Charles G. D. Brook

Spatial abilities following prenatal androgen abnormality: targeting and mental rotations performance in individuals with congenital adrenal hyperplasia.

In most mammals, behaviors that show sex differences are influenced by androgen during early life. In the current study, the hypothesis that androgen influences the development of human spatial abilities was investigated. Participants included 40 females and 29 males with congenital adrenal hyperplasia (CAH), a genetic disorder that causes overproduction of adrenal androgens beginning prenatally, and 29 unaffected female and 30 unaffected male relatives of individuals with CAH. Participants ranged in age from 12-45 years. Measures of spatial abilities included two mental rotations tasks and two targeting tasks, all of which showed large sex differences favoring males in the unaffected relative controls. Females with CAH (exposed to higher than normal levels of androgen prenatally) performed better than unaffected females on the targeting tasks, and resembled unaffected males and males with CAH in this respect. However, females with CAH did not perform better than unaffected females on the measures of mental rotations abilities. Males with CAH showed unaltered performance on the targeting tasks, and impaired performance on the mental rotations tasks. Results are discussed in terms of differences in experiential and hormonal contributions to different spatial abilities, as well as in terms of possible differences in critical periods for hormonal influences on targeting versus mental rotations abilities. Specifically, we speculate that, although androgen may influence targeting abilities prenatally, if hormones influence the development of mental rotations ability, they do so at some other time, perhaps during the first six months of postnatal life.

Final height of short normal children treated with growth hormone

BACKGROUND Short-term studies have demonstrated acceleration of growth rate following administration of biosynthetic human growth hormone (r-hGH) to short normal children. We describe the effect of such treatment on final height. METHODS This was an open study of consecutive referrals to a growth disorder clinic from which 16 short children (height standard deviation score [SDS] -2.17 [range -1.8 to -3.3]; height velocity SDS -0.44 [0.33]; peak serum GH response to stimulation 27.9 mU/L [9.2] were treated with r-hGH, and 7 short children who declined treatment (height SDS -2.34 [0.61]; height velocity SDS -0.36 [0.28]; peak serum GH response 28.2 mU/L [6.8]) acted as an observation group. Subcutaneous r-hGH dose ranged between 12.2 and 21.0 U/m2 per week (0.02-0.04 mg/kg per day) for the first 2 years of treatment and 20 U/m2 per week thereafter, 3 untreated children were lost to long-term follow-up. FINDINGS r-hGH significantly increased the difference in final height compared with pretreatment predicted height (+0.42 SDS [0.79], p = 0.03) but this change was not significantly greater than that of the observation group (+0.16 SDS [0.20]). Treatment had no effect on the timing of puberty. Boys progressed slightly faster through puberty, associated with an acceleration in bone-age maturation. No untoward effects on glucose metabolism were observed. Long-term therapy did not alter body-fat distribution or blood pressure. INTERPRETATION Long-term therapy in this group of children appears safe but the small increment in final height, approximately 2.8 cm in boys and 2.5 cm in girls, does not justify the widespread use of r-hGH for short normal children.

Standards for ovarian volume in childhood and puberty

OBJECTIVE To examine the growth of the ovary and the prevalence of polycystic ovaries in childhood and to compare the ovarian volumes of girls with growth disorders. DESIGN A retrospective study of ovarian volume measurements made with ultrasound. SETTING Paediatric Endocrine Outpatient service at The Middlesex Hospital. PATIENTS The control group consisted of girls with no endocrine defect. The study group consisted of girls with GH insufficiency, treated and untreated; skeletal dysplasia (and no endocrine defect) on a trial of recombinant human GH; and tall stature. METHODS The prevalence of polycystic appearance ovaries in the control group was noted. Centiles were calculated for the volumes of normal appearance ovaries in the control group (428 scans from 358 girls). Standard deviation scores were calculated for the ovarian volumes in the study groups. RESULTS There was continuous growth of the ovaries throughout childhood. There was an increase in the prevalence of polycystic ovaries from 6% at 6 years of age, until 26% of the scans showed polycystic ovaries at 15 years of age. The ovarian volume SD score of untreated GH insufficient girls was less than controls but did not achieve statistical significance. It was significantly less than that of GH-insufficient girls on GH, girls with skeletal dysplasia on GH, and girls with tall stature. Tall girls had significantly greater ovarian volume than either of the GH-treated groups. CONCLUSIONS Growth hormone appears to influence ovarian growth. Most women who have polycystic ovarian appearance develop this appearance during childhood and puberty.

Serum Concentrations of the Type I and III Procollagen Propeptides as Biochemical Markers of Growth Velocity in Healthy Infants and Children and in Children with Growth Disorders

ABSTRACT: The reproducibility and specificity of a new, rapid, simple RIA for measuring the concentration of the soluble carboxypropeptide of type I procollagen (PICP) in serum was confirmed. Serum PICP was determined in 442 healthy Caucasian subjects ranging in age from 3 wk to 18 y. Highest PICP values (mean ± SD: 2200 ± 350 μg/L) occurred in infants less than 3 mo of age, falling by 70% at 2 y and by an additional 10% at 4 y. There was no significant change in serum PICP between 4 and 16 y of age (330 ± 130 μg/L), but a decrease to adult levels of <160 μg/L, occurred by 18 y. In 76 children with growth disorders, serum PICP was related to linear growth velocity (p < 0.001), although there were no significant differences in PICP among the 38 children with growth hormone insufficiency, the 21 short children with no endocrinologic abnormality, or the 17 tall children. All 15 prepubertal children treated with growth hormone for 3 mo showed significant increases in both growth velocity and serum PICP, with a significant relationship (p < 0.01) between the degree of increases. The rise in serum PICP at 3 mo (but not baseline PICP values) predicted the increase in growth velocity after 1 y of treatment. Similar changes were observed in the concentration of the aminopropeptide of type III procollagen, except that serum aminopropeptide of type III procollagen showed a definite increase during puberty and a wider spread of values in growth disorders. We conclude that measuring serum PICP by the new, reproducible assay reflects height velocity in prepubertal children and may be a useful biochemical means of monitoring growth rates.

Obesity in 21-hydroxylase deficient patients

OBJECTIVES To evaluate the natural history and timing of adiposity rebound (nadir of body mass index (BMI)) in children with congenital adrenal hyperplasia 21-hydroxylase deficiency (CYP21). STUDY DESIGN A retrospective mixed longitudinal study. METHODS Height and changes in body composition (BMI; weight (kg)/height2 (m)), triceps and subscapular skinfolds) were analysed in 22 (14 girls, eight boys) prepubertal patients with CYP21 for whom continuous anthropometric data were available for at least seven years. BMI and height SD scores were compared at 1, 5, and 10 years of age. Skinfold SD scores were compared at 2.5 and 5.5 years. Thirteen children (nine girls, four boys) had records available from birth which allowed the estimation of the age at adiposity “peak” and “rebound”. RESULTS A significant increase in BMI SD score was found at 5 and 10 years compared with those at 1 year. No significant change in height SD score was observed at these ages. Triceps and skinfold SD score were increased significantly at 5.5 compared with 2.5 years. The “rebound” in BMI SD score took place at 1.74 years (range 0.71–4.57 ) compared with 5.5 years (range 3.5–7.0) in the normal UK population. CONCLUSIONS Normally growing patients with CYP21 increased their BMI throughout childhood. Adiposity rebound took place on average three years earlier than in the general population. These findings suggest that even when well controlled in terms of their disease process, patients with CYP21 are at risk of obesity, which may have important implications for the evolution of reproductive function (polycystic ovaries), diabetes, hypertension, and cardiovascular disease in these subjects.

Increased aggression and activity level in 3- to 11-year-old girls with congenital adrenal hyperplasia (CAH).

Experimental research in a wide range of mammals has documented powerful influences of androgen during early development on brain systems and behaviors that show sex differences. Clinical research in humans suggests similar influences of early androgen concentrations on some behaviors, including childhood play behavior and adult sexual orientation. However, findings have been inconsistent for some other behaviors that show sex differences, including aggression and activity level in children. This inconsistency may reflect small sample sizes and assessment limitations. In the present study, we assessed aggression and activity level in 3- to 11-year-old children with CAH (38 girls, 29 boys) and in their unaffected siblings (25 girls, 21 boys) using a questionnaire that mothers completed to indicate current aggressive behavior and activity level in their children. Data supported the hypotheses that: (1) unaffected boys are more aggressive and active than unaffected girls; (2) girls with CAH are more aggressive and active than their unaffected sisters; and (3) boys with and without CAH are similar to one another in aggression and activity level. These data suggest that early androgens have a masculinizing effect on both aggressive behavior and activity level in girls.

Leptin concentrations in maternal serum and cord blood: relationship to maternal anthropometry and fetal growth

Objective To determine 1. the relationship between maternal serum leptin concentrations and maternal anthropometry and 2. the relationship between cord serum leptin concentrations at birth and neonatal anthropometry.

Personality and congenital adrenal hyperplasia: possible effects of prenatal androgen exposure.

Influences of early androgen exposure on personality were investigated. Participants were either exposed to abnormal levels of androgens prenatally due to congenital adrenal hyperplasia (CAH, 40 females, 29 males), or were unaffected relative controls (29 females, 30 males). Compared to female controls, females with CAH were less tender-minded (p<.001; 16 Personality Factor Inventory (16PF)), and reported greater physical aggression (p=.03; Reinisch Aggression Inventory) and less interest in infants (p<.001; Melsons Questionnaire), but did not differ in dominance (16PF). Males with CAH did not differ from male controls in interest in infants but were less dominant (p=.008), and more tender-minded (p=.033) and reported reduced physical aggression (p=.025). Thus, both males and females with CAH showed alteration in three of the four constructs assessed. Prenatal androgen exposure may shift some, but not all, personality characteristics in the male-typical direction in females. It may also be associated with a decrease in some aspects of male-typical personality development in males, although personality differences in males with CAH could relate to illness.

A Controlled Study of the Psychoanalytic Treatment of Brittle Diabetes

The study compared two equivalent groups of 11 diabetic children with grossly abnormal blood glucose profiles necessitating repeated admissions to a hospital. Patients in the treatment group were offered an intensive inpatient treatment program including psychoanalytic psychotherapy three to four times a week, which took place on the hospital ward and lasted an average of 15 weeks. The intervention was highly effective in improving the diabetic control of the children, and this was maintained at a 1 year follow-up. Patients in the comparison group, who were offered only inpatient medical intervention, returned to their prehospitalization level of metabolic control within a period of 3 months from discharge.

OVARIES IN SEXUAL PRECOCITY

BACKGROUND AND OBJECTIVE Ovarian Uh8SOnOgra‐phy may be helpful in distinguishing the various types of precocious puberty, and the ovarian appearances Increasingly influence choice of therapy In these girls. We examined retrospectively the ovarian volume and prevalence of polycystic ovarian appearance at ultrasound in girls with sexual precocity.