Study examines physician recommendations for initiation, continuation of pediatric GH treatment

Silvers JB. Pediatrics. 2010;126:468-476.

Results of a national study of U.S. physicians revealed that initiation of growth hormone for the treatment of idiopathic short stature is consistent with evidence-based medicine and guidelines; however, decisions about continuing therapy vary and factors such as physician attitudes and family preferences appear to be strong influences in addition to response to treatment.

“With a potential market of 500,000 U.S. children and costs exceeding $10 billion per year, changes in GH use may depend on potentially modifiable physician attitudes and family preferences as much as physiologic evidence.

“Although the FDA has provided guidelines for GH treatment initiation, guidelines for continuation decisions are less clear and controversies about the goals and assessment of treatment persist,” J.B. Silvers, PhD, of Case Western Reserve University, and colleagues wrote in the study.

Based on this, the researchers investigated physician decisions to initiate GH in children with ISS and whether to continue, intensify or stop GH in children with ISS after an initial treatment course using a national census study of 727 pediatric endocrinologists. A questionnaire was sent to all U.S. members of the Pediatric Endocrine Society and the American Academy of Pediatrics endocrine section.

Recommendations to initiate

In children who were previously untreated with GH, physician recommendations to start treatment were consistent with guidelines and evidence-based medicine. The majority of physicians questioned (93%) initiated GH for the very short child with very low predicted adult height and very slow growth velocity.

However, family preference had almost as strong an influence as growth velocity; physicians were more likely to initiate GH if the family wanted the treatment rather than if the family was neutral or ambivalent. Seventy-four percent of pediatric endocrinologists would not initiate GH for the child when growth parameters were less impaired (predicted adult height and current height –2 SDS; growth velocity –1 SD) and when the family was neutral about treatment.

Decisions to change, discontinue GH

In children treated with GH for at least 1 year, recommendations to continue treatment were strongly influenced by growth response to therapy, but were divided regarding course of action. Physician responses indicated a preference for continuation (47.3%) and intensification (36.7%) of GH treatment vs. discontinuation (16%). In children with slow growth response, physicians recommended intensifying the GH dose in more than 60% of cases, recommended discontinuing GH in 26% and recommended no change in 14% of cases.

When presented with identical growth responses to therapy, physician decisions about whether to intensify or discontinue treatment diverged, and were driven by nonphysiologic factors including physician attitudes, family preferences and GH initiation recommendations. Physicians were more likely to recommend discontinuation of the child’s based predicted adult height was only moderately short (–2 SDS) and physicians were more likely to recommend intensifying the dose if baseline predicted adult height was very short (–3 SDS).

“Taken together, attitudinal and contextual factors exerted more influence on continuation decisions than did growth response to therapy,” the researchers wrote. Concerns about emotional well-being, belief in the use of individual GH trials and the price of therapy also had a powerful influence on further treatment decisions.

Overall, more than 28% of physicians believe that GH positively impacts children with ISS, independent of adult height gains. Few reported actually discontinuing GH treatment when ineffective. Respondents overwhelmingly reported that results of individual patient-specific trials of GH are used as a basis for follow-up decisions.

“At a minimum, the results underscore the need for more emphasis and guidance on criteria for discontinuing GH and perhaps other similar medications,” the researchers concluded.

What drives physicians to initiate GH treatment for children with ISS? What drives physicians to change their initial recommendation? The answers to these seemingly simple questions are, for the first time, scientifically approach in the paper by Silvers et al.
They demonstrate that starting GH treatment is generally consistent with evidence-based medicine principles. However, decisions to continue, change or discontinue GH treatment are more influenced by the attitudes of the physician and the family preferences than by rigorous science. This paper is sure to kindle debate on the subject and merits of GH treatment for ISS.

– Mark A. Sperling, MD

Endocrine Today Editorial Board member