A Boy with Optic Glioma
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1 Clin Pediatr Endocrinol 1994;3(Suppl 4): Copyright(C)1994 by The Japanese Society for Pediatric Endocrinology Taisuke Okada, Sumitaka Dohno, Yousei Shimasaki, Takashi Tomoda, Makiko Koga, Kumiko Araki and Takanobu Kurashige Department of Pediatrics, Kochi Medical School, Kohasu, Oko-cho, Nankoku-city, Kochi, Japan Abstract. A 6-month-old boy had nystagmus. Hydrocephalus and a large hypothalamic tumor were found by MRI. After partial resection of the tumor, diabetes insipidus (DI) and ACTH deficiency had developed. The tumor was diagnosed as optic astrocytoma, histologically. Although he had been treated with dexamethasone, DI was not well controlled. At 1.5 years old, he was admitted to our hospital with polyuria, obesity and hypertrichosis. The growth chart showed that he had grown rapidly from birth. The serum level of GH was normal, but insulin like growth factor (IGF)-I value was high. Serum levels of insulin and prolactin were normal. On treatment with low doses of hydrocortisone and DDAVP, the urine volume and serum level of IGF-I decreased. He was diagnosed as having partial GH deficiency by intravenous insulin stimulation test. He has blindness and slight mental retardation now. The etiology of his overgrowth is not known clearly, but some other unknown growth factor may have stimulated his growth. Key words: optic glioma, overgrowth, diabetes insipidus, ACTH deficiency, IGF- I Introduction Gliomas of the optic nerve and chiasm are rare, and occur most commonly in childhood. The majority of these tumors are low-grade astrocytomas histologically, but the clinical course of these tumors is not benign. Tumors involving the optic chiasm and particularly extending outside of the chiasm into the hypothalamus tend to be more aggressive than tumors involving the optic nerve alone Correspondence: Dr. Taisuke Okada, Department Kochi Medical School, Kohasu, Oko-cho, Nankoku-shi, 783 Japan of Pediatrics, Kochi (1). Chiasmatic-hypothalamic gliomas often cause endocrine abnormalities in addition to visual symptoms and have been associated with the diencephalic syndrome of emaciation (2). We report here a case of optic glioma in whom overgrowth in both height and weight developed from birth. Case Report The patient had a normal, full-term, spontaneous delivery. The growth chart showed that he had grown rapidly from birth. He was first noted to have macrocephaly and slightly retarded head control at the age of 4 months. 169
2 170 OKADA et al. Fig. 1. Magnetic resonance T1-weighted image, coronal projection, obtained after administration of gadolinium. Note the enhancing mass in the supra- sellar area. He was admitted to another hospital because of nystagmus at the age of 6 months. Hydrocephalus and hypothalamic tumor were found by MRI and he was referred to our hospital for operation. MRI on admission (Fig. 1) showed a 5cm diameter suprasellar tumor which was enhanced homogenously by administration of gadlinium. The V-P shunt operation and partial resection of the tumor were performed; thereafter, diabetes insipidus (DI) and ACTH deficiency appeared. The diagnosis of astrocytoma was made histologically. Although he had been treated with dexamethasone and 1-deamino-8-D-arginine vasopression (DDAVP) or indomethacin, DI was not well controlled. At age 16 months he was readmitted to our hospital with polyuria, obesity, and hypertrichosis. On admission, his height was 84cm (+ 2.0SD), weight 15.0kg (+ 3.5SD) and his head circumference was 55cm (+3.8SD) (Fig. 2). Bone age was slightly retarded. The urine volume was about 3 liters/day and the specific gravity was Serum osmolarity was 298mOsm/kg, urine Fig. 2. Growth Chart osmolarity was 171mOsm/kg, and antidiuretic hormone (ADH) was 0.8pg/ml. The level of growth hormone (GH) was normal, but IGF-I value was high. Urinary GH secretion was not detected. Serum prolactin level and TSH were within normal limits. ACTH and cortisol levels were low (Table. 1). With administration of hydrocortisone (30mg/day) and DDAVP (1.3pg twice a day), urine volume and serum IGF-I level gradually decreased. At age 19 months, the dosage of hydrocortisone and DDAVP was 17mg/day and 2.5ƒÊg twice a day respectively. The urine volume was about 1.2 liters/day and serum values of ACTH and cortisol were low (Fig. 3). Serum insulin value was normal, but serum prolactin level slightly increased. ACTH, cortisol, and GH showed low responses to hypoglycemia by intravenous insulin stimulation test (0.05U/kg). Rapid ACTH test revealed low adrenal function (Tabled). Therefore, he was diagnosed as having partial GH deficiency. However, his
3 171 Table 1. Laboratory Data (1993, May) Fig. 3. Clinical Course overgrowth has continued in both height and weight. He has blindness and slight mental retardation. The optic glioma has not shown regrowth as followed by MRI examination, without chemotherapy or radiotherapy (Fig. 4). Discussion Optic pathway/hypothalamic astrocytomas in childhood have long been believed to follow a highly unpredictable course (3). Some remain static for many years, while others increase in size and can lead to significant morbidity and even to death. Observation only, or treatments by radiotherapy, chemotherapy, and surgical resection have all been proposed. Consequently, there is no uniform method of management. In this case, the large tumor was placed posteriorly, resulting in hydrocephalus and endocrinological dysfunction without neurofibromatosis. Harold et al. say that anteriorly placed tumors restricted to one orbit and causing unsightly proptosis and significant visual loss had better be resected (3). Posteriorly placed tumors causing hydrocephalus and/or endocrinological Fig. 4. No evidence of tumor regrowth compared to preoperation. dysfunction are treated with shunting and resection, with medical therapy for the endocrinological dysfunction. As these posteriorly placed optic pathway tumors cannot, however, undergo total surgical excision, radiation therapy and/or chemotherapy may be needed. Radiation therapy is sure to be effective in patients with optic glioma with involvement
4 172 OKADA et al. of the chiasm and posterior structures (4)(5), but the side effects of irradiation can be serious (6), so chemotherapy should be considered in the initial management following resection (7). In our patient the symptoms did not progress on clinical and radiographic evaluation without chemotherapy and radiation therapy. He has to be followed carefully by MRI and further treatment may be needed if the tumor should progress. Clinical manifestations of optic glioma may be decreased vision, headache or endocrine dysfunction. A variety of endocrine dysfunctions are reported such as precocious puberty, GH deficiency, delayed puberty, DI, hypothyroidism, and hypopituitarism. Our case had DI, ACTH deficiency, and probably partial GH deficiency. However, he had overgrowth from birth. Overgrowth in patients with optic glioma has not previously been reported, to our knowledge. The etiology of this overgrowth is unknown. Overgrowth already developed before administration of hydrocortisone and contined during therapy. As he had partial GH deficiency, it was suggested that some growth factor, which was secreted by the tumor, might have accelerated his growth from birth. The level of IGF-I was high in spite of GH deficiency, but it de-. creased by reducing the dose of hydrocortisone. Therefore, administration of hydrocortisone was thought to induce the high level of IGF-I. Although IGF-I producing astrocytoma has been reported (8), there is no report of optic glioma that produced some growth factor. On the other hand, it has been reported that some patients with brain tumor had normal or accelerated growth in spite of GH deficiency (9). The mechanisms of the growth in these cases have not been clarified. These patients had hyperphagia and severe obesity. A high level of serum insulin or hyperprolactinemia can be associated with a normal IGF-I value in GH deficient patients. In our case, the serum value of insulin was normal, but prolactin was at a slightly high level. As overgrowth appeared when the serum prolactin level was normal, prolactin might have no direct relation to his overgrowth. Therefore, some other growth factor secreted by the tumor may have acted as a stimulating factor. We must evaluate the bioactivity of IGF-I to clarify the mechanism of his overgrowth. Conclusion 1. We have reported here a case of optic glioma who had DI, ACTH deficiency, partial GH deficiency and overgrowth. 2. DI and ACTH deficiency was well controlled by replacement therapy, but the etiology of overgrowth has not been determined. Some other unknown growth factor may act as a stimulating factor months after operation, the residual tumor had not regrown by MRI and he was watched, without chemotherapy or radiotherapy. If the tumor progresses further treatment may be needed. References 1. John CF, Carlos T, Melvin D. Management of low-grade gliomas of the optic nerve and chiasm. Cancer 1988; 61: Luis AR, Michael SBE, Victor AL. Management of hypothalamic gliomas in children: an analysis of 33 cases. Neurosurgery 1990; 26: Harold JH, Robin PH, James MD, Laurence EB, Derek J, et al. Optic pathway/hypothalamic gliomas: a dilemma in management. Pediatr Neurosurg 1993; Bataini JP, Delanian S, Ponvert D. Chiasmal gliomas: results of irradiation management in 57 patients and review of literature. Int J Radiation Oncology Biol Phys 1991; 21: Susan MP, Patrick DB, Jay SL, Cornelius M, Nancy JT. Definitive radiation therapy in the management of symptomatic patients with optic glioma. Cencer 1990; 65:
5 Leena W, Robert HS, Gerald AK, Chung TC, Ronald LD. Controversy in the management of optic nerve glioma. Cancer 1987; 59: Amar G, Richard LH, Edward HK, James AL, Robert AS, et al. Response of pediatric low grade gliomas to chemotherapy. Pediatr Neurosurg 1993; 19: Walter Z, Maria S, Tiit R. Insulin-like growth factor (IGF)-I, and II and IGFbinding proteins in the cyst fluid of a patient with astrocytoma. 1993; 9: Thomsett MJ, Conte FA, Kaplan SL, Grumbach MM. Endocrine and neurologic outcome in childhood craniopharyngioma. J Pediatr 1980; 97:
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