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Advances in Pediatrics

rhGH Safety and Efficacy Update

      Growth hormone (GH) has been used to treat patients with GH deficiency (GHD) since 1960 when it was originally extracted from cadaveric pituitary glands [
      • Sizonenko P.C.
      • Clayton P.E.
      • Cohen P.
      • et al.
      Diagnosis and management of growth hormone deficiency in childhood and adolescence. Part 1: diagnosis of growth hormone deficiency.
      ]. In 1985, several cases of Creutzfeldt-Jakob disease were identified and attributed to pituitary-derived GH. Later that year, recombinant human GH (rhGH) was approved by the US Food and Drug Administration (FDA). The availability of an unlimited supply of rhGH improved access to therapy for children with GHD and the frequency of dosing increased from 3 times each week to 6 or 7 days each week [
      • Gharib H.
      • Cook D.M.
      • Saenger P.H.
      • et al.
      American Association of Clinical Endocrinologists medical guidelines for clinical practice for growth hormone use in adults and children–2003 update.
      ]. The increased supply of rhGH allowed investigation into treatment of multiple conditions associated with short stature not associated with GHD leading to FDA approval for treatment of children with growth failure associated with chronic renal insufficiency (1993), Turner syndrome (TS; 1996), Prader-Willi Syndrome (PWS; 2000), small for gestational age (SGA) without adequate catch-up growth (2001), idiopathic short stature (ISS; 2003), short stature homeobox (SHOX) deficiency (2006), and Noonan syndrome (NS, 2007). In addition, rhGH therapy was FDA approved for acquired immune deficiency syndrome (AIDS) wasting (1996), adult GHD (1996), and short bowel syndrome (2003) (Table 1). Guidelines for the use of GH therapy have been reported previously by the American Association of Clinical Endocrinologists (AACE), Growth Hormone Research Society (GRS), and The Lawson Wilkins Pediatric Endocrinology Society (LWPES) [
      • Gharib H.
      • Cook D.M.
      • Saenger P.H.
      • et al.
      American Association of Clinical Endocrinologists medical guidelines for clinical practice for growth hormone use in adults and children–2003 update.
      ,
      • Growth Hormone Research Society
      Consensus guidelines for the diagnosis and treatment of growth hormone (GH) deficiency in childhood and adolescence: summary statement of the GH Research Society. GH Research Society.
      ,
      • Wilson T.A.
      • Rose S.R.
      • Cohen P.
      • et al.
      Update of guidelines for the use of growth hormone in children: the Lawson Wilkins Pediatric Endocrinology Society Drug and Therapeutics Committee.
      ].
      Table 1FDA-approved indications for GH therapy by manufacturer
      Genentech Lilly Novo nordisk Pfizer Sandoz Serono Teva
      Indication
      Pediatric GHD Protropin 10/85-12/02

      Nutropin 3/94

      Nutropin AQ 1/96

      Nutropin Depot 12/99-6/04
      Humatrope 3/87 Norditropin 3/97 Genotropin 8/95 Omnitrope 5/06 Saizen 10/96 Tev-Tropin 5/95
      Chronic renal insufficiency Nutropin 11/93

      Nutropin AQ 1/96
      Adult GHD Nutropin 12/97

      Nutropin AQ 12/97
      Humatrope 8/96 Norditropin 3/97 Genotropin 10/97 Omnitrope 5/06 Saizen 11/04
      Turner syndrome Nutropin 12/96

      Nutropin AQ 4/97
      Humatrope 3/97 Norditropin 9/07 Genotropin 4/06
      Prader-Willi syndrome Genotropin 6/00 Omnitrope 4/10
      SGA Humatrope 3/09 Norditropin 10/08 Genotropin 7/01 Omnitrope 4/10
      ISS Nutropin AQ 6/05 Humatrope 7/03 Genotropin 6/08 Omnitrope 8/10
      SHOX deficiency Humatrope 11/06
      NS Norditropin 6/07
      AIDS wasting Serostim 8/96
      Short bowel syndrome Zorbtive 12/03
      Bold indicates that the product was the first to be approved for a given indication.
      Bio-Tropin (Ferring, 5/95), Valtropin (LG Life, 4/07), and Accretropin (Cangene Corporation, 1/08) are rhGH products that have also been approved by the FDA, but are not yet commercially available in the United States.
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