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Growth hormone (GH) replacement treatment in adults with severe growth hormone deficiency is based on its known effects on body composition, physical performance, bone and lipid metabolism, and on improvements in the quality of life. These features must be taken into consideration when planning GH treatment of patients who are in the transition phase (aged between 15 and 25 years), because developmental stages may vary. GH deficiency during the transition phase is defined as GH levels under 6 microg/l in a standard stimulation test, compared to 1.0 SDS or < 2.0 SDS). GH treatment during the transition phase should be monitored by an endocrinologist with expertise in dealing with adolescent and adult patients, as well as having experience in structuring treatment and documentation.

The diagnosis of Crohn's disease with extensive involvement of small intestine and colon was first made in a 12 3/4-year-old girl, now 15 1/2 years old. Despite continued treatment with prednisolone and salazosulfapyridine, as well as azathioprine and metronidazole, no lasting remission was obtained. Widespread severe osteoporosis with vertebral fractures made it necessary to discontinue the prednisolone, despite endoscopically and biochemically confirmed signs of activity of the disease. Administration of cyclosporin A in this situation produced phases of improved clinical and biochemical parameters. Regular control of biochemical levels failed to reveal any drug-specific acute side-effects. Because of the increased incidence of malignant lymphoma under cyclosporin A this drug should be held in reserve in the treatment of Crohn's disease, until results from controlled studies have become available.

Objective The polymorphic deletion of exon 3 of the GH receptor (d3-GHR) has recently been linked to the magnitude of growth response to recombinant human GH (rhGH) therapy in short children with or without GH deficiency. We investigated this association in a large multinational cohort from the Network of European Studies of Genes in Growth (NESTEGG), comprising short children born small for gestational age (SGA). Design The study included short prepubertal SGA children treated with rhGH for 1 or 2 years. Population Two hundred and forty white Caucasian SGA children (138 male, 102 female) aged 6·6 ± 2·3 years with a height at –3·0 ± 0·7 SDS at start of rhGH treatment; 193 ethnically matched controls. Methods The GHR polymorphism (fl/fl, fl/d3 or d3/d3) was genotyped by polymerase chain reaction (PCR) multiplex assay. Growth velocity (G/V) in cm/year and changes in GV during the first and second year of rhGH treatment were evaluated. Results The change in GV was significantly greater in SGA children carrying one or two copies of the d3-GHR allele (P = 0·038 for the first year and P = 0·041 for the second year of GH treatment), but the change in height was not significantly different. Birthweight was significantly lower in SGA children with the d3/d3 genotype than in SGA children with the fl/fl genotype (P = 0·034) and in those with the fl/d3 genotype (P = 0·016). Conclusion Our data, based on a large cohort, showed that the exon 3 GHR polymorphism is associated with responsiveness to rhGH treatment in SGA children with short stature.

Background: Fetal growth failure has been associated with an increased risk of hypertension, cardiovascular disease and diabetes in adulthood. Exploring the mechanisms underlying this association should improve our understanding of these common adult diseases. Patients and Methods: We investigated 225 SNPs in 10 genes involved in growth and glucose metabolism (GH1, GHR, IGF1, IGF1R, STAT5A, STAT5B, MAPK1, MAPK3, PPARγ and INS) in 1,437 children from the multinational NESTEGG consortium: 345 patients born small for gestational age who remained short (SGA-S), 288 who showed catch-up growth (SGA-Cu), 410 idiopathic short stature (ISS) and 394 controls. We related genotype to pre- and/or postnatal growth parameters, response to growth hormone (if applicable) and blood pressure. Results: We found several clinical associations for GH1, GHR, IGF1, IGF1R, PPARγ and MAPK1. One SNP remained significant after Bonferroni's correction: IGF1R SNP rs4966035's minor allele A was significantly more prevalent among SGA and associated with smaller birth length (p = 0.000378) and birth weight (weaker association), independent of gestational age. Conclusion:IGF1R SNP rs4966035 is significantly associated with birth length, independent of gestational age. This and other associations suggest that polymorphisms in these genes might partly explain the phenotype of short children born SGA and children with ISS.

Nowadays, endocrine problems like retarded sexual maturation and growth deficiency, lead to substantial suffering in patients with beta-thalassemia major. The aim of the present study is the differentiation between a possible insufficiency of the pituitary gland and dependent target organs, respectively. 12 patients (age 1.9-18.10 years) were examined by means of a combined pituitary function test. The corticotropic axis turned out to be normal as shown by a regular stimulation of cortisol in all patients tested. The thyrotropic function was unaffected in all children: elevated levels of TSH pointed to primary hypothyroidism. Pubertal values of LH and FSH were found in only 3 out of 7 patients at pubertal age. In 10 out of 12 children, stimulation led to a rise in STH levels above 10 ng/ml. On the whole, there was no evidence for pituitary insufficiency in beta-thalassemia major.

Objective: GH deficiency is diagnosed in children if serum GH fails to rise above a predefined cutoff value in response to at least two stimuli. Diagnostic decisions based on this testing are highly variable between centers and depend on the GH assays used. Considering the large spectrum of commercially available GH assays, we wanted to evaluate the agreement between assays, and to test whether assay-related variability of diagnostic decisions could be reduced by reassessment of peak GH concentrations in a reference center. Design: We reanalysed 699 peak GH serum samples obtained after GH testing of 382 children and adolescents from 19 centers using three reference assays and compared these results with those obtained with the local assays. A subgroup of 132 patients tested with the combination of insulin hypoglycemia test and arginine test was evaluated for changes in the assignment to the diagnostic group of GH deficiency. Results: The mean difference between methods ranged from 5.4 to 10.3 mU/l, slopes of the regression lines from 1.28 to 1.65. Significant non-linearity was detected in five of six assay comparisons, indicating that most assay results cannot be interconverted by the use of a factor. Overall agreement between reference and local assays was only moderate. Significant changes in diagnostic assignment occurred when different assays were used on the same patient (P < 0.0001 -P < 0.0023). Based on GH remeasurement by one reference assay, 36 of 132 patients were categorized differently, with 35 patients changing into the GH-deficient group. Similar findings were obtained with the other reference assays. Conclusions: To decrease variability in GH testing related to assays and cutoff values, we recommend nationwide reassessment of GH peak sera in reference centers. Decisions to treat GH deficiency should incorporate the reference center results. © 2004 Society of the European Journal of Endocrinology.