RESUMO
Growth hormone (GH) and insulin like growth factor-I (IGFI) are key bone trophic hormones, whose rising levels during puberty are critical for pubertal bone accrual. Conditions of GH deficiency and genetic resistance impact cortical and trabecular bone deleteriously with reduced estimates of bone strength. In humans, conditions of undernutrition (as in anorexia nervosa (AN), or subsequent to chronic illnesses) are associated with low IGF-I levels, which correlate with disease severity, and also with lower bone mineral density (BMD), impaired bone structure and lower strength estimates. In adolescents and adults with AN, studies have demonstrated a nutritionally acquired GH resistance with low IGF-I levels despite high concentrations of GH. IGF-I levels go up with increasing body weight, and are associated with rising levels of bone turnover markers. In short-term studies lasting 6-10 days, recombinant human IGF-I (rhIGF-I) administration in physiologic replacement doses normalized IGF-I levels and increased levels of bone formation markers in both adults and adolescents with AN. In a randomized controlled trial in adults with AN in which participants were randomized to one of four arms: (i) rhIGF-I with oral estrogen-progesterone (EP), (ii) rhIGF-I alone, (iii) EP alone, or (iv) neither for 9 months, a significant increase in bone formation markers was noted in the groups that received rhIGF-I, and a significant decrease in bone resorption markers in the groups that received EP. The group that received both rhIGF-I and EP had a significant increase in bone density at the spine and hip compared to the group that received neither. Side effects were minimal, with no documented fingerstick glucose of <50 mg/dl. These data thus suggest a potential role for rhIGF-I administration in optimizing bone accrual in states of undernutrition associated with low IGF-I.
Assuntos
Densidade Óssea , Doenças Ósseas/tratamento farmacológico , Hormônio do Crescimento Humano/administração & dosagem , Fator de Crescimento Insulin-Like I/administração & dosagem , Proteínas Recombinantes/administração & dosagem , Animais , Doenças Ósseas/metabolismo , HumanosRESUMO
OBJECTIVE: To test the hypothesis that bone accrual over a 4-year period is reduced in boys with autism spectrum disorder (ASD) compared with typically developing controls. STUDY DESIGN: Twenty-five boys with ASD and 24 controls were assessed for bone outcomes. Fourteen boys with ASD and 11 controls were assessed both at baseline and after 4 years. The mean subject age was 11.0 ± 1.6 years at study initiation and 14.9 ± 1.6 years at follow-up. Bone mineral density (BMD) was measured at the spine, hip, and whole body using dual-energy X-ray absorptiometry and normalized for age, race, and sex (BMD z-scores). Height adjustments were performed as well. We assessed medical history, physical activity using questionnaires, vitamin D and calcium intake using food records, and serum calcium, phosphorus, 25(OH)-vitamin D, and pubertal hormone levels. RESULTS: Boys with ASD had lower spine, hip, and whole body BMD z-scores compared with controls. In those subjects assessed both at baseline and after 4 years, bone accrual rates did not differ between the 2 groups; however, spine and hip BMD z-scores remained lower in the boys with ASD than in controls at follow-up. Notably, the ASD group was less physically active at both time points. CONCLUSION: Although pubertal bone accrual was similar to that in controls, BMD in children with ASD remained low over a 4-year follow-up period, suggesting that low BMD is a consequence of prepubertal factors, such as low physical activity. Studies are needed to investigate the causes and consequences of decreased BMD, to assess BMD in females and adults with ASD, and to evaluate therapeutic interventions.
Assuntos
Transtorno do Espectro Autista/complicações , Densidade Óssea , Osso e Ossos/fisiopatologia , Absorciometria de Fóton/métodos , Adolescente , Criança , Exercício Físico , Humanos , MasculinoRESUMO
OBJECTIVE: To examine whether current recommendations for thyroid status monitoring in children with congenital hypothyroidism (CH) (monthly in the first 6 months and every 3-4 months subsequently) are adequate, or whether monthly monitoring is necessary throughout the first year. STUDY DESIGN: We reviewed charts of 70 children with CH for initial thyroid-stimulating hormone (TSH), frequency of follow-up, dose changes, and thyroxine (T(4)) and TSH levels in the first year. Need for monthly monitoring was determined on the basis of guidelines to maintain T(4)/free T(4) in the upper half of the normal range and rapidly normalize TSH. RESULTS: Monthly monitoring was justified in 75% in the first 6 months and 36% in the next 6 months. Children requiring monthly monitoring in the second 6 months had higher baseline TSH (P = .02) and lower T(4) (P = .01) than those not requiring monthly monitoring. Thyroid dysgenesis, starting levothyroxine dose, sex, and ethnicity did not predict requirement for monthly monitoring. Thirty percent of children in the first and second 6 months had ≥1 high TSH level, with a T(4)/free T(4) not in the upper half of the normal range. CONCLUSION: More than a third of children with CH require monthly monitoring between 6 to 12 months on the basis of study criteria. Current monitoring guidelines may need to be reexamined.
Assuntos
Hipotireoidismo Congênito/terapia , Fidelidade a Diretrizes , Monitorização Fisiológica/normas , Guias de Prática Clínica como Assunto , Hipotireoidismo Congênito/sangue , Hipotireoidismo Congênito/diagnóstico , Feminino , Fidelidade a Diretrizes/normas , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Testes de Função Tireóidea/normas , Tireotropina/sangue , Tiroxina/sangue , Tiroxina/uso terapêuticoRESUMO
OBJECTIVE: Cardiovascular (CV) risk begins in childhood, and low body weight should result in a favorable risk profile. However, adolescents with anorexia nervosa (AN) have alterations in many hormonal factors that mediate CV risk. We hypothesized that in AN, growth hormone (GH) resistance and hypercortisolemia would increase CV risk through effects on pro-inflammatory cytokines and lipid status despite low weight. STUDY DESIGN: We examined CV risk markers (high sensitivity C-reactive protein [hsCRP], interleukin-6 [IL-6], apolipoprotein-B [Apo-B], and lipid profile) in 23 subjects with AN and in 20 control subjects 12 to 18 years of age, in whom GH, cortisol, leptin, and triiodothyronine (T3) had been previously determined. RESULTS: Subjects with AN had higher Apo-B (P < .0001), IL-6 (P = .03), Apo-B/high-density lipoprotien (HDL) (P = .01), and Apo-B/low-density lipoprotein (LDL) (P < .0001) and lower hsCRP (P = .01) than controls. Triglycerides were lower and HDL higher in subjects with AN. IGF-I predicted hsCRP in controls but not in AN. Log hsCRP correlated positively with GH and inversely with leptin. On regression modeling, the most significant predictor of log hsCRP was leptin; T3 predicted log IL-6, log Apo-B, log Apo-B/HDL, and Apo-B/LDL; and cortisol independently predicted log Apo-B. IL-6 decreased with weight gain. CONCLUSION: CV risk markers are uncoupled in AN, with increased Apo-B and IL-6 and decreased hsCRP, related to hormonal alterations. IL-6 normalizes with weight gain.