[Therapy of pituitary dwarfism with recombinant human growth hormone. A multicenter study]. / Therapie des hypophysären Zwergwuchses mit rekombinantem menschlichem Wachstumshormon. Multizentrische Studie.

During the period from 1982 to 1985, biosynthetic growth hormone (methionyl-hGH) was administered to 55 children with pituitary growth deficiency, 49 with idiopathic, six with other forms of the disorder. Preparations with a relatively high content of Escherichia coli polypeptides (ECP) were given to 32 children (group I), those with a markedly reduced ECP content to 12 (group II), while 11 children received almost ECP-free preparations (group III). The treatment achieved an intensive rise of growth acceleration in all three groups. At the same time, somatomedin C, biological somatomedin activity and alkaline phosphatase rose steeply, reaching a maximum after six months and remaining at high concentrations even thereafter. High antibody titres against ECP and hGH (with high binding capacity) were demonstrated in group I children, significantly lower titres with little binding capacity in those of group II, while most of those in group III had no measurable antibodies. Even in high concentrations the antibodies did not have any inhibiting effect on growth. No positive correlation between antibody titre and growth velocity was demonstrable. An exception was a boy with an allergy in group I, who had a maximal antibody titre and, at the same time, a high serum concentration of IgE. He had marked delay in growth which, however, quickly became normal on administration of extractive hGH.

[Induction of puberty by pulsatile luteinizing hormone releasing hormone (LH-RH)--therapy in a boy with Kallmann syndrome]. / Einleitung der Pubertät durch pulsatile Luteinisierungshormon-Releasing-Hormon (LH-RH)--Therapie bei einem Jungen mit Kallmann-Syndrom.

To induce the lacking development of puberty, a male patient with hypothalamic hypogonadism and anosmia (Kallmann's syndrome) was treated with pulsatile application of gonadotropin-releasing hormone (GnRH) to imitate the endogenous secretion of GnRH. The low-dose pulsatile GnRH treatment which was reported to be successful by various authors proved to be ineffective when administered to our patient subcutaneously as well as intravenously. Serum testosterone levels comparable to the lower normal values in adults and continuous progress of pubertal development were only achieved after increasing the dosage from 2 to 8 micrograms per pulse by subcutaneous application. The course of therapy is reported in detail.

Mass screening for glucose-6-phosphate dehydrogenase deficiency: improved fluorescent spot test.

New data on the reliability of the fluorescent spot test are presented. Improvements in the assay were established. Newborn mass screening for glucose-6-phosphate dehydrogenase (G-6-PD, EC 1.1.1.49) deficiency was performed with dried blood samples on filter paper (Guthrie-cards). Females, known to be heterozygote for G-6-PD deficiency were detected at a rate of approximately 30-70%, depending on the storage conditions of the samples. False positive results in male hemizygotes were eliminated.

[Gonadotropin secretion following pernasal stimulation with synthetic gonadotropin releasing hormone (GnRH) and a highly effective GnRH-analog in healthy men and prepubertal boys]. / Gonadotropinsekretion nach pernasaler Stimulation mit synthetischem Gonadotropin-Releasing-Hormon (GnRH) und einem hochwirksamen GnRH-Analogon bei gesunden Männern und präpubertären Jungen).

Potent long acting analogs of GnRH are of great interest especially in view of pernasal (p.n.) treatmen of hypogonadism of hypothalamic origin and of cryptorchidism. To find the necessary p.n. dosage of such a substance, serum LH and FSH were measured in 6 normal adult human males after p.n. application of various doses of D Leu6-des-Gly10-GnRH ethylamide. 50 microgram of the GnRH analog were necessary to obtain increased serum gonadotropins over a period of at least 8 hours. By repeated p.n. application of 200 microgram of synthetic GnRH every 2 hours in 6 normal adult males a considerable increase of serum gonadotropins could be demonstrated as well. Pernasal application of 200 microgram GnRH repeated at an interval of 1 hour in 3 cryptorchid boys produced a distinct increase of the serum gonadotropins. The intraindividual comparison of 200 microgram GnRH and 20 microgram of the GnRH analog in one boy showed equivalent net increases of the gonadotropins. With the analog the gonadotropin increase lasted for about 6 hours.

Changes of serum testosterone and of LH-RH test after treatment of cryptorchidism by intranasal LH-RH.

The aim of the present investigation was to study, in a collaborative double-blind study, the treatment with intranasal LH-RH application of boys aged 1 1/2 to 12 years, who suffered from unilateral or bilateral cryptorchidism. A total of 88 subjects were randomly and blindly allocated to LH-RH and placebo therapy. Before and after 4 weeks of treatment basal testosterone serum levels were estimated and LH-RH tests were performed. Intranasal treatment with LH-RH resulted in partial or complete descents of testes in 23 out of 88 patients, whereas the position of testes remained unchanged in 17 subjects. 42 boys did not respond to placebo therapy, but complete descents were observed in 6 boys of the placebo group. Hormone analysis data of 4 different laboratories were recorded and statistically evaluated. No changes of LH, FSH and testosterone were found in the placebo groups. Only patients of the Frankfurt group responded to LH-RH test with augmented LH release after therapy (P less than 0.05). All patients treated with intranasal LH-RH showed a significant decrease of FSH release after therapy (P less than 0.05 to P less than 0.01). Basal testosterone serum levels were found to be increased after therapy only in the patients treated at Zürich (P less than 0.05). Data of the present study combine to suggest that chronic application of LH-RH may result in an overstimulation phenomenon, and that LH-RH test as well as basal testosterone levels cannot be used as prognostic index of therapy efficacy.

Treatment of cryptorchidism by intranasal synthetic luteinising-hormone releasing hormone. Results of a collaborative double-blind study.

The effect of intranasal luteinising-hormone releasing hormone (L.H.R.H.) in 84 boys with unilateral or bilateral cryptorchidism was evaluated in a double-blind controlled trial. Boys with retractile testes were not studied. L.H.R.H. caused no side-effects; plasma antibodies to L.H.R.H. were never demonstrated. Four weeks' therapy with intranasal L.H.R.H. administered in six doses daily (1.2 mg/day) led to complete descent in 38% of a total of 61 testes, an improved position in 28%, and no response in 19%; 15% of testes were never palpated. After placebo the position of 25% of testes was improved; there was no response in 75% of a total of 51 testes. The success-rate seemed to be independent of age, but was related to the initial testicular position, with complete descent in only 11% of testes not previously palpated compared with 48% of testes found in the inguinal region.