Autoimmune thyreoiditis in childhood--epidemiology, clinical and laboratory findings in 61 patients.

Autoimmune thyroiditis (AT) is the most common cause of nonendemic goiter and acquired hypothyroidism in children and adolescents. In 61 patients AT was diagnosed following clinical, ultrasonographic, biochemical and cytological examinations. Girls were more often affected than boys, the female/male ratio in our patients was 9:1. Clinically the vast majority of patients had a goiter. Approximately half of the patients were euthyroid (n = 29). In the other patients hyperthyrotropinaemia (n = 16), hypothyroidism (n = 9) and hyperthyroidism (n = 7) were evident. Thyroid microsomal and peroxidase antibodies were elevated in most of the patients, while thyroglobin antibodies were less frequently elevated. As AT without detectable thyroid antibodies can occur, a fine-needle aspiration cytology of the thyroid is important in nontypical cases. This type of cytologic examination should also be considered in patients with euthyroid nonendemic goiter, thyroid nodules and hyperthyroid goiter.

Growth response to recombinant human growth hormone of mammalian cell origin in prepubertal growth hormone-deficient children during the first two years of treatment.

In five clinical studies performed in Austria, France, the FRG, Italy, Switzerland, the UK and the USA, 304 growth hormone (GH)-deficient children were treated with recombinant human GH (rhGH) of mammalian cell origin. Two hundred and twenty-five patients were previously untreated (naive patients), and 79 were transferred from pituitary hGH after interruption of therapy for at least 6 months (transfer patients). Two treatment protocols, differing in both dose and frequency of injections, were used: (1) a dose of 0.6 IU/kg body weight per week was administered in 3 s.c. injections to 203 patients (178 naive, 25 transfer; group 1); and (2) a dose of 0.45 IU/kg body weight per week was administered in 7 s.c. injections to 101 patients (47 naive, 54 transfer; group 2). After 1 and 2 years of treatment, 143 and 109 naive, and 51 and 46 transfer patients, respectively, were still prepubertal, and their data were analyzed for efficacy. During the 1st year of treatment, both naive and transfer patients on daily injections (group 2) demonstrated better growth than those on 3 injections per week (group 1), with height velocities (HVs) of 10.6 +/- 2.7 cm/year (group 2) versus 8.6 +/- 2.0 cm/year (group 1) for naive patients (p < 0.001), and 9.9 +/- 1.9 cm/year (group 2) versus 7.2 +/- 2.7 cm/year (group 1) for transfer patients (p < 0.001). The corresponding changes in height standard deviation score (delta H SDS) for chronological age (CA) were +1.3 +/- 0.6 (group 2) versus +0.8 +/- 0.5 (group 1) for naive patients (p < 0.01), and +1.1 +/- 0.3 (group 2) versus +0.6 +/- 0.4 (group 1) for transfer patients (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Recombinant human growth hormone and oxandrolone in treatment of short stature in girls with Turner syndrome.

91 girls with Turner syndrome (TS) with a mean chronological age (CA) and bone age (BA) of 10.3 +/- 2.3 and 8.9 +/- 1.9 years, respectively, were randomly assigned to subcutaneous treatment with recombinant human growth hormone (rhGH) alone (n = 47), 2.6 IU/m2 body surface area daily or combination treatment (n = 44) with the same dose of rhGH and oxandrolone 0.1 mg/kg body weight orally, for the first 12 months of this study. During the 1st year of therapy, there was a striking increase in height velocity (HV) in both groups, from 4.0 +/- 0.8 to 6.3 +/- 1.3 cm/year [HV standard (standards of untreated Turner patients) deviation score (SDS) for CA from 0.0 +/- 0.7 to 2.9 +/- 1.3] in the rhGH group and from 4.2 +/- 1.2 to 8.5 +2- 1.7 cm/year (HV SDS-CA from +0.3 +/- 1.0 to 5.6 +/- 1.6) in the combination group. The difference between the groups was statistically significant (p < 0.01). During the 2nd year of treatment, the rhGH dose was increased to 3.4 IU/m2 daily for the rhGH-alone group, whereas in the combination treatment group the oxandrolone dose was reduced to 0.05 mg/kg daily. HV was maintained at significantly higher levels than those prior to treatment, at 5.3 +/- 1.1 cm/year (HV SDS-CA: +2.1 +/- 1.3) and 6.2 +/- 1.5 cm/year (HV SDS-CA: +3.6 +/- 1.4) in the rhGH-alone and the combination group, respectively (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

[Hypophyseal microprolactinoma as a cause of delayed puberty]. / Hypophysäres Mikroprolaktinom als Ursache einer Pubertätsverzögerung.

Hyperprolactinaemic hypogonadism in adults is a well defined disease with clinical symptoms like ovarian hypofunction or amenorrhea and galactorrhea in females and loss of sexual activity in males. In pediatrics this special form of hypogonadism is almost unknown. Typical manifestation is delay in puberty or pubertal arrest. We describe a 20 year old man with signs of delay of puberty. Endocrinological work-up revealed a decreased pulse frequency of luteinizing hormone resulting in pathologically low testosterone concentrations. The final cause of hypothalamic hypogonadism was a prolactin producing pituitary microadenoma. During long-term treatment with a dopaminergic drug the elevated prolactin levels decreased to the normal range and testicular function normalized as shown by growth of the testes and increasing testosterone levels.

Effect of different oestrogen doses on final height reduction in girls with constitutional tall stature.

The effects of different doses of oestrogens in constitutionally tall girls were evaluated in two centres for paediatric endocrinology. In one centre, 38 girls were treated with a high oestrogen dose of 0.3 to 0.5 mg ethinyloestradiol (EE) daily. In the other, 44 girls received a comparably low dose of 0.1 mg EE per day. Height prediction (HP), chronological age (CA), and height at the onset of treatment were comparable in both groups. Although the duration of treatment was significantly longer in those receiving the low dose, the cumulative oestrogen dose was still significantly lower. The dose of EE had no effect on final height reduction (high dose group: 4.9 +/- 2.6 cm, low dose group: 5.1 +/- 2.4 cm). Final height was more reduced in both groups when treatment was started at an early bone age (BA) (less than or equal to 13 years). No serious side effects were observed in either group, however weight gain was more pronounced in girls receiving the higher dose. We conclude that treatment of constitutionally tall girls with low doses of oestrogens is equally effective in reducing the final height as the usually administered high doses. The lowest effective dose has to be determined in a randomized, prospective clinical trial.

Spontaneous growth in Turner's syndrome.

Growth in Turner's syndrome can be divided into four phases: intrauterine growth is slightly retarded, normal growth occurs up to a bone age of about 3 years, with a tendency to compensate for the loss in growth during intrauterine life, stunting of growth is severe during childhood, after a bone age of about 10 years - the time when puberty normally starts - the growth phase is prolonged, but total height gain is not essentially reduced. Based on a study of 150 patients with Turner's syndrome whose spontaneous growth was observed, standards of height and height velocity (means and SDs) were calculated to allow mathematical analysis of the spontaneous growth and growth during treatment in these patients. The auxological characteristics in Turner's syndrome do not support the assumption that GH deficiency plays a primary role in the pathogenesis of the growth disorder.

[Infection and neonatal meningitis: epidemiology, pathogen spectrum, therapy]. / Sepsis und Meningitis neonatorum: Epidemiologie, Erregerspektrum, Therapie.

Data from 196 infants were analyzed who had been treated for neonatal septicemia and/or meningitis between 1962-1974 (n = 88) and 1975-1985 (n = 108). In addition to an increase in the incidence of septicemia (1962-1974: 0.88 cases/1000 live births/year; 1975-1985: 1.8 cases/1000 live births/year) there was also a change in the pattern of infection. Group B streptococcal infections were first observed in 1975. Infections with Escherichia coli increased (1962-1974: 0.25 cases/1000 live births/year; 1975-1985: 0.65 cases/1000 live births/year). Although the incidence of meningitis was similar in both periods (1962-1985: 0.45 cases/1000 live births/year) the relative number of cases declined (1962-1974: 51 of 88 patients; 1975-1985 25 of 108). Mortality also decreased during the second period (1962-1974: 53%; 1975-1985: 29%). All infants were primarily treated with a combination of ampicillin and gentamicin. The decision to discontinue this therapy was based on the clinical course of the patient and the results of culture and susceptibility studies. Ampicillin and/or gentamicin were effective in vitro against all microorganisms which caused septicemia and/or meningitis within the first four days of life. In contrast this antimicrobial combination was only active in vitro against 77% of the pathogens isolated after this time period.

Goitre epidemiology: thyroid volume, iodine excretion, thyroglobulin and thyrotropin in Germany and Sweden.

Thyroid volume of 1397 German and 303 Swedish adults were estimated by sonography. Thyroid size of 6-16 year old Germans (n = 619) was determined and compared with findings on palpation. Thyroid volume was more than twice as great in German (21.4 +/- 15.6 ml, mean +/- SD) than in Swedish adults (10.1 +/- 4.9 ml). The echopattern was abnormal in 16% of the Germans and in 3.6% of the Swedes. German children have a thyroid volume ranging from 1.8 +/- 0.4 ml at 6 years to 10.8 +/- 6.0 ml at 16 years of age. Palpation is by comparison an unreliable method for determining thyroid size. In Germany, the iodine excretion was less in children (n = 619, 39.5 +/- 30.5, 34.1 micrograms I/g creatinine, mean +/- SD, median) than in adults (n = 1193, 83.7 +/- 94.4, 62.6), (P less than 0.001) and much lower than that observed in Sweden (adults n = 98, 170.2 +/- 93.3, 141.4; 13 year olds n = 113, 172.9 +/- 224.1, 124), (P less than 0.0001). Serum thyrotropin concentration was significantly higher (P less than 0.001) in Sweden (n = 62, 1.49 +/- 0.82 mU/ml), than in Germany (n = 91, 0.97 +/- 0.52 mU/ml), while serum thyroglobulin was increased in Germany (n = 91, 72.6 +/- 50.6 micrograms/l) as compared to Sweden (n = 62, 23.5 +/- 17.4), (P less than 0.0001). These results indicate the goitrogenic effect of iodine deficiency and the continuing need for an effective iodine prophylaxis in the FRG.

[Continuous subcutaneous deferoxamine infusions in thalassemia major. Improvement in glucose tolerance]. / Kontinuierliche subkutane Deferoxamin-Infusionen bei Thalassaemia major. Verbesserung der Glucosetoleranz.

Exocrine and endocrine pancreatic functions were studied in 30 patients with homozygotic beta-thalassaemia. All were treated with continuous subcutaneous deferoxamine infusions for a mean period of 30 months. Three patients (aged 18-22 years) had insulin-dependent diabetes, two before and one shortly after the onset of deferoxamine administration. There was no improvement during the treatment. An abnormal glucose tolerance test was demonstrated in 14 patients (47%) before and in seven (23%) during deferoxamine infusion. Enzyme activity of alpha-amylase and lipase as an expression of exocrine pancreatic function was normal in all during the observation period. Improvement in endocrine pancreatic function was apparently age-dependent: the younger the patient at the onset of treatment the more likely is normalization of the oral glucose tolerance test.

[Follow-up of a pediatric prolactin-producing hypophyseal tumor]. / Verlaufsbeobachtung eines kindlichen Prolaktinproduzierenden Hypophysentumors.

At the age of 10 years a prolactin-producing pituitary tumor was diagnosed in a boy now aged 16 1/2 years. After surgical removal with a relapse after 1 year, a second surgical intervention and pituitary radiation were necessary. In the cause of further hyperprolactinemia, Pravidel treatment (Bromocriptine) was started with success. After 4 1/2 years medical treatment was discontinued for 1 week, but remains of active tumor tissue activity with increased prolactin concentrations were found, so that further treatment with Pravidel is necessary.

Regional variations of iodine nutrition and thyroid function during the neonatal period in Europe.

In order to evaluate further the possibility that transient hypothyroidism and hyperthyrotropinemia in newborn infants could result from a state of relative iodine deficiency, the urinary concentration of iodine, used as an index of the dietary intake of iodine was determined in casual urine samples collected in 1,076 full-term infants aged 3-6 days in 16 cities in 10 different European countries and in Toronto, Canada. In addition, the results obtained by programs of systematic neonatal screening for congenital hypothyroidism in the same areas were compared. There were marked regional differences in iodine nutrition during the neonatal period in Europe (median urinary iodine: 16.2 micrograms/dl in Rotterdam, the Netherlands, and 1.1 micrograms/dl in Freiburg, FRG. A low iodine supply in newborn populations was accompanied by, and probably explained, an elevated frequency of transient disorders of thyroid function in young infants. Iodine prophylaxis is urgently needed in some European countries not only for the prevention of goiter, but mostly for the prevention of impairment of thyroid function during the critical period of brain development.

[Longitudinal growth of patients with homozygote beta-thalassemia during continuous subcutaneous infusion of deferoxamine]. / Längenwachstum bei Patienten mit homozygoter beta-Thalassämie während kontinuierlicher subkutaner Deferoxamin-Infusionen.

Subcutaneous continuous infusions of deferoxamine were administered to 28 children with thalassaemia major. Longitudinal growth beyond the eleventh year was favourably influenced. The normal growth spurt during puberty was not demonstrable in six patients (three boys and three girls) during their puberty. Taking into account standard height allowing for parents' height, prospective final height and ethnic origin, the treatment favourably influenced longitudinal growth in 26 of the 28 children.

Neonatal septicemia and meningitis in Göttingen, West Germany.

Data were analyzed from 181 infants treated for neonatal septicemia and/or meningitis between 1962 and 1974 (n = 88) and between 1975 and 1982 (n = 93). In addition to an increase in the incidence of septicemia (1962 to 1974, 0.88 case/1000 live births (LB)/year; 1975 to 1982, 2.0 cases/1000 LB/year), there was also a change in the pattern of infection. Group B streptococcal infections were first observed in 1975. Infections with Escherichia coli increased (1962 to 1974, 0.25 case/1000 LB; 1975 to 1982, 0.75 case/1000 LB), while those with Pseudomonas aeruginosa decreased (1962 to 1974, 0.15 case/1000 LB; 1975 to 1982, 0.1 case/1000 LB). Although the incidence of meningitis was similar in both time periods (0.5 case/1000 LB), the relative number of cases declined (1962 to 1974, 51 of 88 patients; 1975 to 1982, 23 of 93 patients). Case fatality also decreased during the second time period (1962 to 1974, 53%; 1975 to 1982, 29%). The most common predisposing factors for septicemia were prolonged rupture of membranes (21 of 93 cases) and prematurity (41 of 93). Blood analysis showed that the immature/total neutrophil ratio was more consistently abnormal (60% of the cases) than were total counts of white blood cells, neutrophils or immature neutrophils.

[Iodine excretion and dietary iodine supply in newborn infants in iodine-deficient regions of West Germany]. / Jodausscheidung und alimentäre Jodversorgung bei Neugeborenen in Jodmangelgebieten der Bundesrepublik.

Urinary iodine excretion was measured on the fifth day of life in 461 neonates from nine different towns in the Federal Republic of Germany. There was a progressive fall in levels from north to south, with highest values in Hamburg (2.9 micrograms/dl) and lowest in Freiburg (1.2 micrograms/dl). All levels were lower than those of neonates in other countries in which iodine is added to salt: Stockholm (61 neonates) 9.6 micrograms/dl, Zurich (63) 4.75 micrograms/dl. Iodine analysis of mothers in G ottingen on the fifth day post-partum indicated that iodine excretion in urine of mothers with goitre (51 cases) was significantly lower than in a control group without goitre (38): 17.6 compared with 30.0 micrograms/g creatinine, and the iodine content of breast milk in the goitre group was significantly lower than that of the control group (1.75 compared with 2.5 micrograms/dl). Iodine content in artificial infant milk preparations was of a similar range. These results indicate that iodine supply during the neonatal period in the Federal Republic of Germany is very low; they support the demand for general iodine-salt prophylaxis.

Pulsatile secretion of luteinizing hormone and sleep-related gonadotropin rhythms in girls with premature thelarche.

The concentrations of LH, FSH and PRL were determined in serum samples obtained at night in 1-2 h intervals as well as at 15 min intervals during a 3 h period between 9 and 12 p.m. and 9 and 12 a.m. in three girls with premature thelarche, who had not developed further signs of precocious puberty for more than 18 months. A sleep-dependent LH and FSH increase was documented in all of them with a predominance of FSH secretion during sleep and after LHRH stimulation. In all three girls an episodic pattern of LH was found during sleep. In daytime minor fluctuations of LH secretion were found in two patients whereas in one patient an episodic LH pattern was demonstrable with minor peak values as during sleep. Normal PRL secretion during sleep as well as after TRH stimulation excludes a permissive role of this hormone in premature thelarche. We conclude that in girls with isolated premature thelarche a matured hypothalamo-pituitary gonadotropin axis is active comparable to normal pubertal children.

[Excessive gynecomastia in boys. Effective medical treatment using danazol (Winobanin)]. / Ausgeprägte Gynäkomastie beim Jungen. Möglichkeit einer effektiven medikamentösen Therapie mit Danazol (Winobanin).

The purpose of this study was to provide a medical alternative to mastectomy in boys with excessive breast development. Eleven boys with bilateral gynecomastia, ranging in size between 9 X 7 cm and 3 X 3 cm in diameter, were treated with 200 mg of Danazol daily for 6 months. This therapy led to a reduction in breast size between 3 X 3 cm and 1,5 X 1,5 cm. The antigonadotropic action of Danazol was documented by inhibition of basal gonadotropin secretion, by disappearance of normal sleep dependent rhythms and by a reduced pituitary response to stimulation. Simultaneously, plasma testosteron secretion was suppressed without reduction of testicular volumes. In all patients the hypothalamo-pituitary gonadal axis normalized within 67 months after termination of therapy and no relapse was observed over a control period up to 26 months. The continuing regression after Danazol treatment emphasizes the effectiveness of drug therapy as an alternative regimen to surgical intervention.