Benign cephalic histiocytosis with diabetes insipidus.

Benign cephalic histiocytosis is a rare skin condition consisting of small tan papules on the face and upper trunk that is believed not to be associated with internal organ involvement. The infiltrating histiocytes are not Langerhans' cells (LCs). We report a 5-year-old girl who presented with diabetes insipidus 1 year after developing multiple small brown asymptomatic skin papules. Histologic examination revealed a non-LC histiocytic proliferation in the dermis without epidermal invasion. She had infiltration of the pituitary stalk on brain imaging. Diabetes insipidus has heretofore been associated with LC histiocytosis and xanthoma disseminatum but not benign cephalic histiocytosis.

Serum prostate specific antigen, sex hormone binding globulin and free androgen index as markers of pubertal development in boys.

OBJECTIVE: Prostate specific antigen (PSA) expression in the prostate gland is regulated by androgens. Serum levels of PSA are undetectable by routine assays in normal boys. Measurable values could serve as a marker for pubertal development. In order to explore this question, we measured serum PSA levels in normal boys throughout puberty and examined the interrelationships with various hormonal and physical developmental changes. DESIGN: Sera from 77 normal boys in Tanner stages I to V (T-I to T-V) were analysed for PSA levels by a sensitive time-resolved fluoro-immunometric assay (sensitivity: 0.012 microgram/l). In addition, sex hormone binding globulin (SHBG), insulin like growth factor I (IGF-I), IGF binding protein 3(IGFBP-3) and testosterone were measured. RESULTS: PSA was detectable in 0% of Stage T-I (n = 16), 33% of T-II (n = 18), 65% of T-III (n = 17) and 100% of T-IV (n = 10) and T-V (n = 16) boys. PSA levels rose significantly according to stage (P < 0.05). Also, there were significant (P < 0.05) increments in serum testosterone, IGF-I and IGFBP-3 levels from stages T-I to T-IV. PSA showed a positive correlation with testosterone (r = 0.86, P < 0.001), IGF-I (r = 0.66, P < 0.001), and IGFBP-3 (r = 0.34, P = 0.004) levels. Both PSA and these analytes, however, showed significant overlap between stages T-I and T-II with only 6/18 (33%) and 12/18 (66%) of T-II subjects having PSA and testosterone levels, respectively, above the T-I range. In contrast, serum SHBG levels decreased markedly from stages I to II (P < 0.001). At the calculated best cut-off point for SHBG of 50 nmol/l, 16/18 T-II subjects had values below the T-I range (sensitivity = 89%). Because of this decrement of SHBG and the increasing testosterone secretion in early puberty, the Free Androgen Index (FAI = Testosterone/SHBG) could even better differentiate the onset of puberty with all except one of the T-II subjects having FAI levels above the T-I range (sensitivity = 94.4%). The decrease of SHBG in T-II subjects coincided with an increase in total body weight (P = 0.001) and body mass index (BMI, P = 0.0003). Despite the continuing pubertal rise in testosterone, SHBG levels showed a rebound increment from T-II-T-III subjects (P = 0.02) with a concomitant decrease in BMI (P = 0.0014). CONCLUSIONS: Prostate specific antigen closely reflects serum free androgen activity during puberty. However, it was unable to differentiate the earliest pubertal development. In comparison, SHBG levels and Free Androgen Index are more sensitive markers for the onset of puberty in boys. The inverse association between SHBG levels and BMI in pubertal stages Tanner stages, I to III suggests that body fatness, via its effect on insulin sensitivity, may play an important role in the regulation of SHBG production during early pubertal development.

Insulin-like growth factor binding protein-I levels are strongly associated with insulin sensitivity and obesity in early pubertal children.

In conditions associated with insulin resistance, insulin-like growth factor binding protein-I (IGFBP-I) levels have been shown to correlate inversely with insulin levels. Puberty is associated with insulin resistance and thus provides a model for comparing the relationship of IGFBP-I to both insulin levels and measures of insulin sensitivity. Our study population consisted of 104 healthy pubertal children, age 9.8-14.6 yr. Each subject had his/her insulin sensitivity (Si) assessed by the modified minimal model of Bergman, which employs a frequently sampled i.v. glucose tolerance test. Results showed that IGFBP-I levels were significantly higher in boys than in pubertally matched girls (P < 0.01). There was a strong positive correlation between IGFBP-I levels and Si (r = 0.65, P < 0.0001) and a weaker negative correlation with fasting insulin levels (r = -0.38, P < 0.0001). An inverse relationship was also found between IGFBP-I levels and body mass index (r = -0.46, P < 0.0001) and with IGF-I levels (girls only, r = -0.41, P < 0.003). Consequently, insulin sensitivity, obesity, and IGF-I are important predictors of IGFBP-I levels in pubertal children. It is possible that insulin-mediated suppression of IGFBP-I in obese children may increase free IGF-I levels and thus contribute to somatic growth. The same mechanism may operate in pubertal children, where insulin resistance and growth acceleration occur simultaneously.

Gender and Tanner stage differences in body composition and insulin sensitivity in early pubertal children.

A cross-sectional analysis examining the impact of gender and early pubertal stage on insulin sensitivity (Si) and body composition was carried out as part of a longitudinal study to determine how Si relates to body composition changes during puberty. The study population consisted of 97 healthy children (age range, 9.7-14.5 yr; 28 Tanner stage 2 boys, 25 stage 3 boys, 22 Tanner stage 2 girls, and 22 stage 3 girls). Si was determined by the modified minimal model of Bergman. Body fatness was assessed by body mass index (BMI), skinfold thickness, hydrodensitometry, and bioelectrical impedance. Results showed that stage 3 girls and stage 2 boys had significantly more body fat than stage 2 girls and stage 3 boys. Si was significantly lower (P < 0.02) and insulin-like growth factor-I levels higher (P < 0.006) in stage 3 girls compared to those in the other 3 groups. The best predictor of Si in all subjects was BMI (r2 = -0.63; P < 0.0001). In a stepwise multiple regression analysis, Si was best predicted from BMI, gender, and Tanner stage. According to this model, Si decreased as BMI increased and was lower in girls and Tanner stage 3 children. In boys, Si was best predicted from total fat mass and Tanner stage. In girls, Si correlated inversely with BMI, parental obesity, and insulin-like growth factor-I levels. Neither testosterone nor estradiol levels were associated with Si. These results demonstrate that Si, like body composition, has gender-dependent changes during puberty. It is, thus, possible that these pubertal changes in Si relate to changes in body composition.