Attention-Deficit/Hyperactivity Disorder Medication Treatment Impact on Response to Growth Hormone Therapy: Results from the ANSWER Program, a Non-Interventional Study

Rose, Susan R.; Reeves, Grafton; Gut, Robert; Germak, John

doi:10.1016/j.jpeds.2015.08.036

Cited by 8 publications

(6 citation statements)

References 19 publications

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“…The high incidence of ADHD (22 out of 106) in our patient group is remarkable and may have attributed to the finding of reduced HRV in patients with symptomatic short stature as there is a well described reduction of HRV in ADHD patients [23] [37]. However according to data from Rose et al there is a similar increased number of ADHD diagnosis by 1190 out of 7230 short patients receiving GH treatment [38] suggesting some coincidence of these two diagnoses. Furthermore diagnosis of ADHD seems to be related to smaller growth velocity induced by GH treatment [38].…”

Section: Is There a Common Link Between Attention Regulation And Growth?supporting

confidence: 54%

“…However according to data from Rose et al there is a similar increased number of ADHD diagnosis by 1190 out of 7230 short patients receiving GH treatment [38] suggesting some coincidence of these two diagnoses. Furthermore diagnosis of ADHD seems to be related to smaller growth velocity induced by GH treatment [38]. Keeping in mind the idea of autonomic imprinting [10] we may speculate about common pathophysiological pathways in the development of both entities.…”

Section: Is There a Common Link Between Attention Regulation And Growth?mentioning

confidence: 93%

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Growth Hormone Treatment, Cardiovascular Risk and Autonomic Maturation in Children and Adolescents with Growth Hormone Deficiency or Born Small for Gestational Age

Buchhorn¹,

Willaschek²

2020

OJPed

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Introduction: The impact of growth hormone therapy in children with short stature on cardiovascular prognosis seems to be unpredictable from big databases. The enhanced cardiovascular risk in this group of patients may be related to adverse autonomic imprinting by early life stress. Autonomic dysfunction and possible effects of growth hormone therapy on the autonomic nervous system can be measured easily by calculating heart rate variability (HRV) from Holter electrocardiogram monitoring. Methods: We performed HRV analysis prior to growth hormone therapy (N = 33), within the first year of growth hormone therapy between 4 and 10 years of age (N = 19), at least a further HRV measurement between 10 and 15 years (N = 30). Additional measurements were performed before and after cessation of growth hormone therapy (N = 14). Data were compared to untreated pediatric patients with short stature and to age matched healthy controls. Results: Untreated patients with short stature due to growth hormone deficiency or intrauterine growth restriction in early childhood have significantly increased heart rates most of all at night and concomitantly reduced global HRV indicated as Standard Deviation of Normal to Normal Intervals (SDNN). Growth hormone treated adolescents and the untreated patients with short stature show significantly elevated mean heart rates and concomitantly reduced vagus activities measured as reduced Route Mean Square Standard Deviation (RMSSD). After cessation of growth hormone treatment SDNN significantly increases and heart rate decreases to normal values in formerly treated patients with catch-up growth. Conclusion: There is a comparable autonomic dysfunction in treated and untreated children with short stature as an indicator for enhanced cardiovascular risk.

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Section: Is There a Common Link Between Attention Regulation And Growth?supporting

confidence: 54%

Section: Is There a Common Link Between Attention Regulation And Growth?mentioning

confidence: 93%

Growth Hormone Treatment, Cardiovascular Risk and Autonomic Maturation in Children and Adolescents with Growth Hormone Deficiency or Born Small for Gestational Age

Buchhorn¹,

Willaschek²

2020

OJPed

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“…The limited data available on concomitant medications showed that stimulant medications were prescribed in the United States at a frequency (8.6%) similar to that in children without growth disorders (reported as 5.1% based on the 2016 National Survey of Children’s Health) (27). A subanalysis of ANSWER data reported that the linear growth response to GH treatment was not modified by ADHD stimulant medication (28); however, in a subanalysis of KIGS data, Miller et al concluded that the ADHD phenotype, alone or in conjunction with stimulant therapy, may impair the short-term growth response to GH treatment (29).…”

Section: Discussionmentioning

confidence: 99%

Treatment of Children With GH in the United States and Europe: Long-Term Follow-Up From NordiNet® IOS and ANSWER Program

Sävendahl

Polak

Backeljauw

et al. 2019

The Journal of Clinical Endocrinology &Amp; Metabolism

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ContextUnderstanding real-world prescribing of GH may help improve treatment of eligible patients.ObjectiveOverall: to assess real-world effectiveness and safety of GH (Norditropin). This analysis: to compare clinical characteristics of GH-treated children in the United States and Europe.DesignThe American Norditropin Studies: Web-Enabled Research Program (ANSWER; 2002 to 2016, United States) and the NordiNet International Outcome Study (NordiNet IOS; 2006 to 2016, Europe) were multicenter longitudinal observational cohort studies.SettingData were recorded in 207 (United States) and 469 (Europe) clinics.ParticipantsPatients with GH deficiency, Turner syndrome, Noonan syndrome, idiopathic short stature, Prader–Willi syndrome, or born small for gestational age, who commenced GH treatment aged <1 year.InterventionGH was prescribed by treating physicians according to local practice.Main Outcomes MeasuresBaseline data and drug doses were recorded. Data on effectiveness and safety were collected.ResultsANSWER had 19,847 patients in the full analysis set (FAS; patients with birthdate information and one or more GH prescription) and 12,660 in the effectiveness analysis set (EAS; GH-naive patients with valid baseline information). NordiNet IOS had 17,711 (FAS) and 11,967 (EAS). Boys accounted for 69% (ANSWER) and 57% (NordiNet IOS). Treatment start occurred later than optimal to improve growth. The proportion of boys treated was generally larger, children were older at treatment start, and GH doses were higher in the United States vs Europe. No new safety signals of concern were noted.ConclusionsIn most indications, more boys than girls were treated, and treatment started late. Earlier diagnosis of GH-related disorders is needed. The data support a favorable benefit–risk profile of GH therapy in children.

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“…After adjusting for baseline age, height, weight, BMI, and sex, the change in BMI z-score was greater for the patients taking ADHD stimulant medication, implying that GH treatment may reduce the appetite suppression seen with stimulant medication. However, after matching for baseline measurements, ADHD stimulant medication did not have an effect on the linear growth response of children treated with GH (20).…”

Section: Stimulant Medicationsmentioning

confidence: 85%

“…After adjusting for various factors, those receiving both GH and ADHD medication had a lower growth rate after a year of GH, compared to those only on GH: 8.5±2 and 9.4±2.6 cm/year, respectively; the difference was not clinically significant (19). Rose et al reported on growth outcomes in children on GH therapy enrolled in the American Norditropin Studies: Web-Enabled Research (ANSWER) Program (20). They compared children only on GH therapy, to children on GH therapy and stimulant medication for ADHD, for the first four years of GH therapy.…”

Section: Stimulant Medicationsmentioning

confidence: 99%

Growth perturbations from stimulant medications and inhaled corticosteroids

Richardson¹,

Seibert²,

Uli³

2017

Transl. Pediatr

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Stimulant medications for the treatment of attention deficit hyperactivity disorder (ADHD) and inhaled corticosteroids (ICS) for the treatment of asthma are two classes of medications that are commonly prescribed in pediatrics. Among other adverse effects of these medications, growth attenuation has long been a focus of investigation. With stimulants, growth deficits of 1-1.4 cm/year have been observed in the short term, mainly in the first 2 years of treatment, in a dose-dependent manner. Long-term studies on stimulants have reported divergent effects on growth, with many studies showing no clinically significant height deficits by adulthood. The study that followed the largest cohort of children on stimulants, however, reported an overall adult height deficit of 1.29 cm in subjects who had received stimulant medications, with mean adult height deficit of 4.7 cm among those taking the medication consistently. With ICS use, mild growth suppression is seen in the short term (particularly in the first year of therapy) with growth rates reduced by 0.4-1.5 cm/year. Available current evidence indicates that the impact of ICS use on adult height is not clinically significant, with effects limited to 1.2 cm or less. There is significant individual variability in growth suppression with ICS use, with the specific pharmacologic agent, formulation, dose exposure, age, puberty, medication adherence, and timing of administration being important modifying factors. Based on currently available evidence, the therapeutic benefits of ICS for management of asthma and stimulant medications for management of ADHD outweigh the potential risk for growth suppression. Strategies to minimize growth attenuation and other potential adverse effects of these medications include using the lowest efficacious dose, frequent assessments and dose titration. Particular vigilance is essential with concomitant use of multiple medications that can attenuate growth and to evaluate for potential adrenal insufficiency from ICS use.

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Attention-Deficit/Hyperactivity Disorder Medication Treatment Impact on Response to Growth Hormone Therapy: Results from the ANSWER Program, a Non-Interventional Study

Abstract: ClinicalTrials.gov: NCT01009905.

Cited by 8 publications

References 19 publications

Growth Hormone Treatment, Cardiovascular Risk and Autonomic Maturation in Children and Adolescents with Growth Hormone Deficiency or Born Small for Gestational Age

Growth Hormone Treatment, Cardiovascular Risk and Autonomic Maturation in Children and Adolescents with Growth Hormone Deficiency or Born Small for Gestational Age

Treatment of Children With GH in the United States and Europe: Long-Term Follow-Up From NordiNet® IOS and ANSWER Program

Growth perturbations from stimulant medications and inhaled corticosteroids

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