Endocrinologists issue new clinical guidelines for managing and treating children with growth failure.
When is it appropriate to treat short children with growth hormone? The answer is not always clear–cut, as many parents and physicians have discovered over the past three decades. Some short but healthy children receive expensive nightly injections of recombinant growth hormone. As with any medicine, there may be side effects — and possibly unknown long–term risks.

A group of medical experts has weighed existing evidence and issued a new set of clinical guidelines for managing children and adolescents with growth failure. Written on behalf of the Pediatric Endocrine Society, the guidelines are the society’s first update since 2003. For children with certain clearly diagnosed medical conditions, the experts recommend hormonal treatments. When the cause of growth failure is unknown, they advise against routine growth hormone use and recommend a more measured decision–making approach.

“The nuances of this issue leave much room for open questions and differences of interpretation,” said study leader Adda Grimberg, MD, a pediatric endocrinologist at Children’s Hospital of Philadelphia (CHOP). “In developing these guidelines, we analyzed not only the results, but the strengths, limitations and potential biases of studies in a large evidence base that continues to evolve.”

Grimberg and colleagues issued their guidelines through two committees of the Pediatric Endocrine Society – the Drug and Therapeutics Committee and the Ethics Committee.

The guidelines appeared online Nov. 25 in the journal Hormone Research in Paediatrics, and in the January 2017 print issue.

The co–authors included seven pediatric endocrinologists from different centers in the U.S. and Canada, plus a pediatric bioethicist and a consultant for the group’s methodological approach. Using that method, called GRADE (Grading of Recommendations, Assessment, Development and Evaluation), the co–authors generated a series of strong recommendations, conditional recommendations and ungraded good practice statements.

The authors focused on three diagnoses: growth hormone deficiency (GHD), primary IGF–I deficiency (PIGFD) and idiopathic short stature (ISS).

“Growth hormone treatment for patients with growth hormone deficiency offers health benefits beyond height,” said Grimberg, “but growth hormone treatment for ISS is solely about height. Another important difference is that, 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 than for growth hormone deficiency.”

Much of the controversy in growth hormone treatment involves ISS. The authors note that, in practice, families of many children who are short but do not meet the FDA definition for ISS have sought growth hormone treatment to make them taller. Grimberg previously showed in national research that gender bias influences both referral and treatment patterns for short children. Short boys are three times more likely than short girls to be treated with growth hormone for ISS, even though equal proportions of both genders fall under the ISS height threshold. One consequence is that short girls with underlying disease may be overlooked, while short, healthy boys may receive unnecessary treatments.

Moreover, short–term gains in height do not always translate into adult height differences. A full study of long–term results would require many years to complete, and thus is often expensive and unfeasible to perform.

Other research gaps exist in diagnosing growth hormone deficiency. Because diagnostic tests have evolved over time, different tests can provide different results for the same sample — making it harder to understand the