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Can an adolescent with bona fide GHD have a trial off of therapy?
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Yes, but it should be patient specific
The answer is a conditional yes. Based on data in the literature from Drake et al (J Clin Endocrinol Metab. 2003;88:1658-1663), Shalet et al (J Clin Endocrinol Metab. 2003:88:4124-4129) and others, the overall theme that emerges is that in patients who completed linear growth and years down the line are retested and still have GHD, GH therapy improved lean body mass and bone mineral content. However, GH therapy did not change measures of quality of life, plasma lipids, muscle strength or cardiac function.
We conducted a placebo-controlled double-blind randomized trial of GH for two years in adolescent patients who just completed their linear growth and upon re-testing of the GH reserves had persistent GHD. We observed no significant differences in a host of metabolic and anthropometric measures, including body composition, BMD, muscle strength, cardiac function, plasma lipids and quality of life between the GH and placebo groups.
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Hence, many patients with idiopathic isolated GHD can, based on our data, pretty safely pause growth hormone therapy and be followed for up to two years. In those patients who fail the GH stimulation test but are doing well and are not missing any other hormones, there is room for monitoring before the patient is committed to GH therapy for life. This does not apply to subjects with multiple hormone deficiencies or those with GHD due to organic pathology; those patients should be continued on GH at age-appropriate doses, likely for life.
Nelly Mauras, MD, is the Chief in the Division of Endocrinology at Nemours Children’s Clinic in Jacksonville, Fla.
Therapy should continue as seamlessly as possible
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More research is required to unravel whether there is a window of opportunity for GH replacement in the transition phase. The study by Shalet et al and Underwood et al (J Clin Endocrinol Metab. 2003;88:5273-5280) examined the effect of recommencement of GH and demonstrated improvement in total body and lumbar spine bone mineral content and BMD. However, the increase in total body bone mineral content and lumbar spine BMD after two years of GH was of similar magnitude to the increase seen after one year of ‘seamless’ continuation in the study by Drake et al. This supports the notion that a period of discontinuation of GH in adolescent GHD patients limits progression towards peak bone mass. This is partly due to an initial reduction in bone mineral content and BMD when GH is restarted after a period of discontinuation, as bone resorption is greater than bone mineralization.
Therefore, patients should be advised to stop GH only to allow re-evaluation of GH status, a period of around four weeks. This is based not only on the majority of the available evidence and consensus document but also that patients probably benefit from a clear message that GH replacement is beneficial and therefore GH replacement should continue as seamlessly as possible to encourage adherence.
Helena Gleeson, MD, is a Consultant in Adolescent Endocrinology at Royal Manchester Children’s Hospital in the United Kingdom.