Effect of Growth Hormone Therapy in Patients with Noonan Syndrome: A Retrospective Study

Apperley, Louise; Ramakrishnan, Renuka; Dharmaraj, Poonam; Das, Urmi; Didi, Mohammed; Blair, Jo; Senniappan, Senthil

doi:10.5812/ijem.107292

Cited by 5 publications

(9 citation statements)

References 18 publications

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“…Many retrospective, observational studies on rhGH treatment in NS patients with and without GHD as well as clinical trials in NS patients with short stature have been carried out over the past 20 years ( 42 , 54 , 59 , 60 , 64 , 68 – 72 , 74 , 75 , 78 – 80 , 83 ). In some studies, auxological and safety data were consequent to rhGH dosages established on the whole cohort of NS patients with no distinction being made between subjects with GHD and subjects without GHD, while other studies included only NS subjects with GHD ( 54 , 59 , 60 , 64 , 69 , 72 , 75 , 78 – 80 , 83 ). In other studies, doses of rhGH varied according to different parameters, for example the pubertal stage of patients ( 21 , 61 , 66 , 76 , 81 ).…”

Section: Effectiveness Of Growth Hormone Treatmentmentioning

confidence: 99%

Inside the Noonan “universe”: Literature review on growth, GH/IGF axis and rhGH treatment: Facts and concerns

Stagi

Ferrari

et al. 2022

Front. Endocrinol.

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Noonan syndrome (NS) is a disorder characterized by a typical facial gestalt, congenital heart defects, variable cognitive deficits, skeletal defects, and short stature. NS is caused by germline pathogenic variants in genes coding proteins with a role in the RAS/mitogen-activated protein kinase signaling pathway, and it is typically associated with substantial genetic and clinical complexity and variability. Short stature is a cardinal feature in NS, with evidence indicating that growth hormone (GH) deficiency, partial GH insensitivity, and altered response to insulin-like growth factor I (IGF-1) are contributing events for growth failure in these patients. Decreased IGF-I, together with low/normal responses to GH pharmacological provocation tests, indicating a variable presence of GH deficiency/resistance, in particular in subjects with pathogenic PTPN11 variants, are frequently reported. Nonetheless, short- and long-term studies have demonstrated a consistent and significant increase in height velocity (HV) in NS children and adolescents treated with recombinant human GH (rhGH). While the overall experience with rhGH treatment in NS patients with short stature is reassuring, it is difficult to systematically compare published data due to heterogeneous protocols, potential enrolment bias, the small size of cohorts in many studies, different cohort selection criteria and varying durations of therapy. Furthermore, in most studies, the genetic information is lacking. NS is associated with a higher risk of benign and malignant proliferative disorders and hypertrophic cardiomyopathy, and rhGH treatment may further increase risk in these patients, especially as dosages vary widely. Herein we provide an updated review of aspects related to growth, altered function of the GH/IGF axis and cell response to GH/IGF stimulation, rhGH treatment and its possible adverse events. Given the clinical variability and genetic heterogeneity of NS, treatment with rhGH should be personalized and a conservative approach with judicious surveillance is recommended. Depending on the genotype, an individualized follow-up and close monitoring during rhGH treatments, also focusing on screening for neoplasms, should be considered.

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Section: Effectiveness Of Growth Hormone Treatmentmentioning

confidence: 99%

Inside the Noonan “universe”: Literature review on growth, GH/IGF axis and rhGH treatment: Facts and concerns

Stagi

Ferrari

et al. 2022

Front. Endocrinol.

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“…Although abnormal growth is a characteristic feature of NS, some individuals will display normal growth patterns and adult height. Birth weight and length tend to be within a normal range (45,46); however, there is a subsequent deceleration of height and weight to -2.0 SD or less (43,44). Mean adult heights range from -2.3 to -2.5 SD for males and -2.1 to -2.2 SD for females based on height references from four different patient populations (43,44,47,48).…”

Section: Featuresmentioning

confidence: 99%

“…Early initiation of GH therapy for NS-associated short stature can lead to significant short-and long-term increases in height velocity, height standard deviation score (SDS), and adult height (Table 3 and Figures 1A, B) (45,62,102,(110)(111)(112). Earlier initiation, longer duration of therapy, and increased height SDS at the time of treatment initiation are all positive predictors of response to GH treatment (110)(111)(112)(113).…”

Section: Growth/pubertymentioning

confidence: 99%

“…Several concerns have been raised about the safety of GH in individuals with NS, particularly in those with cardiac-related comorbidities. However, multiple studies have revealed no changes in cardiac parameters, including left ventricular wall thickness, and few cardiac-related adverse events in GH-treated individuals with NS (1,45,46,62,112). Further studies are needed to substantiate the continued safety of GH use in NS with respect to cardiac risks.…”

Section: Growth/pubertymentioning

confidence: 99%

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Genetic conditions of short stature: A review of three classic examples

et al. 2022

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Noonan, Turner, and Prader-Willi syndromes are classical genetic disorders that are marked by short stature. Each disorder has been recognized for several decades and is backed by extensive published literature describing its features, genetic origins, and optimal treatment strategies. These disorders are accompanied by a multitude of comorbidities, including cardiovascular issues, endocrinopathies, and infertility. Diagnostic delays, syndrome-associated comorbidities, and inefficient communication among the members of a patient’s health care team can affect a patient’s well-being from birth through adulthood. Insufficient information is available to help patients and their multidisciplinary team of providers transition from pediatric to adult health care systems. The aim of this review is to summarize the clinical features and genetics associated with each syndrome, describe best practices for diagnosis and treatment, and emphasize the importance of multidisciplinary teams and appropriate care plans for the pediatric to adult health care transition.

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“…Thus there are concerns about the use of rGH in NS because of the already existing cardiac involvement in the pathophysiology of the disease and the high frequency of cardiac hypertrophy. Theoretically, the risk of increased ventricular wall thickness and cardiac side effects associated with the use of rGH is predicted, but studies providing empirical evidence in this area are very limited ( Table 1 ) ( 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ).…”

Section: Introductionmentioning

confidence: 99%

The Effect of Growth Hormone Therapy on Cardiac Outcomes in Noonan Syndrome: Long Term Follow-up Results

Cetin¹,

Ramoğlu²,

Şıklar³

et al. 2022

Jcrpe

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Objective: Cardiac involvement is common in Noonan syndrome (NS). Concerns have been raised regarding the effect of recombinant growth hormone (rGH) use on ventricular wall thickness and a possible increased risk of cardiac side effects. This study aimed to investigate the effect of rGH on the development of hypertrophic cardiomyopathy and other cardiac findings in NS Methods: Patients under the age of 18 years and diagnosed with NS according to the Van der Burgt criteria, were included. Patients were divided into two groups according to those receiving rGH or not at the time of obtaining cardiac measurements. Before and after the treatment, electrocardiographic and echocardiographic (ECHO) assessments were made, including interventricular septal thickness, left ventricular internal diameter, and left ventricular posterior thickness. Results were expressed as Z scores. Results: Twenty-four NS subjects (16 boys, eight girls) were included. At the beginning of the follow up, the overall height standard deviation score was -2.56±0.94. Sixteen were on rGH. The mean rGH treatment duration was 8.3±3.8 years, and the mean dose was 0.22±0.04 mg/kg/week. The final height was 169±8.2 cm, and 10 of 11 patients who reached the final height received rGH. There was no difference between the rGH and non-rGH groups in terms of ECHO parameters pre-and post-treatment. Conclusion: In this cohort, there was no change in ECHO parameters on rGH and during follow-up. These results suggest that rGH is safe in NS patients with cardiac pathology under close follow-up.

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Effect of Growth Hormone Therapy in Patients with Noonan Syndrome: A Retrospective Study

Cited by 5 publications

References 18 publications

Inside the Noonan “universe”: Literature review on growth, GH/IGF axis and rhGH treatment: Facts and concerns

Inside the Noonan “universe”: Literature review on growth, GH/IGF axis and rhGH treatment: Facts and concerns

Genetic conditions of short stature: A review of three classic examples

The Effect of Growth Hormone Therapy on Cardiac Outcomes in Noonan Syndrome: Long Term Follow-up Results

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