GH treatment in deficient adults: clinical vs. biochemical endpoints

The Endocrine Society's 90th Annual Meeting

Growth hormone replacement is beneficial in adults with growth hormone deficiency; however, some experts disagree on the parameters used when deciding how to treat, who to treat and why.

“It is a given that GH replacement in adults with GH deficiency is of benefit. So, the questions being asked are, should GH replacement be offered to all GHD adults, or only to some? And if the answer is that it should only be offered to some, then how do you choose the some?” Stephen M. Shalet, MD, FRCP, said during a debate yesterday at The Endocrine Society’s 90th Annual Meeting, held in San Francisco. Shalet is a professor in the department of endocrinology at Christie Hospital, Manchester, United Kingdom.

The current GH/IGF-1 cut-offs used to diagnose and treat GHD are imperfect, said Mark E. Molitch, MD, professor in the division of endocrinology at Northwestern University. Due to a lack of outcomes-based criteria, Molitch proposed the creation of objective criteria for response to GH therapy in children and adults in order to assess the baseline GH response to stimuli such as IGF-1.

“What we really need to do is determine what levels would be needed to show a good response,” he said. “This brings us to the idea of what responses might be possible and what we seek as prospective benefits.”

Benefits and pitfalls

Molitch cited the benefits of treatment, such as increased muscle mass, decreased fat mass, increased BMD and significant improvement in quality of life, though he recognized the modest changes in CVD risk factors. However, Shalet remained unconvinced about the benefits to QOL and said that mortality data will never be available.

In terms of treating GHD, Shalet argued for treating those with very severe GHD first because patients with GHD and low IGF-1 are worse than those with normal IGF-1.

“Why identify a condition biochemically if it has no clinical benefit,” Molitch said during his rebuttal. “Identify those likely to be deficient, determine whether or not they feel normal after everything else and begin insulin-induced hypoglycemia if combined criteria are not met.”

“Mark’s proposal represents the dumbing down of your principles as an endocrinologist,” said Shalet. “As of now, you treat severe GHD but not partial. Therefore, it is your duty to maintain standards for treatment of GHD; avoid dumbing down and treat very severe before severe and before partial.” – by Stacey L. Adams

For more information:
Molitch ME, Shalet SM. Adults with growth hormone deficiency receiving GH replacement: clinical endpoints are superior to biochemical endpoints. Presented at: The Endocrine Society’s 90th Annual Meeting; June 15-18; San Francisco.