Background
Insulin-like growth factor I (IGF-I) is the effector of growth induced by growth hormone (GH). IGF-I deficiency can be the result of GH resistance or insensitivity due to genetic disorders of the GH receptor causing GH receptor deficiency (growth hormone receptor deficiency [GHRD], Laron syndrome) or postreceptor defects, including the principal transduction agent STAT5b, the IGF-I/IGFBP3 stabilizer acid labile subunit (ALS), the IGF-I gene, or the IGF-I receptor.
Acquired forms of GH insensitivity include the rare GH1 mutation (in which GH inhibiting antibodies develop after a few months of replacement therapy with recombinant GH) and, far more commonly, malnutrition, hepatic disease, renal disease, and diabetes. The table below compares the clinical and biochemical features associated with these various causes of GH resistance.
Table. Features of GH Resistance Causes (Open Table in a new window)
|
Condition |
Growth failure |
GH |
GH binding protein |
IGF-I |
IGFBP3 |
|
Genetic |
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|
GHRD – Recessive forms |
Severe |
Elevated |
Absent-low* |
Very low |
Very low |
|
GHRD – Dominant negative forms |
Mild-moderate |
Elevated |
Increased |
Very low |
Low-normal |
|
STAT5b mutation |
Severe |
Elevated |
Normal |
Very low |
Very low |
|
ALS mutation |
None-moderate |
Normal |
Normal |
Very low |
Very low |
|
IGF-I gene mutation |
Severe |
Elevated |
Normal |
Absent-high** |
Low-normal |
|
IGF-I receptor mutation |
Mild-moderate |
Normal-elevated |
Normal |
Normal-elevated |
Normal-elevated |
|
Acquired |
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|
GH inhibiting antibodies |
Severe |
Absent |
Normal |
Very low |
Low |
|
Malnutrition |
None-mild |
Elevated |
Decreased |
Variable |
Variable |
|
Diabetes mellitus |
None-mild |
Elevated |
Decreased |
Decreased |
Increased |
|
Renal disease |
Mild-severe |
Normal |
Decreased |
Normal |
Increased |
|
Hepatic disease |
Mild-severe |
Elevated |
Normal-increased |
Decreased |
Normal |
|
*Increased in mutations of or near the transmembrane domain of the GH receptor**Absent with partial IGF1 gene deletion; very high with abnormal IGF-I |
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