What is the role of medications in the treatment of 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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Human IGF-I was synthesized by recombinant DNA techniques in 1986 and preparations of rhIGF-I for subcutaneous injection became available in 1990. The initial manufacturers in Japan (Fujisawa) and Sweden (Kabi) provided rhIGF-I for approximately 70 children with GHRD internationally and a handful of GH gene deletion patients with acquired GH insensitivity due to GH inactivating antibodies developing after treatment with rhGH.

Eventually, the 3 manufacturers stopped production of rhIGF-I because of the limited market. Subsequently, a company licensed by Genentech (Tercica Inc, Brisbane, California) obtained orphan drug approval of their rhIGF-I (mecasermin, [Increlex]) from the US Food and Drug Administration (FDA) in late 2005. Soon thereafter, an equimolar preparation of rhIGF-I and rhIGFBP3 (mecasermin rinfabate [Iplex], Insmed Inc, Glen Allen, Virginia) was approved by the FDA. In addition to the purported pharmacokinetic advantage permitting once daily injection for the latter preparation, a lower risk for hypoglycemia was proposed. [41] As a result of legal action, Iplex is no longer available for growth therapy; this is not a problem because the preparation was less effective than rhIGF-I alone. [42]

Pharmacokinetic profiles done at doses of 40, 80, and 120 mcg/kg suggested a plateau effect for circulating IGF-I concentrations between 80 and 120 mcg/kg per dose. It was considered that the carrying capacity of the IGFBPs was saturated at this level. [43] In a randomized, double-blind, placebo-controlled trial, 17 prepubertal Ecuadorian patients were given IGF-I at 120 mcg/kg SC bid for 6 months, following which all subjects received IGF-I. The 9 placebo-treated patients had a modest but not significant increase in height velocity from 2.8 ± 0.3 to 4.4 ± 0.7 cm/y, accounted for by 3 individuals with 6-month velocities of 6.6-8 cm/y. [40]

This response was attributed to improved nutritional status as noted with nutrition-induced catch up growth by Crosnier et al [39] in their GHRD patient with anorexia. For those receiving IGF-I, the height velocity increased from 2.9±0.6 to 8.8±0.6 cm/y and all 16 patients had accelerated velocities during the second 6-month period when all were receiving IGF-I.

Six-month, placebo-controlled, double-blind study Six-month, placebo-controlled, double-blind study of rhIGF-I in 16 Ecuadorian children with GHRD, followed by 6 months open label rhIGF-I therapy of the entire group.

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