Growth in children with craniopharyngioma following surgery

Hypopituitarism, including severe GH deficiency, is an almost inevitable outcome of craniopharyngioma. However, some GH deficient children with this tumour may grow normally or even have accelerated growth postoperatively. To study this phenomenon we have investigated the endocrine status, including IGF-1 and its binding proteins IGFBP-1 and IGFBP3, in children referred for follow-up at various time intervals after surgery.

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 tumour was intrasellar in 11 cases and suprasellar in 14.

Height and height velocity were recorded as SDS values. Body mass index (BMI) was calculated as weight/height2. GH secretory status was evaluated by stimulation both with oral clonidine and with GH releasing hormone. Serum insulin (INS) levels were studied following an oral glucose load. IGF-1, IGFBP-3, IGFBP-1 and prolactin serum concentrations were evaluated in fasting samples. All hormones were measured by radioimmunoassay.

All patients had growth hormone (GH) deficiency. Height (HtSDSCA) and height velocity SDS for chronological age (HVSDSCA) decreased progressively after surgery (r = -0.47, P = 0.005, and r = -0.4, P = 0.032, respectively) but four patients had normal HtSDSCA 6.1 to 10.8 years following their first surgery. There was a significant correlation between BMI and HtSDSCA (r = 0.37, P = 0.03). BMI in children with suprasellar craniopharyngioma was significantly greater than that in patients with intrasellar tumour (23.3 +/- 7.0 vs. 17.3 +/- 1.4 kg/m2; P = 0.001). In 13 of 33 cases oral glucose load was accompanied 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 lesion (6945.5 +/- 4411.8 vs. 2495.5 +/- 1768.8 mU/l. min P = 0-001). The log INSAUC correlated significantly with HtSDSCA (0.37, P = 0.03). Fasting serum IGF-1 and IGFBP3 levels were normal in 8 and 12 of the 31 measurements, respectively. Both IGF-1SDS and IGFBP-3SDS correlated significantly with HtSDSCA (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-1SDS was the single most important predictor of HtSDSCA (R2 = 0.33, P = 0.001) in the subset mode.

A few children with craniopharyngioma grew normally after surgery, in spite of being GH-deficient. This growth phenomenon, which is usually accompanied by obesity, was more common in patients with suprasellar tumour and is likely to be associated with the effect of IGF-1 bioavailability, which, in turn, may be modulated largely by insulin.