GHRH-GH-IGF1 axis in pediatric Down syndrome: A systematic review and mini meta-analysis

Shaki, David; Hershkovitz, Eli; Tamam, Shai; Bollotin, Arkadi; David, Odeya; Yalovitsky, Guy; Loewenthal, Neta; Carmon, Lior; Walker, Dganit; Haim, Alon

doi:10.3389/fped.2023.1132296

Cited by 3 publications

(4 citation statements)

References 24 publications

(16 reference statements)

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“…Recent studies have reported a certain degree of impairment of the GHRH-GH-IGF1 axis in subjects with trisomy 21. In detail, some authors have highlighted that short stature in DS can result from a combination of unsatisfactory hypothalamus–pituitary secretion and reduced bioactivity of endogenous GH ( 76 ).…”

Section: Auxologymentioning

confidence: 99%

“…The recurrent lack of controls, the limited follow-up, as well as the heterogeneous outcomes among treated patients has led to poorly reproducible conclusions ( 77 ). A recent meta-analysis reports a short-term efficacy of rhGH treatment on the growth of children with DS, irrespectively of endogenous GH secretion patterns ( 76 ). Nevertheless, most studies did not manage to demonstrate a longer-lasting and durable positive effect of the treatment on growth attainment ( 78 – 80 ).…”

Section: Auxologymentioning

confidence: 99%

“…Accordingly, though DS patients should not be precluded from GH therapy per se , no clear indication can be provided and rhGH is often proscribed to date. Benefits and disadvantages should be discussed with the parents and child and the approach should be patient-tailored ( 76 ).…”

Section: Auxologymentioning

confidence: 99%

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Endocrine, auxological and metabolic profile in children and adolescents with Down syndrome: from infancy to the first steps into adult life

Molinari,

Fossati,

Nicolosi

et al. 2024

Front. Endocrinol.

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Down syndrome (DS) is the most common chromosomal disorder worldwide. Along with intellectual disability, endocrine disorders represent a remarkable share of the morbidities experienced by children, adolescents and young adults with DS. Auxological parameters are plotted on syndrome-specific charts, as growth rates are reduced compared to healthy age- and gender-matched peers. Furthermore, children with DS are at increased risk for thyroid dysfunctions, diabetes mellitus, osteopenia and obesity compared to general population. Additionally, male individuals with DS often show infertility, while women tend to experience menopause at an overall younger age than healthy controls. Given the recent outstanding improvements in the care of severe DS-related comorbidities, infant mortality has dramatically decreased, with a current average life expectancy exceeding 60 years. Accordingly, the awareness of the specificities of DS in this field is pivotal to timely detect endocrine dysfunctions and to undertake a prompt dedicated treatment. Notably, best practices for the screening and monitoring of pediatric endocrine disorders in DS are still controversial. In addition, specific guidelines for the management of metabolic issues along the challenging period of transitioning from pediatric to adult health care are lacking. By performing a review of published literature, we highlighted the issues specifically involving children and adolescent with DS, aiming at providing clinicians with a detailed up-to-date overview of the endocrine, metabolic and auxological disorders in this selected population, with an additional focus on the management of patients in the critical phase of the transitioning from childhood to adult care.

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Section: Auxologymentioning

confidence: 99%

Section: Auxologymentioning

confidence: 99%

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Endocrine, auxological and metabolic profile in children and adolescents with Down syndrome: from infancy to the first steps into adult life

Molinari,

Fossati,

Nicolosi

et al. 2024

Front. Endocrinol.

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“…Obesity results in decreased GH and IGF-1 secretion ( 2 ), and it is more severe in patients with DS than in the general population ( 3 ). Reports indicate that patients with DS may have hypothalamic GH deficiency (GHD), which results from an impaired GH-releasing hormone (GHRH)–GH–IGF-1 axis ( 3 ). However, changes in hypothalamic GHD in adults with DS following weight loss remain unknown.…”

Section: Introductionmentioning

confidence: 99%

Weight Loss Improved Hypothalamic GH Deficiency but not Hypogonadotropic Hypogonadism in a Man With Down Syndrome

Nakagawa,

Taki

2024

JCEM Case Reports

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Down syndrome (DS) is associated with several endocrine disorders, including diabetes, obesity, and primary hypogonadism. Here, we present a man with DS who manifested with atypical hypogonadotropic hypogonadism and in whom weight loss resulted in the improvement of hypothalamic GH deficiency. A 27-year-old man with DS and severe obesity was admitted for hypoxia resulting from obesity hypoventilation syndrome. Laboratory tests showed normal levels of LH and FSH despite low testosterone and free testosterone levels. Moreover, thyroid stimulating hormone and prolactin levels were slightly elevated, although a euthyroid function was observed, and GH and IGF-1 levels were low. Endocrinological stimulation tests revealed hypogonadotropic hypogonadism and hypothalamic GH deficiency. Reduction in body weight by 35.3% resulted in the improvement of the IGF-1, thyroid stimulating hormone, and prolactin levels to the reference range, whereas the LH and FSH levels remained low, despite slight elevation. Levels of leptin, which suppresses the hypothalamus–gonadotroph–gonadal axis and upregulates thyrotropin-releasing hormone expression, decreased with weight loss. Furthermore, ghrelin, whose levels increase with weight loss, stimulates GH secretion. Thus, leptin and ghrelin could have contributed to the observed changes in the pituitary hormone profile after weight loss.

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GH treatment in pediatric Down syndrome: a systematic review and mini meta-analysis

et al. 2023

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ObjectiveTo analyze and determine the safety and efficacy of growth hormone (GH) treatment in Down syndrome (DS) pediatric patients and to weigh ethical aspects involved.DesignSystematic review and mini meta-analysis of the literature.MethodsA search was performed in PubMed, Embase, Scopus, and PsycINFO through August 2022. Eligible studies included those who answered at least one of the following two questions: 1) What is the effect of growth hormone treatment in children with Down syndrome? 2) What are the ethical arguments in favor and against growth hormone treatment for children with Down syndrome? Multiple reviewers independently screened each article for eligibility.ResultsIn total sixteen reports detailed medical effects of GH treatment in pediatric DS patients and eight studies dealt with ethical aspects of GH treatment. Treatment with GH resulted in significantly higher growth velocity in patients with DS. The ethical complexity is great but does not present insurmountable difficulties to the therapeutic option.ConclusionsAs GH treatment is safe and effective for short-term height growth, GH therapy should be considered in long-term treatment of DS children.

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GHRH-GH-IGF1 axis in pediatric Down syndrome: A systematic review and mini meta-analysis

Cited by 3 publications

References 24 publications

Endocrine, auxological and metabolic profile in children and adolescents with Down syndrome: from infancy to the first steps into adult life

Endocrine, auxological and metabolic profile in children and adolescents with Down syndrome: from infancy to the first steps into adult life

Weight Loss Improved Hypothalamic GH Deficiency but not Hypogonadotropic Hypogonadism in a Man With Down Syndrome

GH treatment in pediatric Down syndrome: a systematic review and mini meta-analysis

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