Thomas BC, Stanhope R, Plowman PN, Leiper AD. Endocrine function following single fraction and fractionated total body irradiation for bone marrow transplantation in childhood. Acta Endocrinol 1993;128:508-12. Forty-nine children who had undergone treatment with cyclophosphamide and total body irradiation before bone marrow transplantation were investigated for impaired endocrine function. Twenty-six patients received single fraction total body irradiation as a dose of 9\p=n-\10 Gy, whereas 23 patients received fractionated total body irradiation as a total dose of either 12 Gy divided into six fractions or 14.4 Gy divided into eight fractions, administered over 3 or 4 days. Half of the patients in the single fraction group and nine in the fractionated group had received cranial irradiation prior to total body irradiation. Pathological changes in thyroid function were observed in 19 patients (73%) of the single fraction group (elevated thyrotrophin (58%) and decreased thyroxine levels (15%)). whereas in the fractionated group only six patients (25%) developed transient raised thyrotrophin levels; the mean observation period was 3.2 years in the single fraction group and 2.7 years in the fractionated group. The stimulated growth hormone peak concentration was influenced significantly by previous cranial irradiation and was independent of the type of total body irradiation administered. In the patients who had received cranial irradiation, the mean growth hormone peak levels were 8.4 mU/l (single fraction group) and 13.9 mU/l (fractionated group), whereas in those who received only total body irradiation they were 24.9 mU/l (single fraction group) and 28.1 mU/l (fractionated group). The basal gonadotrophin concentration in children older than 9 years showed elevated levels in nine patients (50%) of the single fraction group and in only three patients (30%) of the fractionated group. A further 10 patients (38%) in the single fraction group and one girl (10%) in the fractionated group demonstrated abnormal stimulated follicle stimulating hormone levels.Bone marrow transplantation has been used as treat¬ ment for haematological diseases more frequently over the last 10 years, resulting in an ever-increasing number of survivors. Patients receive an intensive preparative regimen prior to bone marrow transplantation, in order to eradicate the underlying haematological disorder or malignancy and to suppress the immune system. This regimen includes chemotherapy and total body irradia¬ tion (TBI), which at our hospital was initially given as a single fraction TBI (SF-TBI) of 9-10 Gy. This irradiation regimen led to endocrine dysfunction, particularly thy¬ roid failure (1), permanent gonadal failure (2-4) and decreased growth (5, 6). From 1987 onwards the regimen of TBI was given in a fractionated manner in an attempt to reduce damage sustained by normal tissues, and thus a total dose of 12 Gy ( 18 patients) was divided into six fractions given over 3 days or 14.4 Gy (five patients) was divided into eight fractions given ov...

Bone mineral density (BMD) was evaluated by dual energy x ray absorptiometry in 60 adults (33 males, 27 females; aged 50, range 23-76 years) who were growth hormone deficient from various causes for 10-4 (1-31) years. Adult patients who had acquired growth hormone deficiency before completion of puberty had significantly reduced mean (SEM) BMD compared with age matched healthy controls at the lumbar spine: 0-87 (0.09) v 1-20 (0.03) g/cm2, femoral neck: 0-81 (0-06) v 1-08 (0.04) g/cm2, and Ward's triangle: 0-68 (0.07) v 1-04 (0.05) g/cm2. These values were also reduced compared with those of patients who had received human growth hormone during puberty. Untreated growth hormone deficiency when present during puberty results in reduced adult bone density.

Having noted symptomatic osteoporotic vertebral collapse in young adult survivors of childhood malignancy, bone mineral density (BMD) was examined at three sites by dual‐energy X‐ray absorptiometry in 64 patients treated in childhood for intracranial malignancy (group 1; n = 21) or acute leukaemia (group 2; n = 43). Patients in group 1 were selected for growth hormone deficiency (GHD) by auxological and biochemical criteria before the end of puberty (Tanner stage V). Seven patients (six men; mean (± SEM) age at study, 28.0 ± 2.9 years; mean age at diagnosis, 8.7 ± 1.5 years) in this group had been treated with human pituitary growth hormone (GH) for 1–12 years; and 14 patients (nine men; mean age at study, 26.8 ± 1.0 years; mean age at diagnosis, 10.7 ± 1.4 years) had not received GH. Bone densities in group 1 were normal in the GH‐treated patients at the femoral neck (98.4 ± 3.8% of control), lumbar spine (100.4 ± 6.1% of control) and Ward's triangle (101.0 ± 6.1% of control) but markedly reduced in the untreated group (femoral neck, 81.2 ± 2.6% of control (p= 0.002); lumbar spine, 79.1 ± 4.1% of control (p= 0.04); Ward's triangle, 80.1 ± 3.6% of control (p= 0.01)). The majority of patients in group 2 had been treated for acute lymphoblastic leukaemia (ALL) and were in three subgroups. Fifteen (ten men; mean age at study, 22.1 ± 0.8 years; mean age at diagnosis, 5.7 ± 0.8 years) had no auxological evidence of GHD, ten (six men; mean age at study, 18.8 ± 0.7 years; mean age at diagnosis, 6.6 ± 1.2 years) received GH therapy for a mean of 2.6 years (range, 0.5–5.0 years), while 14 patients (three men; mean age at study, 20.9 ± 0.4 years; mean age at diagnosis, 5.1 ± 0.8 years) had GHD but did not receive GH. A small group of four patients (three men; mean age at study, 23.2 ± 2.1 years; mean age at diagnosis, 8.0 ± 2.3 years) who had been treated for acute myeloid leukaemia (AML) in childhood was also studied. The patients with AML had normal bone densities at all three sites (femoral neck, 106 ± 6.1% of control; lumbar spine, 96.5 ± 3.0% of control; Ward's triangle, 110.8 ± 9.3% of control), as did the patients with ALL who did not have GHD (femoral neck, 102.3 ± 2.9% of control; lumbar spine, 98.6 ± 1.7% of control; Ward's triangle, 108.3 ± 3.2% of control). The patients with ALL and GHD not treated with GH had markedly reduced BMD at all three sites (femoral neck, 90.5 ± 2.6% of control; lumbar spine, 88.4 ± 2.5% of control; Ward's triangle, 94.5 ± 3.7% of control), but those treated with GH had a BMD no different from control (femoral neck, 100.6 ± 3.3% of control; lumbar spine, 95.7 ± 4.6% of control; Ward's triangle, 106.2 ± 4.9% of control). It is concluded that GHD during childhood and adolescence predisposes to osteopenia.

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