Información del artículo
Los factores de crecimiento similares a la insulina (IGF, de insulin-like growth factors) son unos péptidos estructuralmente relacionados con la insulina, que tienen acción estimuladora del crecimiento, potencian la acción de la insulina y regulan la proliferación celular. Aunque la expresión de IGF es ubicua, la mayor parte del IGF circulante es de origin hepático. Parece ser que una de las principales funciones del IGF-I circulante es el retrocontrol inhibitorio de la secreción de somatotropina, tanto hipofisaria como hipotalámica. En el plasma y en los fluidos biológicos, las IGF circulan unidas en su mayor parte a proteínas transportadoras de alta afinidad, las insulin-like growth factor binding proteins (IGFBP) que modulan su vida media, su interacción con el receptor y posiblemente desempeñen acciones directas en la proliferación celular. A estas proteínas, junto a los propios IGF y sus receptores, se les engloba actualmente en el llamado sistema IGF, que tiene una gran trascendencia en el crecimiento y la diferenciación de células normales y malignas. La determinación de los diferentes componentes del sistema IGF tiene gran utilidad en el diagnóstico y la monitorización del tratamiento en pacientes con alteraciones del eje GH-IGF. En este artículo se revisarán los aspectos preanalíticos y analíticos que deben conocerse para la correcta interpretación de los resultados.
Palabras clave:
Factores de crecimiento similares a la insulina
IGF-I
IGF-II
Proteínas enlazantes de los factores de crecimiento similares a la insulina
IGFBP-3
Subunidad acidolábil
Métodos de laboratorio
Condiciones preanalíticas
Insulin-like growth factors (IGFs) are peptides which are structurally related to insulin and which stimulate growth,enhance the action of insulin, and regulate cell proliferation. Although IGF expression is ubiquitous, most circulating IGF is produced in the liver. One of the main functions of circulating IGF-I is to exercise inhibitory feedback on growth hormone (GH) secretion, in both the pituitary gland and hypothalamus. In plasma and biological fluids, IGFs mainly circulate together with insulin-like growth factor binding proteins (IGFBPs), which modulate their half-life and interaction with the receptor and possibly exert direct actions on cell proliferation. These proteins,together with IGFs and their receptors, are currently included under the term IGF system, which is of great importance in the growth and differentiation of both normal and malignant cells. Determination of the distinct components of the IGF system is highly useful in the diagnosis and monitoring of treatment in patients with alterations in the IGF-GH axis. The present article reviews the preanalytical and laboratory features that should be known for correct interpretation of results.
Key words:
Insulin-like growth factors
IGF-1
IGF-II
Insulin-like growth factor binding proteins
IGFBP-3
Acid-labile subunit
Laboratory methods
Preanalytical conditions
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Bibliografía
[1.]
S. Rajaram, D.J. Baylink, S. Mohan.
Insulin-like growth factorbinding proteins in serum and other biological fluids: regulation and functions.
Endocr Rev, 18 (1997), pp. 801-831
[2.]
V. Hwa, Y. Oh, R.G. Rosenfeld.
The insulin-like growth factorbinding protein (IGFBP) superfamily.
Endocr Rev, 20 (1999), pp. 761-787
[3.]
J. Argente, V. Barrios, J. Pozo, M.T. Muñoz, F. Hervas, M. Stene, et al.
Normative data for insulin-like growth factors (IGFs), IGF binding proteins, and growth hormone-binding protein in a healthy Spanish pediatric population: age- and sex-related changes.
J Clin Endocrinol Metab, 77 (1993), pp. 1522-1528
[4.]
M.A. Andrade Olivié, R.V. García-Mayor, D. González Lestón, T. Rodríguez Sousa, A. Segura Domínguez, R. Álvarez-Novoa, et al.
Serum insulin-like growth factor (IGF) binding protein-3and IGF-I levels during childhood and adolescence. A crosssectional study.
Pediatr Res, 38 (1995), pp. 149-155
[5.]
A. Juul, P. Bang, N.T. Hertel, K. Main, P. Dalgaard, K. Jorgensen, et al.
Serum insulin-like growth factor-I in 1,030 healthy children,adolescents, and adults: relation to age, sex, stage of puberty,testicular size, and body mass index.
J Clin Endocrinol Metab, 78 (1994), pp. 744-752
[6.]
G. Bravant, A. Von zur Muhlen, C. Wuster, M.B. Ranke, J. Kratzsch, W. Kiess, et al.
Serum Insulin-like growth factor I reference values for an automated chemiluminescence immunoassay system:results from a multicentre study.
Horm Res, 60 (2003), pp. 53-60
[7.]
K. Landin-Wilhelmsen, L. Wilhelmsen, G. Lappas, T. Rosen, G. Lindstedt, P.A. Lundberg, et al.
Serum insulin-like growth factor I in a random population sample of men and women: relation to age, sex, smoking habits, coffee consumption and physical activity, blood pressure and concentrations of plasma lipids, fibrinogen, parathyroid hormone and osteocalcin.
Clin Endocrinol (Oxf), 41 (1994), pp. 351-357
[8.]
A. Juul, P. Dalgaard, W.F. Blum, P. Bang, K. Hall, K.F. Michaelsen, et al.
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.
J Clin Endocrinol Metab, 80 (1995), pp. 2534-2542
[9.]
A. Juul, K. Holm, K.W. Kastrup, S.A. Pedersen, K.F. Michaelsen, T. Scheike, et al.
Free insulin-like growth factor I serum levels in 1,430 healthy children and adults, and its diagnostic value in patients suspected of growth hormone deficiency.
J Clin Endocrinol Metab, 82 (1997), pp. 2497-2502
[10.]
M.L. Granada, J. Murillo, A. Lucas, I. Salinas, M.A. Llopis, I. Castells, et al.
Diagnostic efficiency of serum IGF-I, IGF-binding protein-3 (IGFBP-3), IGF-I/IGFBP-3 molar ratio and urinary GH measurements in the diagnosis of adult GH deficiency: importance of an appropriate reference population.
Eur J Endocrinol, 143 (2000), pp. 243-253
[11.]
C. Löfqvist, E. Andersson, L. Gelander, S. Rosberg, W.F. Blum, K. Albertsson Wikland.
Reference values for IGF-I throughout Childhood and adolescence: a model that accounts simultaneously for the effect of gender, age, and puberty.
J Clin Endocrinol Metab, 86 (2001), pp. 5870-5876
[12.]
C. Löfqvist, E. Andersson, L. Gelander, S. Rosberg, L. Hulthen, W.F. Blum, et al.
Reference Values for Insulin-Like Growth Factor-Binding Protein-3 (IGFBP-3) and the Ratio of Insulin-Like Growth Factor-I to IGFBP-3 throughout Childhood and Adolescence.
J Clin Endocrinol Metab, 90 (2005), pp. 1420-1427
[13.]
J.M. Gomez, F.J. Maravall, N. Gomez, M.A. Navarro, R. Casamitjana, J. Soler, et al.
The IGF-I system component concentrations that decrease with ageing are lower in obesity in relationship to body mass index and body fat.
Growth Horm IGF Res, 14 (2004), pp. 91-96
[14.]
D.R. Clemmons.
Commercial assays available for insulin-like growth I and their use in diagnosing growth hormone deficiency.
Horn Res, 55 (2001), pp. 73-79
[15.]
V. Quamby, C. Quan, V. Ling, P. Compton, E. Canova-Davis.
How much insulin-like growth factor I (IGF-I) circulates? Impact of standardization on IGF-I assay accuracy.
J Clin Endocrinol Metab, 83 (1998), pp. 1211-1216
[16.]
P. Bang, Participants in the 3rd International symposium on insulin-like growth factors.
Valid measurements of total IGF concentrations in biological fluids.
Endocrinology, 136 (1995), pp. 816-817
[17.]
S. Mohan, D.J. Baylink.
Development of a simple valid method for the complete removal of insulin-like growth factor IIGF)-binding proteins from IGFs in human serum and other biological fluids: comparison with acid-ethanol treatment and C18 Sep-Pak separation.
J Clin Endocrinol Metab, 80 (1995), pp. 637-647
[18.]
W.H. Daughaday, M. Kapdiaq, I. Mariz.
Serum somatomedin binding proteins: physiologic significance and interference in radioinmunoassays.
J Lab Clin Med, 109 (1987), pp. 355-363
[19.]
W.F. Blum, B.H. Breier.
Radioimmunoassays sor IGFs and IGFBPs.
Growth Regul, 4 (1994), pp. 1-19
[20.]
J. Frystyk, C. Skjærbæk, B. Dinesen, H. Ørskov.
Free insulin-like growth factors (IGF-I and IGF-II) in human serum.
FEBS Lett, 348 (1994), pp. 185-191
[21.]
J. Frystyk, P. Ivarsen, R.K. Støving, R. Dall, T. Bek, C. Hagen, et al.
Determination of free insulin-like growth factor-I in human serum: comparison of ultrafiltration and direct immunoradiometric assay.
Growth Horm IGF Res, 11 (2001), pp. 117-127
[22.]
R. Rajah, B. Valentinis, P. Cohen.
Insulin-like growth factor-binding protein-3 induces apoptosis and mediates the effects of transforming growth factor-β on programmed cell death through a p53- and IGF- independent mechanism.
J Biol Chem, 272 (1997), pp. 12181-12184
[23.]
L. Giudice, E. Farrell, H. Pham, G. Lamson, R. Rosenfeld.
Insulin-like growth factor binding proteins in maternal serum throughout gestation and in the puerperium: effect of a pregnancy associated serum protease activity.
J Clin Endocrinol Metab, 71 (1990), pp. 806-816
[24.]
A. Diamandi, J. Mistry, R.G. Krishna, J. Khosravi.
Immunoassay of insulin-like growth factor-binding protein-3 (IGFBP-3): new means to quantifying IGFBP-3 proteolysis.
J Clin Endocrinol Metab, 85 (2000), pp. 2327-2333
[25.]
C. Lassarre, M. Binous.
Measurement of intact insulin-like growth factor-binding protein-3 in human plasma using a ligand immunofunctional assay.
J Clin Endocrinol Metab, 86 (2001), pp. 1260-1266
[26.]
R.C. Baxter.
Characterzation of the acid-labile subunit of the growth hormone-dependent insulin-like growth factor binding protein complex.
J Clin Endocrinol Metab, 67 (1988), pp. 265-272
[27.]
K.M. Morrison, Z. Wu, M. Bidlingmaier, C.J. Strasburger.
Findings and theoretical considerations on the usefulness of the acid-labile subunit in the monitoring of acromegaly.
Growth hormone & IGF Research, (2001), pp. S61-S63
[28.]
A.G. Renehan, A.A. Toogood, W.D. Ryder, J. Jones, C.S. Potten, S.T. O’Dwyer, et al.
Paradoxical elevations in serum IGF-II and IGF binding protein-2 in acromegaly: insights into the regulation of these peptides.
Clin Endocrinol (Oxf), 55 (2001), pp. 469-475
[29.]
D. Le Roith, A.A. Butler.
Insulin-like growth factors in pediatric health and disease.
J Clin Endocrinol Metab, 84 (1999), pp. 4355-4361
[30.]
R.C. Baxter, W.H. Daughaday.
Impaired formation of the ternary insulin-like growth factor-binding protein complex in patients with hypoglicemia due to nonislet cell tumors.
J Clin Endocrinol Metab, 73 (1991), pp. 696-702
[31.]
H. Yu, J. Mistry, M.J. Nicar, M.J. Khosravi, A. Diamandis, J. Van Doorn, et al.
Insulin-like growth factors (IGF-I, free IGF-I,and IGF-II) and insulin-like growth factor binding proteins (IGFBP-2, IGFBP-3, IGFBP-6, and ALS) in blood circulation.
J Clin Lab Analysis, 13 (1999), pp. 166-172
[32.]
J. Khosravi, A. Diamandi, U. Bodani, N. Khaja, R.G. Krishna.
Pitfalls of immunoassay and simple for IGF-I: comparison of different assay methodologies using various fresh and stored serum simples.
Clin Chem, 38 (2005), pp. 659-666
[33.]
R. Casamitjana, M. Mauri.
Sociedad Española de Bioquímica Clínica y Patología Molecular Comisión de Hormonas. Diagnóstico bioquímico del retraso de crecimiento.
Quim Clin, 16 (1997), pp. 36-42
[34.]
Consensus guidelines for the diagnosis and treatment of GH deficiency in childhood and adolescence: summary statement of the GH Research Society. J Clin Endocrinol Metab. 2000; 85:3990-3.
[35.]
S.M. Shalet, A. Toogood, A. Rahim, B.M. Brennan.
The diagnosis of growth hormone deficiency in children and adults.
Endocr Rev, 19 (1998), pp. 203-223
[36.]
Consensus guidelines for the diagnosis and treatment of adults with GH deficiency: summary statement of the GH Research Society workshop on adult growth hormone deficiency. J Clin Endocrinol Metab. 1998;83:379.
[37.]
J. Frystyk.
Use of free and total IGF assays in clinical practice and research.
Pituitary and periphery:communication in and out, pp. 175-191
[38.]
A. Giustina, A. Barkan, F.F. Casanueva, F. Cavagnini, L. Frohman, K. Ho, et al.
Criteria for cure of acromegaly: a consensus statement.
J Clin Endocrinol Metab, 85 (2000), pp. 526-529
[39.]
C. Parkinson, W.D. Ryder, P.J. Trainer.
The relationship between serum GH and serum IGF-I in acromegaly is gender-specific.
J Clin Endocrinol Metab, 86 (2001), pp. 5240-5244
[40.]
A.L. Barkan, I. Halassz, K.J. Dornfeld, C.A. Jaffe, R. DeMott, W.F. Chandler, et al.
Pituitary irradiation is ineffective in normalizing plasma insulin-like growth factor I in patients with acromegaly.
J Clin Endocrinol Metab, 82 (1997), pp. 3187-3191
[41.]
M.O. Thorner, C.J. Strasburger, Z. Wu, M. Straume, M. Bidlingmaier, S.S. Pezzoli, et al.
Growth hormone (GH) receptor blockade with a PEG-modified GH (B2036-PEG) lowers serum insulinlike growth factor-I but does not acutely stimulate serum GH.
J Clin Endocrinol Metab, 84 (1999), pp. 2098-2103
[42.]
Biochemical assessment and long-term monitoring in patients with acromegaly: statement from a joint consensus conference of the Growth Hormone Research Society and the Pituitary Society. J Clin Endocrinol Metab. 2004;89:3099-102.
[43.]
A. Mukherjee, J.P. Monson, P.J. Jonsson, P.J. Trainer, S.M. Shalet.
Seeking the optimal target range for insulin-like growth factor I during the treatment of adult growth hormone disorders.
J Clin Endocrinol Metab, 88 (2003), pp. 5865-5870
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