Growth Hormone Outgrows Growth

Growth Hormone Outgrows Growth
Growth hormone (GH) replacement has been offered to GH-deficient (GHD) children for approximately 40 years whereas it has only been a licensed indication for the treatment of GHD adults since 1996. Nonetheless, the advent of GH replacement for adult GHD patients (Jorgensen et al., 1989; Salomon et al., 1989) has proved informative about the overall management of the GHD child and teenager; equally, the longstanding experience of the paediatric endocrinologist with GH replacement has provided some guidance about potential pitfalls in the diagnosis and management of the adult GHD patient. It is the knowledge exchange at this professional interface that forms the focus of this article.

The type of underlying pathophysiology differs in childhood-onset (CO) compared with adult-onset (AO) GHD. In childhood the commonest aetiology is isolated idiopathic GHD (August et al., 1990; Vanderschueren-Lodeweyckx, 1994), a blanket term that includes some children with distinctive pathophysiology that may be demonstrated radiologically, and others in whom the pathological insult is unknown and the explanation for the GHD ill-understood. By contrast, AOGHD is most frequently due to a pituitary adenoma and/or treatment with surgery or radiotherapy (Rosen & Bengtsson, 1990; Toogood et al., 1994). In GHD children poor growth dominates the clinical imperative to offer GH replacement whereas in adult life there is no single symptom or sign that is pathognomonic of GHD; nonetheless, GHD in adult life is associated with increased fat mass, particularly distributed in the truncal region (Salomon et al., 1989; DeBoer et al., 1992), reduced lean mass (Salomon et al., 1989; DeBoer et al., 1992), osteopenia (Johansson et al., 1992; Kaufman et al., 1992; Holmes et al., 1994), an adverse cardiovascular risk factor profile (Amato et al., 1993; Beshyah et al., 1994; Johansson et al., 1994, 1995), reduced exercise capacity (Cuneo et al., 1991; Nass et al., 1995) and reduced quality of life (Rosen et al., 1994). In addition, the standardized mortality rate is increased in hypopituitary adult patients on full replacement therapy with glucocorticoids, thyroxine and sex steroids but in whom GHD remains untreated; thus the increased mortality has been attributed to the GHD to a varying degree dependent on the interpretation of the literature by different endocrinologists (Murray and Shalet, 2000).

Dose requirements and the biochemical severity of the hormone deficiency also vary between GHD children and adults; children with all grades of GHD from mild to severe, but only adults with severe GHD, are considered for GH replacement and the replacement dose of GH is significantly greater in children than in adults, the variation in dose requirement reflecting the evolution of change in endogenous GH secretion with age in normal individuals.