Postprandial Hyperglycemia Corrected by IGF-I (Increlex®) in Laron Syndrome

Abstract

Background: Laron syndrome is caused by a mutation in the growth hormone (GH) receptor and manifests as insulin-like growth factor-I (IGF-I) deficiency, severe short stature, and early hypoglycemia. We report a case with postprandial hyperglycemia, an abnormality not reported previously. Postprandial hyperglycemia was due to chronic IGF-I deficiency, and was reversed by IGF-I replacement therapy. Methods: A Moroccan girl referred for short stature at 7 years and 8 months of age had dwarfism [height, 78 cm (–9 SDs); weight, 10 kg (–4 SDs)], hypoglycemia, and truncal obesity. Her serum IGF-I level was very low, and her baseline serum GH level was elevated to 47 mIU/l. Molecular analysis showed a homozygous mutation in the GH receptor gene. Results: Continuous glucose monitoring before treatment showed asymptomatic hypoglycemia with postprandial hyperglycemia (2.5 g/l, 13.75 mmol/l). Treatment with recombinant human IGF-I (mecasermin, Increlex®) was started. The blood glucose profile improved with 0.04 µg/kg/day and returned to normal with 0.12 µg/kg/day. Conclusion: Postprandial hyperglycemia is a metabolic consequence of chronic IGF-I deficiency. The beneficial effect of IGF-I replacement therapy may be ascribable to improved postprandial transfer of glucose.

An unusual cause of short stature-Laron syndrome

“…GH can bind either defectively to the ectodomain of GHR or there is diminished effectiveness in dimerization of the receptor after the hormone occupies receptor leading to block in signalling cascade which finally results in decreased IGF-1 and ultimately holds up the mitogenic effects of GH. [2][3][4][5][6] Hence in Laron syndrome though the growth hormone levels are high IGF-1 levels are remarkably low.…”

“…The prognosis with respect to final height in males is 116 to 142 cms and Females is 108 to 136 cms. 5 Despite the appearance of premature aging signs, like thin and wrinkled skin, patients with LS have a long life. 4,11 There is delay in attainment of puberty by 3-7 year and does not display the typical pubertal growth spurt.…”

“…14 Complications of GHI include seizures due to low blood sugar and bone fractures because of osteopenia were not present in our case. 5,12,14…”

Use of Continuous Glucose Monitoring to Identify Glucose Dysregulation in Growth Hormone Insensitivity Syndrome

“…Laron et al [3] demonstrated relative insulinopenia in young adults with GHI following chronic IGF-1 deprivation, and there are reports of patients with GHI developing insulin resistance [25]. The youngest age at which postprandial hyperglycaemia has been reported is 7.7 years, although this was measured before treatment [26]. …”

Insulin-like Growth Factors in a clinical setting: Review of IGF-I

“…The Food and Drug Administration (FDA) has approved clinical use of mecasermin, a recombinant human IGF-I analog intended for subcutaneous application 50,51 and also of mecasermin rinfabate, a binary complex of equimolar IGF-I and IGFBP-3 (ref. 52,53 ).…”