Policy challenges in the fight against childhood obesity: low adherence in San Diego area schools to the California Education Code regulating physical education.

OBJECTIVE: Assess the adherence to the Physical Education (PE) requirements per California Education Code in San Diego area schools. METHODS: Surveys were administered anonymously to children and adolescents capable of physical activity, visiting a specialty clinic at Rady Children's Hospital San Diego. The main questions asked were their gender, grade, PE classes per week, and time spent doing PE. RESULTS: 324 surveys were filled, with 36 charter-school students not having to abide by state code excluded. We report on 288 students (59% females), mostly Hispanic (43%) or Caucasian (34%). In grades 1-6, 66.7% reported under the 200 min per 10 school days required by the PE code. Only 20.7% had daily PE. Average PE days/week was 2.6. In grades 7-12, 42.2% had reported under the 400 min per 10 school days required. Daily PE was noted in 47.8%. Average PE days/week was 3.4. Almost 17% had no PE, more so in the final two grades of high school (45.7%). CONCLUSIONS: There is low adherence to the California Physical Education mandate in the San Diego area, contributing to poor fitness and obesity. Lack of adequate PE is most evident in grades 1-6 and grades 11-12. Better resources, awareness, and enforcement are crucial.

Greater prevalence of iron deficiency in overweight and obese children and adolescents.

OBJECTIVE: To assess whether overweight children and adolescents, who often have poor dietary habits, are at increased risk of iron deficiency (ID). METHODS: The study sample included 321 children and adolescents followed in two endocrine centers in Israel between 1999 and 2001. The subjects were divided into three groups on the basis of body mass index (BMI) for age and gender as follows: group 1-BMI below 85th percentile (normal weight); group 2-BMI above 85th, but below 97th percentile (overweight); and group 3-BMI above 97th percentile (obese). ID was defined as iron levels <8 micromol/l (45 mcg/dl), and iron-deficiency anemia (IDA) was defined as ID and hemoglobin level below 2 standard deviation score (SDS) for the mean for age and gender. RESULTS: Iron levels below 8 micromol/l (45 mcg/dl) were noted in 38.8% of the obese children and 12.1% of the overweight children, compared with 4.4% of the normal-weight group (P<0.001). There was a significant negative correlation of low iron levels with BMI SDS (r=-0.44, P<0.001), but not with age or gender. Among the children with ID, 26.6% also had IDA. Groups 1, 2, and 3 accounted for 6.7%, 35%, and 58.3% of the children with IDA, respectively. CONCLUSIONS: ID is common in overweight and obese children. A significantly greater proportion of obese than normal-weight children have IDA. Insufficient dietary intake of iron, whether absolute or relative to body mass, and increased iron needs may be a result of unbalanced nutrition or repeated short-term restrictive diets. Because of potentially harmful effects of ID, obese children should be routinely screened and treated as necessary.

Resistance to multiple steroids in two sisters.

A 14-year-old Native American girl from the Iroquois Nation was referred as a potential patient with the syndrome of Apparent Mineralocorticoid Excess. Instead, her evaluation revealed resistance to glucocorticoids, mineralocorticoids, and androgens. She lacked Cushingoid features in spite of significantly high cortisol levels. Menstruation was regular and there was no clinical evidence of masculinization despite high serum androgen levels in the male range. The patient's sister had similar clinical features. Partial resistance to exogenous glucocorticoid and mineralocorticoid administration was well demonstrated in both patients. It is proposed that these patients represent the first cases of partial resistance to multiple steroids, possibly owing to a coactivator defect.

Graves' disease in childhood.

The vast majority of thyrotoxicosis cases in children are caused by Graves' disease (GD) and these account for 10-15% of all childhood thyroid diseases. The major clinical features of thyrotoxicosis in children are, in general, similar to those in adults. As in adults, the three conventional methods of treatment are antithyroid drugs (ATD), thyroidectomy and ablative radioiodine (131I). Although ATD are associated with side effects and a high relapse rate even after prolonged therapy, they still seem to be chosen as the first line of therapy for GD in childhood by most pediatric endocrinologists, although some have started using 131I as their first therapeutic modality. However, when ATD therapy has to be discontinued, or after relapse which may occur during or following ATD therapy, a definitive mode of therapy has to be chosen. Since thyroidectomy has the disadvantages of hospitalization and surgical complications, there is now an increasing tendency to advocate radioiodine as a choice of treatment in children older than five years old who achieve a high rate of remission. It should be kept in mind that with both thyroidectomy and radioiodine treatment, permanent hypothyroidism is very common and requires lifelong replacement therapy. According to the long-term follow-up data which have been published, radioiodine treatment in older children and adolescents seems to be safe and effective. Although studies of children with GD treated with ablative doses of radioiodine have not revealed an apparent increased risk of thyroid malignancy, a long-term study of larger populations is needed in order to define the true incidence of thyroid neoplasia, and other possible side effects, in children treated with radioiodine. Although the relatively low risks, low cost and practicability of radioiodine treatment has favored this therapy for children, as it has for adults, in the United States, it is still less attractive for European physicians. Progress in the immunological understanding of GD and of its genetic background will hopefully elucidate the pathways leading to GD, as well as the factors determining who is at high risk of developing GD, and may thus ultimately promote novel strategies for a more successful and safe therapy.

Long-term mifepristone (RU486) therapy resulting in massive benign endometrial hyperplasia.

Mifepristone (RU486) is a potent antiprogestagen, and at high doses it also acts as an antiglucocorticoid drug. Mifepristone, administered as a single 600 mg dose, is commonly employed to induce medical abortion in conjunction with prostaglandins. The long-term safety profile of mifepristone, especially at high doses, is less well-established. Long-term mifepristone is considered efficacious in treating uterine myomas, endometriosis (25--100 mg/day), and possibly in inoperable meningiomas (200 mg/day), as well as inoperable Cushing's syndrome. Many animal studies document an antiproliferative effect (antioestrogenic), as do some reports in humans. However, there are also data to suggest that, as an antiprogestagen, mifepristone may promote an unopposed oestrogen milieu, and thus have a proliferative effect upon the endometrium. We hereby describe the first reported case of an adolescent female with Cushingoid features and morbid osteoporosis who was treated with mifepristone for its antiglucocorticoid effect (400 mg/day) in an attempt to prevent further bone loss. The patient's striae, weight gain, and buffalo hump markedly improved, and further bone loss was halted. However, with each of the two 6-month courses of mifepristone (9 months apart) she developed massive simple endometrial hyperplasia and a markedly enlarged uterus. This reversed to normal after cessation of mifepristone treatment. In conclusion, High doses of the antiprogestagen mifepristone over a prolonged period of time may promote an unopposed oestrogen milieu leading to endometrial hyperplasia. Therefore, interval pelvic imaging in women who receive long-term mifepristone may be prudent.

Normocortisolemic Cushing's syndrome initially presenting with increased glucocorticoid receptor numbers.

A girl who developed Cushingoid features in peripuberty, but was eucortisolemic, was previously reported to have markedly elevated lymphocyte glucocorticoid receptor sites per cell with normal binding affinity as a potential cause of her phenotype. Her circadian rhythm of cortisol and pituitary-adrenal axis were initially intact, but later proved to be dysregulated. The patient presented at age 10.8 yr with centripetal obesity, moon facies, buffalo hump, and purple striae, but no statural stunting, which is a cardinal sign of Cushing's syndrome. At 11.5 yr she suffered a compression fracture of the L1 vertebra. That prompted treatment with the antiprogestin drug mifepristone (RU486), which was administered at high dose to achieve an antiglucocorticoid effect. From ages 13.75 yr through 15.5 yr, RU486 was administered in various intervals to suppress her Cushingoid features. Once RU486 was introduced, however, a consistent correlation over time between the Cushingoid features and glucocorticoid receptor sites per cell was no longer observed. However, the number of glucocorticoid receptor sites per cell tended to decrease in response to administering RU486. Ultimately, her Cushingoid phenotype proved to be transient.

Resistance to several steroids in two sisters.

A 14-yr-old native American girl from the Iroquois Nation was referred as a potential patient with the syndrome of apparent mineralocorticoid excess. Instead, her evaluation revealed resistance to glucocorticoids, mineralocorticoids, and androgens, but no resistance to vitamin D or thyroid hormones. She lacked Cushingoid features despite significantly high cortisol levels. Menstruation was regular, and there was no clinical evidence of masculinization despite high serum androgen levels in the male range. The patient's sister had similar clinical features. Partial resistance to exogenous glucocorticoid and mineralocorticoid administration was well demonstrated in both patients. It is proposed that these patients represent the first cases of partial resistance to multiple steroids, possibly due to a coactivator defect.

Prenatal diagnosis and treatment of 11beta-hydroxylase deficiency congenital adrenal hyperplasia resulting in normal female genitalia.

Congenital adrenal hyperplasia (CAH) consists of autosomal recessive disorders of cortisol biosynthesis, which in the majority of cases result from 21-hydroxylase deficiency. Another enzymatic defect causing CAH is 11beta-hydroxylase deficiency. In both forms, the resulting excessive androgen secretion causes genital virilization of the female fetus. For over 10 yr female fetuses affected with 21-hydroxylase deficiency have been safely and successfully prenatally treated with dexamethasone. We report here the first successful prenatal treatment with dexamethasone of an affected female with 11beta-hydroxylase deficiency CAH. The family had two girls affected with 1beta-hydroxylase deficiency born with severe ambiguous genitalia who were both homozygous for the T318M mutation in the CYP11B1 gene, which codes for the 11beta-hydroxylase enzyme. In the third pregnancy in this family, the female fetus was treated in utero by administering dexamethasone to the mother, starting at 5 weeks gestation. The treatment was successful, as the newborn was not virilized and had normal female external genitalia. A second family with two affected sons was also studied in preparation for a future pregnancy. We report a novel 1-bp deletion in codon 394 (R394delta1) in the CYP11B1 gene in this family.

Examination of genotype and phenotype relationships in 14 patients with apparent mineralocorticoid excess.

Apparent mineralocorticoid excess (AME) is a genetic disorder causing pre- and postnatal growth failure, juvenile hypertension, hypokalemic metabolic alkalosis, and hyporeninemic hypoaldosteronism due to a deficiency of 11 beta-hydroxysteroid dehydrogenase type 2 enzyme activity (11 beta HSD2). The 11 beta HSD2 enzyme is responsible for the conversion of cortisol to the inactive metabolite cortisone and therefore protects the mineralocorticoid receptors from cortisol intoxication. Several homozygous mutations are associated with this potentially fatal disease. We have examined the phenotype, biochemical features, and genotype of 14 patients with AME. All of the patients had characteristic signs of a severe 11 beta HSD2 defect. Birth weights were significantly lower than those of their unaffected sibs. The patients were short, underweight, and hypertensive for age. Variable damage of one or more organs (kidneys, retina, heart, and central nervous system) was found in all of the patients except one. The follow-up studies of end-organ damage after 2-13 yr of treatment in six patients demonstrated significant improvement in all patients. The urinary metabolites of cortisol demonstrated an abnormal ratio with predominance of cortisol metabolites, i.e. tetrahydrocortisol plus 5 alpha-tetrahydrocortisol/tetrahydrocortisone was 6.7-33, whereas the normal ratio is 1.0. Infusion of [11-3H]cortisol resulted in little release of tritiated water, indicating the failure of the conversion of cortisol to cortisone. Thirteen mutations in the HSD11B2 gene have been previously published, and we report three new genetic mutations in two patients, one of whom was previously unreported. All of the patients had homozygous defects except one, who was a compound heterozygote. Our first case had one of the most severe mutations, resulting in the truncation of the enzyme 11 beta HSD2, and died at the age of 16 yr while receiving treatment. Three patients with identical homozygous mutations from different families had varying degrees of severity of clinical and biochemical features. Due to the small number of patients with identical mutations, it is difficult to correlate genotype with phenotype. In some cases, early and vigilant treatment of AME patients may prevent or improve the morbidity and mortality of end-organ damage such as renal or cardiovascular damage and retinopathy. The outcome of treatment in more patients may establish the efficacy of treatment.

Eikenella corrodens infections. Case report in two adolescent females with IDDM.

OBJECTIVE: To alert physicians caring for patients with diabetes to the microorganism Eikenella corrodens and to discuss the appropriate preventive and therapeutic measures to take against this potentially morbid opportunistic Gram-negative bacilli. CASES: We present two cases of extra-oral E. corrodens infections in adolescent females with IDDM. The first patient had diabetes of 4 years' duration, which was moderately well controlled. Chronic finger biting resulted in a complex felon that evolved gradually and worsened while the patient received cephalexin orally. Delay in seeking further intervention resulted in necrosis of her distal fingertip and nail bed. The second patient had poorly controlled diabetes for 5 years. She developed an acute thigh abscess at an insulin injection site that resolved after drainage and intravenous antibiotics. CONCLUSIONS: E. corrodens commonly inhabits the human oral cavity and becomes a pathogen mostly when host defenses are impaired, causing abscesses and infections that are at times fatal. Patients with IDDM are compromised hosts and with daily microtrauma to their skin via glucose monitoring and insulin injections, are prone to develop E. corrodens infections that can be introduced through oral secretions by licking or biting their skin. Educational efforts aimed at preventing exposure of traumatized skin to oral secretions can minimize the risk of E. corrodens infections in compromised hosts. Early intravenous administration of antibiotics, bearing in mind E. corrodens resistance to clindamycin, metronidazole, and other antibiotics, coupled with prompt surgical intervention, is essential in successfully managing E. corrodens infections.