Hyposomatotropism is a deficiency in the release of pituitary growth hormone (somatotropin), resulting in short stature. Achievement of final adult height consistent with a child’s genetic potential remains the primary therapeutic endpoint for recombinanat human growth hormone (rhGH) therapy in the pediatric population. In addition to its effects on bone mass, GH regulates muscle mass, muscular strength, body composition, lipid and carbohydrate metabolism, and cardiac function. Patients with growth hormone deficiency (GHD) typically have hyperlipidemia, increased body fat, premature atherosclerotic plaques, delayed bone maturation, and impaired cardiac function.
GHD in adults is recognized as a distinct clinical syndrome that encompasses reduced psychological well-being and specific metabolic abnormalities. Such abnormalities, including hypertension, central obesity, insulin resistance, dyslipidemia, and coagulopathy, closely resemble those of metabolic insulin resistance syndrome.
The increased rates of cardiovascular morbidity and mortality reinforce the close association between the syndromes.
Recombinant human growth hormone
The commercial introduction of recombinant human growth hormone (rhGH) in 1985 dramatically changed the field of therapy for growth hormone (GH). Since then, rhGH has been administered to tens of thousands of children worldwide, making it one of the most extensively studied therapies in the pediatric pharmacopoeia.
The initial GH replacement therapy limited to GH-deficient patients has evolved into a pharmacologic therapy to include different conditions of non-GH deficient short stature.
US Food and Drug Administration (FDA)–approved indications for the administration of rhGH in children include the following:
Growth failure associated with growth hormone deficiency (GHD)
Small size for gestational age, with failure to catch up
Idiopathic short stature
SHOX gene deficiency
The European Medicines Agency (EMA) has also approved rhGH for all the above indications except idiopathic short stature (ISS) and Noonan syndrome.
While available evidence suggests that long-term GH therapy reduces the adult height deficit in children with ISS, questions remain as to whether the impact of the height gained on physical and psychosocial well-being outweigh the burden for patients and parents, potential adverse effects, cost of therapy, and patients’/parents’ expectations.
Replacement of GH in adults with GHD markedly reduces central obesity and substantially reduces total cholesterol levels but has produced little change in other risk factors, particularly insulin resistance and dyslipidemia.
For these patients, concerns are the persistent insulin resistance and dyslipidemia, together with the elevated plasma insulin and lipoprotein(a) levels observed with GH replacement.
The large commercial supply of rhGH fuels research and debate over the proper indications for this potent and expensive therapy. Few disagree that many patients with childhood-onset GHD require continuous GH replacement therapy into adulthood. However, the diagnostic criteria for GHD in patients of any age remain controversial. This ambiguity stems from the wide variability in current tools used to diagnose GHD.
Clinicians and researchers alike will continue to grapple with these dilemmas in the foreseeable future. However, commercial interests and patient advocates continue to pressure the medical community to expand the accepted indications for rhGH. Therefore, the clinician and the clinical researcher must examine published data critically and must educate individual patients and their families about the risk-benefit ratio of rhGH therapy for them.
The diagnosis of growth hormone (GH) deficiency (GHD), or hyposomatotropism, remains controversial. The diagnosis of GHD is a multifaceted process requiring comprehensive clinical and auxologic assessment combined with biochemical testing of the GH-insulinlike growth factor (IGF) axis and radiologic evaluation. Biochemical testing of the GH-IGF axis includes radioimmunoassays (RIAs) of GH, IGF, and insulinlike growth factor binding proteins (IGFBPs)