Craniopharyngioma: The Role of Insulin in Promoting Postoperative Growth GERTRUDE COSTIN, MAURICE D. KOGUT, LAWRENCE S. PHILLIPS, AND WILLIAM H. DAUGHADAY Division of Endocrinology and. Metabolism, Childrens Hospital of Los Angeles, and the Department of Pediatrics, University of Southern California School of Medicine and the Metabolism Division, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri idiopathic hypopituitary children. In 2 obese children with craniopharyngioma peak IRI levels were 255 and 107 /lU/ml after glucose and 208 and 103 fx\J/ml after tolbutamide, respectively. The patient with suboptimal growth had low IRI responses to stimuli similar to hypopituitary children. Although there was a significant correlation between peak IRI levels following glucose (r = 0.63, P < 0.025) and tolbutamide (r = 0.75, P < 0.01) and the rates of growth of the combined data from obese and non-obese patients, no correlation was found between the growth rates of only the non-obese craniopharyngioma patients and their peak IRI levels. No significant correlation was found between mean somatomedin level and mean rate of growth. Normal postoperative growth in all children with craniopharyngioma was associated with normal serum somatomedin activity and pancreatic /3-cell responsiveness to stimuli despite GH deficiency. The results suggest that insulin may be important in the control of somatomedin and growth in these children. (J Clin Endocrinol Metab 42: 370, 1976)

ABSTRACT. To elucidate the mechanism for growth following surgery in children with craniopharyngioma, serum somatomedin and prolactin levels, and plasma insulin (IRI) levels in response to oral glucose and intravenous tolbutamide, were determined in 5 and 8 children, respectively, at variable intervals following removal of the tumor. All patients had growth hormone (GH) deficiency following surgery. Seven of 8 children had normal growth (5 cm per year or greater) postoperatively for varying periods of time; 2 children continued to grow normally 6 and 8 years after surgery. Mean (±SE) somatomedin level was 0.78 ± 0.1 U/ml (normal 0.4-1.5 U/ml). Serum somatomedin was normal in 4 children with normal postoperative growth and was also normal in a child who grew poorly. Mean (±SE) prolactin level was 6.9 ± 3.3 ng/ml (normal 0-20 ng/ml). In 5 non-obese children with craniopharyngioma mean (±SE) peak IRI level was 104.4 ± 24.4 /iU/ml after oral glucose and 56.7 ± 8.4 ju.U/ml after intravenous tolbutamide. These values are similar to mean (±SE) peak IRI levels following glucose and tolbutamide in normal children, and significantly higher (P < 0.05) than those of

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ATIENTS with craniopharyngioma may have normal postoperative growth (1-5) despite GH levels which are comparable to those of hyposomatotropic children. Somatomedin, a serum growth factor originally characterized as GH dependent (6) has been demonstrated in normal amounts in the plasma of some growing children following removal of craniopharyngioma (7-9). Several observations suggested that factors other than GH, such as prolactin

maintaining somatomedin and growth in these patients. Accordingly, in order to elucidate the mechanism of growth in this disorder blood levels of somatomedin, prolactin and insulin and their relation to the rate of growth were determined in 5 and 8 GH deficient children, respectively, following surgical ablation of craniopharyngioma.

(7) and insulin (1,2,9), may be important in

The study group consisted of 8 children, 3 boys and 5 girls, aged 4V2 to 12 years at the time of surgery (Table 1). All children had craniotomy for removal of craniopharyngioma; 5 patients (MP, AP, MS, DS, VT) received radiation therapy postoperatively. Prior to surgery, one patient (DS) had diabetes insipidus, 3 of 4 patients tested (AP, MS, VT) were hypothyroid and one patient (MS) tested had GH deficiency. The mean (±SD) growth rate in the year prior

Received February 7, 1975. Supported in part by a grant (RR-86) from the General Clinical Research Centers Program of the Division of Research Resource, National Institute of Health and by Research Grants 5R01AM-01526 and AM05105 from the National Institute of Arthritis, Metabolism and Digestive Diseases, Bethesda, Maryland. Reprints: Gertrude Costin, M.D., 4650 Sunset Boulevard, Los Angeles, California 90027.

Materials and Methods

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CRANIOPHARYNGIOMA: INSULIN AND GROWTH TABLE

Patient (Sex)

cc

1. Height, weight and bone age at the time of surgery

Age (yr)

Height (cm)

Percentile for age

Weight (kg)

Percentile for age

Bone age (yr)

6

119.2

75

28.0

>97

5 6/12

RDH (M)

7 2/12

125.0

50

38.6

>97

ND*

KK (F)

6 5/12

114.2

25

22.7

75

9 2/12

124.8

10

22.7

7

AP (M)

5 2/12

99.0