Jasper, H.G.
El factor de crecimiento insulinosímil tipo I (IGF-I) es el intermediario para la mayoría de las acciones de la hormo – na de crecimiento (GH). La mayor parte del IGF-I circulante está unido a proteínas de transporte específicas y de alta afinidad (IGFBPs, designadas IGFBP-1 a IGFBP-6). En condiciones fisiológicas la mayor parte del IGF-I sérico (~ 80%) se encuentra en un complejo ternario de alto peso molecular (150 kDa) junto con IGFBP-3 y una proteína ácido-lábil (ALS). La mayor parte del remanente (~ 20%) está en complejos binarios (de 40 – 50 kDa) asociado a otras IGFBPs. Se acepta que las IGFBPs modulan la acción del IGF-I. En los fluidos biológicos una pequeña pero significativa cantidad de IGF-I se encuentra libre. Se ha sugerido que éste IGF-I libre es el que está disponible para unirse a su receptor específi – co y ejercer sus acciones biológicas. La concentración en suero de IGF-I libre es menor al 0.5% del IGF-I total. Para da – tos bibliográficos acerca de éstos antecedentes ver citas 1 a 4.
The method developed by Frystyk et al 7 has been widely accepted as the standard of reference. It involves ultrafiltration of serum at stable physiologic conditions of temperature and pH; and the availability of an IGF-I assay of great sensitivity and specificity, capable to measure quantities of the order of 0.1 ng/ml. There is also commercially available an IRMA assay, based upon a capture antibody, supposedly able to recognize only free IGF-I. Lately, the manufacturer stated it measures free plus easily dissociable IGF-I 6,8. Studies with IRMA free IGF-I: normal infants, below age 1 yr, show free IGF-I levels close to 2% of total IGF-I, higher than those of adults and prepubertal and pubertal children (~1%) 9,10. Absolute values peak markedly during puberty 9,11, albeit earlier in girls than in boys. When used to diagnose childhood GH deficiency, IRMA f ree IGF-I levels 1 2 show sensitivity of 94%, specificity of 80%, and a diagnostic efficiency of 83%. The values for total IGF-I were 100%, 82%, and 88%, respectively. As far as we know, in most reports the diagnostic eff i c i e n c y of total IGF-I has been equal to, or higher than that of IRMA free IGF-I. When applied to an adult population for the diagnosis of active acromegaly 13, both IRMA free IGF-I and total IGF-I showed similar sensitivity (94 and 100 %, respectively). Diagnosing GH deficiency their sensitivity was reduced, and again that of IRMA free IGF-I was lower than that of total IGF-I (35 vs 41 %) 13. Studies with ultrafiltered free IGF-I (IGF-I uf): there is scant normal data, although it is known that during puberty there is an increase in IGF-I uf values over prepubertal levels 14. When comparing IGF-I uf vs the free IGF-I IRMA completely different results were obtained if the same samples were analized by both methods 8, confirming that one is measuring free IGF-I and the other free plus easily dissociable IGF-I. IGF-I uf is low in GH deficient adults, although some values overlap with controls 7; it is clearly increased in active acromegalics, and reduced in type I diabetics 1 6. Uremic patients, and subjects with nervous anorexia also show reduced IGF-I uf 8. Due to the relatively reduced number of patients included in the published reports, the sensitivity, specificity and diagnostic efficiency for GH excess or deficiency remain to be elucidated. When considering which form of IGF-I, the total circulating, the free circulating, the bioactive circulating, or the locally produced at the target organ level, is most directly related to growth, some data from human pathology was found relevant 20-25. It tends to indicate to the locally produced IGF-I as the one most directly related to growth.