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Changes in Height, Weight, and Body Mass Index in Children with Craniopharyngioma after Three Years of Growth Hormone Therapy: Analysis of KIGS (Pfizer International Growth Database)

The Saban Research Institute of Childrens Hospital Los Angeles (M.G.), University of Southern California Keck School of Medicine, Los Angeles, California 90027; KIGS/KIMS Outcomes Research (M.L., M.K.-H., P.J.), Pfizer Endocrine Care, Stockholm, Sweden; University Hospital (R.A.), Antwerp, Belgium; Algemeen Ziekenhuis Middelheim (J.V.), Antwerp, Belgium; University Hospital (E.M.E.), Lund, Sweden; University of Newcastle (P.K.-T.), Newcastle upon Tyne, United Kingdom; Royal Manchester Children’s Hospital (D.A.P.), Manchester, United Kingdom; and Pfizer Global Pharmaceuticals (B.B.), Worldwide Medical, Pfizer Endocrine Care, New York, New York 10017-5755

Address all correspondence and requests for reprints to: Mitchell E. Geffner, M.D., Childrens Hospital Los Angeles, 4650 Sunset Boulevard, Mailstop 61, Los Angeles, California 90027.

Extreme degrees of obesity may occur in association with hypothalamic tumors, usually after surgical intervention. This phenomenon has been reported to occur in as many as 25–75% of children undergoing extensive surgical extirpation of craniopharyngiomas (Cranio). Because less is known about the auxology of children with Cranio with milder alterations in growth, we undertook a 3-yr longitudinal analysis, using the KIGS database (Pfizer International Growth Database), to study their growth patterns and evolution of weight. We compared the effect of GH therapy on height, weight, and body mass index (BMI) in 199 prepubertal children with diagnosed Cranio treated by surgery and/or radiotherapy to two other groups of children with other causes of organic GH deficiency (OGHD): one with postsurgical and/or postirradiated OGHD (OGHD + S/I; n = 92) and the other with OGHD not due to Cranio and not having undergone either surgery or irradiation (OGHD – S/I; n = 85). At the start of GH therapy, 1) mean chronological (P < 0.0001) and bone (P = 0.0002) ages were youngest in OGHD – S/I and oldest in OGHD + S/I; 2) the mean height SD score (SDS) was lowest in OGHD – S/I and comparably higher in the other two groups (P < 0.0001); 3) mean weight and BMI SDS were greatest in Cranio and least in OGHD – S/I (both P < 0.0001); and 4) the mean initial GH dose prescribed was highest in OGHD – S/I and comparable in the other two groups (P < 0.0001). After 3 yr of GH therapy, 1) mean bone age remained youngest in OGHD – S/I and oldest in OGHD + S/I (P < 0.0001); 2) mean height SDS was highest in Cranio and comparably lower in the other two groups (P = 0.0159); 3) mean weight and BMI SDS remained greatest in Cranio and least in OGHD – S/I (P < 0.0001 and P = 0.0003, respectively); and 4) the mean GH dose remained highest in the OGHD – S/I group and least in the Cranio group (P = 0.0082). There were statistically significant increases within each group between the start of treatment and after 3 yr of GH therapy in height and weight, but not in BMI SDS. Lastly, after 3 yr of GH treatment, children in the Cranio group continued to have disproportionately heavier weight and higher BMI (with the greatest values in those with lower stimulated peak GH concentrations) compared with members of the other two groups, with no salutary effect of GH treatment on weight SDS and a mild improvement in BMI SDS. After S/I treatment, children with Cranio are disproportionately prone to varying degrees of weight gain compared with children with other forms of OGHD. In the present cohort of prepubertal children with Cranio, GH therapy induced excellent linear growth, but failed to have an ameliorative effect on weight gain and had only a slight beneficial effect on BMI gain. Because affected children may have resultant significant long-term medical morbidity and diminished quality of life, it is critical that the mechanism of this phenomenon be determined to devise helpful preventive or therapeutic interventions.

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