Final height in a patient with Laron syndrome after long-term therapy with rhIGF-I and short-term therapy with LHRH-analogue and oxandrolone during puberty

Abstract

To report our experience on long-term treatment with recombinant-human-IGF-I (rhIGF-I) of a female patient with Laron syndrome (mutation G223G in the GH receptor gene), who received short-term treatment (1 yr) with LHRH analogue at the start of puberty and subsequently with oxandrolone. The patient started IGF-I therapy (dose 40 microg/kg bid for 9 months, 80 microg/kg bid until 13.7 yr of age and 120 microg/kg bid thereafter) when she was 7.6 yr old (height -6 sds), and was treated for 9.4 yr until final height (cm 129.7; -5.5 sds). At first signs of puberty (age 12.7 yr; height 116.3; -5.3 sds), LHRH analogue was started (3.75 mg/28 days) and bone age progressed by 6 months in the 12-month period. Growth velocity decreased in the 6-12th month of combined treatment (0.9 cm/6 months), and treatment was suspended. At age 14.8 (height 124.5; -6.6 sds), oxandrolone was added (0.1 mg/kg/day), but after 12 months (height 128 cm; -5.7 sds) bone age increased from 11.5 to 13.5 yr and the drug was stopped. No side effects occurred during the various treatments. Body segments progressed harmonically: there was a tendency towards improvement in the upper to lower body segment ratio and in cranial growth. Only biiliac diameter did not increase during LHRH treatment. During the 9-yr period, body mass index (BMI), subscapular and triceps skinfold centiles did not show any significant variations. Our patient with Laron syndrome after long-term treatment showed a final result below the initial expectations, confirming that IGF-I used with the present schedule is less effective than GH in GH-deficient patients. LHRH analogue therapy at puberty was associated with a slower bone age maturation but with an almost complete arrest of growth. On the contrary, oxandrolone sustained growth but caused an excessive maturation of bone age. Other strategies are necessary to improve final height in these patients.