delay in maturation and incomplete
switching from the foetal to the GH-dependent form of IgF-1. Barreca et
al measured IgF-1 plasma levels in 39 children affected by Down syndrome,
and found a positive correlation with age. In Down syndrome obesity is frequent
1985), probably due to eating behaviour disorders and/or reduced physical
The aim of this study was to detect the IgF-1 plasma levels in subjects
with Down syndrome, and to determine whether there is a correlation with
age and BMI.
Materials and Methods
One hundred and thirteen subjects with Down syndrome (68 males and 45 females,
aged 1-23.66 years and 1-23.8 years respectively), followed routinely at
the Oasi Institute, were submitted to IgF-1 plasma assay. Body weight was
measured on standard scales and height was measured using a Harpenden stadiometer.
Pubertal stage was recorded, using Tanner's method. There was no evidence
of severe congenital malformations, malnutrition, coeliac disease, or alterations
of thyroid or adrenal function. None of the patients were taking any medication
which might have influenced the study. Blood samples were collected in test-tubes
containing EDTA, and were immediately separated and frozen at -20º C until
Body Mass Index (BMI) was also calculated, (body weight divided by height
IgF-1 radio-immuno assay (RIA) was performed (Nichols Institute diagnostic
kit, san Juan Capistrano, USA). Plasma samples were matched beforehand with
an ethanol-chloridric acid mix (ratio 87.5% ethanol 12.5% chloridric acid).
The supernatant was neutralized by adding 0.855 M Tris-base, and was transferred
into test-tubes containing 1.4 ml of buffer solution. Final dilution was
IgF-1 standards, obtained with DNA-recombinant techniques, were necessary
to produce a standard curve. This was calibrated against the WHO 1st International
Reference Reagent 1998, Insulin-like Growth Factor-1 87/518. Values were
expressed in ng/ml. The curve ranged from 0.3 to 4.9 ng/ml. The sensitivity
of levels was calculated to 0.06 ng/ml. The IgF-1 antiserum does not show
cross-reactivity with other peptide hormones.
This study was approved by the Ethical Committee of Oasi Institute. Informed
consent was obtained from the parents of all the subjects enrolled.
Multiple regression analysis was utilized to correlate IgF-1 with age, and
IgF-1 plasma levels were assayed for each pubertal stage in people with
Down syndrome. Table 1 shows the standard deviation and the mean of IgF-1
levels, age and BMI in Down syndrome males and females respectively.
Table 1. IgF-1 level, age and BMI found in Down syndrome
||Down syndrome females (n= 45)
||Down syndrome males (n=68)
|IgF-1 level (ng/ml)
Table 2 shows the multiple regression analysis of IgF-1 levels against age,
and IgF-1 levels against BMI in the two groups. The two groups show a significant
positive correlation of IgF-1 levels with age. However, no correlation was
found between IgF-1 levels and BMI.
Table 2. Multiple regression analysis between IgF-1 level,
age and BMI in Down syndrome
||Down syndrome females (n= 45)
||Down syndrome males (n=68)
We have confirmed a positive correlation between IgF-1 levels and age (Barreca,
1994). We believe that early reports (Anneren
et al, 1990) suggesting an IgF-1 selective deficiency in Down syndrome
similar to that in Pygmies must have been based on a different methodology.
The BMI figures were significantly higher in Down syndrome compared with
normal subjects, and this is further evidence suggesting higher levels of
obesity in this group (Cronck
et al, 1985).
No correlation between IgF-1 and BMI was found. It follows that BMI remains
a reliable tool for the diagnosis of overweight and/or obesity in Down syndrome.
The same, however, cannot be said for IgF-1 levels, because, as shown above,
they do not correlate with BMI.
Letizia Ragusa, MD, Department of Endocrinology, OASI Institute (IRCCS).
Via Conte Ruggero 73; 94018 Troina (En), Italy. (Phone: 39-935-936111, Fax:
39-935-653327, E-mail: firstname.lastname@example.org)
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