Discordance of congenital bilateral anorchia in uniovular twins: 17 years of observations on growth and development.

We have reported observations of growth and development made over a 16-year period on a subject who suffered bilateral congenital anorchia and his uniovular twin brother. The anorchic individual was treated with oxandrolone for a period of 3.6 years prior to the testosterone replacement therapy. The oxandrolone therapy produced a significant increment in the height age without excessive gain in bone age. At the age of 20.9 years the anorchic twin is 5.4 cm taller than his normal twin. Other differences observed between the twins reported here include the following: the anorchic subject had longer extremities, greater biacromial and biiliac distances and a smaller penis than his normal sibling. Oxandrolone therapy does appear to modify the ultimate height in children.

Cloprednol therapy in steroid-dependent asthma.

Cloprednol is a new oral corticosteroid with a short half-life that is presently under investigation for use in asthma. Seventeen steroid-dependent children and adolescents were switched from daily treatment with prednisone to cloprednol for a one-year study. Patients showed a statistically significant improvement in symptoms while receiving cloprednol therapy. Two patients had extraordinarily good responses. Growth trends, bone age, and chest roentgenograms were not remarkably changed by cloprednol. Pulmonary function was stable. There was a significant improvement in fasting morning cortisol levels and ability to respond to metyrapone and adrenocorticotropic hormone (ACTH) challenge. Cloprednol appears to be a promising drug for steroid-dependent patients who require oral corticosteroid therapy.

Studies of anabolic steroids: v. effect of prolonged oxandrolone administration on growth in children and adolescents with uncomplicated short stature.

A total of 130 patients with uncomplicated short stature (4 to 17 years of age) were treated with oxandrolone, 0.25 mg/kg/day, for up to four years. Oxandrolone therapy resulted in a two-fold increase in mean growth velocity in the first six months of therapy and was an effective growth stimulant for the full four-year period. There was no overall adverse effect of oxandrolone on post-treatment mean growth velocity or on skeletal maturation relative to height gain. There were 37 patients with greater increase in height age than bone age and 22 patients with greater increase in bone age than height age. Assessment of the contribution of oxandrolone therapy to the latter group is difficult because of inadequate methodology and the wide variation in individual growth patterns. Taken in their entirety, the data suggest that oxandrolone is useful in the prolonged treatment of uncomplicated short stature and is not associated with undesirable acceleration of skeletal maturation.

Pulmonary and endocrine function before and after therapy with cromolyn sodium in asthma. Studies in steroid-dependent and nonsteroid-dependent asthmatic children and adolescents.

This study evaluated growth, chest radiographic manifestations, pulmonary function, and function of the pituitary-adrenal axis before and after therapy with cromolyn sodium in two groups of asthmatic youngsters, ie, 18 steroid-dependent patients and ten nonsteroid-dependent patients. The following three groups evolved: (1) steroid-dependent patients; (2) patients weaned from therapy with steroids; and (3) nonsteroid-dependent patients. Growth failure and cataracts were limited to the steroid-dependent group, while abnormalities of the lungs and pituitary-adrenal axis occurred in all three groups. Symptomatic benefits from therapy with cromolyn were striking for all groups. Chest x-ray films and the distribution of alveolar ventilation were more likely to reflect this clinical improvement than tests of pulmonary function and analyses of blood gas levels. Endocrine abnormalities in the steroid-dependent group were significant and were not quickly reversed by withdrawal of therapy with steroids. Even nonsteroid-dependent patients had abnormalities which may be related to having chronic asthma. Therapy with cromolyn seemed to promote some restoration of the function of the pituitary-adrenal axis, as indicated by better responsiveness to administration of metyrapone, which correlated with improved symptomatic control of asthma.

Children who age rapidly--progeroid syndromes: case report of a new variant.

A case report of an apparently unique progeroid syndrome is reported here. Major clinical characteristics included growth failure with onset of senility in the early teens, atrophic skin, hypogonadism, and retinal and vascular sclerosis. Mental retardation was present, but could have been attributable to trauma. The replicative life spans of several lines of cultured skin fibroblasts were within the normal range, in contrast to the limited life-spans of such cultures from patients with Werner's syndrome, whom our patient most closely resembles. Also, in contrast to Werner's syndrome, our patient did not have white or gray hair or cataracts.

Ultrastructural changes induced by chronic aflatoxicosis in chickens.

Effects in chickens of a low concentration of aflatoxin in the diet were investigated. After eight weeks, heart, pancreas, and liver tissues were examined by electron microscopy. Most damage was to liver; changes were observed both in individual parenchymal cells and in tissue organization. Proliferation of bile duct epithelial cells was extensive. The pancreas showed little change and was, therefore, a good organ for observation of early and/or mild ultrastructural changes associated with aflatoxicosis. The priority of initial nuclear change over cytoplasmic change was indicated in this organ. In the myocardium, the only significant changes were in mitochondria. Mitochondria of liver and pancreas were not altered. Leukoviruses were observed in the tissues of one aflatoxin-treated bird.

Use of anabolic agents in treatment of short children.

As indicated in previous sections of this review, all anabolic steroids produce acceleration in linear growth in children with short stature. However, the rapid masculinization induced by testosterone and other anabolic steroids and especially the disproportionately rapid epiphyseal maturation produced by these compounds have brought this form of therapy for short stature into disrepute. Not all investigators concur that testosterone therapy inevitably results in reduction of eventual adult height attainment and, depending on the age of onset of therapy and the dose employed, it has been reported that adult height attainment equals or exceeds the adult height prediction at the time of instituting therapy. Attempts to synthesize anabolic steroids with improved anabolic/androgenic ratios have been continuing for many years. Among currently available anabolic steroids it appears that the best separation of anabolic and androgenic properties has been attained with oxandrolone. This is reflected by the fact that most recent studies of growth promotion by anabolic steroids have employed this compound. From the results of these studies, it appears that doses of this drug capable of significant stimulation of growth generally do not cause excessive masculinization or unacceptably rapid acceleration of epiphyseal maturation and do not compromise eventual height attainment. Certain studies mentioned above suggest that it might be possible to devise therapeutic programmes employing other anabolic steroids which would produce equally satisfactory results. However, because of the more favourable anabolic/androgenic ratio of oxandrolone it seems likely that the increasing trend toward use of this drug for growth promotion will continue.

Simulated congenital adrenal hyperplasia in a male neonate associated with medroxyprogesterone therapy during pregnancy.

PIP: A case report of stimulated congenital adrenal hyperplasia in a newborn male following a medroxyprogesterone-treated pregnancy is presented. Because of intermittent vaginal spotting, the 26-year-old multiparous mother was administered 10 mg medroxyprogesterone acetate daily from Week 20 to Week 32 of gestation. At birth the child displayed early symptoms of hyperglycemia and idiopathic hyperbilirubinemia. At 17 days of age genital hyperpigmentation and penile enlargement were noted and tests revealed hypochloremic metabolic acidosis with hyponatremia. Urinary androgens were high but glucocoritcoids and pregnanetriol were normal. Desoxycorticosterone acetate supplemental salt were administered. After 28 days of age the infant developed normally without hypoglycemia or hyponatremia and the hyperpigmentation and penile enlargement disappeared. It is speculated that the infant could have undergone temporary underproduction of gluco-and mineralocorticoid" and overproduction of androgens that was induced by the mother's medroxyprogesterone treatment. Though the evidence for such a relationship in this case in not conclusive, further study should be conducted.^ieng

Androgen Therapy in an "excessively" tall boy.

An "excessively" tall, early pubertal boy was treated with androgen for a period of 33 months. Sexual development and fusion of epiphyses was accelerated with achievement of shorter stature than that predicted prior to therapy. Testicular size did not appear to be impaired by the therapy. Androgen administration in this young boy appeared to be effective in shortening the eventual adult stature.

Epilepsy and abnormal calcium metabolism in institutionalized mentally retarded patients.

A group of epileptic and nonepileptic patients from an institution for mentally retarded persons was surveyed for roentgenographic and biochemical abnormalities of calcium metabolism. Osteoporosis, hypocalcemia, and increased alkaline phosphatase were found to be significantly increased in incidence in the epileptic group. The only significant difference among the osteoporotic and nonosteoportic epileptic patients was the increase fo the alkaline phosphatase in the former. Ambulation did not appear to influence the significance of the above parameters.

Prevalence of thyroid disorder in Down syndrome.

Thyroid function has been studied in 121 patients between 13 and 48 years old with proven Down syndrome. Chemically, hypothyroidism was found in 17% and hyperthyroidism in 2.5% of the patients; 18% of patients had goiter. Thyroid antibodies were detected in 33% of subjects studied. The abnormal findings were almost equally distributed between the sexes above 20 years of age; however, females had significantly more thyroid disease than males in the younger age group.

Some aspects of carbohydrate metabolism in Prader-Willi syndrome.

Three patients with Prader-Willi syndrome are reported. The subjects presented chemical diabetes mellitus. All patients were hypersentsiive to exogenous insulin and they showed poor adrenal medullary response to hypoglycaemics. It was postulated that the poor adrenal medullary response to the insulin injection may be a contributing factor in the excessive hypoglycaemic response, and that the diabetes mellitus observed in the patients could be due to inactivation of endogenous insulin.

Plasma somatomedin-C as a screening test for growth hormone deficiency in children and adolescents.

Random plasma somatomedin-C (SM-C) levels were measured in 143 children and adolescents with growth at or below the 5th percentile. 124 patients had short stature due to constitutional delay or genetic predisposition and 19 patients were growth hormone deficient (GHD). When analyzed according to bone age, mean somatomedin-C levels rose gradually with increasing bone age in non-GHD patients, while there was no change with increasing bone age in GHD patients. All patients with SM-C levels less than 0.05 U/ml underwent growth hormone testing to rule out GHD. This criterion resulted in 52% accuracy in identifying non-GHD patients and 100% accuracy in identifying GHD patients. Comparison of the SM-C test with the exercise GH screening test demonstrated the advantage of greater convenience for the SM-C test, and comparable cost effectiveness despite a lower specificity associated with the SM-C test. SM-C levels were not predictive of peak growth hormone response nor could they be used to differentiate constitutional delay of growth and maturation from genetic short stature.

Detection of heterozygotes for congenital adrenal hyperplasia: 21-hydroxylase deficiency-a comparison of HLA typing and 17-OH progesterone response to ACTH infusion.

We have studied nine families in which at least one member has congenital adrenal hyperplasia, to compare the predictive value of HLA typing and the 17-hydroxy progesterone response to ACTH as methods for detection of heterozygotes. In each of six families, two children were affected and were HLA genotypically identical. None of the unaffected siblings were HLA identical with their affected siblings. When the 17-OHP response to ACTH and the HLA haplotypes of parents and unaffected siblings were compared, there was a 79% concordance for identification of heterozygotes. Two siblings were carriers according to HLA typing, but had normal 17-OHP responses consistent with the carrier state. Three individuals with recombinations involving the HLA region of chromosome number 6 were detected. Analysis of these recombinant individuals provided additional evidence suggesting that the 21-OH degrees gene is closely associated with the B-locus of HLA. When an affected individual has been identified, HLA typing is a direct and reliable method for determining the carrier state among family members.

Physiology of steroid dependent and non-steroid dependent asthmatic youths.

This study was designed to compare physical findings, pulmonary function and pituitary-adrenal function in steroid dependent (SD) and non-steroid dependent (NSD) children and adolescents in order to clarify similarities and differences between these groups. Study patients included 20 steroid dependent and 14 non-steroid dependent subjects. Abnormalities confined to the SD group included growth suppression, bone age retardation and cataracts. Pulmonary function abnormalities were severe in both groups. While the SD group also showed a degree of pituitary-adrenal abnormality. This suggests that chronic pulmonary disease may have physiologic consequences extending beyond the pulmonary tree.

Studies of anabolic steroids. VI. Effect of prolonged administration of oxandrolone on growth in children and adolescents with gonadal dysgenesis.

Twenty-five patients with Turner Syndrome were treated with oxandrolone for six or more months. Mean growth velocity for the first year of treatment was significantly greater than pretreatment control growth velocity. Overall, there was no excessive skeletal maturation. Mean "final" height in nine XO patients (146.4 cm) was significantly greater than mean adult height of an estrogen-treated control group (140.3 cm), while that for five mosaic patients (148.2 cm) was not significantly different from a mean untreated mosaic adult height (145.2 cm).

Studies of the development of congenital anomalies in rats. III. Effects of inhibition of mitochondrial energy systems on embryonic development.

Pregnant rats were treated with various inhibitors of mitochondrial oxidative energy metabolism and with lowered oxygen tension, and the embryo fetuses examined for the occurrence of congenital malformations and for changes in enzymatic activities. Treatment with all agents tested resulted in the production of skeletal anomalies. Sodium phenobarbital was the most teratogenic of the drugs tested and produced a high incidence of malformations which included cleft palate, tail anomalies, spinal retroflexion, domed head, and facial hypoplasia. Diphenylhydantoin produced a low incidence of syndactyly and oligodactyly. In addition to its effects on fetal growth and development chloramphenicol appeared to interfere with implantation. Tissue preparations from embryos exposed to sodium phenobarbital and chloramphenicol showed markedly lowered levels of DPNH oxidase activity. Cytochrome oxidase activity was also markedly lowered in the preparations from chloramphenicol-exposed embryos. Enzyme activities in preparations from embryos exposed to malonate and diphenylhydantoin appeared unaffected, although the drugs are strong inhibitors of electron transport in vitro; the lack of apparent effect may be due to the fact that both drugs do not bind to the enzyme preparations and were diluted 100- to 200-fold during preparation and assay of the tissue homogenates.