Is growth without IGF1 possible? A case report

According to the growth hormone – insulin-like growth factor 1 axis (GH/IGF1 axis) theory, the actions of GH on promoting growth are mediated by IGF1. In the blood, IGF1, insulin-like growth factor 1 binding protein 3 (IGFBP3) and acid-labile subunit (ALS) form ternary complexes, hence the accumulation of IGF1. We report a case of 10-year-old male with short stature due to GH deficiency diagnosed with hypopituitarism. Therapy with recombinant human GH (rhGH) was initiated at 11 years and 4 months. After twenty three months on treatment clinical effects were as follows: increase in the patient’s height by 19.2 cm (initial height 12.4 cm vs. 140.6 cm; hSDS -4.35 vs. -2.7; predicted adult height 176 cm vs. 182 cm, respectively). Despite good clinical response to the therapy, serum levels of IGF1 and IGFBP3 remained diminished: IGF1 – 28 ng/ml initially, vs. 23 ng/ml 19 months on therapy and IGFBP3 – 1116 ng/ml initially, vs. 1888 ng/ml after 11 months on therapy. We attempt to justify this phenomenon by reconsidering the IGF1-independent GH actions, assessing the endocrine role of hepatic IGF1 in comparison to the autocrine/paracrine role of its bone tissue fraction, and evaluating the functions of ALS. The exact explanation for the positive response to rhGH treatment without the expected increase in IGF1 in our patient remains unknown. Serum levels of IGF1 and IGFBP3 seem not always to be reliable markers of the response to rhGH treatment in GH-deficient patients.