Growth in children with craniopharyngioma following surgery

OBJECTIVE Hypopituitarism, including severe GH deficiency, is an almost ine vitable outcome of craniopharyngioma. However, some GH deficient children w ith this tumour may grow normally or even have accelerated growth postopera tively. To study this phenomenon we have investigated the endocrine status, including IGF-1 and its binding proteins IGFBP-1 and IGFBP3, in children r eferred for follow-up at various time intervals after surgery. PATIENTS Twenty-five patients (14 boys and 11 girls, aged 3.8-18.9 years), were studied on 34 occasions between 0.5 to 10.8 years after surgery. The t umour was intrasellar in 11 cases and suprasellar in 14. METHODS Height and height velocity were recorded as SDS values. Body mass i ndex (BMI) was calculated as weight/height(2). GH secretory status was eval uated by stimulation both with oral clonidine and with GH releasing hormone . Serum insulin (INS) levels were studied following an oral glucose load. I GF-1, IGFBP-3, IGFBP-1 and prolactin serum concentrations were evaluated in fasting samples. All hormones were measured by radioimmunoassay. RESULTS All patients had growth hormone (GH) deficiency. Height (HtSDS(CA)) and height velocity SDS for chronological age (HVSDSCA) decreased progress ively after surgery (r = -0.47, P = 0.005, and r = -0.4, P = 0.032, respect ively) but four patients had normal HtSDS(CA) 6.1 to 10.8 years following t heir first surgery. There was a significant correlation between BMI and HtSDS(CA) (r = 0.37, P = 0.03). BMI in children with suprasellar craniopharyngioma was significant ly greater than that in patients with intrasellar tumour (23.3 +/- 7.0 vs. 17.3 +/- 1.4 kg/m(2); P = 0.001). In 13 of 33 cases oral glucose load was a ccompanied by hyperinsulinaemia with serum INS levels greater than 50 mU/l. The mean area under the curve (AUC) of INS after glucose load (INSAUC) in the suprasellar group was greater than in the patients with intrasellar les ion (6945.5 +/- 4411.8 vs. 2495.5 +/- 1768.8 mU/l. min P = 0.001). The log INSAUC correlated significantly with HtSDS(CA) (0.37, P = 0.03). Pasting se rum IGP-1 and IGPBP3 levels were normal in 8 and 12 of the 31 measurements, respectively. Both IGF-1SDS and IGPBP-3SDS correlated significantly with H tSDS(CA) (r = 0.77, P = 0.0002 and r = 0.65, P = 0.0001, respectively) and the log INSAUC (r = 0.39, P = 0.035, r = 0.56, P = 0.002, respectively). As determined by forward stepwise regression analysis, IGF-1(SDS) was the sin gle most important predictor of HtSDS(CA) (R-2 = 0.33, P = 0.001) in the su bset mode. CONCLUSION A few children with craniopharyngioma grew normally after surger y, in spite of being GH-deficient. This growth phenomenon, which is usually accompanied by obesity, was more common in patients with suprasellar tumou r and is likely to be associated with the effect of IGP-1 bioavailability, which, in turn, may be modulated largely by insulin.