Endocrine Abstracts

Isolated growth hormone deficiency (IGHD) type 1a is caused by defects of the GH-I gene resulting in severe short stature. Treatment with growth hormone may become ineffective due to significant production of growth hormone antibodies. However, this has only been reported in patients treated with pituitary derived growth hormone. We present five cases with IGHD type 1a successfully treated with recombinant human growth hormone (rhGH).

Five patients from four families (four females, one male) showed severe short stature beginning in the first year of life. All of them had undetectable levels of growth hormone and were subsequently found to be homozygous for a 6.7 kb deletion in the GH-1 gene. Two families were known to be consanguineous. Treatment with rhGH normalized growth in all subjects with a current duration of treatment of 1–10 years (mean 5.25 years). One patient has reached final height (initial height SDS – 7.92 at age 2 10/12 years; final height SDS 0.98).

Another patient (initial height SDS – 8.83 at 1 11/12 years; current height SDS 0.9 at 9 5/12 years) has two affected brothers who already had high titers of GH antibodies after having possibly been treated with pituitary derived GH. They remained unresponsive to rhGH even in excessive doses of up to 0.35 mg/kg.

In our experience treatment of IGHD type 1a with rhGH is not associated with a risk of GH antibody production leading to growth arrest. Prior to considering IGF-I as first-line treatment in IGHD type 1a further experimental and epidemiologic studies should evaluate the risk of antibody production on rhGH treatment.