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Growth hormone insensitivity syndromes

Alan D Rogol, MD, PhD
Section Editor
Mitchell E Geffner, MD
Deputy Editor
Alison G Hoppin, MD


Growth hormone insensitivity (GHI) is a group of inherited disorders in which there is a reduction in or absence of the biological effects of growth hormone (GH) despite normal or above normal production and secretion of GH. These disorders are characterized by growth failure and normal or increased circulating levels of GH, in contrast with GH deficiency. In addition, many affected individuals also have low circulating levels of GH-binding protein (GHBP, which is equivalent to the shed extracellular-binding domain of the GH receptor) and is measured in a commercially available clinical test reflecting the number of GH receptors. (See "Diagnosis of growth hormone deficiency in children".)

The classic model of GHI is in patients with Laron syndrome, caused by mutations in the GH receptor gene. However, subsequent experience has shown that there is a spectrum of GHI caused by a variety of defects along the GH–insulin-like growth factor-I (IGF-I) axis (figure 1). These disorders will be discussed in this topic review.

A growing body of literature suggests that some patients with idiopathic short stature often have a component of GH resistance, which may call for alternative treatment approaches such as adjusting GH doses based on IGF-I levels. These considerations are discussed in a separate topic review. (See "Growth hormone treatment for idiopathic short stature".)


GHI can be caused by loss-of-function mutations in the GH receptor gene or in its downstream mediators, the most important of which is insulin-like growth factor-I (IGF-I). These syndromes are characterized by normal or elevated levels of GH and low levels of IGF-I (except for IGF-I receptor mutations, in which IGF-I levels are normal or high) (table 1).

Growth hormone receptor mutations (Laron syndrome) — Laron syndrome (MIM #262500), the most common known cause of genetically-mediated GHI, is characterized by severe postnatal growth failure [1]. It is caused by homozygous or compound heterozygous mutations in the growth hormone (GH) receptor gene; a variety of mutations have been identified, most of which affect the extracellular GH-binding region of the receptor [2-4].

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Literature review current through: Dec 2017. | This topic last updated: Apr 08, 2017.
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