There are currently four known genetic causes of GH insensitivity/primary IGF deficiency: GH receptor deficiency (also known as Laron syndrome or GH insensitivity syndrome), IGF-1 deficiency, signal transducer and activator of transcription 5b (STAT5b) deficiency and acid labile subunit (ALS) deficiency.
It combines with insulin-like growth factor-I (IGF-I) to form a complex (IGF-I/IGFBP-3) that can treat growth hormone insensitivity syndrome (GHIS) and reduce insulin requirement in patients with diabetes.
Patients present with short stature associated with high GH and low IGF-I levels and may have midfacial hypoplasia (typical Laron syndrome facial features).
Expression of heterozygosity for the defect in the growth hormone (GH) receptor has been proposed to be reflected in stature, and in GH binding protein (GHBP) and insulin-like growth factor I (IGF-I) levels in parents and other relatives of patients with GH receptor deficiency (GHRD; Laron syndrome).
Mutations or deletions in the growth hormone receptor cause an autosomal disorder called Laron-type dwarfism (LS) characterized by high circulating levels of serum GH and low levels of insulin like growth factor-1 (IGF-1).
Laron-type dwarfism is an autosomal recessive genetic disorder that is characterized by high levels of growth hormone and low levels of insulin-like growth factor I in the circulation.
Insulin-like growth factor-I and insulin-like growth factor binding protein-3 cotreatment versus insulin-like growth factor-I alone in two brothers with growth hormone insensitivity syndrome: effects on insulin sensitivity, body composition and linear growth.
Conclusions Sequential measurements of serum IGF-I, glucose and potassium in patients with Laron syndrome may aid in optimizing and individualizing rhIGF-I treatment.
Clinical investigations started in 1958 of a group of children with characteristics resembling GH deficiency, but who had extremely high levels of plasma GH, led to the description of the syndrome of primary GH resistance or insensitivity (Laron syndrome), the discovery of its molecular defect, and the clinical application of biosynthetic insulin-like growth factor-I.
GH-dependent IGF-I and IGFBP-3 secretion is not affected by heterozygosity for the E180 splice mutation that causes GHRD/Laron syndrome in the Ecuadorian population.
These findings are consistent with clinical data showing that IGF-I replacement therapy in patients with Laron syndrome does not achieve full skeletal growth.
Classic Laron Syndrome (LS) is a recessive disease of insulin-like growth factor I (IGF-I) deficiency and primary growth hormone insensitivity, clinically characterized by dwarfism and marked obesity.
As all patients with LS are IGF-I-deficient, it must be assumed that other as yet unknown factors related to the molecular defects in the GH-R are the major cause of the differences in intellect and brain abnormalities.
Recombinant human IGF-I is an effective treatment of severe primary IGF deficiency, which is typical of patients with GH receptor defects (Laron syndrome).
Most of the syndromes respond well to therapy with recombinant GH; exceptions are antibody-mediated resistance in GHD type IA (not all patients) and cases of Laron syndrome (GHR deficiency).Such patients respond to IGF-I therapy.
To identify IGF1-dependent genes and signaling pathways associated with cancer protection in LS, we conducted a genome-wide analysis using immortalized lymphoblastoid cells derived from LS patients and healthy controls of the same gender, age range, and ethnic origin.
The absence of convincing evidence of GH insensitivity in a substantial number of children with ISS, the limited ability of endocrine IGF-I to restore normal growth in those with unequivocal GH unresponsiveness, the suppression of endogenous GH (and thereby, local GH effects on growth) that occurs with IGF-I administration, the risk profile, and the absence of data on efficacy in other than proven severe GH insensitivity, led the Drug and Therapeutics Committee of the Lawson Wilkins Pediatric Endocrine Society to conclude that rhIGF-I use is only justified in conditions approved by the FDA and that other growth promotional use should only be investigational.