Growth impairment and gonadal axis abnormalities are common in survivors of paediatric brain tumours.

AIM: Childhood brain tumour survivors have a high risk of endocrine morbidity. This study evaluated the growth, pubertal development and gonadal function in survivors of childhood brain tumours and identified factors associated with the problems we observed. METHODS: The 52 subjects (52% male) were diagnosed in 1983-1997 and treated for brain tumours at Tampere University Hospital, Finland. They were followed up at a mean age of 14.2 (3.8-28.7) years, a mean of 7.5 (1.5-15.1) years after diagnosis. RESULTS: We found that 30 (58%) participants had a lower height standard deviation score at follow-up than at diagnosis and short stature at follow-up was associated with tumour malignancy (p = 0.005), radiotherapy (p = 0.004), chemotherapy (p = 0.024), growth hormone deficiency (p < 0.001), hypogonadism (p = 0.044) and delayed puberty (p = 0.021). We found that five needed sex hormones to induce puberty, one had precocious puberty, 12 (23%) had growth hormone deficiency and eight (22%) of the 36 pubertal or postpubertal patients had hypogonadism. Testicular volume was low in 83% of late or postpubertal male survivors. CONCLUSION: Growth impairment, growth hormone deficiency and hypogonadism were common in childhood brain tumour survivors and low testicular volume was also common in male survivors. Lifelong annual follow-up checks are indicated for survivors.

Electroretinography and Visual Evoked Potentials in Childhood Brain Tumor Survivors.

This population-based cross-sectional study evaluates the clinical value of electroretinography and visual evoked potentials in childhood brain tumor survivors. A flash electroretinography and a checkerboard reversal pattern visual evoked potential (or alternatively a flash visual evoked potential) were done for 51 survivors (age 3.8-28.7 years) after a mean follow-up time of 7.6 (1.5-15.1) years. Abnormal electroretinography was obtained in 1 case, bilaterally delayed abnormal visual evoked potentials in 22/51 (43%) cases. Nine of 25 patients with infratentorial tumor location, and altogether 12 out of 31 (39%) patients who did not have tumors involving the visual pathways, had abnormal visual evoked potentials. Abnormal electroretinographies are rarely observed, but abnormal visual evoked potentials are common even without evident anatomic lesions in the visual pathway. Bilateral changes suggest a general and possibly multifactorial toxic/adverse effect on the visual pathway. Electroretinography and visual evoked potential may have clinical and scientific value while evaluating long-term effects of childhood brain tumors and tumor treatment.

Neurological outcome of childhood brain tumor survivors.

We assessed neurological and neurocognitive outcome in childhood brain tumor survivors. Altogether, 75 out of 80 brain tumor survivors diagnosed below 17 years between 1983 and 1997; and treated in Tampere University Hospital, Finland, were invited to participate in this population-based cross-sectional study. Fifty-two (69%) participated [mean age 14.2 (3.8-28.7) years, mean follow-up 7.5 (1.5-15.1) years]. Neurological status was abnormal in 69% cases. All were ambulatory, but only 50% showed normal motor function. Twenty-nine percent showed clumsiness/mild asymmetry and 21% hemiparesis. One suffered from intractable epilepsy. According to structured interview, 87% coped normally in daily living. Median full-scale IQ was 85 (39-110) in 21 6-16 year olds (70%); in 29% IQ was <70. Thirty of the 44 school-aged subjects attended school with normal syllabus and 32% needed special education. Six of the 16 patients over 18 years of age were working. Regarding quality of life, 38% were active without disability, 33% active with mild disability, 21% were partially disabled, but capable of self-care, and 8% had severe disability, being incapable of self-care. Supratentorial/hemispheric tumor location, tumor reoperations, shunt revisions and chemotherapy were associated with neurological, cognitive and social disabilities. In conclusion, of the 52 survivors, neurological status was abnormal in 69%; 71% lived an active life with minor disabilities, 29% had major neurological, cognitive and social disabilities, and 8% of them were incapable of self-care. Predictors of these disabilities included supratentorial/hemispheric tumor location, tumor reoperations, shunt revisions and chemotherapy. Survivors need life-long, tailor-made multiprofessional support and follow-up.

Obesity and metabolic changes are common in young childhood brain tumor survivors.

BACKGROUND: A population based cross-sectional study was used to examine the prevalence of metabolic syndrome and its components in childhood brain tumor survivors. PROCEDURE: Fifty-two survivors were examined at a mean age of 14.4 years (range 3.8-28.7). Lipid and glucose metabolism, thyroid function, and plasma uric acid were evaluated. Fat mass and fat percentage were assessed by dual-energy X-ray absorptiometry (DXA). Metabolic syndrome was defined on International Diabetes Federation criteria. RESULTS: Ten (19%) patients were overweight and four (8%) were obese. According to DXA, 16/46 (35%) patients were obese. Central obesity was found in 11 (21%) patients. Cranial irradiation, hypothalamic/hypophyseal damage, growth hormone (GH) deficiency and impaired mobility were associated with overweight/obesity and central obesity. Thirteen (25%) subjects had hypercholesterolemia, 14 (27%) had raised low-density lipoprotein cholesterol (LDL-C), 12 (23%) had raised blood pressure, four (8%) had metabolic syndrome, two (4%) had hyperinsulinemia and five (10%) had hyperuricemia. Cranial irradiation was associated with hypercholesterolemia (P = 0.019), raised LDL-C (P = 0.028), raised blood pressure (P = 0.040), and metabolic syndrome (P = 0.018). Impaired mobility was associated with hypercholesterolemia (P = 0.034). Hypothalamic/hypophyseal damage was associated with metabolic syndrome (P = 0.003) and hyperuricemia (P = 0.011) as was GH deficiency (P = 0.034 and P = 0.008). GH supplementation alleviated adverse metabolic outcomes among brain tumor survivors with GH deficiency. CONCLUSIONS: Obesity/overweight, dyslipidemia, hypertension, metabolic syndrome, and hyperuricemia were common in young childhood brain tumor survivors. Cranial irradiation, hypothalamic/hypophyseal damage, growth hormone deficiency, and/or impaired mobility were associated with higher risk for obesity and metabolic changes among these patients.

Renal impairment and hypertension in brain tumor patients treated in childhood are mainly associated with cisplatin treatment.

BACKGROUND: This study was designed to evaluate the renal consequences of the treatment of brain tumor patients diagnosed in childhood. PROCEDURE: One hundred four primary brain tumor patients diagnosed before 17 years of age from 1983 to 1997 had been treated in Tampere University Hospital, Finland. Of the 80 survivors 52 (65.0%) were examined at a median age of 14.4 years (range 3.8-28.7) and median 6.0 years (range 1.2-14.8) after the last treatment. The main outcome measures were blood pressure (BP), renal function, and calcium metabolism. RESULTS: Eight patients (15.4%) were hypertensive. Elevated BP was observed especially after exposure both to cisplatin and cranial irradiation. Spinal radiation did not increase the risk of elevated BP. Other adverse effects were observed only in patients treated with cisplatin. Five out of 14 patients treated with cisplatin evinced renal glomerular dysfunction (GFR < 87 mL/min/1.73 m2) immediately after treatment. They had a high cumulative dose of cisplatin (490-880 mg/m2). Recovery from renal glomerular dysfunction was observed in one patient. Nine of 14 patients were hypomagnesemic at the close of cisplatin treatment. Thereafter the magnesium level decreased in 10/14 cases (P = 0.006). During the study 10/14 were hypomagnesemic (P < 0.001); one evinced severe symptomatic hypomagnesemia. Low plasma phosphate (P = 0.016) and potassium levels (P = 0.026), tubular proteinuria (P = 0.055), metabolic alkalosis (P = 0.071), and hyperuricemia (P = 0.114) were also more common in patients on cisplatin treatment. CONCLUSIONS: Elevated BP is common among brain tumor patients treated in childhood. After cisplatin treatment renal glomerular dysfunction appears mostly to be permanent. Persistent and even progressive changes in renal tubular function are seen.