Nonislet pancreatic autoantibodies in sibship with permanent neonatal insulin-dependent diabetes mellitus.

Neonatal insulin-dependent diabetes mellitus (IDDM) occurs rarely. A sibship of two HLA-Dw3/4-positive boys who developed IDDM within the 1st wk of life is described. Although the HLA-D region genotype would be consistent with IDDM associated with islet autoimmunity, islet cell antibodies were negative, but both boys exhibited the presence of a novel autoantibody that reacted specifically with a conspicuous, yet unidentified, determinant in the interstitial tissue among the acinar cells. The possible relationship between this acinar nonislet autoantibody and permanent neonatal diabetes remains to be established.

Improved final height in girls with Turner's syndrome treated with growth hormone and oxandrolone.

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.

Common bile duct obstruction due to an intraluminal mass of candidiasis in a previously healthy child.

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.

Growth hormone treatment in Léri-Weill syndrome.

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.

Effect of growth hormone (GH) during puberty in GH-deficient children: preliminary results from an ongoing randomized trial with different dose regimens.

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.

Lack of effect of hyperglycaemia on apomorphine induced growth hormone release in normal man.

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.

Spondylometaepiphyseal dysplasia in a mother and her child.

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.

Neurological complications associated with Mycoplasma pneumoniae infection in children.

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.

Influence of sex and growth hormone deficiency on sweating.

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.

Gingival inflammation in diabetic children related to degree of metabolic control.

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.

Fanconi's anaemia associated with haemophilia A.

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.

Insulin sensitivity in the initial phase of type 1 diabetes mellitus.

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.

Absence of insulin resistance in 4 cases of mild juvenile diabetes. A preliminary report.

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.

The influence of short term submaximal work on the plasma concentrations of catecholamines, pancreatic glucagon and growth hormone in man.

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.

The effect of apomorphine on basal and TRH stimulated release of thyrotrophin and prolactin in man.

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.

Ultrasonography of the pelvic organs in prepubertal and postpubertal girls.

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.

Erythrocyte insulin receptors and insulin sensitivity in adrenocortical insufficiency. Report of a case of diabetes mellitus type I with superimposed Addison's disease.

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.

Influence of suckling and of suckling followed by TRH or LH-RH on plasma prolactin, TSH, GH and FSH.

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.

PIP: The influence of suckling and of suckling followed by thyrotropin re leasing hormone (TRH) or luteinizing hormone-releasing hormone (LH-RH) o n plasma prolactin, thyrotropin (TSH), growth hormone (GH) and follicle stimulating hormone (FSH) was studied in 10 humans. Suckling (20 minute s) induced a significant (p less than .005) rise in plasma prolactin in all subjects, reaching a maximum at 20-45 minutes after start of suckling and then returning to presuckling levels after 120 minutes. TSH, GH and FSH levels were not changed by suckling. The injection of 200 mcg TRH immediately after suckling resulted in an additional increase in plasma prolactin and a rise in TSH. The mean absolute increase in TSH was the same whether the TRH test was performed immediately after suckling or at 120 minutes after the end of suckling. FSH levels could not be detected before or after suckling and neither FSH nor prolactin showed any changes following the injection of LH-RH when given immediately after and 120 minutes after suckling. These results indicate that TRH is probably not involved in the suckling induced increase in prolactin secretion and that the specificity of the releasing effects of TRH and LH-RH, respectively, is not changed during the early postpartum period or influenced by suckling.