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Article: Georges Gelwane, Catherine Garel, Didier Chevenne, Priscilla Armoogum, Dominique Simon, Paul Czernichow, and Juliane Léger Subnormal serum IGF-I levels in young adults with childhood-onset non acquired GH deficiency who recover normal GH secretion may indicate less severe but persistent pituitary failure J Clin Endocrinol Metab 2007; 0: jc.2007-1003v1 [Abstract]

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The Diagnosis of GHD in Young Adults With Recovery of GH Testing and Subnormal IGF-I Values

Mohamad Maghnie, Natascia Di Iorgi   (28 November 2007)

The Diagnosis of GHD in Young Adults With Recovery of GH Testing and Subnormal IGF-I Values 28 November 2007
Mohamad Maghnie, MD, PhD Department of Pediatrics, IRCCS G Gaslini, University of Genova, Natascia Di Iorgi Send letter to journal: Re: The Diagnosis of GHD in Young Adults With Recovery of GH Testing and Subnormal IGF-I Values mohamadmaghnie{at}ospedale-gaslini.ge.it Mohamad Maghnie, et al.	We read with great interest the paper by Gelwane and colleagues (1). The authors have carefully reported the characteristics of 98 patients with childhood-onset non-acquired GH deficiency who recovered normal peak GH secretion at the time of adult height achievement. Although serum IGF-I levels were significantly lower in those with structural hypothalamic-pituitary abnormalities than in those with normal pituitary gland, the latter subjects displayed lower serum IGF-I values compared to age-, sex- and BMI-matched controls, suggesting persistent pituitary impairment after recovery of GH testing. These findings have important clinical implications in the diagnosis and prognosis of GHD after adult height achievement since patients with ectopic posterior pituitary gland are at risk of deterioration of pituitary function and of developing additional pituitary hormone deficits (2). In our experience, a high percentage of children with GH deficiency who have normal or small pituitary glands show normalization of GH secretion at the completion of rhGH treatment, whereas all patients with ectopic posterior pituitary demonstrate permanent GH deficiency (3). Our recent study highlighted the importance of reassessing pituitary function in young adults with GH deficiency of childhood-onset and “normal” post-stimulation GH responses, since evolving pituitary failure and additional anterior pituitary deficits were documented in our study in 8 out of 20 patients with ectopic posterior pituitary during follow-up (2). The diagnosis of GHD in some young adults has recently been shown to be less definitive when based on the adopted predictive criteria for permanent GHD (4), suggesting that GH response after stimulation test is related to the secretagogue, patient age, time of evaluation, number of pituitary hormone deficits and BMI. Some of our patients with childhood-onset GH deficiency and normal GH retesting, normal pituitary gland and low serum IGF-I values exhibited low 12-hr spontaneous GH secretion, emphasizing the advantage of measuring spontaneous GH secretion over pharmacologic stimulation tests in some subjects with childhood-onset GH deficiency and low serum IGF-I levels (5). The diagnosis of GH deficiency in young adults represents a major clinical challenge. In some young adults with childhood-onset hypopituitarism, a strongly suspected diagnosis of permanent GHD should be re-investigated more accurately by means of an integrated analysis that includes clinical history, the presence of additional hormone deficits, serum IGF-I concentrations, MRI phenotype and spontaneous GH secretion as opposed to only by a GH cut-off point after stimulation test before the patient’s discharge or before making a commitment to lifelong GH replacement. References 1. Gelwane G, Garel C, Chevenne D, Armoogum P, Simon D, Czernichow, P Leger J 2007 Subnormal serum insulin-like growth factor-I levels in young adults with childhood-onset nonacquired growth hormone (GH) deficiency who recover normal GH secretion may indicate less severe but persistent pituitary failure. J Clin Endocrinol Metab. 92:3788-3795 2. di Iorgi N, Secco A, Napoli F, Tinelli C, Calcagno A, Fratangeli N, Ambrosini L, Rossi A, Lorini R, Maghnie M 2007 Deterioration of growth hormone (GH) response and anterior pituitary function in young adults with childhood-onset GH deficiency and ectopic posterior pituitary: a two-year prospective follow-up study. J Clin Endocrinol Metab.92:3875-3884 3. Maghnie M, Strigazzi C, Tinelli C, Autelli M, Cisternino M, Loche S, Severi F 1999 Growth hormone (GH) deficiency (GHD) of childhood onset: reassessment of GH status and evaluation of the predictive criteria for permanent GHD in young adults. J Clin Endocrinol Metab. 84:1324-1328 4. Maghnie M, Amaretti G, Bellone S, Bona G, Bellone J, Balzelli R, de Sanctis C, Gargantini L, Gastaldi R, Ghizzoni L, Secco A, Tinelli C, Ghigo E 2005 Diagnosis of growth hormone deficiency in the transition period: Accuracy of insulin tolerance test and insulin-like growth factor I measurement. Eur J Endocrinol 152:589-596 5. Radetti G, di Iorgi N, Paganini C, Gastaldi R, Napoli F, Lorini R, Maghnie M 2007 The advantage of measuring spontaneous growth hormone (GH) secretion compared with the insulin tolerance test in the diagnosis of GH deficiency in young adults. Clin Endocrinol (Oxf) 67:78-84