Déficit do crescimento e alterações do eixo GH/IGF1 em pacientes tratados para a leucemia linfoblástica aguda na infância

Abstract

Growth deficit is a frequent complication of the treatment of Acute Lymphoblastic Leukemia (ALL) in childhood. In order to evaluate final height and GH/IGF-1 axis a contact was made, between 2007 and 2009, with patients treated for Acute Limphoblastic Leukemia (ALL) in three institutions: Hospital das Clínicas (UFMG), Hospital Felício Rocho (Belo Horizonte, MG) e Hospital Araújo Jorge (Goiânia, GO). Seventy five patients agreed to participate in the study. Only girls younger than 10 and boys younger than 12 years old at diagnosis were included. Children with central nervous system involvement, treatment with cerebrospinal irradiation, previous or current hormone therapy and lack of adequate growth data at diagnosis were excluded. The chemotherapeutic protocol used was based on the German BMF protocol. The median period of follow-up after starting treatment was 13.7 years. Height and body mass index (BMI) were analysed as standard deviation score (SDS). Mid-parental target height was calculated in 41 patients. Twenty seven patients were submitted to hormonal tests (growth hormone after insulin tolerance test, IGF-1, cortisol, T4 and estradiol/testosterone). Central nervous system prophylaxis included either no cranial radiation therapy (n=33), irradiation with 24 Gy (n=3), 18 Gy (n=38), or 12 Gy (n=1). Final height was significantly reduced in comparison with a reference population (mean SDS for height between final height and diagnose, HAZ=-0.61, P=0.0001). Patients ≤ 4 years of age at diagnosis had a greater loss in final height, compared with patients > 4 years of age (P=0.001). Irradiated and non-irradiated patients had loss in final height, although it was greater in the first group (P= 0.008). No significant effect of gender on the relative growth deficit was observed. No increase in BMI SDS was observed. Abnormalities in the GH/IGF-1 axis was observed in five patients, two had GH peak < 6 ng/ml and three had serum IGF-1 concentration < -2SDS for age and gender. Growth deficit was significantly greater in patients with hormonal deficiency compared with patients with no hormonal deficiency (P<0.001). Target height was compromised in patients with hormonal deficiency. Thyroid function was normal in all patients. One patient had low concentrations of cortisol. In conclusion, treatment of ALL in children is associated with deficit in final height, particularly in the ones younger than 4 at diagnosis and in those who received prophylactic cranial irradiation, although chemotherapy also play an important role in the process. GH/IGF-1 deficiency is particularly found in irradiated patients.