Growth suppression associated with stimulant therapy has occasionally been reported in patients with attention-deficit hyperactivity disorder (ADHD).1, 2 We encountered a case in which treatment with methylphenidate, a central nervous system stimulant, was associated with a transient reduction in growth velocity, followed by recovery without discontinuation of the medication. A 21-year-old male was born at 39 weeks of gestation with a birth weight of 3106 g. His growth chart is shown in Figure 1. At 8 years of age, he was referred to our hospital because of hyperactivity and impaired concentration. His father and mother were 183 and 154 cm tall, respectively, yielding a target height of 177 cm. Following a diagnosis of ADHD, treatment with osmotic-release oral system (OROS) methylphenidate was initiated at a dose of 18 mg/day at 8 years and 4 months of age. The dose was increased to 27 mg/day after 3 months and to 36 mg/day after 1 year. Height velocity was 5.2 cm/year during the first year of treatment but decreased to 2.9 cm/year during the second year. At 10 years and 11 months, his insulin-like growth factor 1 level was 128 ng/mL (reference range 99–423 ng/mL for the same age group); thyroid-stimulating hormone was 1.398 μIU/mL (0.5–5.0); free thyroxine was 1.37 ng/dL (0.9–1.7). Serum adrenaline level was 0.07 ng/mL (<0.17), noradrenaline level was 0.23 ng/mL (0.15–0.57), dopamine level was <0.02 ng/mL (<0.03). Testicular volume was 2 mL bilaterally. Appetite suppression associated with methylphenidate resulted in weight loss, with body mass index decreasing from 19.1 to 16.5; however, body weight gradually recovered over the subsequent 2 years. Because ADHD symptoms remained severe, methylphenidate was continued without interruption. Pubertal onset occurred at 11 years and 9 months of age. At 12 years of age, bone age assessed using the radius–ulna–short bone method was 12 years and 2 months, consistent with chronological age. At 15 years and 8 months of age, due to persistent attention-deficit symptoms, methylphenidate was switched to atomoxetine, and pharmacological treatment was discontinued at 16 years and 9 months. The patient ultimately achieved an adult height of 178 cm, consistent with his predicted height, and a final body weight of 80 kg. In this case, a reduction in height velocity was observed after the initiation of methylphenidate, particularly during the dose-escalation period. Methylphenidate enhances dopaminergic activity and may transiently stimulate growth hormone (GH) secretion; however, prolonged exposure may lead to dopamine receptor downregulation or desensitization, potentially resulting in reduced hypothalamic secretion of growth hormone–releasing factor (GRF) and subsequent impairment of GH secretion. Additionally, the concurrent presence of weight loss and reduced height velocity suggests that the observed growth impairment may have been influenced by inadequate weight gain. The patient's appetite gradually improved over time. Although gastrointestinal prokinetic agents have been reported as a treatment option for stimulant-induced appetite suppression,3 appetite improvement in this case occurred without pharmacological intervention, possibly reflecting habituation to methylphenidate. Importantly, ADHD symptoms showed sustained improvement throughout the treatment period, and the therapeutic efficacy of methylphenidate was maintained despite fluctuations in appetite and weight gain. This clinical course suggests that the development of clinically meaningful pharmacological tolerance was unlikely. After discontinuation of methylphenidate, the patient became overweight in adulthood. This finding may indicate that compensatory eating behaviors acquired during the period of appetite suppression persisted after treatment cessation, contributing to excessive caloric intake once appetite normalized. In summary, we experienced a case of methylphenidate-associated growth impairment in which growth velocity improved without discontinuation of treatment. As this is a single case report, the findings cannot be generalized. Growth impairment associated with methylphenidate is a clinically relevant adverse effect and often leads to dose reduction or discontinuation.4, 5 However, this case suggests that, in selected patients, catch-up growth may occur without discontinuing treatment, underscoring the importance of individualized clinical decision-making. YK contributed to the conception and design of this study. HY and FK contributed to patient care and the acquisition and analysis of patient data. YK prepared the manuscript. All authors critically revised the manuscript and approved the final manuscript. Informed consent was obtained from the parents and patient for the publication of this report. This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper. The data that support the findings of this study are available from the corresponding author upon reasonable request.
Katsushima et al. (Thu,) studied this question.