Which novel treatments of hyposomatotropism (growth hormone deficiency [GHD]) have been proposed?

Updated: Jan 24, 2019
  • Author: Sunil Kumar Sinha, MD; Chief Editor: Robert P Hoffman, MD  more...
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Answer

Several novel treatment modalities for GHD have emerged, as folows:

  • Oral GH secretagogs

  • Growth hormone-releasing hormone

  • Oral liquid formulations of rhGH

  • Depot GH (administered once or twice a month)

Evaluation of most of these modalities remains incomplete at this time. Depot rhGH had been approved for use in GHD but was subsequently removed from the market. Data from clinical trials reported to date suggest that the depot form is less effective for stimulating growth than the daily form. This result was also found with clinical use.

Children with GHD have dramatic and clearly distinguishable responses to rhGH treatment compared with children given placebo. Data regarding the potential benefits of high doses are still being collected. The dose response of rhGH is nonlinear.

A double-blind, placebo-controlled, crossover trial of rhGH therapy in adults with GHD suggested sex-related differences in GH responsiveness. An identical dose of rhGH per body surface area was administered to men and women. With treatment, men had less basal body fat, as well as higher basal levels of serum insulinlike growth factor (IGF)-1, greater basal lean body mass, enhanced lowering of cholesterol levels, and more increases in markers of bone metabolism than did the women. These sex-related differences in the response to rhGH treatment resemble differences found in children.

Of interest, boys have a linear dose-response curve, with maximal effects observed with dosages of 0.1 mg/kg/day, whereas girls have a bell-shaped dose-response curve, with maximal effect at 0.05 mg/kg/day. This evidence suggests that estrogen and testosterone play a role in regulating the secretion and action of GH. As a result, optimal dosing strategies for the treatment of GHD may differ in boys and girls.

The dosage of rhGH may be a valuable parameter for optimizing the response to therapy. In patients who are receiving GH replacement, serum IGF-1 and insulinlike growth factor binding protein-3 (IGFBP-3) concentrations should be monitored carefully, for 2 reasons:

  1. IGF-1 and IGFBP-3 are direct biomarkers of tissue responsiveness to rhGH therapy. The standard of practice in adults with GHD is titrating the dosage of rhGH to maintain serum growth factor levels within an age-appropriate reference range; this approach may become standard practice in pediatric patients. Some have proposed mathematical prediction models that can be used to predict the growth response to a specific dosage and to guide the pediatric endocrinologist in modifying therapy when a patient's observed growth falls short of the predicted outcome.

  2. Monitoring of growth factors is useful for evaluating compliance and for assessing risk. Results of several studies have linked high serum IGF-1 levels to an increased risk of cancer in otherwise healthy patients. Although the data did not indicate a causal relationship, further consideration of this issue is warranted, as is monitoring of IGF-1 and IGFBP-3 levels during rhGH therapy. Individually defined treatment is the goal in patients with GHD. The ability to adjust rhGH dosing on the basis of clinical and biochemical information provides an ideal strategy.


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