Department of Pediatrics (G.R.), Regional Hospital of Bolzano, 39100 Bolzano, Italy; and Department of Pediatrics (M.M.), University of Pavia, Istituto di Ricovero e Cura a Carattere, Scientifico Policlinico S. Matteo, 27100 Pavia, Italy
Address correspondence to: Dr. Giorgio Radetti, Department of Pediatrics, Regional Hospital of Bolzano, via L. Boehler no. 5, 39100 Bolzano, Italy. E-mail: giorgio.radetti{at}asbz.it; or Mohamad Maghnie, M.D., Ph.D, Department of Pediatrics, University of Pavia, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico S. Matteo, I-27100, Pavia, Italy. E:mail: maghnie{at}smatteo.pv.it.
To the editor:
We read with great interest the paper by Shulman et al. (1). The authors report the beneficial effect of 1-yr recombinant human (rh) GH treatment on cardiac mass and function in children with classical GH deficiency (GHD). These findings have important clinical implications in the long-term follow-up because there is a well-established relationship between GHD and increased cardiovascular mortality in untreated adults (2). We would like, however, to make some comments.
In the study, 10 young children with a relatively early onset of GHD at a median age of less than 5 yr were treated with rhGH at a dose of 0.3 mg/kg·wk for 12 months; seven had structural abnormalities of the hypothalamic-pituitary axis, a diagnosis compatible with permanent GHD. Their main findings consisted in increased left ventricular mass indexed by body surface area, height or height2.7 after 1 yr of rhGH therapy. The trophic effect of GH on the heart was confirmed, but the results raise questions about the long-term safety of subjects with childhood onset GHD treated at the above-mentioned dose.
In a group of 14 GHD children treated with the same dosage (0.3 mg/kg·wk) for a mean period of 5 yr, we reported a significant increase in left ventricular (LV) mass, mass/volume ratio, and an alteration of LV diastolic function compared with a group of normal children (3). No differences in morphofunctional cardiac indices were shown between patients and controls after 1 yr of treatment (4). Moreover, in another study we carried out, no adverse effects on the heart were observed in a group of patients with Turners syndrome treated with the same rhGH dose for 1 yr (5).
The discrepancy between our results and those reported by Shulman et al. (1) could be explained either by the duration of treatment or by a different tissue responsiveness to rhGH among patients. Indeed, tissue sensitivity is inversely correlated to serum GH levels (6). This would also explain the findings in Turners syndrome patients, who are not GH deficient and thus relatively resistant to the GH action. We think that the severity of GHD in the young patients of Shulman et al. (1) is indeed an important factor that should not be underestimated because these patients are probably more sensitive to GH action and, consequently, to its potential adverse effects on the heart in the long-term treatment. Furthermore, unlike our cohort of patients with isolated GHD (3), Shulmans patients suffer from a combined pituitary hormone deficiency and thus from a more severe GH deficit that would make them even more sensitive to GH therapy. Indeed, this is supported by the negative correlation that Shulman found between the LV mass and the response to rhGH treatment. Hypothalamic-pituitary abnormalities in GHD are highly predictive of severe, "true," and permanent GHD in adult life. We therefore believe that the amount of rhGH administered to children with severe GH deficit, as the one reported by Shulman et al., should be reduced to the lowest possible effective dosage to avoid a potential damage to cardiac mass and function later on in life.
Footnotes
A response to this letter was invited, but the authors of the original article chose not to provide one.
Received July 2, 2004.
References
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