Background: Recombinant human Insulin-like growth factor-1 (rhIGF-1) is the only treatment for short stature due to primary IGF-1 deficiency and related disorders. However, treatment needs meticulous monitoring for adverse effects, especially hypoglycemia, obstructive sleep apnoea (OSA), raised intracranial hypertension, cardiac complications and skin reactions.
Method: To determine therapeutic potential, efficacy and safety of rhIGF-1 treatment, case notes were reviewed for all patients treated in a tertiary care centre. Diagnosis, rhIGF-1 doses, height velocities (HV) and adverse effects were documented.
Results: 11 patients (8 male) received rhIGF-1 over 15 years. Underlying diagnoses included: Laron syndrome (n=3); GH insensitivity due to signaling defects (n=3) or unknown aetiology (n=3); GH gene deletion with GH antibodies (n=1); syndrome with complex panhypopituitarism unresponsive to GH therapy (n=1). Median presentation was 2.23(1.5713.97) years. Starting rhIGF-1 dose was 7380 (g/kg/day at 5.14(222.6) years. In 10 patients, HV increased; the syndromic child with panhypopituitarism was unresponsive to rhIGF-1. Mean HV pre-treatment was 3.66(1.756.46)cm/year. With rhIGF-1, maximal HV occurred within 36 months (7.55 cm/year), followed by gradual decline to 6.30 cm/year at 1 year, 6.25 cm/year at 2 years, and 4.73 cm/year after 4 years. Hypoglycaemia (n=7, 63.63%) was the most frequent adverse effect, then adeno-tonsillar hypertrophy leading to OSA (n=3), and cardiac left ventricular dysfunction (n=1). Hypoglycaemia, always pre-meal or fasting, occurred in the first 3 months of treatment; the earliest after only one rhIGF-1 dose. In 5 cases, hypoglycaemia resolved by giving rhIGF-1 post meals. However, in one case, bedtime cornstarch, and in another, overnight continuous feeds were needed to manage hypoglycaemia. The 3 OSA cases were within 410 months of starting treatment. One patient developed left ventricular dysfunction after 2 years. There were no reports of skin reactions or raised intracranial pressure.
Conclusion: rhIGF-1 therapy is a promising treatment for children with IGF-1 deficiency, resulting in increased HV. Hypoglycaemia is the most frequent side effect but can be successfully managed with dietary interventions. Clinicians must be mindful of other potentially life-threatening complications (OSA, cardiac failure), the need for monitoring and joint decision making with families. Further follow-up should take place within international registries.
27 - 29 Nov 2019
British Society for Paediatric Endocrinology and Diabetes