Christian Moëll

Prevalence of coeliac disease in Turner syndrome.

This study was undertaken to investigate the prevalence of coeliac disease in children and adolescents with Turner syndrome. Eighty‐seven children and adolescents with Turner syndrome were screened for IgA‐antiendomysium antibodies (EMA) and IgA‐antigliadin antibodies (AGA), 5% (4/87) being found to be EMA‐positive, and 15% (13/87) to have AGA levels above normal. Of the 10 patients who were either AGA‐ or EMA‐positive and further investigated with intestinal biopsy, four manifested villous atrophy (i.e. all three of the EMA‐positive patients, but only one of the seven AGA‐positive patients). The results suggest EMA‐positivity to be a good immunological marker for use in screening for coeliac disease, and such screening to be justified in patients with Turner syndrome. □Coeliac disease, IgA‐antiendomysium antibodies, IgA‐antigliadin antibodies, Turner syndrome

Growth in Children Treated for Acute Lymphoblastic Leukemia with and without Prophylactic Cranial Irradiation

ABSTRACT. Growth and weight gain were studied longitudinally over a period of four years in thirty‐nine children treated for acute lymphoblastic leukemia. The children were divided into two groups according to treatment. Twenty‐eight children were given prophylactic cranial irradiation and eleven children were treated without such irradiation. The duration of cytostatic treatment was three years in all cases. Average growth during the first two years was similar in the two groups, and the standard deviation scores (SDS) were below average. The rate of growth (in height) during the fourth year was significantly higher among those children who had not received cranial irradiation (p<0.01). After four years the average attained height had declined 0.5 SD for children treated with cranial irradiation and 0.2 SD for children without such treatment. Weight velocity was significantly greater than the expected mean in the non‐irradiated group during the first year and in the irradiated group during the fourth year of the study. Attained weight after four years had increased 0.4 SD more among those children who had not received irradiation. The results suggest that prophylactic cranial irradiation is responsible for the greater part of the prepubertal growth inhibition in these children.

Hypogonadism Risk in Men Treated for Childhood Cancer.

CONTEXT Pediatric cancer treatment may imply an increased risk of hypogonadism, leading to metabolic disorders and osteoporosis. Such complications are potentially preventable. OBJECTIVE The aim of this study was to assess diagnosis- and treatment-dependent risk of hypogonadism in male childhood cancer survivors (CCS). DESIGN Male CCS who were treated during the period 1970-2002 and who in 2004 were 18-45 yr of age were eligible. SETTING The study was conducted in a university hospital clinic. PATIENTS A consecutive group of CCS treated at Lund University Hospital was selected for the study, of whom 151 (38%) agreed to participate. Furthermore, 141 healthy fertile men served as controls. INTERVENTIONS We measured serum levels of free and total testosterone, SHBG, and LH. MAIN OUTCOME MEASURES Odds ratios (OR) for biochemical hypogonadism, defined as total testosterone less than 10 nmol/liter and/or LH above 10 IU/liter, were calculated and related to type of cancer, treatment received, as well as testicular volume. RESULTS Hypogonadism was more commonly detected in CCS than in controls (OR, 6.7; 95% CI, 2.7, 17). The increased presence of hypogonadism was noted in the following treatment groups: brain surgery, chemotherapy (with and without radiotherapy), and testicular irradiation. Low total testicular volume (<or=24 ml) was associated with a high risk of hypogonadism (OR, 31; 95% CI, 11, 92). CONCLUSION Adult male survivors of childhood cancer are at risk of hypogonadism, which should be acknowledged in the long-term follow-up of these men.

Reduced growth hormone secretion with maintained periodicity following cranial irradiation in children with acute lymphoblastic leukaemia

OBJECTIVE Low dose cranial irradiation in children with acute lymphoblastic leukaemia (ALL) has been reported to reduce GH secretion in puberty. A recent study also reported a disturbed periodicity of GH secretion during puberty. We have focused on the different stages of puberty in studying these two parameters of GH secretion and have also compared the effects of 18 vs 24 Gy radiation dose.

Disturbed pubertal growth in girls treated for acute lymphoblastic leukemia

Pubertal growth was studied in 10 girls previously treated for acute lymphoblastic leukemia. The average age at menarche was 12.2 years, which is significantly lower (p less than 0.01) than the expected 13.1 years. Compared with normal girls, these girls showed a subnormal (p less than 0.05) peak height velocity during the second year before menarche. The remaining growth before menarche as well as the total postmenarchal growth was close to the normal average. The average final standing height was 1 SD less than what would be expected from their height 1 year after the cessation of therapy. A relative growth hormone deficiency in combination with early onset of puberty could account for this loss in final height.

Suppressed spontaneous secretion of growth hormone in girls after treatment for acute lymphoblastic leukaemia.

The spontaneous secretion of growth hormone during a 24 hour period and the response of growth hormone to growth hormone releasing hormone was studied in 13 girls who had received treatment for acute lymphoblastic leukemia that included cranial irradiation with 20-24 Gy in 12-14 fractions. At the time of investigation the girls were at varying stages of puberty and had normal concentrations of thyroid hormones. The mean interval between the end of treatment and investigation was 4.6 years. The mean age at onset of the disease was 3.2 years and at investigation 10.7 years. The average attained height equalled -0.3 SD at onset, and -1.0 SD at the time of investigation. Secretion of growth hormone was substantially reduced compared with controls and did not increase during puberty. A prompt rise in growth hormone secretion was seen after injection of growth hormone releasing hormone, but the mean maximum growth hormone concentration was, however, only 25 mU/l. There was no correlation between the 24 hour secretion and growth hormone response to growth hormone releasing hormone, or the time since irradiation. These results confirm earlier work that suggested that girls who had received treatment for acute lymphoblastic leukaemia, that included cranial irradiation, have a comparative growth hormone insufficiency characterised by normal prepubertal growth and slow growth during puberty because of an inability to respond to the increased demands for growth hormone at that time.

Thyroid autoantibodies, Turner's syndrome and growth hormone therapy

The prevalence of thyroid autoantibodies, i.e. thyroglobulin antibodies and antibodies to thyroid peroxidase, was analyzed in 89 girls, aged 3‐16 years (mean age 10 years), with Turners syndrome. The analyses were performed before the start of growth‐promoting treatment and during a follow‐up period of 1‐5 years. The patients were divided into four groups according to karyotype as follows: group 1, 45, X (n= 63); group 2 with structural abnormalities of the X chromosome (n= 4); group 3 with mosaicism but no structural abnormalities of the X chromosome (n = 10); and group 4, with isochromosome X of the long arm (n = 12): 199 healthy girls aged 12 years, served as controls. Thyroid autoantibodies were demonstrated in 46 of 89 (52%) patients with Turners syndrome compared with 34 of 199 (17%) age‐matched control girls (p < 0.001), thus confirming the relationship between thyroid abnormalities and Turners syndrome. There was also an increase in the prevalence of thyroid antibodies with age. Simultaneous presence of both autoantibodies was significantly more frequent in group 1 (45, X) and group 4 (isochromosome X of the long arm) than in group 3 (mosaicism) (p= 0.04 and p < 0.002, respectively) and significantly more frequent in group 4 than in group 1 (p < 0.05). During 12‐60 months of growth‐promoting treatment, no increase in the prevalence of thyroid antibodies was observed. The findings demonstrate the importance of continuous monitoring of thyroid function in girls with Turners syndrome.

High risk of azoospermia in men treated for childhood cancer.

Childhood cancer survivors (CCS) have an increased risk of impaired spermatogenesis, but data regarding the disease- and treatment-related risk factors of azoospermia are scarce. Such information is crucial both for counselling CCS and for selecting patients for testicular tissue cryopreservation. The proportion of azoospermic men in CCS was 18% [95% confidence interval (CI): 12-26], specifically for leukaemias (19%; 95% CI: 5.5-42), Hodgkins disease (53%; 95% CI: 29-76), non-Hodgkins lymphoma (11%; 95% CI: 0.28-48) and testicular cancer (11%; 95% CI: 0.28-48). In CCS treated with high doses of alkylating agents, the proportion of azoospermic men was 80% (95% CI: 28-99) and if radiotherapy was used additionally, the proportion was 64% (95% CI: 35-87). In CCS with subnormal Inhibin B levels, the proportion of azoospermic men was 66% (95% CI: 47-81) and for those with elevated follicle-stimulating hormone (FSH) levels, the proportion was 50% (95% CI: 35-67). Among CCS with subnormal testicular volume (≤ 24 mL), azoospermia was found in 61% (95% CI: 39-80) of the cases. Most childhood cancer diagnoses are associated with an increased risk of azoospermia, especially in CCS receiving testicular irradiation, high doses of alkylating drugs and other types of cytotoxic treatment, if combined with irradiation. Inhibin B, FSH and testicular volume can be used as predictors for the risk of azoospermia.

Effect of growth hormone (GH) during puberty in GH-deficient children : preliminary results from an ongoing randomized trial with different dose regimens

Albertsson Wikland K, Alm F, Aronsson S, Gustafsson J, Hagenas L, Hager A, Ivarsson S, Kristrom B, Marcus C, Moe11 C, Nilsson KO, RitzCn M, Tuvemo T, Westgren U, Westphal 0, Aman J. Effect of growth hormone (GH) during puberty in GH‐deficient children: preliminary results from an ongoing randomized trial with different dose regimens. Acta Pxdiatr 1999; Suppl 428:80‐4. Stockholm. ISSN 0803‐5326

Adult survivors of childhood acute lymphoblastic leukaemia with GH deficiency have normal self-rated quality of life but impaired neuropsychological performance 20 years after cranial irradiation.

Objective  Cranial radiotherapy (CRT) was, until recently, important for achieving long‐term survival in acute lymphoblastic leukaemia (ALL). Because survival rates have improved markedly, the long‐term complications, such as GH deficiency (GHD) and neuropsychological impairment, have become increasingly important.