Biomedical subjects
A Prader
Publications and source records attributed to A Prader.
Growth and sexual development in children with meningomyelocele.
Forty-five children (25 girls; 20 boys) with meningomyelocele (MMC) were assessed for growth, skeletal maturation and pubertal development. The spinal defects were operated on shortly after birth and all children required cerebral drainage for hydrocephalus. Standard deviation scores for height, sitting height, sub-ischiac leg length, head circumference, weight and bone age were compared with aged-matched data from a normal Swiss population. The children with MMC were shorter (height SDS boys -2.34 +/- 1.57; girls -2.01 +/- 1.57, mean +/- SD, P less than 0.0005), secondary to a decrease in trunk and lower limb length: Arm length was normal. The head circumference was increased, significantly in the girls (SDS + 1.49 +/- 1.21, P less than 0.005). Weight was decreased in both sexes, this being significant in the boys (SDS -1.11 +/- 1.23, P less than 0.005); however, comparison of weight with height suggested that children with MMC were relatively obese. Bone age was significantly advanced in both boys (SDS + 1.07 +/- 2.13, P less than 0.025) and girls (SDS + 1.36 +/- 1.77, P less than 0.0001). Secondary sex characteristics appeared early in both boys and girls and one girl and one boy presented with puberty advanced by several years. Cryptorchidism occurred in 25% of boys with MMC.
Hereditary defects of adrenal cortical steroid biosynthesis.
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Head circumference, height, bone age and weight in 103 children with congenital hypothyroidism before and during thyroid hormone replacement.
Head circumference, height, bone age and weight were studied in 103 children with congenital hypothyroidism before and up to 8 years of thyroid replacement therapy. The patients were divided into 4 groups according to the age at start of treatment: group I (diagnosed by neonatal screening): less than 2 weeks (n = 55); group II: 1-3 months (n = 7); group III: 4-12 months (n = 15); group IV: greater than 1 year of age (n = 26). Before treatment, group I showed a head circumference significantly larger than normal and a delay in bone maturation in the presence of normal length and weight. In the other groups length as well as bone age were significantly lower than normal, head circumference, in contrast, was normal (groups II and III) or even increased (group IV). During therapy, head circumference and bone age of group I became normal as were length and weight from the beginning. In the other groups, therapy led to a further increase of head size resulting in a mean head circumference significantly larger than normal during 8 years of observation in group IV. There was a catch-up of height, bone age and weight in groups II, III and IV; mean height of late treated children (group IV), however, remained significantly lower than normal even after 8 years of therapy. - Our study shows that congenital hypothyroidism is associated with increased head circumference, either absolutely or in relation to stature. Thyroid hormone therapy resulted in a normalization of head growth when treatment was initiated early, and in a further increase when treatment was started late. There was a catch-up of height, bone age and weight; complete normalization, however, occurred only in those children treated before one year of age.
Ovarian steroidogenesis in an adrenalectomized girl with 21-hydroxylase deficiency.
A girl with congenital adrenal hyperplasia due to 21-hydroxylase deficiency could not be controlled by conventional treatment, and was adrenalectomized at age 8.5 years (bone age 13.5 years). After surgery, puberty and menarche occurred. On replacement therapy, her progress was uneventful up to the age of 16 years, when menstruations ceased and signs of virilization reappeared. Testosterone, androstenedione, and 17-hydroxyprogesterone in plasma, and pregnanetriol in urine were high, but DHEA in plasma, and pregnenetriol and pregnanetriolone in urine were low. Oestrogens in plasma were normal. There was no steroid response to ACTH, and marked, but somewhat slow suppression by dexamethasone. HMG induced a strong rise in oestrone and oestradiol. Ethinyloestradiol reduced not only oestradiol in plasma, but also testosterone, androstenedione, and 17-hydroxyprogesterone. With subsequent dexamethasone treatment, menstruation restarted, and the values returned to normal. It is concluded that virilization may reoccur in patients with 21-hydroxylase deficiency even after adrenalectomy, and that the ovaries in this patient contain some tissue, which has properties of adrenal (suppressibility by dexamethasone) and ovarian tissue (suppressibility by ethinyl oestradiol, preference for delta 4-pathway, low steroid 11-oxygenation) at the same time.
Influence of oestrogen in high and low doses on plasma steroid concentrations in girls with tall stature and Turner syndrome.
Plasma DHA, 17-OH-progesterone, androstenedione, testosterone, cortisol, oestrone and oestradiol were determined before and on high dose oestrogen treatment (1, 3, 6 and 16 months) given to excessively tall girls to reduce future adult height. Basal values were normal: DHA 16.4 +/- 0.8 nmol/l (n = 90), 17-OH-progesterone 4.9 +/- 0.3 (n = 20), androstenedione 5.6 +/- 0.3 (n = 25), testosterone 2.6 +/- 0.3 (n = 24) and cortisol 395 +/- 20 (n = 90). On treatment, DHA, 17-OH-progesterone and androstenedione decreased to a minimum of 9.3 +/- 1.0 nmol/l (3 months, n = 13), 2.4 +/- 0.3 (6 months, n = 7) and 2.6 +/- 0.2 (6 months, n = 9), respectively, while testosterone remained unchanged, and cortisol increased to a maximum of 825 +/- 99 nmol/l (16 months, n = 23). In 15 girls with XO gonadal dysgenesis, basal DHA was low (11.8 +/- 1.0 nmol/l), and did not significantly change on low dose oestrogen replacement (13.3 +/- 1.4). The cause of the fall in plasma concentrations of androstenedione, DHA and 17-OH-progesterone in treated tall girls is unknown, but it is speculated that it might be related to peripheral conversion in the augmented adipose tissue mass. The rise in plasma cortisol, on the other hand, is probably due to increased transcortin.
Timing of pubertal growth and maturation in the first Zurich longitudinal growth study.
Definitions and normal age values are given for start, peak and end of the pubertal growth spurt. In spite of a sex difference in chronological age and bone age, general maturity at the start and at the peak of the growth spurt was identical in both sexes, i.e. it occurred at the same stage of skeletal maturation and at the same relative distance from adult height. Normal values for the main steps of sexual maturation are also given. The overall pattern of the growth spurt, skeletal maturation and sexual maturation was strikingly similar in both sexes.
Neonatal severe primary hyperparathyroidism and alkaptonuria in a boy born to related parents with familial hypocalciuric hypercalcemia.
We describe a study of a boy with neonatal severe primary hyperparathyroidism (NSPHP) and alkaptonuria born to related parents of Turkish origin. The clinical and chemical courses (e.g. of mineral metabolism, of urinary excretion of amino acids and collagen metabolites) in response to various therapeutic approaches including total parathyroidectomy (PTX) are reported. Urinary excretion of calcium was unusually low before and immediately after PTX, and later during an inadvertent vitamin D intoxication. It corresponded to values typical for patients with familial hypocalciuric hypercalcemia (FHH), an autosomal dominant disorder. Both parents and one sibling had episodes of hypercalcemia with inappropriately high parathormone levels; in the father there was also relative hypocalciuria consistent with FHH. On the basis of the genetic and pathophysiologic data reported here, we speculate that homozygosity for the 'FHH-gene' is the cause of the life-threatening manifestation of NSPHP, whereas heterozygosity for the same gene leads to FHH, by comparison a mild disorder. The association of the two very rare recessively transmitted disorders, alkaptonuria and NSPHP, is unique; close linkage of the two genes, one coding for homogentisic acid oxidase, the other for the unknown gene product defective in NSPHP, can be suspected.
Idiopathic osteoporosis in a three-year-old girl. Follow-up over a period of 6 years by computed tomography bone densitometry (CT).
In a girl suffering from idiopathic transient osteoporosis the development of vertebral deformation and recovery could be followed from the age of 3.4 to 9.3 years. Computed bone densitometry (CT) revealed values below normal for trabecular bone density (-2.6 SD at 4.3 years and -2.8 SD at 5.3 years) during the clinically symptomatic phase of the disease and normalization after the age of 6 years (-0.2 SD at 6.7 and 9.3 years). Cortical bone mineral parameters measured by CT and metacarpal bone measurements from conventional X-rays showed values at the lower range of normal and only a weak correlation with clinical symptoms, vertebral deformation and recovery, respectively. CT may probably allow to diagnose osteoporosis before the appearance of deformities or fractures; in milder forms of osteoporosis the diagnosis may be possible by CT only.
Insulin-like growth factors I and II, prolactin, and insulin in 19 growth hormone-deficient children with excessive, normal, or decreased longitudinal growth after operation for craniopharyngioma.
We studied insulin-like growth factors (IGF) I and II, prolactin, and the insulin response to arginine in 19 children with craniopharyngioma and documented growth hormone deficiency. Patients were divided into three groups according to their growth rate during the first postoperative year. Seven patients with excessive growth (Group A) had hyperinsulinism, normal IGF values, elevated basal prolactin levels, and a delayed thyrotropin response to thyrotropin-releasing hormone, which was compatible with hypothalamic lesions. In the six patients with normal growth (Group B), the insulin level was low; all other hormone values were similar to those of Group A. In the six patients with decreased growth (Group C), levels of IGF I, insulin, prolactin, and thyrotropin were low, indicating the presence of severe pituitary damage and explaining the failure to grow. Patients in all groups had low or undetectable basal levels of growth hormone. We conclude that in Group B, normal IGF permitted normal growth, and prolactin hypersecretion may have been responsible for normal IGF I values. Excessive growth in Group A may have been caused by hyperinsulinism associated with hyperphagia and obesity of hypothalamic origin.
Presence of H-Y antigen in female patients with sex-chromosome mosaics and absence of testicular tissue.
H-Y antigen was tested in five women with sex chromosome mosaicism and gonadal streaks. Three patients had a 45,X/46,XY or 46,X,der(Y) and two a 45,X/46,X, der(X) chromosome constitution. All patients were H-Y antigen positive. Lack of testis differentiation in these women may be explained by subthreshold expression of H-Y antigen, different H-Y antigen molecules, and/or different tissue distribution of the chromosome mosaicism.
Correlation between testicular tissue and H-Y phenotype in intersex patients.
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Clinical and biochemical variability of congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency. A study of 25 patients.
Twenty five patients (10 males and 15 females) aged 0-23 yr with congenital adrenal hyperplasis due to 11 beta-hydroxylase deficiency were studied. They were divided into 13 classic (group A), and 12 mild (group B) patients. The patients of group A were diagnosed at a younger age and had more severe clinical symptoms (ambiguous genitalia in girls, pseudoprecocious puberty in boys). Two had neonatal salt wasting before treatment, and one gynecomastia. Seven had moderate to severe hypertension. Their mean 3 alpha,17,21-trihydroxy-5 beta-pregnan-20-one (THS) and 3 alpha, 21-dihydroxy-5 beta-pregnane-11,20-dione (THDOC) excretion was 14.2 +/- 4.1 and 7.2 +/- 4.2 mg/m2 . day, respectively. The patients of group B had mostly late onset of symptoms (hirsutism, amenorrhea in girls, pseudoprecocious puberty in boys, tall stature, and advanced bone age in both sexes). One boy had bilateral cryptorchidism. Four had moderate hypertension. In seven patients, THS (5.3 +/- 2.3 mg/m2 . day) and THDOC (3.9 +/- 0.5 mg/m2 . day) responded to ACTH. In five, only THS (4.3 +/- 1.1 mg/m2 . day) responded, but THDOC remained undetectable. It is concluded that the clinical and biochemical expression of 11 beta-hydroxylase deficiency is variable, that hypertension in not directly related to deoxycorticosterone, and that, regardless of the intensity of the defect, there are patients in whom the 11 beta-hydroxylation of 17 alpha-hydroxylated steroids only is impaired, and others in whom both the conversion of 17,20-dihydroxy-4-pregnene-3,20-dione and deoxycorticosterone are reduced.
[Pubertal development: What is normal? What is unusual or pathological? Various fundamental observations].
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Pubertal development in Swiss boys.
Pubertal development between 8 and 18 years is reported in 142 Swiss males of the First Zurich Longitudinal Study (1954-1980). Genital and pubic hair development were rated according to TANNER [14]. Testicular growth was assessed by comparative palpation with the orchiometer of PRADER [10]. The age at which pubertal development was initiated varied between the eighth and the fifteenth year of life. Reaching a testicular volume of 3 ml was found to be the most reliable indicator for the onset of pubertal development. The various pubertal stages of genital and pubic hair development tended to occur at earlier ages in this study than previously reported. This was particularly true for PH6 which was observed in 73% of the boys by age 20. Standard deviations of 1.0 to 1.5 years for the ages at which the pubertal stages were reached reflected the large variations in the timing of pubertal development. The mean duration of genital development was 3.5 +/- 1.1 years, of pubertal penis growth 1.8 +/- 0.7 years, of pubertal testicular growth 3.5 +/- 1.0 years and of pubic hair development 2.7 +/- 1.0 years. Moderate correlations were found between the ages at which genital development, pubic hair development and pubertal testicular growth were initiated. The ages at completion of these pubertal characters and the age at which the peak of the adolescent growth spurt was reached were highly positively correlated with each other. For a given stage of a pubertal character at least 80% of the children were within two successive stages of any other pubertal character, e.g. 87% of the boys were either in G2 or G3 when they reached PH2. No significant relationship between the durations of genital development, pubic hair development and pubertal testicular growth could be established. Likewise no significant relationship could be found between the timing and duration of pubertal development.
Pubertal development in Swiss girls.
Pubertal development between 8 and 18 years is reported in 142 Swiss females of the First Zurich Longitudinal Study (1954-1980). Genital and pubic hair development were rated according to TANNER [9]. Pubertal development was initiated at the earliest between 8 and 9 years and at the latest between 14 and 15 years of age. The first secondary sex character in 53% of the girls was the onset of pubic hair development and in 18% the onset of breast development. In 29% both the initiation of breast and that of pubic hair development were observed as the first pubertal signs. Pubertal development was completed at the earliest between 12 and 13 years and at the latest between 17 and 18 years of age. Most pubertal stages of breast and pubic hair development tended to be reached at earlier ages than previously reported. Omissions of stages occurred only in a few percent of the girls. A notable exception was breast stage 4 which was absent in 33%. Reversions of stages, particularly of breast stage 5 to a lower breast stage, were occasionally observed. The mean duration of breast development was 3.2 +/- 1.4 years and pubic hair development 3.6 +/- 1.1 years. The mean age at menarche was 13.4 +/- 1.0 years. Menarche was reached on the average 2.2 years after the initiation of breast development and 2.7 years after the initiation of pubic hair development. In spite of large variations in timing and duration of pubertal stages some significant relationships were noted between the pubertal characters. Moderate correlations were found between the ages at initiation of breast and pubic hair development and menarche. The ages at completion of breast and pubic hair development, menarche and the age at which the peak of the adolescent growth spurt (PHV) was reached were highly correlated with each other. There was no significant relationship between the duration of breast development and that of pubic hair development. Furthermore, no clear relationship between the timing of pubertal development and its duration could be established. In contrast to previous reports the temporal relationship between pubertal development and the adolescent growth spurt was found to be similar in both sexes.
The SPONASTRIME dysplasia: familial short-limb dwarfism with saddle nose, spinal alterations and metaphyseal striation. Report of 4 siblings.
We report clinical, anthropometric and radiological findings in 4 siblings with a new type of skeletal dysplasia. 4 normally intelligent girls exhibit dwarfism between -3.4 and -4.6 standard deviations with accentuated shortening of the lower limbs, moderate deformity of the vertebral bodies, mildly striated metaphyses, saddle nose, frontal bossing, and relatively large head. The family pedigree suggests autosomal recessive inheritance. We propose the designation of SPONASTRIME dysplasia, derived from spondylar and nasal alterations with striation of the metaphyses.
[Growth of the fetus and child].
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