Efficacy and safety of a new ready-to-use recombinant human growth hormone solution.

We report 24-month interim results of two multicenter phase III studies in previously untreated children with growth failure secondary to GH deficiency (GHD) that were paramount to the development of a new recombinant human GH (rh- GH, somatropin), approved as the first 'biosimilar' in Europe. Study 1 consisted of 3 parts performed in 89 children. The objective was to compare efficacy and safety of the lyophilized formulation of the new somatropin [Somatropin Powder (Sandoz)] with a licensed reference rhGH preparation and the liquid formulation of the new somatropin [Somatropin Solution (Sandoz)] and to assess long-term efficacy and safety of this ready-to-use Somatropin Solution. Study 2 was performed in 51 children and designed to demonstrate efficacy and safety of Somatropin Powder and to confirm its low immunogenic potential; rhGH was given sc at a daily dose of 0.03 mg/kg. Primary [body height, height SD score (HSDS), height velocity, and height velocity (HV) SD score (HVSDS)] and secondary [IGF-I and IGF binding protein 3 (IGFBP-3)] efficacy endpoints and safety parameters were assessed regularly. In study 1, all treatments showed comparable increases in growth. The baseline-adjusted difference between Somatropin Powder and the reference rhGH product in mean HV was -0.20 cm/yr (95% confidence interval (CI) [-1.34;0.94]) and in mean HVSDS was 0.76 (95% CI [-0.57;2.10]) after 9 months. These very small differences demonstrate comparable therapeutic efficacy between the two treatments. The results of study 2 were consistent with those seen in study 1. Equivalent therapeutic efficacy and clinical comparability in terms of safety and immunogenicity between Somatropin Powder and the reference rhGH product and between Somatropin Powder and Somatropin Solution was demonstrated. The safety and immunogenicity profiles were similar and as expected from experience with rhGH preparations.

Appropriate sampling times for growth hormone (GH) measurement during insulin tolerance testing (ITT) in children.

BACKGROUND: The Pfizer International Metabolic Database (KIMS), a large pharmacoepidemiologic database for adults with growth hormone deficiency (GHD), was recently analyzed to determine which tests are in use to assess GHD and how well they correlate. At the time of this analysis, a total of 15,724 tests had been reported to KIMS. The most frequently used is the insulin tolerance test (ITT), followed in order by the arginine stimulation test (AST), the glucagon stimulation test (GST) and the GH-releasing hormone+arginine (GHRH+arg) test. The ITT correlated with both the AST and the GST, but not with the GHRH+arg. CONCLUSIONS: For the AST and GST, use of a diagnostic threshold of 3 mug/l does not attenuate the effects of severe GHD.

Association between the occurrence of the anticardiolipin IgM and mite allergen-specific IgE antibodies in children with extrinsic type of atopic eczema/dermatitis syndrome.

BACKGROUND: As the literature has only controversial data on the role of nonallergen-specific antibodies in atopic eczema dermatitis syndrome, the authors investigated the link between the occurrence of the antiphospholipid [anticardiolipin (ACL), anti-beta2-glycoprotein I] and allergen-specific immunoglobulin E (IgE) antibodies in 72 children with atopic eczema/dermatitis syndrome (AEDS). METHODS: The measurement of antiphospholipid antibodies was carried out by enzyme-linked immunosorbent assay (ELISA), serum total IgE by nephelometry, and allergen-specific IgE by immunoblotting assay. The statistical analysis was carried out by Fisher's exact test and odds ratio was calculated. RESULTS: Thirteen of 72 children with AEDS (mean age 8.3 years) had elevated serum levels of ACL, and eight anti-beta2-glycoprotein I antibodies. The presence of allergen-specific IgE against inhalant allergens and nutritive allergens was among eight of 13 and three of eight in the cases with elevated ACL. The ratio of patients with highly increased severity scoring of atopic dermatitis (SCORAD) index (>75) was significantly higher in the group with elevated (4/13) than in those with the normal ACL levels (2/59). There was a significant association between the appearance of mite (Dermatophagoides pteronyssinus, D. farinae)-specific IgE and ACL IgM antibodies (6/13). CONCLUSION: These findings show that there are significant linkage and association between the appearance of ACL IgM or the production of allergen-specific IgE against inhalant (mainly mite) allergens in children with atopic eczema/dermatitis syndrome.

[Precocious puberty caused by a testicular Leydig cell tumor]. / Korai nemi érést okozó here Leydig-sejttumor.

Testicular tumors are very rare in boys, approximately 1.5% of these are Leydig cell tumors. The authors present a 4.5 year-old boy with Leydig cell tumor of left testis, which was associated with increased sex steroid production that caused precocious puberty. These tumors are benign processes in prepubertal children. Beyond the rarity of this case the authors would like to report about its diagnostic difficulties and testis-sparing remove of it. The plasma 17-hydroxyprogesterone levels provide the distinction between congenital adrenal hyperplasia and Leydig cell tumor in patient with precocious puberty.

[Final body height affecting factors in Turner syndrome]. / Végmagasságot befolyásoló tényezök vizsgálata Turner-szindrómában.

The treatment with growth hormone of girls with Turner syndrome can only be improved further if the factors promoting growth are identified and the treatment is adjusted to the patient's special needs. From among these factors the authors have examined the correlation of age, bone age, target height and height SDS existing at the beginning of the treatment on the one hand, and the projected final height determined at the beginning of the treatment on the other. Relationship of data were determined with linear regression analysis. According to the recent scientific literature early initiation and correct dosage of growth hormone treatment is emphasized.

[Possibilities to increase the efficacy of growth hormone therapy in Turner syndrome]. / Lehetöség a Turner-szindrómában alkalmazott növekedési hormonkezelés hatékonyságának fokozására.

The authors gave an account of the results of the first two years treatment of Turner's syndrome with growth hormone. They used the international reference standards to evaluate the treatment aimed at promoting the growth of girls having Turner's syndrome. The applied the projected final height method to predict height. Their results proved that their treatment which improved growth had favourably accelerated height velocity and increased the projected final height, which they hoped to lead to adult final height. They dealt with the trend of costs/benefit rate of treatment which improved the growth in children with Turner syndrome and on its basis they emphasized the importance of individual treatment. The continuous control of growth hormone treatment not only purported to the improvement of the efficiency of the therapy but also makes possible to avoid raising exaggerated expectations in the parents.

"Dot-17 alpha-hydroxyprogesterone" radioimmunoassay for identification of congenital adrenal hyperplasia in young infants.

Using a simplified radioimmunoassay method for the determination of 17-hydroxyprogesterone (17-OHP) concentration in blood dried on filter paper seven untreated cases of congenital adrenal hyperplasia were identified among newborns and infants at risk for congenital adrenal hyperplasia (CAH) having ambiguous genitalia and/or failure to thrive with electrolyte disturbances. In three additional cases the diagnosis of congenital adrenal hyperplasia was confirmed by high 'dot-17-OHP' values even after glucocorticoid therapy had been started. Capillary blood samples taken in a local hospital on a filter paper routinely used for the screening of phenylketonuria can be sent by mail into a central laboratory for performing the analysis. Assays of 'dot-17-OHP' are clearly of diagnostic value in the C21-hydroxylase form of CAH and permit a rapid diagnosis of this condition in the newborn period.