New Guidelines Cover Growth Hormone, IGF-1 Use in Kids, Teens

Marlene Busko

February 02, 2017

The Pediatric Endocrine Society has issued new guidelines for treating children and adolescents with growth failure due to growth-hormone (GH) deficiency, idiopathic short stature (ISS), or primary insulinlike growth factor-1 (IGF-1) deficiency.

The document, which was published in the January issue of Hormone Research in Paediatrics, updates recommendations issued by the society in 2003 and for the first time provides information about the use of recombinant IGF-1 therapy as well as GH treatment.

While GH therapy is evolving, there are still important knowledge gaps; notably, "we do not know the long-term outcome on adult height," lead author Adda Grimberg, MD, a pediatric endocrinologist at Children's Hospital of Philadelphia (CHOP), Pennsylvania, and colleagues write.

They note that much of the treatment for short height is based on "the supposition that taller stature will lead to improved quality of life," so there is a need to validate appropriate quality-of-life measures for this. Also required are long-term safety data from adults who were treated for short stature in childhood, they state.

In addition, hospitals and clinicians should adopt universal standardized IGF-1 and GH assays, they note.

"Given the unanswered questions, the nuanced distinctions, and the dynamic status of the field, we recommend that only pediatric endocrinologists manage the evaluation for [growth hormone deficiency, ISS, and primary IGF-1 deficiency] and their treatment," they summarize.

In the meantime, "we reiterate the importance of individualized patient care."

"Administering growth-hormone treatment may help very short children gain a few inches in height, but it also exposes them to a powerful hormone when we do not fully know the long-term implications," coauthor Chris Feudtner, MD, PhD, a pediatrician and director of the department of medical ethics at CHOP, cautioned in a statement issued by CHOP.

Benefits of Treatment Outweigh Harms in Severe GH Deficiency

In 1985, the US Food and Drug Administration approved recombinant human growth hormone to treat pediatric patients with growth failure due to inadequate secretion of endogenous growth hormone, Dr Grimberg and colleagues note.

Then in 2003, the FDA expanded the indication to include treatment of ISS, defined as a height that was 2.25 standard deviations below the mean, which corresponds to being shorter than 5' 3" (160 cm) for a male adult and below 4' 11" (150 cm) for a woman.

In 2005, the FDA approved IGF-1 for the long-term treatment of growth failure in pediatric patients with severe primary IGF-1 deficiency (IGF-1 levels and height below 3 standard deviations) but not as a result of secondary IGF-1 deficiency from growth-hormone deficiency, malnutrition, hypothyroidism, or other causes.

Thus, in this newest look, and on behalf of the Drug and Therapeutics Committee and the Ethics Committee of the Pediatric Endocrine Society, the guideline writers evaluated the evidence and developed recommendations using a GRADE approach (grading of recommendations; assessment; development; and evaluation).

"Children with severe [GH deficiency] clearly benefit from [GH] treatment, so much so that the benefits markedly outweigh any potential harms," they write.

For ISS With No GH Deficiency, Treatment Is a Judgment Call

However, for children with ISS who do not have GH deficiency, the benefits of achieving taller stature via GH treatment are "uncertain and of a lesser magnitude."

Moreover, the high cost of GH therapy (US $35,000–$50,000 per inch of height gained) "is difficult to justify for those in whom it is unclear if there are benefits of treatment," state Dr Grimberg and colleagues.

The authors thus offer a conditional recommendation, advising against routinely using GH treatment for ISS. Instead, they recommend that parents and clinicians take a shared decision-making approach, weighing physical and psychological burdens for the child, along with a discussion of risks and benefits

"Growth-hormone treatment for patients with growth-hormone deficiency offers health benefits beyond height, but growth-hormone treatment for ISS is solely about height," Dr Grimberg observes in the CHOP press release.

Moreover, "unlike patients with growth-hormone deficiency, not all patients with ISS increase their height in response to growth-hormone treatment. So a decision for treating ISS is more of a subjective judgment call."

Some parents of children who are short but do not meet the FDA definition of ISS have sought GH treatment for their children, often paying for this out of pocket, since it is frequently not covered by insurance.

And there is a gender bias at play here — as previously reported, Dr Grimberg and colleagues determined in a recent study that short boys were three times more likely than short girls to be treated with growth hormone for ISS.

Dr Grimberg received an honorarium from Scherer Clinical Communications for a lecture in a course supported by a grant from Novo Nordisk, and he joined the Steering Committee of the Pfizer International Growth Study (KIGS) database after the guidelines had been written and submitted for review. Disclosures for the coauthors are listed in the paper.

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Horm Res Paediatr. 2016;86:361–397. Article


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