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Objective: To study the impact of GH dose and age at GH start in girls with Turner syndrome (TS), aiming for normal height and age at pubertal onset (PO) and at adult height (AH). However, age at diagnosis will limit treatment possibilities., Methods: National multicenter investigator-initiated studies (TNR 87-052-01 and TNR 88-072) in girls with TS, age 3-16 years at GH start during year 1987-1998, with AH in 2003-2011. Of the 144 prepubertal girls with TS, 132 girls were followed to AH (intention to treat), while 43 girls reduced dose or stopped treatment prematurely, making n=89 for Per Protocol population. Age at GH start was 3-9 years (young; n=79) or 9-16 years (old; n=53). Treatment given were recombinant human (rh)GH (Genotropin ® Kabi Peptide Hormones, Sweden) 33 or 67 µg/kg/day, oral ethinyl-estradiol (2/3) or transdermal 17β-estradiol (1/3), and, after age 11 years, mostly oxandrolone. Gain in height SDS , AH SDS , and age at PO and at AH were evaluated., Results: At GH start, height SDS was -2.8 (versus non-TS girls) for all subgroups and mean age for young was 5.7 years and that of old was 11.6 years. There was a clear dose-response in both young and old TS girls; the mean difference was (95%CI) 0.66 (-0.91 to -0.26) and 0.57 (-1.0 to -0.13), respectively. The prepubertal gain SDS (1.3-2.1) was partly lost during puberty (-0.4 to -2.1). Age/height SDS at PO ranged from 13 years/-0.42 for GH 67young to 15.2 years/-1.47 for GH 33old . At AH, GH 67old group became tallest (17.2 years; 159.9 cm; -1.27 SDS; total gain SDS , 1.55) compared to GH 67young group being least delayed (16.1 years; 157.1 cm; -1.73 SDS; total, 1.08). The shortest was the GH 33young group (17.3 years; 153.7 cm: -2.28 SDS; total gain SDS , 0.53), and the most delayed was the GH 33old group, (18.5 years; 156.5 cm; -1.82 SDS; total gain SDS , 0.98)., Conclusion: For both young and old TS girls, there was a GH-dose growth response, and for the young, there was less delayed age at PO and at AH. All four groups reached an AH within normal range, despite partly losing the prepubertal gain during puberty. Depending on age at diagnosis, low age at start with higher GH dose resulted in greater prepubertal height gain, permitting estrogen to start earlier at normal age and attaining normal AH at normal age, favoring physiological treatment and possibly also bone health, hearing, uterine growth and fertility, psychosocial wellbeing during adolescence, and the transition to adulthood., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kriström, Ankarberg-Lindgren, Barrenäs, Nilsson and Albertsson-Wikland.)

Context: The effect of GH therapy in short non-GH-deficient children, especially those with idiopathic short stature (ISS), has not been clearly established owing to the lack of controlled trials continuing until final height (FH)., Objective: The aim of the study was to investigate the effect on growth to FH of two GH doses given to short children, mainly with ISS, compared with untreated controls., Design and Setting: A randomized, controlled, long-term multicenter trial was conducted in Sweden., Intervention: Two doses of GH (Genotropin) were administered, 33 or 67 microg/kg.d; control subjects were untreated., Subjects: A total of 177 subjects with short stature were enrolled. Of these, 151 were included in the intent to treat (AllITT) population, and 108 in the per protocol (AllPP) population. Analysis of ISS subjects included 126 children in the ITT (ISSITT) population and 68 subjects in the PP (ISSPP) population., Main Outcome Measures: We measured FH sd score (SDS), difference in SDS to midparenteral height (diff MPHSDS), and gain in heightSDS., Results: After 5.9+/-1.1 yr on GH therapy, the FHSDS in the AllPP population treated with GH vs. controls was -1.5+/-0.81 (33 microg/kg.d, -1.7+/-0.70; and 67 microg/kg.d, -1.4+/-0.86; P<0.032), vs. -2.4+/-0.85 (P<0.001); the diff MPHSDS was -0.2+/-1.0 vs. -1.0+/-0.74 (P<0.001); and the gain in heightSDS was 1.3+/-0.78 vs. 0.2+/-0.69 (P<0.001). GH therapy was safe and had no impact on time to onset of puberty. A dose-response relationship identified after 1 yr remained to FH for all growth outcome variables in all four populations., Conclusion: GH treatment significantly increased FH in ISS children in a dose-dependent manner, with a mean gain of 1.3 SDS (8 cm) and a broad range of response from no gain to 3 SDS compared to a mean gain of 0.2 SDS in the untreated controls.

Aim: To evaluate haemostatic effects and clinical outcome of oestrogen treatment of constitutionally tall stature in girls., Methods: We conducted a single-centre cohort study, 63 girls referred over a period of 15 years were investigated. The girls were given oestrogen treatment for constitutional tall stature at a median initial dose of 300 ug ethinyl estradiol/day and were consecutively examined for changes in coagulation. Medical records were retrospectively reviewed, additional data were collected at follow-up by blood sampling and interviews., Results: After 1 year of treatment, levels of antithrombin and von Willebrand factor (VWF) were significantly decreased (p<0.001 and p=0.015, respectively), whereas there was no significant change in levels of plasminogen inhibitor type 1. No venous thromboembolism (VTE) or major side effects were observed. Genetic risk factors for thrombosis were present, as was expected. The mean height reduction was 5.5 cm. The height-reducing effect was inversely correlated with chronological age (r=-0.44, p<0.01) and bone age (r=-0.61, p<0.01)., Conclusions: Changes in coagulation parameters occurred both towards pro- and anticoagulation. Treatment with high-dose ethinyl estradiol can successfully limit final height, and it is most effective when started at a younger bone age.

Background: Girls adopted from developing countries often have early or precocious puberty, requiring treatment with gonadotrophin-releasing hormone (GnRH) analogues. During such treatment, decreased growth velocity is frequent., Aim: To study whether the addition of growth hormone (GH) to GnRH analogue treatment improves final height in girls with early or precocious puberty., Methods: Forty-six girls with early or precocious puberty (age < or =9.5 y) adopted from developing countries were randomized for treatment for 2-4 y with GnRH analogue, or with a combination of GH and GnRH analogue., Results: During treatment, the mean growth velocity in the GH/GnRH analogue group was significantly higher compared to the control group. Combined GH/GnRH analogue treatment resulted in a higher final height: 158.9 cm compared to 155.8 cm in the GnRH analogue-treated group. Three out of 24 girls (13%) in the combined group and nine of the 22 girls (41%) treated with GnRH analogue alone attained a final height below -2 standard deviation scores (SDS)., Conclusion: The difference between the two groups is statistically significant, and possibly of clinical importance. A future challenge is to identify a subgroup with clinically significant advantage of GH addition to GnRH analogue treatment. Being very short on arrival in Sweden and being short and young at start of treatment are possible indicators.

An androgen receptor (AR) variant (E653K) was found in two unrelated Swedish families. One family had two girls affected with congenital adrenal hyperplasia (CAH) due to steroid 21-hydroxylase deficiency. The girls, who showed mild virilization in relation to their CYP21 genotype, had inherited the AR gene mutation from their father, who showed no symptoms of androgen insensitivity. The other family had a boy with partial androgen insensitivity and ambiguous genitalia, and he had inherited the AR gene mutation from his mother. The mutant receptor showed a transactivating capacity in the same range as the normal receptor at high concentrations of ligand (1 and 10 nM dihydrotestosterone), but absent or reduced transactivation at low levels (0.01 and 0.1 nM). The receptor variant was not found among 250 additional unselected Swedish men. Sequencing of the AR gene in five unrelated CAH girls with the I172N mutation in CYP21 and minimal virilization did not reveal any additional deviations from the normal reference sequence. In addition, there was no difference in lengths of the polymorphic CAG repeat in the AR gene between CAH girls with the I172N mutation who showed minimal and severe virilization, and we found no evidence of skewed X-inactivation. We conclude that AR gene mutations or polymorphisms are not a common factor influencing the degree of hyperandrogenic symptoms displayed by CAH girls, and that the AR E653K mutation is compatible with normal genital development, although it can cause genital malformations in susceptible individuals.

Objective: To study patients with autosomal recessive pseudohypoaldosteronism type 1 and to relate pulmonary disease to gene mutations of the epithelial sodium channel (ENaC)., Study Design: Clinical and laboratory data were collected from 4 Swedish patients with pseudohypoaldosteronism type 1. The genes for ENaC and cystic fibrosis transmembrane conductance regulator were analyzed for mutations with methods including DNA sequencing., Results: Three novel mutations were found in the alpha-gene of ENaC, 2 frameshifts (1449delC and 729delA) and 1 missense mutation resulting in the substitution of leucine for serine 562 in the alpha-chain (S562L). The 1449delC mutation was found in all patients in either homozygous or heterozygous form and seems to be the predominant cause of pseudohypoaldosteronism in Sweden. The allele coding for S562L also contained a transition converting tryptophan 493 to arginine (W493R), which seems to be a rare polymorphism. All patients had pulmonary symptoms to various degrees. The bacterial findings resembled, to some extent, those in cystic fibrosis, but development of chronic lung disease and progressive decline in lung function were not observed., Conclusions: Genetic deficiencies of the alpha subunit of the ENaC are associated with prominent lung symptoms, which are, however, clearly different from those in cystic fibrosis.

This study was undertaken to investigate the prevalence of coeliac disease in children and adolescents with Turner syndrome. Eighty-seven children and adolescents with Turner syndrome were screened for IgA-antiendomysium antibodies (EMA) and IgA-antigliadin antibodies (AGA), 5% (4/87) being found to be EMA-positive, and 15% (13/87) to have AGA levels above normal. Of the 10 patients who were either AGA- or EMA-positive and further investigated with intestinal biopsy, four manifested villous atrophy (i.e. all three of the EMA-positive patients, but only one of the seven AGA-positive patients). The results suggest EMA-positivity to be a good immunological marker for use in screening for coeliac disease, and such screening to be justified in patients with Turner syndrome.

This paper reports results from an ongoing, randomized, multicentre national trial. The aim is to elucidate whether a dose of growth hormone (GH) of 0.2 IU/kg (0.07 mg/kg), given either as once-daily or twice-daily injections during puberty, is more effective than a once-daily dose of 0.1 IU/kg/day (0.03 mg/kg/day) in improving final height in children with GH deficiency (GHD). The twice-daily regimen comes closer to the spontaneous GH secretion pattern in puberty. Ninety-two children with GHD who had been receiving GH therapy for at least 1 year, and with spontaneous puberty or who were prepubertal and due to be started on replacement therapy to induce puberty, were randomly assigned to receive GH as follows: group A, 0.1 IU/kg/day (0.03 mg/kg/day), administered once daily; group B, 0.2 IU/kg/day (0.07 mg/kg/day), administered once daily; and group C, 0.2 IU/kg/day (0.07 mg/kg/day), divided into two equal injections given at 12-hour intervals. Pubertal height gain was 0.7, 0.7 and 1.3 SDS for groups A, B and C, respectively. The gain in height during puberty was thus most marked in group C. Mean final height, when corrected for parental height, was between 0 and 1 SDS in all treatment groups. All but seven children reached a final height within +/- 2 SD of the general population. There was a wide range of final heights in all three treatment groups. This variation in response suggests the need to individualize treatment in order to achieve an appropriate final height for most individuals.

Five children with dyschondrosteosis (Léri-Weill syndrome) were found to have insufficient growth hormone (GH) secretion and were treated with GH. After one year of treatment height velocity SDS as well as height SDS increased significantly. In three children who had completed their second year of treatment, the increase in height velocity was sustained and for all patients predicted adult height increased during the GH treatment.

The spontaneous growth process in Turner's syndrome is characterized by a progressive decline in height velocity during childhood and no pubertal growth spurt. Therefore, therapy aimed at improving height during childhood as well as increasing final height is desirable for most girls with Turner's syndrome. Forty-five girls with Turner's syndrome, 9-16 yr of age (mean age, 12.2 yr), were allocated to three study groups. Group 1 (n = 13) was initially treated with oxandrolone alone; after 1 yr of treatment, GH without (group 1a; n = 6) or with (group 1b; n = 7) ethinyl estradiol was added. Group 2 (n = 17) was treated with GH plus oxandrolone. Group 3 (n = 15) was treated with GH, oxandrolone, and ethinyl estradiol. The dosage were: GH, 0.1 IU/kg.day; oxandrolone, 0.05 mg/kg.day; and ethinyl estradiol, 100 ng/kg.day. A height of 150 cm or more was achieved in 61%, 75%, and 60% of the girls in groups 1, 2, and 3, respectively. The most impressive increase in height was seen in group 2. In this group the mean final height was 154.2 cm (SD = 6.6), which is equivalent to a mean net gain of 8.5 cm (SD = 4.6) over the projected final height. In group 3, in which ethinyl estradiol was included from the start of therapy, the initially good height velocity decelerated after 1-2 yr of treatment. Their mean final height was 151.1 (SD = 4.6) cm, equivalent to a mean net gain of 3.0 cm (SD = 3.8). A similar growth-decelerating effect of ethinyl estradiol was seen in group 1b. We conclude that in girls with Turner's syndrome who are older than 9 yr of age, treatment with GH in combination with oxandrolone results in significant growth acceleration, imitating that in normal puberty, leading to a more favorable height during childhood. This mode of treatment also results in a significantly increased final height, permitting a great number of the girls to attain a final height of more than 150 cm. However, early addition of estrogen decelerates the height velocity and reduces the gain in height.

The prevalence of thyroid autoantibodies, i.e. thyroglobulin antibodies and antibodies to thyroid peroxidase, was analyzed in 89 girls, aged 3-16 years (mean age 10 years), with Turner's syndrome. The analyses were performed before the start of growth-promoting treatment and during a follow-up period of 1-5 years. The patients were divided into four groups according to karyotype as follows: group 1, 45, X (n = 63); group 2 with structural abnormalities of the X chromosome (n = 10); group 3 with mosaicism but no structural abnormalities of the X chromosome (n = 10); and group 4, with isochromosome X of the long arm (n = 12): 199 healthy girls aged 12 years, served as controls. Thyroid autoantibodies were demonstrated in 46 of 89 (52%) patients with Turner's syndrome compared with 34 of 199 (17%) age-matched control girls (p < 0.001), thus confirming the relationship between thyroid abnormalities and Turner's syndrome. There was also an increase in the prevalence of thyroid antibodies with age. Simultaneous presence of both autoantibodies was significantly more frequent in group 1 (45, X) and group 4 (isochromosome X of the long arm) than in group 3 (mosaicism) (p = 0.04 and p < 0.002, respectively) and significantly more frequent in group 4 than in group 1 (p < 0.05). During 12-60 months of growth-promoting treatment, no increase in the prevalence of thyroid antibodies was observed. The findings demonstrate the importance of continuous monitoring of thyroid function in girls with Turner's syndrome.

A six-year-old boy with severe intermittent diarrhoea was subjected to extensive diagnostic investigation and treatment before the administration of a laxative (sodium sulphate) by his mother was discovered. Early suspicion and analysis of faecal fluid for electrolytes and known laxative substances would have prevented the hazardous clinical course of this case.

In a Swedish prospective study of congenital cytomegalovirus (CMV) infection, 76 infants were shown to be infected among 16,474 newborns screened by virus isolation in urine. Seventy-three of the excreters were followed up and one developed Type 1 diabetes, as compared to 38 of the 19,483 children born during the same period (p = 0.14, Fisher's one-tailed test). Thus we found no evidence that the combined finding of congenital CMV infection and Type 1 diabetes mellitus was related.

Two unrelated young males with the unusual simultaneous presence of insulin-dependent diabetes mellitus, ulcerative colitis and primary sclerosing cholangitis are reported. Both patients manifested homozygosity for the DR3-DQw2 (DQB*0201) HLA genotypes. We believe that homozygosity for this genotype may predispose for this type of multi-organ autoimmune disease.

We report a case of Takayasu's disease with severe renovascular hypertension in a girl from Eritrea. In the "burn-out" phase after the erythrocyte sedimentation rate had normalized, reconstructive vascular surgery was performed as further progression of the disease seemed unlikely. However, probably due to her growth, the graft rotated and a second operation was successfully performed.

We report the finding of mitochondrial ATP-synthase deficiency in a child with persistent 3-methylglutaconic aciduria. The child presented in the neonatal period with severe lactic acidosis, which was controlled by Na-HCO3 and glucose infusions. During the 1st y of life, there were several episodes of lactic acidosis precipitated by infections or prolonged intervals between meals. The excretion of lactate in urine was variable, but there was a persistent high excretion of 3-methylglutaconic acid. The activity of 3-methylglutaconyl-CoA hydratase in fibroblasts was normal. The child had a hypertrophic cardiomyopathy and magnetic resonance images revealed hypoplasia of corpus callosum. The gross motor and mental development was retarded, but there were no other neurologic signs. Investigation of muscle mitochondrial function at 1 y of age revealed a severe mitochondrial ATP-synthase deficiency (oligomycin-sensitive, dinitrophenol-stimulated Mg2+ ATPase activity: 27 nmol x min-1 x (mg protein)-1, control range 223-673 nmol x min-1 x (mg protein)-1. The mitochondrial respiratory rate was low and tightly coupled. The respiratory rate was normalized by the addition of an uncoupler. Low Mg2+ ATPase activity was also demonstrated by histochemical methods. Morphologic examination revealed ultrastructural abnormalities of mitochondria. There was no deletion of mitochondrial DNA. The sequences of the ATP synthase subunit genes of mitochondrial DNA were in accordance with published normal sequences.

We describe spontaneous longitudinal growth in girls with Turner's syndrome (TS), using the infancy-childhood-puberty (ICP) growth model. Length/height during the first 12 years of life was studied in 58 Swedish girls with TS. Their mean length at birth was 47.8 cm (SDS -1.4) and mean height at 12.0 years of age 127.3 cm (SDS -3.0). A clear age-dependent subnormality was observed in the change in length-height SDS (delta SDS). Mean delta SDS values at ages 0.0 to 0.5 and 3.0 to 6.0 years were normal. In contrast, the mean delta SDS at ages 0.5 to 3.0 and 6.0 to 12.0 years were subnormal. The onset of the childhood growth component (normally located between 0.5 and 1.0 year of age) was, on the average, delayed by 0.28 year. This accounts for the subnormality of delta SDS at 0.5 to 3.0 years of age. About 50% of the variation in height at 12.0 years of age, as determined by a multiple linear regression analysis, was significantly explained by length at 0.5 year of age, age at the onset of the childhood component, and delta SDS at 6.0 to 12.0 years of age.

Sweat secretion rate (SSR) was measured by the pilocarpine iontophoresis test in (a) 254 healthy children and adolescents (aged 6.0 to 19.2 years, mean age 11.2 years); in (b) 58 healthy adults (aged 20.4 to 75.2 years, mean age 37.6 years); and in (c) eight prepubertal patients with growth hormone (GH) deficiency (aged 4.2 to 13.5 years, mean age 8.9 years). Boys had higher median values for SSR than girls (pre-pubertal children: 92.7 vs 64.5 mg 30 min-1 pubertal children: 110.3 vs 73.1 mg 30 min-1), and men showed higher values than women (135.5 vs 49.2 mg 30 min-1). In addition, the change in sweat excretion rate from childhood to adulthood showed a difference between the sexes. Both pre-pubertal and pubertal boys had a lower secretion value than adult men (p less than 0.001 and 0.01, respectively), whereas girls showed higher secretion values than adult women (p less than 0.01 and p less than 0.001, respectively). There was a significant increase in SSR from prepuberty to puberty (p less than 0.001) for both sexes. The children with GH deficiency, all pre-pubertal, showed significantly reduced SSR (p less than 0.001) compared with the healthy children (median values: 32.8 vs 80.0 mg 30 min-1). We conclude that (a) sweat secretion pattern in children shows a significant sex difference and (b) sweating in children is dependent on growth hormone.

The differential diagnosis between Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetes is complicated since no specific markers are available for either disease. In this study, 244 consecutive patients were diagnosed with diabetes mellitus during two years in Malmö (230,000 inhabitants), corresponding to an incidence rate of 53.100,000(-1).year-1. Age, body mass index, HbA1c, C-peptide, and levels of islet cell antibodies were determined at the clinical onset, and related to the classification at diagnosis and at follow-up (n = 233) after a median time of 31 (range 1-49) months. After diagnosis, 42 of 244 (17%) were started on insulin while 202 of 244 (83%) were not. Islet cell antibodies were present in 25 of 42 (60%), and in 18 of 183 (10%), respectively. In the non-insulin treated group, patients with islet cell antibodies had lower body mass index (p less than 0.001), higher HbA1c (p less than 0.004), and lower C-peptide (p less than 0.001) than patients without. At follow-up, 11 of 18 (61%) islet cell positive patients were changed to insulin treatment, as were six other patients. Insulin was discontinued in five initially insulin-treated but islet cell antibody negative patients. The sensitivity, specificity and predictive value for insulin treatment at follow-up were for islet cell antibody positivity; 72%, 96% and 84%, respectively, and for low C-peptide value; 60%, 96%, and 80%, respectively. Islet cell antibodies and low C-peptide at diagnosis of diabetes mellitus are concluded to be useful markers to predict insulin dependence.

Studies were performed in 6 healthy, male volunteers to explore the effect of a work load on the blood concentrations of catecholamines in relation to pulse rate and blood pressure and the blood levels of pancreatic glucagon, insulin, growth hormone, glucose and glycerol. The work load consisted of 300 kpm/min for 5 min, followed by 600 kpm/min during the next 5 min and 900 kpm/min under a third 5 min period. The work load resulted in a marked increase in noradrenaline and adrenaline at 10 and 15 min of exercise. The pulse rate, the systolic pressure and the mean blood pressure were correlated to the blood levels of both adrenaline and noradrenaline. In spite of the rather marked activation of the sympathetic nervous system no increase occurred in glucagon as measured under exercise and up to 60 min after its completion. In 4 of the subjects the work load was followed by a prompt growth hormone response. The same 4 subjects also showed a marked increase in catecholamines. The 2 remaining subjects presented no change in growth hormone and their increase in catecholamines was relatively minor. Glycerol increased significantly during work and there was a positive correlation between the values recorded for glycerol and adrenaline. No significant changes occurred in blood sugar or insulin during work.

Meningoencephalitis associated with serological evidence of Mycoplasma pneumoniae infection is reported in two children, aged 11 and 12. In both cases the neurological illness started with an attack of generalised convulsions, followed by changes in the electroencephalogram, which lasted up to 5 wks. Both children recovered completely without signs of sequelae. Attention is drawn to the wide spectrum of neurological complications which can be associated with this infection.

125I-insulin binding to erythrocytes was studied in 24 children with type I diabetes mellitus before institution of insulin therapy, and in 10 normals. Mean specific 125I-insulin binding in the diabetics was significantly lower than in the controls (10.2 +/- 0.4% (SEM), as against 11.6 +/- 0.5%, P less than 0.05). In 8 diabetics the study was repeated after 3-6 weeks of therapy, at which time the insulin binding had increased to normal (12.1%, range 10.7-13.6). No correlation was found between insulin binding and blood glucose, plasma insulin or plasma beta-hydroxybutyrate. We conclude that insulin binding to the receptors is altered in the early phase of type I diabetes.

Studies on erythrocyte insulin receptors were performed in a boy with type I diabetes mellitus and superimposed adrenocortical insufficiency before and during treatment with hydrocortisone and 9-alpha-fluorohydrocortisone. The development of the adrenal insufficiency was associated with a progressively increased sensitivity to insulin which reverted after therapy. The maximum specific insulin binding of the erythrocytes was low during threatening addisonian crisis (6.9%) but normalized during hydrocortisone treatment (12.0%). These findings suggest that the increased insulin sensitivity characteristic for adrenocortical insufficiency is not an effect of an increased insulin receptor concentration and that hypocortisolaemia is associated with a down-regulation of the insulin receptors.

Reference curves for the growth of the uterus and ovaries were established for prepubertal and postpubertal girls by examining 34 healthy schoolgirls of age 7, 10, 13, and 17 years by grayscale ultrasound. Uterine volume increased from mean 0.9 cm3 at 7 years to 53 cm3 at 17 years. The ovaries could not be detected by ultrasound in girls of 7 years, but ovarian volume increased from mean 0.7 cm3 at 10 years to 5.8 cm3 at 17 years. There was good correlation between the Tanner score and uterine and ovarian volumes (r = 0.91 and 0.82 respectively). To test the reference curve, the uterine volume was assessed in 10 girls with abnormal sexual development. Five girls with precocious puberty had values greater than mean + 2 SD and 5 girls with primary amenorrhoea had values less than mean - 2 SD. Good reference values for ovarian and uterine size are necessary before ultrasound can be used to evaluate these organs in children with abnormal development of the reproductive system.

A 3 6/12-year-old previously healthy girl had intermittent attacks of abdominal pain following a blunt abdominal trauma. At admission to the hospital, she had jaundice and hepatomegaly. Results of laboratory tests indicated an obstructive pattern, and ultrasonography revealed an intraluminal mass in the distal common bile duct. At surgery, the mass was confirmed as the cause of obstruction, and it was removed. Microscopic analysis indicated that the amorphous material was fungi infested. Growth cultures from bile and feces yielded Candida albicans. Postoperative treatment with T-tube drainage and antimycotic drugs led to an uneventful recovery. Clinical, biochemical, and ultrasonographic follow-up have shown no evidence of recurrence. A possible cause and effect relationship between the trauma and the development of biliary obstruction is suggested.

Earlier studies indicate that diabetic children are less resistant to periodontal disease than healthy children. As the degree of metabolic control of the diabetes ranges widely in a juvenile population, the susceptibility to gingival inflammation may vary. The aim of the present study was to compare the gingival status in diabetic children, subgrouped for control of the disease, with that in non-diabetic children. All comparisons were performed under controlled plaque conditions. 43 diabetic children took part in the study. The controls consisted of age- and sex-matched healthy children. The degree of gingival inflammation and the amount of bacterial plaque were assessed in terms of the Gingival Index and the Plaque Index, respectively. The Plaque Index scores constituted the basis for all comparisons of gingival status. The metabolic control of the diabetics was assessed from the amount of glycosylated hemoglobin fraction HbA1c. For children with the highest Plaque Index scores, diabetics showed statistically significantly higher Gingival Index scores. Only minor differences were seen in the other Plaque Index classes. The diabetic children with poor metabolic control showed a clear tendency towards higher Gingival Index scores than the non-diabetics, while no such tendency was seen between the diabetics with good metabolic control and the non-diabetics.

Studies were performed in two groups of healthy male volunteers to evaluate the effect of apomorphine on the secretion of thyrotrophin (TSH) and prolactin under basal conditions and following the administration of thyrotrophin releasing hormone (TRH). Apomorphine HCl, administered sc in a dose of 0.75 mg had no effect on the basal levels of plasma TSH or serum prolactin. The iv injection of 200 mug TRH was followed by an increase in TSH and prolactin in all subjects, with a maximum 20-30 min after the injection. When 0.75 mg of apomorphine was injected sc 30 min before TRH, the increase in prolactin was significantly reduced whereas the TSH response was unaltered. Our studies indicate that the TRH induced secretion of prolactin in man can be suppressed through a dopaminergic mechanism whereas the secretion of TSH is not influenced.

Ten women were studied during the first post-partum week. Suckling for 20 min induced a marked increase in plasma prolactin, reaching a maximum within 0-25 min after the end of suckling and then returning to pre-suckling levels after 120 min. Suckling induced no changes in plasma thyrotrophin (TSH), growth hormone (GH) or follicle stimulating hormone (FSH). The iv injection of 200 mug of thyrotrophin releasing hormone (TRH) immediately after suckling resulted in an additional increase in plasma prolactin and a rise in TSH. When given 120 min after suckling TRH was followed by increased plasma levels of prolactin and TSH, which for both hormones were of a magnitude comparable to the TRH induced increment seen immediately after suckling. Thus, suckling did not inhibit the effect of TRH on the release of TSH. These studies indicate that TRH is probably not involved in the suckling induced increase in prolactin secretion. The mean plasma FSH level was below the limit of detection before and after suckling. Neither plasma FSH nor prolactin showed any appearant changes following the iv injection of 25 mug of luteinizing hormone releasing hormone (LH-RH), when given immediately after and 120 min after suckling. When given after suckling as indicated above, TRH induced no changes in plasma GH or FSH and similarly LH-RH was without influence on plasma GH and TSH.

Fanconi's anaemia and haemophilia A are born inherited diseases creating haemostatic defects. The association of these two rare diseases in one patient is described. The patient's haemophilia was studied with a newly developed immunological technique determining the plasma antigen associated with Factor VIII activity, and was found to be a genetic variant of moderately severe haemophilia A. It was not possible to demonstrate a common bone marrow defect or a common immunological or genetical background of the two diseases. The double haemostatic defect created, i.e. Factor VIII deficiency and thrombocytopenia, resulted in only a slight increase in bleeding tendency. A favourable result was obtained with corticosteroid and androgenic treatment.

Four children with a mild non-insulin-requiring diabetes were studied. They had no insulin response at intravenous glucose tolerance test. When insulin was infused at a rate which simulated a normal early insulin response to intravenous glucose, blood glucose decreased to the same extent as it did in healthy subjects. When a normal early insulin response was simulated during the intravenous glucose tolerance test, the glucose assimilation rate was normalized. These results suggests that a peripheral resistance to insulin is unlikely in mild juvenile diabetes, and that the primary defect is a deficient release of insulin.

Day-to-day fluctuations in blood concentration of the glycosylated hemoglobin, HbA1c or HbA1, are mainly due to variations in content of the intermediate aldimide form, preHbA1c. Using electrofocusing we have studied this component adjacent to the HbA1c band, which represents the stable ketoamine form. The fraction of preHbA1c present rapidly increases upon incubation of erythrocytes in 20 mM glucose at +37 degrees C, and the reaction is fully reversible if glucose is removed. In children with insulin-dependent diabetes mellitus with different degrees of metabolic control, levels of preHbA1c varied between 0.2 and 3.7% of total hemoglobin (median value 1.3%, N = 25). A clear correlation was found between preHbA1c and urinary glucose concentrations during the 12 hours preceding blood sampling (r = 0.75, p less than 0.001, df = 18). As expected, pre-HbA1c did not correlate to HbA1c or glycosylated albumin, which reflect long- and medium-term diabetic control.

Variant types of spondylometaepiphyseal dysplasia in a mother and her child is reported. Several stages of the disorder are presented, demonstrating the principal difficulties in distinguishing variant types of skeletal dysplasia.

Six healthy adult males were studied to evaluate the effect of apomorphine on growth hormone (GH) secretion under normoglycaemic and hyperglycaemic conditions. Both under normoglycaemia and hyperglycaemia all subjects responded to the subcutaneous injection of 0.75 mg apomorphine hydrochloride with a marked increase in plasma GH concentration reaching a maximum after 30-60 min. In control studies no significant changes in plasma GH were observed following the injection of physiological saline. As apomorphine is considered a selective dopamine receptor stimulating agent, the results support the view that GH release in man can be modulated through a dopaminergic mechanism. The finding that the plasma GH rise after the administration of apomorphine is not suppressible by glucose indicates that apomorphine activates dopaminergic receptors localized distally in the hypothalamus or in the anterior pituitary. Amorphine in low dosage may be used clinically to test the capacity of the pituitary to release GH in man, at least in special cases.

We report a retrospective study of diabetic children, 0--14 years of age, from seven Swedish departments of paediatrics. There were 359 new cases in the years 1970--1975. Notification suggested that there was a mean yearly incidence of 19.6 cases per 100 000 with a year to year variation of 10.0--26.4 per 100 000. Consequently about 330 new cases of childhood diabetes would be expected in Sweden every year. Incidence varied considerably between different geographical areas. The age distribution was bimodal with a main peak at about 12 years and another peak at about 7 years. There was some evidence for clustering of new cases in January and the autumn. The mean prevalence of childhood diabetes in the seven districts was 1.3 per 1 000.

The prevalence and incidence of bacteriuria in 304 girls and 337 boys with type I diabetes was studied by screening for bacteriuria at their regular outpatient controls. In 90 girls and 108 boys a urine specimen was sampled every third month during a year. The prevalence of bacteriuria was 3/304 in girls and 0/337 in boys. During the one year follow-up one of the 90 girls had pyelonephritis and two cystitis while none of the boys had bacteriuria. It is concluded that the rate of urinary tract infection in young diabetic persons does not differ from that present in healthy young people.

Eight children with Cushing's disease aged 6-18 years were treated with external radiation to the pituitary gland using 60Co gamma radiation given with stereotactic technique. The dose given varied between 50 and 70 Gy. The observation time was 2.6 to 6.75 years. Seven children had a clinical remission with normal urinary cortisol excretion. One child had insufficient effect of two irradiations and underwent bilateral adrenalectomy. In the patients in remission the growth velocity increased during the first year after treatment but growth retardation occurred again during the second year. Insufficient growth hormone secretion was demonstrated in all subjects. Two patients were given thyroxine substitution and three showed evidence for secondary hypogonadism. In conclusion, stereotactic pituitary irradiation was effective in normalizing the excessive glucocorticoid production in children with Cushing's disease. However, with the doses used, it was not possible to maintain a normal anterior pituitary function.

This is a prospective study of the incidence of insulin-dependent diabetes mellitus (IDDM) in children 0-14 years of age, including all newly diagnosed cases in the whole of Sweden from July 1, 1977 until June 30, 1980. All 45 Swedish departments of paediatrics participated. During the three-year-period studied, 1108 Swedish children, 0-14 years of age had their onset of diabetes. That means around 369 new diabetics yearly in the age groups studied. The mean yearly incidences in the years 1977-80 were 22.6, 22.8 and 22.6 per 100000 children, respectively. Mean prevalence on June 30, 1980 and 1.48 per 1000 children 0-14 years with a wide range of 0.71-2.65. The age distribution at onset showed a gradual increase and peak incidences at 11 years of age for the girls and 4 and 13 years of age for the boys. There was a consistently higher incidence for boys in the younger age groups during the three-year-period studied. Peak incidences of new cases were reached in January, March and July through October for the age groups 5-9 and 10-14 years of age. No such seasonal variation was seen for children 0-4 years of age. The cumulative incidence of IDDM at 14 years of age was 3.2 per 1000 for the boys and 2.9 per 1000 for the girls. The degree of ascertainment in this study was 93.4%.

The blood glucose response to a brief infusion of insulin (0.012 U/kg body wt) was studied in the initial phase of Type 1 diabetes in 21 children and in 20 healthy controls. The insulin effect was impaired in most of the diabetics and the mean blood glucose decrement was 14.3 +/- 3.5% (SEM) as compared with 20.9 +/- 2.1% in the normals. Subgrouping the diabetics according to the severity of the diabetic condition revealed normal (or even supranormal) sensitivity in the diabetics with mild metabolic derangement (mean blood glucose decrement 36.2 +/- 6.0%). In children with more disturbed metabolism mean blood glucose decrement was only 5.6 +/- 0.8% indicating a marked insulin resistance. Further evidence for a relationship between the insulin sensitivity and the severity of the diabetic state was found in the correlation between the percentual blood glucose decrement and the fasting blood glucose (r = -0.79, p less than 0.01), the glucose assimilation rate (r = 0.71, p less than 0.01), as well as the blood glucose level at 120 min during the OGTT (r = -0.76, p less than 0.01). Four of the insulin-resistant patients were re-tested during remission and exhibited then normal insulin sensitivity.

Girls with adolescent idiopathic scoliosis are taller than nonscoliotic girls of the same age. This observation may be related to factors regulating longitudinal growth. Plasma growth hormone was determined in a group of scoliotic girls by double antibody radioimmunoassay under the following conditions: 1) Insulin induced hypoglycemia, 2) glucose tolerance test, 3) exercise. Somatomedin A was determined by a method based on the ability of serum to stimulate the incorporation of radioactive sulphate in embryonic chick cartilage. The results were compared with those obtained in a control group of healthy nonscoliotic girls of comparable age. After overnight fasting and after at least one hour's rest the basal growth hormone level was 9.8+/-11.1 (+/-S.D.) ng/ml in the scoliotic girls (n=48) and 2.2+/-1.1 ng/ml in the controls (n=15). This difference is significant. In the hypoglycemia test the peak growth hormone level tended to be higher in the scoliotic girls but the difference is not significant. In the exercise test the maximal value was reached at different times in the two groups: at 20 min after start of the exercise in the scoliotic girls (n=14, 17.3+/-11.8 ng/ml) and at 40 min in the controls (n=9, 16.0+/-6.6 ng/ml). In the glucose tolerance test the growth hormone level was suppressed in both groups but the mean values tended to be higher during the first 120 min in the scoliotic girls. The serum somatomedin levels were higher in the group of scoliotic girls (n=19, 1.13+/-0.17 U/ml) than in the controls (n=14, 0.88+/-0.16 U/ml) and the difference is significant. The results obtained are difficult to interpret but suggest that growth hormone secretion is higher in girls with adolescent idiopathic scoliosis than in healthy girls of comparable age.