Normal Variant Short Stature: Subclassification Based on Responses to Exogenous Human Growth Hormone*

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Abstract
Normal variant short stature (NVSS), constituting about 40% of short children, is defined as height below the third percentile; negative physical/x-ray examination, except for proportionate short stature, with or without retarded bone age; birth weight greater than 2.5 kg; normal plasma immunoreactive GH response to pharmacological stimuli; and predicted adult height below the third percentile. This study investigated whether NVSS is related to peripheral resistance to GH. Twenty-eight NVSS children, aged 8–10 yr, were given human GH (0.532 U/kg BW3/4-day for 10 days). Two responses were measured: 1) the anabolic response of the soft tissues in terms of daily retention of N, P, and K and 2) the linear growth response of the skeleton in terms of the increment in height during the next 12 weeks. The anabolic and linear growth reactions were measured for comparison in nine GH-deficient children, and the anabolic responses were measured in nine normal control subjects. The GH-deficient children responded vigorously to GH in both respects. Nine NVSS children (subgroup 1) showed neither anabolic nor linear growth response to the hormone. Ten NVSS cases (subgroup 2) showed no linear growth response but had anabolic responses comparable to the nine normal control subjects. Six NVSS cases (subgroup 3) exhibited linear growth and anabolic responses 25–50% as great as those of the GH-deficient children. Three NVSS cases (subgroup 4) displayed anabolic and linear growth responses equal to those of the GH-deficient group. When subgroup 4 children were treated with 6 U GH weekly for 4–15 months, their linear growth rate increased from <2.5 to 6.8– 8.3 cm/yr. Measuring both anabolic and linear growth reactions to a 10-day course of GH provides a new approach to subclassifying children with NVSS. Subgroup 4 patients are candidates for long term GH treatment.

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