Volume 20, Issue 1, March 2004

Table of Contents 20-1

Growth Hormone Effects on Quality of Life of Young Adults

Stouthart PJ, et al. Quality of Life of Growth Hormone (GH) Deficient Young Adults During Discontinuation and Restart of GH Therapy. Psychoneuroendocrinology 2003;28:612-626.

Abstract

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The investigators' goals were to document changes in quality of life (QoL) over the course of the first year post-growth hormone (GH) withdrawal, and to subsequently assess the psychological effects of reinstating GH. Participants in the GH discontinuation study were recruited from a Dutch outpatient clinic and comprised of 14 males, 8 females (ages 15 to 22 years, mean = 19 years), 11 with isolated GH deficiency (IGHD), and 11 with multiple pituitary hormone deficits (MPHD). All had achieved adult height and were receiving adequate replacement of other hormones. Although all tested GH deficient (GHD) as children, 8 of 11 IGHD retested GH-sufficient as young adults. In contrast, all MPHD patients retested as GHD in early adulthood.

During the first six months of discontinuation of GH, a statistically significant increase in psychiatric symptoms (assessed by Hopkins Symptom Checklist) was observed, with no further increases between 6 and 12 months. There were no differences in symptoms between IGHD and MPHD, or between GHD and non-GHD. These findings corresponded temporally with a decline in IGF-I. IGF-I concentrations did not differentiate the MPHD and IGHD groups. Depressive symptoms, assessed by the Profile of Mood States (POMS), increased in both IGHD and MPHD groups by 6 months of GH discontinuation and thereafter increased further for the IGHD, but decreased within the MPHD group. The opposite pattern was observed for the POMS Tension scale, which increased across the 12 months for the MPHD group, but declined for those with IGHD. Lower IGF -I concentrations were associated with more negative mood states and somatic complaints for the combined group, whereas higher IGF-I was associated with greater ‘vigor'.

Nine of 14 patients (64%; 4 males, 5 females; 2 with IGHD and 7 with MPHD) from the GH discontinuation study who remained GHD when retested as adults subsequently participated in the GH treatment study. This sample was augmented with an additional 11 patients (6 males and 5 females; 3 IGHD and 8 MPHD) who were GHD both as children and adults, had not been treated with GH in the past year, and had not participated in the GH discontinuation study. Upon reintroduction of GH to only those patients meeting adult criteria for GHD, IGF-I levels increased between 0 and 6 months in both IGHD and MPHD, but without further change by 12 months. Accompanying this increase, scores on the insecure and depression scales (of the SCL-90) decreased across the entire 12 months for both IGHD and MPHD groups, whereas anxiety (assessed by the State-Trait Anxiety Scale) decreased significantly only from baseline to 6 months. QoL scores showed a significant improvement from 0 to 6 months of GH treatment. IGF-I levels were negatively correlated with negative mood states, but positively correlated with vigor, QoL, and short-term memory. The investigators concluded that GH-modulation of IGF-I concentrations is responsible both for deteriorating mood states during GH discontinuation and improved psychological status during the return to treatment.

Editor ' s Comment: As recognition has grown that the actions of GH extend beyond linear growth, the practice of treating GHD in adulthood has become more widely accepted. Unlike most studies assessing the benefits of adult GH replacement, these outcome variables were psychological rather than metabolic. In this study, both the IGHD (73% of whom retested GH-sufficient by adult criteria) and MPHD subgroups exhibited similar deterioration in emotional state upon discontinuation of GH with improvement after reinstating GH therapy. The investigators related these psychological changes to lower and subsequently improved IGF-I concentrations.

Several methodological features of this study should be taken into account before factoring them into clinical management algorithms. For instance, the investigators provide no indication of how representative study participants were of those in this clinic in meeting diagnostic and age criteria. Were those who agreed to participate more emotionally symptomatic? Research suggests considerable variability among patients in responsiveness to the QoL benefits of adult GH replacement.1,2 The potential contribution of a placebo effect to mental health indices also needs to be considered. A meta-analysis suggests that placebo effects are stronger in small trials with continuous subjective outcomes.3 The investigators may be attributing some psychological benefits to GH that are potentially due to response bias or placebo effect. Nonetheless this study is of great interest and provides important information.

David E. Sandberg, PhD

References - (linked to )

1. Holmes SJ, Shalet SM. Clin Endocrinol 1995;43:151-157.
2. Holmes SJ, Shalet SM. Clin Endocrinol 1995;42:613-618.
3. Hrobjartsson A, Gotzsche PC. N Engl J Med 2001;344:1594-1602.

Key words:

Growth hormone, GH, quality of life, isolated growth hormone disorder, multiple pituitary hormone deficits

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