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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.

Four children with severe congenital eye anomalies are described of which three had related symptoms. Two had bilateral anophthalmia, the optic nerves not detectable by computed cranial tomography and magnetic resonance imaging, and the third child had bilateral microphthalmia and coloboma iridis. The fourth patient had bilateral cryptophthalmia as part of Fraser syndrome. All four patients were of small stature. In three of them growth hormone deficiency was demonstrated which was of hypothalamic origin as shown by growth hormone releasing hormone tests. In the fourth child hypogonadotropic hypogonadism and tertiary thyroid deficiency were diagnosed which responded well to thyroxine treatment. Pathogenetically the described disorders are due to congenital defects of midline structures as a common "developmental field".

Constitutional delay of growth and adolescence (CDGA) is characterized by simultaneous retardation of growth, skeletal maturation and sexual development. Primarily longitudinal growth is impaired. The late occurrence of puberty is a secondary phenomenon brought about by the retarded physical development. Plasma levels of sex hormones and gonadotrophin correlate with bone age, not with chronological age. The provocation tests for growth hormone (GH) show normal results. In contrast, the spontaneous secretion of GH, measured half-hourly through the night or over 24 hours, is markedly reduced. Plasma somatomedin C is diminished. According to these data, CDGA is not a genuine GH deficiency but represents a cybernetic disorder coinciding with a false threshold for GH. As shown by large series of investigations, the final height of the patients lies on average 1.85 SD below the mean of healthy adults, with large individual variations. The decision as to whether treatment by growth promoting hormones should be performed should be made with regard to the individual height prognosis. With GH in physiological doses growth velocity can be considerably increased. Bigger doses of the hormone appear to be necessary in order to enhance final height. Treatment by anabolics and testosterone increases height velocity only, not adult height.

The acid-stable subunit of the GH-dependent large mol wt somatomedin-binding protein (SmBP) was isolated from human plasma Cohn fraction IV by a three-step procedure, and a specific RIA was developed which allowed measurement in unextracted serum. Although in normal human serum most of immunoreactive material was present as the large mol wt complex (150K), considerable amounts of smaller components were found by high performance liquid exclusion chromatography in the 60K, 42K, and 32K range. Normal serum levels were low at birth, rose sharply during the first weeks of life, and showed a moderate peak at puberty. To assess the diagnostic efficacy of SmBP for GH deficiency (GHD), patients previously diagnosed as GH-deficient by conventional criteria (n = 132) were compared to short statured children without GHD (n = 130). Taking the fifth centile as a limit of normality the majority of patients with GHD had subnormal levels, yielding high sensitivity of the test (0.97). In contrast, most of the non-GH-deficient children had SmBP levels within the normal range, resulting in high specificity (0.95) and, consequently, high accuracy (0.96). These results suggest that the large mol wt SmBP is an excellent screening parameter and is highly informative for GHD.

In the 19th century the natural sciences took a rapid rise, connected with a mainly biological interpretation of all vital processes. To the physician fell the role of the analytical observer who--according to the findings obtained - made a precise diagnosis which in consequence led to the adequate therapy. Patient and disease were the objects of observation and treatment. In the twentieth of our century a radical change took place. R. von Weizsäcker and R. Siebeck established the "anthropologic medicine" resp. the "medicine of the person" where the doctor and the patient enter into a personal relationship. The significance of the patient's biography in the course of this disease was recognized. The "psychosomatic medicine" was developed. Our own time requires the reorientation to those values and principles and, moreover, and improved integration of the advanced medical technology.

The spontaneous growth of 150 patients with Turner syndrome from three German centers--90 with 45,X0 constitution, 60 with other chromosomal abnormalities--has been analyzed. The mean adult height was found to be (n = 14) 146.8 cm. It was observed that growth in these patients can be divided into four phases: (1) Intrauterine growth, which is retarded; (2) Height development, which is normal up to a bone-age of about 2 years; (3) Between a bone-age of 2 and 11 years when stunting of growth is most marked; (4) After a bone-age of 11 years--the time at which puberty should normally start--the growth phase is prolonged, but total height gain is only little below normal levels. No difference in height could be observed between cases with X0 karyotype and other chromosomal variants. The data are compared with those in the literature.

Basing on previous experience, with alcohol embryopathy the authors recommended interruption of pregnancy in three chronic alcoholics, two of whom were in the chronic phase and one in the critical phase of alcohol addiction. All the three fetuses were hypertrophic, two severely malformed. In the authors' opinion there is eugenically speaking an absolute indication of interruption of pregnancy in alcoholics in the chronic phase of addiction. In women who are in the critical phase of addiction, each case requires close scrutiny, whereas interruption is not indicated from the eugenic aspect in women in the prodromal stage.

In 33 patients with Turner's syndrome growth during a one year period of treatment with low doses of estrogens was evaluated (group A: (N=12) PresomenR 5–9 μg/kg d; group B: (N=9) PresomenR 10–21 μg/kg d; group C: (N=12) ethinylestradiol 45–155 ng/kg d) and compared to a group (N=37) of untreated patients. The auxological evaluation was made using SDS derivations based on control data derived from 150 untreated patients. Based on chronological age (CA) SDS levels for height velocity and the increments in height at the end of treatment increased marginally. Compared to untreated patients no effect was seen when calculations were based on bone age (BA) due to an advancement in bone maturity. It is concluded that low doses of estrogens are not suitable to improve the height development in Turner's syndrome.

Es wird uber 24 Kinder mit efAS berichtet. Die Symptomatik entsprach in den Grundzugen dem von Lemoine et al. und Jones et al. mitgeteilten Krankheitsbild; die von Jones et al. angegebene Hypoplasie des Oberkiefers und Mikrophthalmie konnten wir jedoch nicht bestatigen. Zusatzlich beobachteten wir bei 2 Madchen Virilisationen des Genitales, die einem Pseudohermaphroditismus femininus entsprachen.

Bierich, J. R. (Department of Paediatrics, University of Tubingen, Tubingen, West Germany). Multicentre clinical trial of authentic recombinant somatropin in growth hormone deficiency. Acta Paediatr Scand [Suppl] 337:135, 1987. A German multicentre trial of recombinant somatropin was cdmmenced in March 1986. A total of 77 patients with hGH deficiency were recruited, with heights at least 2.5 SD below the normal mean. Of these, 49 were previously untreated (naive) and 28 had previously received pituitary hGH. Recombinant somatropin, 12 IU/m2/week was administered subcutaneously, divided into six doses. In the naive group, the height velocity reached 14.9 cm/year in the first 3 months, and thereafter stabilized at 12 cm/year. In the previously treated patients, the growth rate was 10.7 cm/year in the first 3 months, and 8.5 cm/year at 9 and 12 months. There were no abnormal findings in tests of laboratory parameters. No anti-hGH antibodies were detected in any of the patients; seven patients had anti-ECP antibodies, but in six of these the antibodies were already present before treatment.

The results of long term treatment with human growth hormone (Crescormon, 12.4 IU/m2/week) in 36 patients with idiopathic growth hormone deficiency are given. Birth trauma--in particular assisted breech delivery (30%)--is the major aetiological cause. Twelve patients had isolated growth hormone deficiency (IGHD), 24 had multiple pituitary hormone deficiencies (MPHD) of which 19 were treated with additional thyroid hormones. The results were judged by the criteria of height velocity, total height gain and change of height prediction (TW2, age based). It is concluded that the growth hormone dose chosen in many cases is insufficient to maintain high growth rates after the first year of treatment, when "catch-up" no loner takes place. The tendency of patients supplemented with thyroid hormone to grow better--without additional bone-age advancement--calls for careful search for hypothyroidism and suggests the use of thyroxin in cases of doubt.

Maternal chronic ethanol abuse during pregnancy causes malformations of the offspring. Three children (aged 6 months, 9 months, 4 1 2 years) and 3 fetuses (17th, 18th, and 20th gestational week) showed a wide spectrum of disorders ranging from severe dysraphic state, arhinencephaly, porencephaly, agenesis of corpus callosum, a range from hydranencephaly to microdysplasias (p.e. reduced gyration of dentate nucleus and inferior olives), and a range from gastrochisis or congenital heart defects to craniofacial dysmorphogenesis and palmar crease anomalies. The patterns of the cerebral malformations were not as uniform as the clinical phenotype of the alcohol embryopathy. The observations did not support the assumption that there exists a specific period for alcohol teratogenicity.

A specific antiserum for human IGF-II has been produced by immunizing rabbits against the synthetic peptide IGF-II(33-40). With this antiserum and IGF-II as tracer a radioimmunoassay for IGF-II has been developed. Cross-reactivity with IGF-I was 0.05% and half-maximal displacement occurred at 2.5 micrograms IGF-II per 1. It was demonstrated that residual IGF-binding protein (IGF-BP) in acid-ethanol extracts interferes with IGF-II measurements and may produce erroneously high values. This interference could be completely blocked by excess IGF-I (25 ng per tube). Utilizing this method IGF-II was measured in subjects at various developmental stages. In newborns, the mean serum level was 237 micrograms/l (N = 56) with a range of 132-430 micrograms/l (5- and 95-percentile, respectively). During the first year of life a considerable increase occurred. Thereafter IGF-II increased only slightly with age from 520 micrograms/l (range 368-735) to 647 micrograms/l (range 507-823) in adults. In patients with growth hormone deficiency (N = 57) IGF-II levels were significantly (P less than 0.001) lower than in controls (mean 261 micrograms/l, range 126-542). It is concluded 1) that residual IGF-binding proteins in acid-ethanol extracts may cause considerable error in IGF-II measurements, and 2) that this interference can be completely blocked by excess IGF-I, if highly specific antisera are used.

In the serum of two infant sisters with a congenital renal salt-losing syndrome, Na was rather low and K considerably increased. Even with Na levels of 126 mval/1, sodium was excreted in the urine. Creatinine and hippurate clearances were normal. Primary disturbances of the steroid metabolism were not detectable; plasma cortisol was normal, aldosterone and renin were compensatorily increased. Treatment with DOCA was unsuccessful. Whereas the first infant died (in another hospital), the second one throve well with high oral substitution of NaCl. There was no pathological findings other than a moderate hyperplasia of the juxtaglomerular apparatus, in a kidney biopsy. Except for minimal activity in the ascending limb of Henle's loop, there was no membrane bound Na, K-ATPase in the microdissected tubules. This finding most probably explains the renal salt loss, as this enzyme is necessary for the transcellular flow of sodium and potassium.

Nine patients (8 girls and 1 boy) suffering from precocious puberty received daily 100 mg/m2 cyproterone acetate orally. This treatment inhibited the vaginal bleeding; breast-size and the axillary hair and pubic hair did not further increase. The height increment per year and the bone maturation slowed down. The urinary excretion of androgens was temporarily diminished. It is probable that the growth prognosis could be improved by the administration of cyproterone acetate.

Die Beurteilung des Metopirontests durch Bestimmung der Gesamtcorticosteroidausscheidung ist in Grenzfallen auch nach getrennter Bestimmung der polaren und apolaren Steroide durch Losungsmittelverteilung schwierig. Es wird eine dunnschichtchromatographische Fraktionierung durch mehrfache Entwicklung eines Urinextraktes in 5 Losungsmitteln aufsteigender Polaritat aufeiner Kieselgelplatte angegeben. Nach Eluierung einer THF+THE-Fraktion sowie einer THS-Fraktion wird der Gehalt an reduzierenden Steroiden semiquantitativ mit Blautetrazolium bestimmt. Die Ergebnisse der Auswertung nach Losungsmittelverteilung und nach Dunnschichtchromatographie werden bei 15 unausgewahlten Metopirontests mitgeteilt. In 7 der 15 Tests war der geforderte 2,5fache Anstieg der Porter-Silber-Chromogene nicht erreicht worden. In 3 Fallen (supra-sellarer Tumor, M. Addison) war die Ursache des pathologischen Testausfalls offensichtlich. In 2 Fallen mit primarer Hypothyreose lies erst die differenzierte Auswertung die ausreichende Stimulierung aufgrund des starken Anstiegs der THS-Fraktion erkennen. Bei 2 Kindern mit M. Cushing mit sehr fruhem Krankheitsbeginn konnte durch die differenzierte Bestimmung das Ausbleiben der corticotropen Stimulation trotz ausreichender Blockade der 11-Hydroxylase nachgewiesen werden. Es wird empfohlen, die Losungsmittelverteilung in jedem Fall zur Auswertung des Tests zu benutzen. In Grenzfallen, in denen das Ausmas der Blockade und der Grad der adrenocorticotropen Stimulierung genauer beurteilt werden soll, ist die dunnschichtchromatographische Auftrennung nutzlich, da die Trennung exakter ist.

I. Physiologie: Die Reifung der Keimdrusen erfolgt unter dem Stimulus der Gonadotropine. Produktion, und Sekretion von FSH und LH werden durch die zwei hypothalamischen Releasing Factors FRF und LRF kontrolliert; der erste Faktor wird im Sexualzentrum des Tuber cinereum gebildet, der zweite wahrscheinlich im vorderen Hypothalamus. Die Produktion, der Releasing Factors hangt uber einen negativen Feed-back-Mechanismus von der Konzentration der Keimdrusenhormone im Blut ab. Das Relais, das den Sexualhormonspiegel registriert und die erhaltenen Informationen in regulatorische Impulse, namlich Hemmung oder Nichthemmung des Sexualzentrums, transformiert, liegt bei der Ratte im vorderen Hypothalamus; seine Entfernung fuhrt zur Fruhreife. Beim Menschen ist die Lokalisation des Hemmzentrums nicht sicher geklart, wird aber in der Gegend der Pinealis angenommen. Die Empfindlichkeit des Zentrums gegenuber den Keimdrusenhormonen nimmt im Laufe der Pubertat ab; um eine Hemmung hervorzurufen, werden zunehmend hohere Sexualhormonspiegel erforderlich. Der Zeitpunkt, zu dem diese zentrale Umstellung erfolgt, korreliert mit dem biologischen Entwicklungsstatus des Gesamtorganismus, der am besten durch die Feststellung der Skelettreifung erfast wird. II. Pathologie a) Nichteintritt und Verzogerung der Pubertat. Unter 37 zusammen mitBraun beobachteten Kindern und Jugendlichen mit Zwischenhirntumoren war in 8 Fallen eine fehlende oder verzogert eintretende sexuelle Reifung zu verzeichnen. Sechsmal handelte es sich um meist suprasellar lokalisierte Geschwulste im mittleren Hypothalamus, in 2 Fallen um Geschwulste, die vorwiegend im occipitalen Hypothalamus lagen. Diese Feststellung entspricht der angenommenen Lokalisation des Sexualzentrums im Bereich des Tuber cinereum. — Den organisch verursachten Reifungsstorungen stehen 20 Falle mit “konstitutioneller, Entwicklungsverzogerung” gegenuber, bei denen die Pubertat in Ubereinstimmung mit der Verzogerung von Wachstum und Skelettentwicklung 3 bis 7 Jahre verspatet auftrat. b) Fruhreife. Die Lage des menschlichen Sexualzentrums ist vor allem durch die Beobachtung der Hamartome des Tuber cinereum geklart worden, die mit Pubertas praecox einhergehen; wir verfugen uber keinen derartigen Fall*. Bei unseren zehn cerebral bedingten Fallen handelte es sich zweimal um ein Pinealom, achtmal um Hydrocephali des III. Ventrikels. Wir nehmen an, das die Fruhreife hier durch Fortfall der normalen Hemmechanismen zustande kommt. — 15 unserer Fruhreifefalle gehoren zur idiopathischen Form, 3 zum Weil-Albright-Syndrom, bei dem die Pathogenese der Reifungsbeschleunigung ahnlich, sein durfte. Bei diesen Patienten scheint eine vorzeitige Empfindlichkeitsminderung des hypothalamischen Registrier-und Hemmzentrums gegen die Keimdrusenhormone einzutreten. Mit hohen Gestagendosen gelingt es jedoch, das Sexualzentrum und die Gonadotropinsekretion jedenfalls partiell zu unterdrucken. Uber entsprechende therapeutische Erfahrungen wird berichtet.

Fur die klinische Prufung der NNR-Funktion hat sich in den letzten Jahren vor allem die Bestimmung des Anstiegs der Plasma-17-OH-CS unter intravenoser Infusion von ACTH und die Messung der Corticoidzunahme im Harn bei mehrtagiger Verabreichung von Depot-ACTH durchgesetzt. Die vorliegenden Untersuchungen, die wir an Kindern durchfuhrten, wurden mit dem Ziel vorgenommen, die optimalen Bedingungen fur ein einfaches kurzdauerndes Testverfahren festzulegen, das dem Patienten die intravenose Dauerinfusion erspart. Nach intramuskularer Injektion eines langwirkenden Depot-ACTH-Praparates* in einer Dosis von 60 IE/m2 Korperoberflache stiegen die Plasma-OH-CS von Ausgangswerten um 10µg/100 ml in 4 Std auf einen Mittelwert von 39,3±7,5µg/100 ml an. Die Mittelwerte nach 6 und 8 Std zeigten keine signifikante Differenz. Der Eosinophilensturz betrug 91,9±5,6%. Eine Steigerung der ACTH-Dosis auf 90 IE/m2 bewirkte gegenuber der Dosis von 60 IE/m2 keine Erhohung des 17-OH-CS-Spiegels. Nach Applikation von 30 IE/m2 blieb der Anstieg submaximal. Die Streuung der Maximalwerte war deutlich groser als diejenige der Ausgangswerte. Sie ist nicht methodisch bedingt, sondern entspricht unterschiedlichen Reaktionen der Einzelindividuen auf die gleiche Menge ACTH. Der Vergleich unserer Werte mit den im Schrifttum veroffentlichten Resultaten der intravenosen ACTH-Tests ergibt eine weitgehende Ubereinstimmung. Es ist mit beiden Applikationsformen in gleicher Weise moglich, die Nebennierenrinde maximal zu stimulieren.

Es wurde der Einflus langerdauernder Behandlung mit Cortison in klinisch ublicher Dosierung auf die allergische Hautreaktion sensibilisierter Kaninchen gepruft

Es wird uber Erfahrungen mit der Corticoidbestimmungsmethode nachStaudinger undBauer berichtet. Mit diesem Verfahren werden die freien und conjugierten Corticoide gleichzeitig erfast. Ihr Ausscheidungsverhaltnis betragt etwa 1:9. Die Steroidwerte steigen mit dem Alter der Kinder kontinuierlich an. Nach den ersten Lebensjahren zeigen sie etwa gleichbleibende Relationen zu Korperoberflache und -gewicht. Ein Vergleich der Corticoidwerte mit den ausgeschiedenen Harnmengen ergibt fur die ersten Lebensjahre ein proportionales Verhalten der beiden Grosen. Mit zunehmendem Alter vermindert sich diese Korrelation; die Steroidausscheidung wird unabhangiger vom Harnvolumen. Ursachlich kommen fur diese Beziehungen sowohl eine gesteigerte adrenale Produktion wie eine verstarkte Clearance der Steroide unter dem Einflus vermehrter Wasserzufuhr in Betracht. Wir mochten die zweite Erklarung fur die wahrscheinlichere halten.

300 microgram of potassium iodide daily were administered over a period of two weeks to 12 children with goitre. Basal TSH concentrations, maximal TSH increase after TRH and integrated TSH secretion after TRH were significantly decreased in this group whereas the increase of total thyroxine (T4-RIA) did not reach significance. It appears that in the development of iodine deficiency goitre in children a sensitive feed-back system is predominant. Early administration of iodine or even better general iodinated salt prophylaxis seem to be the pathogenetically correct approach in solving the common goitre problem.

According to recent investigations more than half of all growth disorders are due to growth hormone (GH) deficiency. I. The cause of the classic hypothalamo-pituitary dwarfism is: 1. perinatally acquired lesions of the hypothalamus; 2. suprasellar tumours; 3. brain malformations; 4. hereditary disturbances of GH-synthesis. - II. Constitutional delay of growth and adolescent development is clinically characterised by harmonious delay of growth, skeletal development and sexual maturation. The typical aspect of the pituitary dwarf is missing. Whereas provocation tests for GH do not show reliable deviations, assessment of the spontaneous GH secretion during sleep usually demonstrates a significant GH-deficit. - III. Impairments of GH synthesis with production of a hormone which reacts in the RIA but exhibits reduced biological effectivity causes the same clinical picture as constitutional delay. The disorders I--III can successfully be treated by GH. - IV. Familial short stature is based on the summation of hereditary anlages of the parents. In principle, it is no endocrine disorder. However, the combination with disorders II and III occurs frequently ("Small/Delay" acc. to Tanner). - V. Intrauterine growth retardation is caused by maternal, placental or fetal factors. With most of the "small for dates" growth prognosis is good. However, if teratogenic agents, particularly alcohol is involved, and if the damage occurs in the first months of gestation, the prognosis is unfavorable. - VI. A great number of genetic disorders is connected with pre- and/or postnatal growth retardation, combined with typical malformations. Apart from few exceptions these syndromes are rare. Endocrine deviations are missing. - The therapeutic possibilities of GH and anabolics are thoroughly discussed.

The pubertal growth spurt is based on synergistic effects of hGH and androgenic steroids. It fails to appear in androgen deficiency as well as in complete absence of hGH. Apart from the synergism of biological functions there are interactions with regard to the secretion of hGH and androgens. Investigating the nocturnal hGH-secretion in puberty stage 3 we found twice as high secretion rates as in stage 1. Children with anorchia or constitutional delay of growth and adolescence during treatment with testosterone secreted more than threefold amounts of hGH as before. In two cyproterone acetate-treated adolescents, and in four 12-19 years old patients with hypogonadism, the nocturnal secretion rates of hGH as well as the maximal hGH-peaks attained were lower than in normal prepubertal children. The conclusion is drawn that the androgen-secretion during adolescence is not only prerequisite to the hGH-increment necessary for the pubertal growth spurt but also to the preservation of basal hGH-secretion.

Basing on previous experience, with alcohol embryopathy the authors recommended interruption of pregnancy in three chronic alcoholics, two of whom were in the chronic phase and one in the critical phase of alcohol addiction. All the three fetuses were hypertrophic, two severely malformed. In the authors' opinion there is eugenically speaking an absolute indication of interruption of pregnancy in alcoholics in the chronic phase of addiction. In women who are in the critical phase of addiction, each case requires close scrutiny, whereas interruption is not indicated from the eugenic aspect in women in the prodromal stage.

In constitutional delay of growth and adolescence (CDGA), all growth and maturation parameters are delayed by 2–4 years. Provocation tests of hGH secretion give normal values, but spontaneous (endogenous) secretion is low. This can be assessed by measuring night-time hGH secretion, when the differences between normal subjects and CDGA patients are highly significant. Replacement therapy with hGH produced growth spurts in all but one patient, improving their growth prognosis. A new series of 16 CDGA patients has now been treated with hGH for 1–3 years. Catch-up growth was seen during the first year, which decreased to normal growth velocity by the third year. This normal growth rate is still faster than the pretreatment velocity. Although hGH therapy may be effective in CDGA, it may only be justified in cases with psychological problems arising from their short stature.

Two patients with the Dubowitz syndrome are presented. This presumably recessive inherited syndrome was first defined by Grosse et al. (1971). So far 11 patients with this syndrome have been described. Major clinical findings are intrauterine and postnatal growth retardation, considerable microcephaly, mild mental retardation, hyperactivity, hyperextensibility of joints, eczema and a characteristic appearance of the face due to marked epicanthic folds, blepharophimosis, broadening of the bridge and tip of the nose and retrognathia. Minor anomalies as clinodactylyl of the firth digits, cutaneous syndactyly of toes, foot deformity, sacral dimple and cryptorchidism may be seen. The exclusion of the non genetic fetal alcohol syndrome presents serious diagnostic problems.

According to the results reported in the literature and from our own experience, the following recommendations for the treatment of children with GHD can be given: In order to start GH replacement therapy in early childhood the diagnosis of GHD should be made as early as possible. The growth hormone dose during prepubertal age should not fall short of 12 IU/m2 per week. During spontaneous or induced puberty, the dose needs to be increased, possibly by a factor of two. Daily subcutaneous injections appear most suitable. Treatment with growth hormone releasing factors in cases with hypothalamic GHD, although a promising alternative to the treatment with hGH (Thorner et al, 1985), must be considered experimental at this point. Thyroxine replacement at a daily dose of 75-100 micrograms/m2 should be given in cases of secondary hypothyroidism. Glucocorticoid replacement, if required, should be given at low doses (e.g. hydrocortisone 10 (to 15) mg/m2 per day in divided doses). In cases with additional gonadotropin deficiency, sex steroids (or anabolic steroids) should be given with frequent monitoring of bone maturity not before the age of 13 in girls or 15 years in boys. In boys depot testosterone starting at low doses (e.g. 50-100 mg/month i.m.) will induce a puberty-like increment in height velocity. Since the effect of oestrogens--even in low doses--on growth is uncertain, their administration before achievement of near-normal adult height should be avoided. With the advancement of diagnostic techniques and with the experience in treatment accumulated over the past 25 years, patients with GHD need no longer become dwarfs.

Das Symposium wurde auf Veranlassung des Bundesministers fur Jugend, Familie und Gesundheit unter der Federfuhrung der hiesigen Abteilung Ernahrungsmedizin und Ernahrungsphysiologie mit dem Ziel durchgefuhrt Anforderungen fur diatetische Lebensmittel zur Behandlung von Aminosaurestoffwechselstorungen fur eine Anderung der Diat-Verordnung festzulegen.

Human somatomedins (Sm) are heterogeneous on separation by chromatofocussing. Besides the 'classic' insulin-like growth factor I and II (IGF-I/Sm-C and IGF-II), a number of minor peaks emerge which can be classified as IGF-I/Sm-C-like or as IGF-II-like. The aim of the current study was to investigate whether or not polymorphism of somatomedins is present in individuals and whether or not the polymorphic pattern changes during development. Serum extracts from normal healthy children and adults were fractionated by chromatofocussing and the various somatomedin-like peptides were quantitated by specific radioimmunoassays for IGF-I/Sm-C or IGF-II. The results demonstrate 1) that heterogeneity of somatomedins is a common phenomenon existing in all individuals studied, and 2) that the polymorphic patterns of the IGF-I/Sm-C-family and of the IGF-II-family remain rather stable during development, although minor changes are evident.

300 microgram of potassium iodide daily were administered over a period of two weeks to 12 children with goitre. Basal TSH concentrations, maximal TSH increase after TRH and integrated TSH secretion after TRH were significantly decreased in this group whereas the increase of total thyroxine (T4-RIA) did not reach significance. It appears that in the development of iodine deficiency goitre in children a sensitive feed-back system is predominant. Early administration of iodine or even better general iodinated salt prophylaxis seem to be the pathogenetically correct approach in solving the common goitre problem.

In five cases of Sotos Syndrome serum somatomedin activities were measured. In two of these cases elevated levels and an increased secretion of growth hormone was observed. In one case (index case) a suspected hypothalamic tumor mass could be excluded, but hydrocephalus with increased intracranial pressure was present. The pathogenesis of gigantism in this syndrome is discussed.

Six somatomedin-like peptides were purified from human plasma Cohn fraction IV by a six-step procedure which included ethanol precipitation, reversed-phase extraction, gel filtration, chromatofocusing and reversed-phase high pressure liquid chromatography (HPLC). Purification was monitored with a competitive protein binding assay using a crude preparations of somatomedin carrier protein. The peptides isolated were homogeneous by reversed-phase HPLC and sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). Their apparent isoelectric points determined by chromatofocusing were 9.2 (Sm I), (Sm II), 8.2 (Sm III), 6.7 (Sm IV), 6.3 (Sm V), and 6.15 (Sm VI). SDS-PAGE under reducing conditions revealed that they are composed of a single peptide chain with apparent molecular weights of 6800 for Sm I, II and IV and 6400 for Sm III, V, and VI. They were equally potent in the porcine costal cartilage in vitro bioassay. The basic peptides (Sm I–III) were significantly more active in radioimmunoassays for somatomedin C (SmC) and insulin-like growth factor I C-peptide (IGF-I (30–41)), while only the slightly acidic peptides were active in a radioimmunoassay for insulin-like growth factor II C-peptide (IGF-II (33–40)). When receptor binding was tested with human placental cell membranes and Sm III as tracer, the basic peptides were significantly more potent than Sm IV–VI. With rat liver cell membranes and Sm V as tracer the slightly acidic peptides were more potent. These findings suggest 1) that human plasma may contain other somatomedin-like peptides besides the major components IGF-I/SmC and IGF-II, and 2) that the basic peptides are structurally related to IGF-I/SmC and the slightly acidic peptides are related to IGF-II.

Somatomedins are peptide hormones with insulin-like structure and effects. Their synthesis is governed by growth hormone. Somatomedins stimulate growth of cartilage tissue and other tissues. Synthesis of somatomedins occurs in various tissues, predominantly in the liver. For clinical practice determinations of somatomedin C (= IGF I) levels in blood have become valuable, since they give insights into the growth hormone secretory state, being low in growth hormone deficiency and high in acromegaly. In other growth disorders somatomedin C measurements can give new insights into the underlying pathogenesis. The role of IGF II and other peptides with somatomedin-like characteristics is presently under investigation.

The case of an infant is described who at birth was already small and postnatally grew extremely slowly. At age 3 the girl's height was 65 cm, weight 5.6 kg, bone age 21 months. Basal plasma GH was 36-66 ng/ml, basal SM activity was rather high, being around 2.0 U/ml. RIA- and RRA-SM were also increased. Prolonged GH administration did not raise plasma SM. There was a tendency for hypoglycemic episodes in the presence of low insulin levels. Receptor studies with skin fibroblasts showed a diminution of the specific binding of SM-C by 50%. Apparently only the specific IGF-receptor is defective whereas the insulin receptor responds to the increased SM with hypoglycemia. The observation that the high plasma SM did not suppress the enhanced GH-secretion suggests that perhaps the hypothalamic IGF-receptor was also defective.