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Effect on Adult Height of Pubertal Growth Hormone Retesting and Withdrawal of Therapy in Patients with Previously Diagnosed Growth Hormone Deficiency

Department of Pediatrics, University of Bologna, S. Orsola-Malpighi Hospital, 40138 Bologna, Italy

Address all correspondence and requests for reprints to: Stefano Zucchini, Department of Pediatrics, via Massarenti 11, 40138 Bologna, Italy. E-mail: zucchini{at}med.unibo.it.

Context: GH replacement therapy in GH-deficient (GHD) patients is usually continued until adult height despite the fact that most of these subjects display a normal secretion when retested at the end of growth. Puberty is the most likely time for normalization of GH secretion.

Objectives: The objectives of this study are to establish the characteristics and the percentage of the subjects with isolated GHD who normalized secretion at puberty and to compare their statural outcomes with those of the subjects with persistent deficiency treated also after retesting.

Design and Setting: This was a prospective, nonrandomized, open-label study conducted in a university research hospital.

Patients and Intervention: Sixty-nine subjects (40 male, 29 female) with a diagnosis before puberty of isolated GHD by means of arginine and l-dopa tests were reevaluated with the same tests after at least 2 yr of therapy and after puberty onset. If GH peak at retesting was more than 10 µg/liter, therapy was withdrawn.

Main Outcome Measures: Percentage and characteristics of normalized subjects at retesting, outcome of treatment in the subjects treated or untreated to adult height, and factors predictive of growth outcome were measured.

Results: At retesting, 44 subjects (63.7%) confirmed a GH peak less than 10 µg/liter (24 of 40 male and 20 of 29 female). Apart from a less delayed bone age at diagnosis in females, the subjects with confirmed GHD were not different at diagnosis from the other group for height deficit at diagnosis, first year growth response to GH, age and height at puberty onset, height, and IGF-I at retesting. Mean adult height was 165.1 ± 4.5 cm in the male group treated until adult height vs. 164.0 ± 3.4 cm in the group who suspended therapy at retesting. Mean adult height was 153.2 ± 4.1 cm in the female group treated until adult height vs. 152.9 ± 5.2 cm in the group that suspended therapy at retesting. As regards the parameters expressing the final outcome, the only difference was found in the mean increment adult height-target height SD score in favor of the male group treated until adult height. In both sexes, therapy duration and GH levels at diagnosis and at retesting were unrelated to adult height parameters and to height increments during the period of observation.

Conclusions: One third of our GHD subjects diagnosed before puberty presented a normal secretion at puberty. The withdrawal of GH therapy in these subjects after retesting was not associated with a catch down growth, and they obtained an adult height similar to those obtained by the GHD subjects treated until adult height. It seems convenient, in subjects with nonsevere GHD, to retest GH secretion at midpuberty and to withdraw treatment for the subjects that are no longer deficient.

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