OBJECTIVE: The incidence of congenital hypothyroidism (CH) detected by newborn screening in the US has increased significantly since the early 1990s. We defined the characteristics associated with the increased incidence. PATIENTS: A cohort of children with CH born during an earlier period of low incidence (1991-94) was compared with a cohort born during a later period when the incidence of CH had doubled (2001-04). MEASUREMENTS: Screening was performed with T4 as the primary marker and thyroid stimulating hormone (TSH) on selected specimens. Follow-up on hypothyroid children determined whether they had permanent or transient hypothyroidism. Cases were classified based on laboratory results: initial TSH >/=100 mU/l was 'severe,' initial TSH /l but >/=20 mU/l was 'mild' and initial TSH /l with subsequent abnormal TSH was 'delayed'. RESULTS: The overall incidence of CH almost doubled between the two time periods, from 1:3010 to 1:1660. Excess cases were found in the mild and delayed categories, with no increase in severe cases. The proportion of transient cases was CONCLUSION: The rising incidence of CH in Massachusetts is confined to mild and delayed cases. Our findings suggest that this rise is attributable to enhanced detection rather than an absolute increase in numbers.

BACKGROUND: Studies of regional fat distribution in adults with anorexia nervosa (AN) have shown decreased extremity fat at baseline and increased trunk fat with weight recovery, resulting in truncal adiposity. Little is known about fat distribution in adolescents with AN, especially with weight recovery. OBJECTIVE: We sought to determine whether regional fat distribution in adolescents with AN is comparable with that in healthy adolescents and whether weight recovery results in increased trunk fat and truncal adiposity. DESIGN: In 21 adolescent girls with AN and 21 control subjects matched for age and pubertal stage, we measured body-composition variables with dual-energy X-ray absorptiometry at baseline, 6 mo, and 12 mo. Weight recovery was defined as a > or = 10% increase in body mass index. RESULTS: At baseline, the girls with AN had a lower percentage of trunk fat than did the control subjects, whereas the percentage of extremity fat was not significantly different between the groups. Weight recovery in 13 subjects with AN resulted in an increased percentage of trunk fat and an increased ratio of trunk fat to extremity fat; however, this ratio did not exceed that of control subjects. CONCLUSIONS: In adolescents with AN, trunk fat rather than extremity fat is reduced. Weight recovery is associated with increased trunk fat and an increased ratio of trunk fat to extremity fat. In contrast with previous findings in adults, this most likely represents normalization of fat distribution rather than development of truncal adiposity.

Osteopenia is a frequent, often persistent, complication of anorexia nervosa (AN) in adolescent girls and occurs during a critical time in bone development. Little is known about bone metabolism in this patient population. Therefore, we measured bone density (BMD) and body composition by dual energy x-ray absorptiometry, nutritional status, bone turnover, calcium, and hormonal status in 19 adolescent girls with AN (mean +/- SEM, 16.0+/-0.4 yr) and 19 bone age-matched controls. The mean duration of AN was 19+/-5 months. Spinal (L1-L4) osteopenia was common in AN. Lumbar anterioposterior BMD was more than 1 SD below the mean in 42% of patients, and lateral spine BMD was more than 1 SD below in 63% of patients compared with controls. Lean body mass significantly predicted lumbar bone mineral content (r = 0.75; P < 0.0001) in controls only. In AN, duration of illness was the most significant predictor of spinal BMD (lumbar: r = -0.44; P = 0.06; lateral: r = -0.59; P = 0.008). AN adolescents with mature BA (15 yr and greater) were hypogonadal [estradiol, 16.2+/-1.9 vs. 23.3+/-1.6 pg/mL (P = 0.01); free testosterone, 0.70+/-0.17 vs. 1.36+/-0.14 pg/mL (P = 0.01)] although dehydroepiandrosterone sulfate and urinary free cortisol levels did not differ. Leptin levels were reduced in AN (2.9+/-2.1 vs. 16.5+/-1.8 ng/mL; P < 0.0001). Insulin-like growth factor I (IGF-I) was reduced in AN to 50% of control levels (219+/-41 vs. 511+/-35 ng/mL; P < 0.0001) and correlated with all measures of nutritional status, particularly leptin (r = 0.80; P < 0.0001). Surrogate markers of bone formation, serum osteocalcin (OC) and bone-specific alkaline phosphatase (BSAP), were significantly (P = 0.02) reduced in AN vs. controls (OC, 39.1+/-6.4 vs. 59.2+/-5.2 ng/mL; BSAP, 27.9+/-4.0 vs. 40.6+/-3.4 U/L). The majority of the variation in bone formation in AN was due to IGF-I levels (OC: r2 = 0.72; P = 0.002; BSAP: r2 = 0.53; P = 0.01) in stepwise regression analyses. Bone resorption was comparable in patients and controls. These data demonstrate that bone formation is reduced and uncoupled to bone resorption in mature adolescents with AN in association with low bone density. Lean body mass was a significant predictor of BMD in controls, but not AN patients. The major correlate of bone formation in AN was the nutritionally dependent bone trophic factor, IGF-I. Reduced IGF-I during the critical period of bone mineral accumulation may be an important factor in the development of osteopenia in adolescents with AN.