Insulin-like growth factor I (IGF-I) and IGF-binding protein 3 as diagnostic markers of growth hormone deficiency in infancy

BACKGROUND: The diagnosis of growth hormone deficiency (GHD) in infancy is difficult, and no specific cutoff value during GH provocative testing is recommended in early life.

METHODS: Serum insulin-like growth factor I (IGF-I) and serum IGF-binding protein 3 (IGFBP-3) levels were evaluated as diagnostic markers of GHD. Measurements of IGF-I and IGFBP-3 during the 1st year of life were analyzed in 11 patients clinically suspected of having GHD (neonatal hypoglycemia, micropenis, or evidence of other pituitary hormone deficiencies), in whom the diagnosis was later verified. A prospective cohort of 51 healthy infants served as controls.

RESULTS: The sensitivity of IGF-I as a diagnostic marker of GHD was 90% (10 out of 11 patients) with a cutoff value of -2 standard deviations (SD), and the sensitivity of IGFBP-3 measurements was 81% (9 out of 11 patients) with a cutoff value below -2 SD. One patient had serial measurements before initiation of GH treatment where the IGF-I was fluctuating (3 of 6 slightly above -2 SD), whereas all IGFBP-3 measurements were below -2 SD.

CONCLUSIONS: The IGF-I had a high sensitivity in detecting infants with GHD. The combination of IGF-I and IGFBP-3 increased the diagnostic sensitivity. We speculate that assessment of IGF-I and IGFBP-3 may add diagnostic value in infants suspected of having GHD and furthermore that values below -2 SD are highly suggestive of GHD.