What is growth hormone receptor deficiency (GHRD)?

Updated: Jan 15, 2019
  • Author: Arlan L Rosenbloom, MD; Chief Editor: Robert P Hoffman, MD  more...
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Answer

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. [1]

 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

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

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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