Renal osteodystrophy in nondialysed adolescents. Long-term treatment with 1alpha-hydroxycholecalciferol.

The effects of small oral doses (1-2 microgram/day) of 1alpha-hydroxycholecalciferol, given for 1 to 2 years, have been examined in four nondialysed adolescents with chronic renal failure and bone disease. Treatment increased calcium retention and plasma calcium, and decreased plasma levels of alkaline phosphatase, hydroxyproline, and immunoreactive parathyroid hormone. X-ray abnormalities of bone regressed, and 2 patients underwent successful surgical correction of knock-knees; bone histology in these 2 was normal at the time of operation. 2 patients developed hypercalcaemia which promptly reversed when 1alpha-hydroxycholecalciferol was withdrawn. In one patient treatment was initially successful, but later there was biochemical, radiographic, and histological evidence of relapse. Long-term treatment of such patients with 1alpha-hydroxycholecalciferol may be effective and facilitate the surgical correction of deformities, but this is not invariable. Toxic effects are similar to those of vitamin D itself, but are more readily reversible.     

Long-term follow-up of tamoxifen treatment in adolescents with gynecomastia

Ten pubertal boys treated with tamoxifen for gynecomastia for more than 3 months were evaluated after 2.5-7 years (mean 4.6 years) to determine the side effects of this therapy. We assessed the safety of long duration in adolescents with pubertal gynecomastia treated with tamoxifen. We did not find any serious side effects of tamoxifen in these patients.     

Late neonatal hypocalcemia. Apropos of 33 cases treated with 1 alpha-hydroxycholecalciferol

Thirty-three observations of late-onset neonatal hypocalcemia were reviewed retrospectively. Their etiological, clinical and biological features were consistent with a transient congenital hypoparathyroidism, associated with a materno-foetal vitamin D deficiency. 1 alpha-hydroxycholecalciferol was used for rapid correction of calcemia and proved to be satisfactorily metabolized after its oral administration.     

Long-term atomoxetine treatment in adolescents with attention-deficit/hyperactivity disorder

OBJECTIVE: To determine the efficacy and safety of atomoxetine in adolescent subjects treated for attention-deficit/hyperactivity disorder (ADHD) for up to 2 years. STUDY DESIGN: Data from 13 atomoxetine studies (6 double-blind, 7 open-label) were pooled for subjects age 12 to 18 with ADHD as defined by the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders IV. RESULTS: Of the 601 atomoxetine-treated subjects in this meta-analysis, 537 (89.4%) completed 3 months of acute treatment. A total of 259 subjects (48.4%) are continuing atomoxetine treatment; 219 of these subjects have completed at least 2 years of treatment. The mean dose of atomoxetine at endpoint was 1.41 mg/kg/day. Mean ADHD Rating Scale IV, parent version, investigator-administered and -scored total scores showed significant improvement (P < .001) over the first 3 months. Symptoms remained improved up to 24 months without dosage escalation. During the 2-year treatment period, 99 (16.5%) subjects discontinued treatment due to lack of effectiveness, and 31 (5.2%) subjects discontinued treatment due to adverse events. No clinically significant abnormalities in height, weight, blood pressure, pulse, mean laboratory values, or electrocardiography parameters were found. CONCLUSIONS: Two-year data from this ongoing study indicate that atomoxetine maintains efficacy among adolescents with ADHD, with no evidence of drug tolerance and no new or unexpected safety concerns.     

Renal osteodystrophy in children undergoing continuous ambulatory peritoneal dialysis

This paper describes a retrospective evaluation of the course of renal bone disease in 14 children undergoing treatment with continuous ambulatory peritoneal dialysis (CAPD) for an average of 11.9 +/- 1.5 months (mean +/- SE). The patients were divided in two groups according to the changes in serum alkaline phosphatase activity during the period of observation: five patients had alkaline phosphatase activity that decreased or was relatively stable (group I), and nine patients exhibited a rising serum alkaline phosphatase activity (group II). Serial radiological examinations showed adequate control of renal osteodystrophy in the patients of group I, whereas the patients of group II had no improvement or worsening of their bone disease. Group I had higher serum calcium and lower parathyroid hormone levels than group II at the end of period of observation despite similar dosage of vitamin D metabolite. The progression of bone disease was not related to the duration of CAPD or type of previous treatment for end stage renal disease. The observation that the radiological manifestations of secondary hyperparathyroidism were prevented in patients whose serum calcium levels were frequently above 2.62 mmol/liter (group I) while serum calcium levels between 2.25 and 2.50 mmol/liter in group II patients failed to lead to regression of secondary hyperparathyroidism is consistent with the existence of altered "set-point" regulation of the parathyroid gland in children undergoing CAPD.     

Long-term outcome of adolescents with anorexia nervosa

The long-term outcome of 49 adolescent girls hospitalized for the treatment of anorexia nervosa on a pediatric service was determined by personal interview an average of 80 +/- 21 months after admission to the hospital. The mean age at follow-up was 22.7 years. Between admission to the hospital and follow-up, body weight increased, on average, from 72.1% to 96.1% of ideal. Amenorrhea occurred in all subjects, but menstruation began or resumed in 80% of patients after hospitalization, at a mean body weight 90.3% +/- 6.5% of ideal. A total of 15 pregnancies resulted in 2 elective abortions, 3 ongoing pregnancies, and 10 healthy newborns. No subject who desired to become pregnant was unable to conceive. Almost half of the subjects (22 of 45) acquired binge eating patterns after hospitalization. Overall, 86% had a satisfactory outcome. These data indicated that adolescents with anorexia nervosa can be successfully treated with a developmentally oriented, multidisciplinary approach that includes inpatient and outpatient management based in pediatrics.     

Effect of low dose 1 alpha-hydroxycholecalciferol on glomerular filtration rate in moderate renal failure.

Serial measurements of 51Cr edetic acid clearance were made over a period of one year in two groups of 8 children, in a double blind trial of 1 alpha-hydroxycholecalciferol (10 ng/kg/day) and calciferol (670 ng/kg/day). Glomerular filtration rate (GFR) at the beginning of the trial was 20-50 ml/min/1.73 m2; it rose in the children given 1 alpha-hydroxycholecalciferol (group A) after 6 months but was not appreciably different from the pretreatment value after 12 months. The GFR in the children given calciferol (group B) showed no significant difference at 6 or 12 months. Parathyroid hormone values fell markedly in group A after 6 months but not in group B. Quantitative bone histology improved considerably in group A but not in group B at 12 months. Low dose 1 alpha-hydroxycholecalciferol may be used effectively for renal osteodystrophy in children with moderate but stable renal failure without jeopardising renal function.     

Insulin pump treatment in children and adolescents with type 1 diabetes

Within children and adolescents with type 1 diabetes insulin pump treatment is of increasing interest. Frequency of insulin pump therapy shows a rapid and steep increase in toddlers and young children. Insulin pumps allow a close to physiologic insulin delivery due to basal rates programmed over 24 hours with circadian rhythms taken into account. Furthermore, another advantage of technical devices as insulin pumps is the application of extremely small amounts of insulin, as needed in very young children, with the possibility of titration of infusion rates down to 0.01E/h. Dawn Phenomenon and hypoglycemic events are main indications for insulin pump treatment in children and adolescents. A significant reduction of severe hypoglycemia, especially nocturnal hypoglycemia was shown, whereas a reduction of HbA1c and an improvement of metabolic control has been reported in short term and in some but not all long term studies. Ketoacidosis rate did not increase in insulin pump therapy. Complications due to continuous subcutaneous insulin infusion, like local infections and dermatological changes are frequent but were not associated with glycemic control and did not lead to discontinuation of insulin pump treatment. Pump discontinuation rate in general is low, varying from 1% in very young children up to 6% in pubertal adolescent girls. Insulin pump treatment was shown to be safe and efficient and the simplicity of handling the devices as well as an improvement of quality of life may explain the rapid increase of pump treatment in young children and adolescents with type 1 diabetes.     

A treatment program for adolescents with phenylketonuria.

A treatment program for adolescents with phenylketonuria (PKU), incorporating education, goal-setting, self-monitoring, contracts, and rewards, was evaluated by measuring knowledge of PKU, blood phenylalanine concentrations, and health locus of control (LOC) before and after participation in the program. Of the 16 subjects, seven subjects successfully completed the program by achieving behavioral goals. These subjects increased their knowledge of PKU and decreased their blood phenylalanine concentrations, but the nine nonsuccessful subjects did not. There was no significant change in LOC scores for either group. There was a significant relationship between baseline blood phenylalanine levels and success with the program. Therefore, this pilot study demonstrates that adolescents who have already achieved some measure of metabolic control can be expected to be most successful with this program and realize the greatest benefits from it in the form of increased knowledge of PKU and even better metabolic control.     

Parathyroid autotransplantation in renal osteodystrophy.

Severe renal osteodystrophy with metaphyseal fractures developed in two children with hypoplastic-dysplastic kidneys and chronic renal failure despite therapy with vitamin D, CaCO3, phosphate-binding agents, and protein restriction. Serum immunoreactive parathyroid hormone (iPTH) levels were elevated to 709 and 1,537 pg/mL (N = 255 +/- 92 pg/mL). Total parathyroidectomy and then autotransplantation of a small portion of parathyroids into the left brachioradialis muscle resulted in complete healing of renal osteodystrophy with the same dose of vitamin D. Serum iPTH and histological studies have demonstrated functioning parathyroid autotransplants, 19 and 20 months postoperatively in these two patients. Advantage of such a procedure over 3 3/4 parathyroidectomy is that this transplanted parathyroid tissue is easily accessible for partial removal in case of recurrence of uncontrollable hyperparathyroidism. We believe that total parathyroidectomy and autotransplantation can be successfully performed even in small children.     

Slipped epiphyses in renal osteodystrophy.

Clinical, biochemical, roentgenological, and histological features of slipped epiphyses (epiphysiolysis) in 11 out of 112 children with renal osteodystrophy have been analysed. Characteristic age-related patterns of involvement of different epiphyses are described. Quantitative measurements of iliac bone histology, serum parathyroid hormone levels, and clinical history show the presence of more advanced osteitis fibrosa in children with epiphysiolysis than in those without. A good correlation was found between serum parathormone levels and osteoclastic resorption, endosteal fibrosis as well as osteoid. Histological studies show that the radiolucent zone between the epiphyseal ossification centre and the metaphysis in x-rays is not caused by accumulation of cartilage and chondro-osteoid (as usually found in vitamin D deficiency rickets) but by the accumulation of woven bone and/or fibrous tissue. The response to vitamin D therapy in most cases was good. Parathyroidectomy was required in only one case.     

Cerebellar-ataxic syndrome in children and adolescents with hypothyroidism under treatment.

Animal experiments and observations on quantitative growth of human cerebellum suggest a critical period when its development is particularly vulnerable to hypothyroidism. Sixty-seven patients aged 7-24 years with hypothyroidism under long-term treatment were examined for ataxic symptoms. These were found in 24 of 39 patients (60%) hypothyroid before or during the third month of life. Only 4 of 18 patients (20%) hypothyroid later had cerebellar symptoms. Such symptoms could be evidence for the onset of hypothyroidism before or during the 3rd month of life. Seventeen (80%) of mentally retarded patients had cerebellar symptoms compared with 11 (30%) of 45 attending normal school. Even retrospectively, these data might permit a more accurate prognosis of further mental development in hypothyroid children.     

Long-term treatment with GHRH [1-44] amide in prepubertal children with classical growth hormone deficiency.

A cohort of 20 GH deficient prepubertal patients were treated with GHRH [1-44] 10 micrograms/kg or 20 micrograms/kg twice daily for up to four years (5 patients). GHRH treatment resulted in sustained improvement in height velocity. The mean prepubertal height velocity was 3.57 +/- 1.05 cm/yr pretreatment; 8.49 +/- 1.45 cm/yr at year 1; 6.86 +/- 1.45 cm/yr at year 2; 6.22 +/- 0.74 cm/yr at year 3; and 6.16 +/- 0.97 cm/yr at year 4. IGF-I levels increased and remained within normal range. The difference between the children's and the parents' Ht SD scores significantly diminished from a pretreatment difference of -2.43 to -0.48 after four years of treatment. No adverse effects were noted during treatment. We conclude that twice-daily GHRH [1-44] treatment in a small group of prepubertal GH deficient children resulted in sustained improvement in height and growth velocity, and achieved height SDS approaching closely those of their parents.     

Renal arteriography in the evaluation of unexplained hypertension in children and adolescents.

Arteriography demonstrated renal artery stenosis in 24% of 101 selected patients whose hypertension was first diagnosed before the age of 20 years. Arteriographic findings were normal in 58%. The prevalence of RAS was greater in the younger than in the older age groups. An abdominal bruit and urographic abnormalities were frequently observed in association with RAS. Adequate follow-up information was available for 16 patients who underwent vascular repair or nephrectomy for RAS. In 14 of the 16, the hypertension was eliminated (81%) or definitely reduced (6%).