Metabolic Health in Short Children Born Small for Gestational Age Treated With Growth Hormone and Gonadotropin-Releasing Hormone Analog: Results of a Randomized, Dose-Response Trial

Manouk van der Steen*, Annemieke J. Lem, Danielle C. M. van der Kaay, Willie M. Bakker-van Waarde, Flip J. P. C. M. van der Hulst, Floor S. Neijens, Cees Noordam, Roelof J. Odink, Wilma Oostdijk, Eelco J. Schroor, Ciska Westerlaken, Anita C. S. Hokken-Koelega

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    24 Citations (Scopus)

    Abstract

    Context: Previously we showed that pubertal children born small for gestational age (SGA) with a poor adult height (AH) expectation can benefit from treatment with GH1 mg/m(2) per day (similar to 0.033 mg/kg/d) in combination with 2 years of GnRH analog (GnRHa) and even more so with a double GH dose. GnRHa treatment is thought to have negative effects on body composition and blood pressure. Long-term effects and GH-dose effects on metabolic health in children treated with combined GH/GnRHa are unknown.

    Objective: This study aimed to investigate body composition, blood pressure, and lipid profile during GH treatment, either with or without 2 years of additional GnRHa. To assess whether GH 2 mg/m(2) per day (similar to 0.067 mg/kg/d) results in a similar or even more favorable metabolic health at AH than GH 1 mg/m(2) per day.

    Methods: This was a longitudinal, randomized, dose-response GH trial involving 107 short SGA children (58 girls) treated with GH until AH (GH randomized 1 or 2 mg/m(2)/d during puberty). Sixty-four children received additional GnRHa. At AH, metabolic parameters were compared between children treated with combined GH/GnRHa and those with only GH. The GH dose effect on metabolic health was evaluated in a subgroup of 47 children who started GH treatment in early puberty (randomized 1 or 2 mg/m(2)/d) with 2 years of GnRHa.

    Results: At AH, fat mass percentage (FM%) SD score (SDS), lean body mass (LBM) SDS, blood pressure SDS, and lipid profile were similar between children treated with combined GH/GnRHa and those with only GH. In the pubertal subgroup, FM% SDS was lower during treatment with GH 2 mg/m(2) per day. There was no GH dose-dependent effect on LBM SDS, blood pressure, and lipid profile.

    Conclusions: Combined GH/GnRHa treatment has no long-term negative effects on metabolic health compared with only GH. Started in early puberty, a GH dose of 2 mg/m(2) per day results in a similar metabolic health at AH and a more favorable FM% than GH 1 mg/m(2) per day.

    Original languageEnglish
    Pages (from-to)3725-3734
    Number of pages10
    JournalJournal of Clinical Endocrinology and Metabolism
    Volume100
    Issue number10
    DOIs
    Publication statusPublished - Oct-2015

    Keywords

    • BONE-MINERAL DENSITY
    • FOLLICLE-STIMULATING-HORMONE
    • CENTRAL PRECOCIOUS PUBERTY
    • TREATMENT PANEL-III
    • BODY-COMPOSITION
    • GH TRIAL
    • BLOOD-PRESSURE
    • ADULT HEIGHT
    • LONG-TERM
    • DIABETES-MELLITUS

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