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Departments of Endocrinology (H.K.G., L.S., S.M.S.), Clinical Oncology (H.R.G.), and Paediatric Oncology (B.M.B.), Christie Hospital, Manchester, M20 4BX, United Kingdom
Address all correspondence and requests for reprints to: Professor S. M. Shalet, Department of Endocrinology, Christie Hospital, Wilmslow Road, Withington, Manchester, M20 4BX, United Kingdom. E-mail: Helena.Gleeson{at}christie-tr.nwest.nhs.uk.
The most appropriate way to manage GH replacement in the transition period to adulthood in children treated with GH for GH deficiency (GHD) is controversial. The Growth Hormone Research Society suggests that the retesting of GH status at final height (FH) is unnecessary in the presence of severe organic GHD, and cranial irradiation falls into this etiological category. This recommendation has never been validated.
To investigate whether patients diagnosed in childhood as GHD secondary to irradiation require retesting after FH, GH status has been reassessed in a large cohort of irradiated children treated with GH during childhood.
Seventy-three children underwent biochemical assessment of GH status after irradiation and again at FH after GH therapy had been discontinued; 66 and 67 of the 73 patients underwent two provocative tests at the two time points, respectively. The characteristics of the cohort include a median age at irradiation of 5 yr (range, 1–11 yr), a median biological effective dose (BED) of irradiation to the hypothalamic pituitary axis of 54 Gy (range, 23–82 Gy), and a median time of GH status reassessment after FH of 0.4 yr (range, 0–8.4 yr).
During childhood, patients with all degrees of GHD (peak GH responses to provocative test < 6.7 ng/ml) are treated, whereas in adulthood, only patients with severe GHD (peak GH responses to provocative test < 3 ng/ml) are considered for GH replacement. GH status has been grouped as follows: group 1, peak GH less than 3 ng/ml to both tests (severe GHD); group 2, one test with a peak GH less than 3 ng/ml and the other test with a peak of 3 ng/ml or greater; group 3, peak GH of 3–6.7 ng/ml to both tests; group 4, one test with a peak GH of 3–6.7 ng/ml and the other test with a peak of more than 6.7 ng/ml; and group 5, peak GH more than 6.7 ng/ml to both tests (normal GH status). In childhood, the number of patients in groups 1, 2, 3, and 4 were 33, 22, 17, and one, respectively. At retesting, severe GHD was diagnosed in 21 (64%) of 33 patients who were diagnosed in childhood with severe GHD (group 1) and 17 (44%) of 39 patients who were diagnosed in childhood with moderate GHD (groups 2 and 3). In total, 35 (48%) of 73 patients in the whole cohort and 12 (36%) of 33 patients with severe GHD in childhood did not fulfill the severe GHD biochemical criteria for GH replacement in adulthood. Using multiple linear regression, GH status at retesting is predicted by BED, age at irradiation, and use of chemotherapy.
In conclusion, the diagnosis of severe GHD in childhood secondary to irradiation should not be taken as irrefutable evidence of permanent severe organic GHD, and our recommendation is that retesting of GH status at FH should be mandatory.
Abbreviations: ALL, Acute lymphoblastic leukemia; AST, arginine stimulation test; BED, biological effective dose; BMI, body mass index; CI, cranial irradiation; CT, chemotherapy; FH, final height; GHD, GH deficiency; GRS, Growth Hormone Research Society; GST, glucagon stimulation test; ITT, insulin tolerance test; ln, natural log; TBI, total body irradiation.
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