IGF-I Treatment of Growth Hormone Insensitivity

Rosenbloom, Arlan L.

doi:10.1007/978-1-59259-712-3_31

Cited by 16 publications

(5 citation statements)

References 114 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…28 Seventeen prepubertal Ecuadorian patients were entered into a randomized, double-blind, placebo-controlled trial. 29 Patients received IGF-I 120 μg/kg s.c. twice year of treatment-with IGF-I the increase was 63% of that with GH treatment of GH deficiency.…”

Section: Gh Insensitivity Disordersmentioning

confidence: 99%

Mecasermin (recombinant human insulin-like growth factor I)

Rosenbloom

2009

Adv Therapy

Self Cite

View full text Add to dashboard Cite

Growth hormone (GH) exercises its growth effects by stimulating insulin-like growth factor I (IGF-I) synthesis in the liver (endocrine IGF-I) and by inducing chondrocyte differentiation/replication and local production of IGF-I (paracrine/autocrine IGF-I). Injectable recombinant human (rh)IGF-I (mecasermin) has been available for nearly 20 years for treatment of the rare instances of GH insensitivity caused by GH receptor defects or GH-inhibiting antibodies. Full restoration of normal growth, as occurs with rhGH replacement of GH deficiency, is not seen, presumably because only the endocrine deficiency is addressed. RhIGF-I has also been effective as an insulin-sensitizing agent in severe insulin-resistant conditions. Although the insulin-sensitizing effect may benefit both type 1 and type 2 diabetes, there are no ongoing clinical trials because of concern about risk of retinopathy and other complications. Promotion of rhIGF-I for treatment of idiopathic short stature has been intensive, with neither data nor rationale suggesting that there might be a better response than has been documented with rhGH. Other applications that have either been considered or are undergoing clinical trial are based on the ubiquitous tissue-building properties of IGF-I and include chronic liver disease, cystic fibrosis, wound healing, AIDS muscle wasting, burns, osteoporosis, Crohn's disease, anorexia nervosa, Werner syndrome, X-linked severe combined immunodeficiency, Alzheimer's disease, muscular dystrophy, amyotrophic lateral sclerosis, hearing loss prevention, spinal cord injury, cardiovascular protection, and prevention of retinopathy of prematurity. The most frequent side effect is hypoglycemia, which is readily controlled by administration with meals. Other common adverse effects involve hyperplasia of lymphoid tissue, which may require tonsillectomy/adenoidectomy, accumulation of body fat, and coarsening of facies. The anti-apoptotic properties of IGF-I are implicated in cancer pathogenesis-a concern for long-term therapy. It is unlikely that mecasermin will be useful beyond the orphan indications of severe insulin resistance and GH insensitivity.

show abstract

Section: Gh Insensitivity Disordersmentioning

confidence: 99%

Mecasermin (recombinant human insulin-like growth factor I)

Rosenbloom

2009

Adv Therapy

Self Cite

View full text Add to dashboard Cite

show abstract

“…The child with GHIS has significant post-natal growth failure starting in early infancy [13,14]. Final adult heights in a cohort of patients reported by Laron et al [13] were only 119.5 (AE8.5 SD) cm for girls and only 124.1 (AE8.5 SD) cm for boys.…”

Section: Igf-i Treatment Of Ghismentioning

confidence: 95%

Therapeutic applications of the insulin-like growth factors

Savage

Camacho‐Hübner

2004

Growth Hormone & IGF Research

View full text Add to dashboard Cite

“…As a consequence the half-life of IGF-I was reduced from 20 h in the normal situation to only 6 h in the Laron dwarfs. Acromegaloid facial changes have been observed in some Laron dwarfs treated with IGF-I alone indicating that the amount of IGF-I reaching certain tissues is supraphysiologic [22]. Long-term exposure to supraphysiologic IGF-I levels may simultaneously induce in some tissues downregulation of IGF receptors, or postreceptor resistance to IGF-I action [20].…”

Section: Free Igf-i and The Igfbpsmentioning

confidence: 99%

Advantages and disadvantages of GH/IGF-I combination treatment

Janssen

2008

Rev Endocr Metab Disord

View full text Add to dashboard Cite

Growth hormone (GH) is the primary regulator of insulin-like growth factor-I (IGF-I) production in a wide variety of tissues. There is much overlap in the endocrine, metabolic and anabolic effects of GH and IGF-I but both hormones have divergent effects on glucose metabolism, insulin sensitivity and differentiation of prechondrocytes. Theoretically combined administration of GH and IGF-I may be more effective than GH alone or IGF-I alone. Arguments in favor for this are: 1] Clearance of IGF-I may be markedly altered by the co-administration of GH and this will provide sustained actions of IGF-I. 2] Higher serum IGF-I levels are achieved with a combination treatment of GH and IGF-I than with GH treatment alone or IGF-I alone. In addition, combination therapy may have additive or synergistic effects. 3] The combination GH and IGF-I counteracts disadvantageous effects on glucose metabolism of either GH alone or IGF-I alone. 4] GH may exert direct actions on tissues independently from IGF-I. 5] Combination of GH and IGF-I may be more effective in improving tissue IGF-I levels. The combination therapy of GH and IGF-I might be beneficial in growth retardation, in certain specific subgroups of critically ill or catabolic patients and in the treatment of GH-deficient subjects with the metabolic syndrome and/or manifest diabetes. It is at present unknown whether an optimal balance between safety and efficacy can be achieved with the combination therapy of GH and IGF-I, since this combination has been evaluated in only a small number of patient populations and in studies of a relatively short duration. In addition, a disadvantage may be the financial costs of combination therapy of GH and IGF-I. In conclusion, there are many reasons for believing that administration of the combination therapy of GH and IGF-I could have advantages above GH alone or IGF-I alone. However, determination of whether co-administration of GH and IGF-I indeed is superior to either agent alone awaits further study.

show abstract

IGF-I Treatment of Growth Hormone Insensitivity

Cited by 16 publications

References 114 publications

Mecasermin (recombinant human insulin-like growth factor I)

Mecasermin (recombinant human insulin-like growth factor I)

Therapeutic applications of the insulin-like growth factors

Advantages and disadvantages of GH/IGF-I combination treatment

Contact Info

Product

Resources

About