Parathyroid hormone (PTH) has variable actions on bone. Chronically increased PTH is catabolic leading to osteoporosis, yet intermittent administration is anabolic and increases bone mass. PTH deficiency is associated with decreased bone remodeling and increased bone mass. However, the effects of PTH replacement therapy on bone in hypoparathyroidism are not well known. We discontinued calcitriol therapy and treated five hypoparathyroid subjects (2 adults and 3 adolescents) with synthetic human PTH 1-34 (hPTH 1-34), injected 2-3 times daily for 18 months, with doses individualized to maintain serum calcium at 1.9-2.25 mmol/L. Biochemical markers and bone density (BMD) were assessed every 6 months; iliac-crest biopsies were performed before and after 1 year of treatment. hPTH 1-34 therapy significantly increased bone markers to supranormal levels. Histomorphometry revealed that treatment dramatically increased cancellous bone volume and trabecular number and decreased trabecular separation. Changes in trabecular width were variable, suggesting that the increase in trabecular number was due to the observed intratrabecular tunneling. Cortical width remained unchanged, however, hPTH 1-34 treatment increased cortical porosity. Cancellous bone remodeling was also stimulated, inducing significant changes in osteoid, mineralizing surface, and bone formation rate. Similar changes were seen in endocortical and intracortical remodeling. BMD Z-scores were unchanged at the spine and femoral neck. Total hip Z-scores increased, however, total body BMD Z-scores decreased during the first 6 months of treatment and then stabilized, remaining significantly decreased compared to baseline. Radial Z-scores also decreased with treatment; this was most pronounced in the growing adolescent. Daily hPTH 1-34 therapy for hypoparathyroidism stimulated bone turnover, increased bone volume, and altered bone structure in the iliac crest. These findings suggest that treatment with hPTH 1-34 in hypoparathyroid adults and adolescents has varying effects in the different skeletal compartments, leading to an increase in trabecular bone and an apparent trabecularization of cortical bone.
Alkaptonuria is a rare, autosomal recessive disorder of tyrosine degradation due to deficiency of the third enzyme in the catabolic pathway. As a result, homogentisic acid (HGA) accumulates and is excreted in gram quantities in the urine, which turns dark upon alkalization. The first symptoms, occurring in early adulthood, involve a painful, progressively debilitating arthritis of the spine and large joints. Cardiac valvular disease and renal and prostate stones occur later. Previously suggested therapies have failed to show benefit, and management remains symptomatic. Nitisinone, a potent inhibitor of the second enzyme in the tyrosine catabolic pathway, is considered a potential therapy; proof-of-principle studies showed 95% reduction in urinary HGA. Based on those findings, a prospective, randomized clinical trial was initiated in 2005 to evaluate 40 patients over a 36-month period. The primary outcome parameter was hip total range of motion with measures of musculoskeletal function serving as secondary parameters. Biochemically, this study consistently demonstrated 95% reduction of HGA in urine and plasma over the course of 3 years. Clinically, primary and secondary parameters did not prove benefit from the medication. Side effects were infrequent. This trial illustrates the remarkable tolerability of nitisinone, its biochemical efficacy, and the need to investigate its use in younger individuals prior to development of debilitating arthritis.
Alkaptonuria; Ochronosis; Nitisinone; Homogentisic acid
The effects of acute (AR) and chronic rejection (CR) on intestinal smooth muscle that are responsible for the dysmotility following small bowel transplantation (SBTX) are incompletely understood. Jejunal and ileal specimens from normal control dogs (n=7), and auto-transplanted dogs were examined at 7 days (n=6) and 1 (n=7), 3 (n=6), 6 (n=6), and 12 months (n=6). Allo-transplanted dogs that developed AR (n=8) and CR (n=5) were examined for gross and microscopic morphology (muscle thickness, the number and size of myocytes, and inflammatory infiltrate), and for contractile and intracellular electrical function in vitro. Auto-SBTX did not alter morphology at any period, but contractile function was impaired at 7 days (73.6%) compared with normal intestine. Acute rejection did not influence myocyte number or size, but was associated with a prominent infiltrate of neutrophils and lymphocytes, and severely impaired contractile function (20.6%) compared with auto-SBTX controls. Acute rejection also significantly inhibited the amplitude of slow waves and of inhibitory junction potentials. Chronic rejection caused thickening of muscularis propria by both hyperplasia (175.5%) and hypertrophy (202.6%) accompanied by moderate inflammatory cell infiltrate compared with auto-SBTX controls. We conclude that the marked inflammatory infiltrate into the muscularis propria indicates that the graft muscle is injured by both acute and chronic rejection; impaired function of intestinal smooth muscle following SBTX results from both rejection and the injury associated with transplantation, and chronic rejection following SBTX is associated with both hyperplasia and hypertrophy of the muscularis propria.
Enlargement of the vestibular aqueduct (EVA) is the most common inner ear anomaly detected in ears of children with sensorineural hearing loss. Pendred syndrome (PS) is an autosomal recessive disorder characterized by bilateral sensorineural hearing loss with EVA and an iodine organification defect that can lead to thyroid goiter. Pendred syndrome is caused by mutations of the SLC26A4 gene. SLC26A4 mutations may also be identified in some patients with nonsyndromic EVA (NSEVA). The presence of two mutant alleles of SLC26A4 is correlated with bilateral EVA and Pendred syndrome, whereas unilateral EVA and NSEVA are correlated with one (M1) or zero (M0) mutant alleles of SLC26A4. Thyroid gland enlargement (goiter) appears to be primarily dependent on the presence of two mutant alleles of SLC26A4 in pediatric patients, but not in older patients. In M1 families, EVA may be associated with a second, undetected SLC26A4 mutation or epigenetic modifications. In M0 families, there is probably etiologic heterogeneity that includes causes other than, or in addition to, monogenic inheritance.
SLC26A4; Pendred syndrome; Hearing; Deafness; Inner ear; Genotype-phenotype correlation
Major depressive disorder (MDD) is associated with immune system dysfunction and disruption of multiple circadian systems. Adiponectin is an adipocytokine with anti-inflammatory and anti-atherogenic effects. Circulating concentrations are inversely related to adiposity and risks of metabolic syndrome and diabetes mellitus. Our goals were to: A) establish whether premenopausal women with MDD exhibit decreased plasma adiponectin concentrations and/or disruption of circadian adiponectin rhythmicity; B) assess whether there is a relationship between adiponectin and MDD; C) explore the temporal relationships among adiponectin, leptin, ACTH and cortisol secretion.
Case-control study of community-dwelling premenopausal women with MDD and age- and BMI-matched-control subjects (N=23/group). Main outcome measures were circulating concentrations of adiponectin, leptin, ACTH, and cortisol measured hourly for 24h.
Women with MDD had approximately 30% lower mean 24h concentrations of adiponectin than did control subjects. Adiponectin was inversely related to depression severity and total duration of disease, suggesting a causal link. In contrast, nocturnal leptin concentrations were higher in the MDD versus control groups. Leptin was inversely related to cortisol and adiponectin both in subjects with depression and in control subjects. In cross-correlation analyses, the relationship between ACTH and cortisol was stronger in women with MDD than in control subjects, consistent with HPA-axis activation in MDD.
Reduced daily adiponectin production may increase the risk of diabetes mellitus, and elevated leptin may contribute to osteoporosis, in premenopausal women with MDD.
women’s health; psychosomatic medicine; antidepressants; stress system; circadian rhythmicity; inflammation; adipocytokines: ACTH; cortisol: insulin resistance, cardiovascular risk; osteoporosis; osteopenia
Obesity is a growing problem in the United States and throughout the world. It is a risk factor for many chronic diseases. The BMI has been used to assess body fat for almost 200 years. BMI is known to be of limited accuracy, and is different for males and females with similar %body adiposity. Here, we define an alternative parameter, the body adiposity index (BAI = ((hip circumference)/((height)1.5) − 18)). The BAI can be used to reflect %body fat for adult men and women of differing ethnicities without numerical correction. We used a population study, the “BetaGene” study, to develop the new index of body adiposity. %Body fat, as measured by the dual-energy X-ray absorptiometry (DXA), was used as a “gold standard” for validation. Hip circumference (R = 0.602) and height (R = −0.524) are strongly correlated with %body fat and therefore chosen as principal anthropometric measures on which we base BAI. The BAI measure was validated in the “Triglyceride and Cardiovascular Risk in African-Americans (TARA)” study of African Americans. Correlation between DXA-derived %adiposity and the BAI was R = 0.85 for TARA with a concordance of C_b = 0.95. BAI can be measured without weighing, which may render it useful in settings where measuring accurate body weight is problematic. In summary, we have defined a new parameter, the BAI, which can be calculated from hip circumference and height only. It can be used in the clinical setting even in remote locations with very limited access to reliable scales. The BAI estimates %adiposity directly.
Metformin can decrease adiposity and ameliorate obesity-related comorbid conditions, including abnormalities in glucose homeostasis in adolescents, but there are few data evaluating the efficacy of metformin among younger children. Our objective was to determine whether metformin treatment causes weight loss and improves obesity-related comorbidities in obese children, who are insulin-resistant.
RESEARCH DESIGN AND METHODS
This study was a randomized double-blind placebo-controlled trial consisting of 100 severely obese (mean BMI 34.6 ± 6.6 kg/m2) insulin-resistant children aged 6–12 years, randomized to 1,000 mg metformin (n = 53) or placebo (n = 47) twice daily for 6 months, followed by open-label metformin treatment for 6 months. All children and their parents participated in a monthly dietitian-administered weight-reduction program.
Eighty-five percent completed the 6-month randomized phase. Children prescribed metformin had significantly greater decreases in BMI (difference −1.09 kg/m2, CI −1.87 to −0.31, P = 0.006), body weight (difference −3.38 kg, CI −5.2 to −1.57, P < 0.001), BMI Z score (difference between metformin and placebo groups −0.07, CI −0.12 to −0.01, P = 0.02), and fat mass (difference −1.40 kg, CI −2.74 to −0.06, P = 0.04). Fasting plasma glucose (P = 0.007) and homeostasis model assessment (HOMA) insulin resistance index (P = 0.006) also improved more in metformin-treated children than in placebo-treated children. Gastrointestinal symptoms were significantly more prevalent in metformin-treated children, which limited maximal tolerated dosage in 17%. During the 6-month open-label phase, children treated previously with placebo decreased their BMI Z score; those treated continuously with metformin did not significantly change BMI Z score further.
Metformin had modest but favorable effects on body weight, body composition, and glucose homeostasis in obese insulin-resistant children participating in a low-intensity weight-reduction program.
Major depressive disorder (MDD) has been associated with adverse medical consequences, including cardiovascular disease and osteoporosis. Patients with MDD may be classified as having melancholic, atypical, or undifferentiated features. The goal of the present study was to assess whether these clinical subtypes of depression have different endocrine and metabolic features and consequently, varying medical outcomes.
Premenopausal women, ages 21 to 45 years, with MDD (N = 89) and healthy controls (N = 44) were recruited for a prospective study of bone turnover. Women with MDD were classified as having melancholic (N = 51), atypical (N = 16), or undifferentiated (N = 22) features. Outcome measures included: metabolic parameters, body composition, bone mineral density (BMD), and 24 hourly sampling of plasma adrenocorticotropin (ACTH), cortisol, and leptin.
Compared with control subjects, women with undifferentiated and atypical features of MDD exhibited greater BMI, waist/hip ratio, and whole body and abdominal fat mass. Women with undifferentiated MDD characteristics also had higher lipid and fasting glucose levels in addition to a greater prevalence of low BMD at the femoral neck compared to controls. Elevated ACTH levels were demonstrated in women with atypical features of depression, whereas higher mean 24-hour leptin levels were observed in the melancholic subgroup.
Pre-menopausal women with various features of MDD exhibit metabolic, endocrine, and BMD features that may be associated with different health consequences.
Background. The prevalence of fecal incontinence varies tremendously as a result of inadequate data collection methods. Few office-based studies have assessed the prevalence of fecal incontinence and none have looked at modifiable risk factors or effect on quality of life.
Design, Settings, Patients, and Main Outcome Measures. Five hundred patients who visited our inner city, university-based gastroenterology practice, were asked about symptoms of fecal incontinence. We also retrospectively reviewed 500 charts to identify the frequency of patient-physician reporting of fecal incontinence.
Results. Of the 500 patients that were directly questioned, 58 (12%, 43 women, 15 men) admitted to fecal incontinence compared to 12 (2.4%) in the retrospective arm. Patients with fecal incontinence and loose/watery stool reported the lowest quality of life scores. While the average severity score was similar between men and women, women had a significantly lower average quality of life score (3.04 versus 2.51; P < 0.03).
Conclusions. The identification of fecal incontinence increases when patients are directly questioned. Identifying and treating patients with loose stool is a potential strategy to improve quality of life in this patient population. In men and women with similar severity of fecal incontinence, women have a significantly lower quality of life.
The most common type of ovarian germ cell tumor is the teratoma. Thyroid tissue, both benign and malignant, may be a component of an ovarian teratoma. Here we review this topic and illustrate major features by presenting multimodal management of a patient with BRAF-positive disseminated follicular thyroid cancer arising in an ovarian teratoma.
Malignant thyroid tissue is often difficult to distinguish from benign thyroid tissue arising in ovarian teratomas. Preoperatively, an elevated thyroglobulin (Tg) level, laboratory or clinical evidence of hyperthyroidism, or ultrasonography appearance of “struma pearl” should prompt referral to oncologist for surgical management of a possibly malignant ovarian teratoma. Postoperatively, tumor tissue should be referred to pathologists experienced with differentiating benign from malignant struma ovarii. Once diagnosed, treatment of this rare condition should be handled by a team of specialists with combined treatment modalities. We cared for woman with disseminated thyroid cancer arising in an ovarian teratoma whose history illustrates the complexity of managing ovarian teratomas with malignant thyroid tissue. At age 33 she had an intraoperative rupture of an ovarian cyst, thought to be struma ovarii. During her next pregnancy, pelvic masses were noted; biopsies revealed well-differentiated papillary thyroid carcinoma, follicular variant. She was euthyroid, but had elevated serum Tg levels. Surgical staging demonstrated widely metastatic intraabdominal dissemination. A thyroidectomy revealed no malignancy. A post-131I treatment scan revealed diffuse uptake throughout the abdomen. She then developed abdominal pain and, on computed tomography, was found to have multiple intraabdominal foci of disease. Serum Tg was 264 ng/mL while on L-thyroxine for hypothyroidism and to obtain thyrotropin suppression. A 18 fluorodeoxyglucose positron emission tomography scan showed no pathological uptake. The tumor was found to be BRAF mutation positive (K601E). She underwent extensive secondary debulking and a second course of 131I with lithium pretreatment. Posttreatment scan revealed diffuse abdominal uptake. Six months posttherapy, the patient is asymptomatic with a serum Tg of 18.1 ng/mL.
Aggressive multimodal management appears to be the most promising approach for malignant thyroid tissue arising in ovarian teratomas.
To evaluate bone mineral density (BMD) in children with Cushing disease before and after transphenoidal surgery (TSS).
Hologic dual-energy x-ray absorptiometry (DXA) scans of 35 children with Cushing disease were analyzed retrospectively. Sixteen of the 35 patients had follow up DXA scans 13–18 months after TSS. BMD and bone mineral apparent density (BMAD) for lumbar spine (LS) L1–L4 and femoral neck (FN) were calculated.
Preoperatively, 38% and 23% of patients had osteopenia of the LS and FN, respectively. Both BMD and BMAD Z-scores of the LS were worse than those for the FN (−1.60 ± 1.37 vs. −1.04 ± 1.19, p=0.003), and (−1.90 ± 1.49 vs. −0.06 ± 1.90, p<.001); postoperative improvement in BMD and BMAD were more pronounced in LS as compared with the FN (0.84 ± 0.88 vs. 0.15 ± 0.62, p<.001) and (0.73 ± 1.13 vs −0.26 ± 1.21, p=0.015). Pubertal stage, cortisol levels, and length of disease had no effects on BMD.
In children with Cushing disease, vertebral BMD was more severely affected than femoral BMD and was independent of degree or duration of hypercortisolism. BMD for the LS improved significantly after TSS; osteopenia in this group may be reversible.
Glucocorticoid; steroid excess; osteopenia
Intestinal dysmotility and stasis after intestinal transplantation are considered to promote bacterial overgrowth and translocation. Two prokinetic agents, KW5139 (13-leu-motilin) and the somatostatin analogue octreotide acetate, were studied to determine whether they can ameliorate intestinal dysmotility during the early postoperative period.
MATERIALS AND METHODS
Motility was recorded by multiple extraluminal strain-gauge transducers in 6 dogs on postoperative days 1, 3, 7, and 14. A barium meal study was performed with a separate group of 8 dogs on postoperative days 3 and 7.
The agent KW5139 induced brief, weak contractions in the graft and had little effect on the dilated bowel; however, octreotide induced motor activity that propelled accumulated intestinal contents into the colon and reduced dilation of the transplanted bowel.
Octreotide, but not KW5139, ameliorates intestinal dysmotility associated with bowel autotransplantation during the early postoperative period. Short-term administration of octreotide may be useful for the treatment of dysmotility following intestinal transplantation.
To evaluate thyroid structure and function in patients with enlargement of the vestibular aqueduct (EVA) and sensorineural hearing loss.
Prospective cohort survey.
National Institutes of Health Clinical Center, a federal biomedical research facility.
The study population comprised 80 individuals, aged 1.5 to 59 years, ascertained on the basis of EVA and sensorineural hearing loss.
Main Outcome Measures
Associations among the number of mutant alleles of SLC26A4; volume and texture of the thyroid; percentage of iodine 123 (123I) discharged at 120 minutes after administration of perchlorate in the perchlorate discharge test; and peripheral venous blood levels of thyrotropin, thyroxine, free thyroxine, triiodothyronine, thyroglobulin, antithyroid peroxidase and antithyroglobulin antibodies, and thyroid-binding globulin.
Thyroid volume is primarily genotype dependent in pediatric patients but age dependent in older patients. Individuals with 2 mutant SLC26A4 alleles discharged a significantly (P ≤ .001) greater percentage of 123I compared with those with no mutant alleles or 1 mutant allele. Thyroid function, as measured by serologic testing, is not associated with the number of mutant alleles.
Ultrasonography with measurement of gland volume is recommended for initial assessment and follow-up surveillance of the thyroid in patients with EVA. Perchlorate discharge testing is recommended for the diagnostic evaluation of patients with EVA along with goiter, nondiagnostic SLC26A4 genotypes (zero or 1 mutant allele), or both.
Hearing loss with enlargement of the vestibular aqueduct (EVA) can be associated with mutations of the SLC26A4 gene encoding pendrin, a transmembrane Cl−/I−/HCO3− exchanger. Pendrin’s critical transport substrates are thought to be I− in the thyroid gland and HCO3− in the inner ear. We previously reported that bi-allelic SLC26A4 mutations are associated with Pendred syndromic EVA whereas one or zero mutant alleles are associated with nonsyndromic EVA. One study proposed a correlation of nonsyndromic EVA with SLC26A4 alleles encoding pendrin with residual transport activity. Here we describe the phenotypes and SLC26A4 genotypes of 47 EVA patients ascertained since our first report of 39 patients. We sought to determine the pathogenic potential of each variant in our full cohort of 86 patients. We evaluated the trafficking of 11 missense pendrin products expressed in COS-7 cells. Products that targeted to the plasma membrane were expressed in Xenopus oocytes for measurement of anion exchange activity. p.F335L, p.C565Y, p.L597S, p.M775T, and p.R776C had Cl−/I− and Cl−/HCO3− exchange rate constants that ranged from 13 to 93% of wild type values. p.F335L, p.L597S, p.M775T and p.R776C are typically found as mono-allelic variants in nonsyndromic EVA. The high normal control carrier rate for p.L597S indicates it is a coincidentally detected nonpathogenic variant in this context. We observed moderate differential effects of hypo-functional variants upon exchange of HCO3− versus I− but their magnitude does not support a causal association with nonsyndromic EVA. However, these alleles could be pathogenic in trans configuration with a mutant allele in Pendred syndrome.
enlargement of the vestibular aqueduct; EVA; deafness; DFNB4; hearing; genotype-phenotype correlation; PDS; pendrin; SLC26A4
Hypocalcemia is a rare complication of osteosarcoma, having been described in only 4 reports. We present the case of a 16-year-old male with metastatic osteosarcoma of the right humerus who was found to have severe asymptomatic hypocalcemia. Cytogenetic analysis of peripheral blood revealed a microdeletion in band 22q11.2. Following amputation of the tumor-bearing extremity, the patient’s calcium levels increased, but did not normalize. These findings suggested that the etiology of his hypocalcemia was osteoblastic utilization of calcium by the tumor, exacerbated by 22q11.2 deletion syndrome.
hypocalcemia; osteosarcoma; 22q11.2 deletion syndrome
Some data suggest that increasing calcium intake may help prevent weight gain.
To test the hypothesis that calcium supplementation can prevent weight gain in people who are overweight or obese.
Randomized placebo-controlled trial. Randomization was computer generated and allocation was assigned by pharmacy personnel who prepared intervention and placebo capsules. Participants, providers, and those who assessed outcomes were blinded to treatment assignment.
Single research center.
340 overweight (BMI between 25 and 30 kg/m2) and obese (BMI ≥ 30 kg/m2) adults, mean age 38.8±10.5 years.
Calcium carbonate (1500mg/d elemental calcium) (n= 170) or placebo (n= 170), with meals for two years.
Changes in body weight and fat mass (primary outcomes);
Seventy-five percent of participants completed the trial (78% given calcium, 73% given placebo). There were no statistically or clinically significant between-group differences in change in body weight (difference between calcium and placebo groups +0.02kg, CI −1.64 to + 1.69, P=.98), body mass index (difference +0.32kg/m2 CI −0.41 to +1.02, P=.39) or body fat mass (difference +0.39kg CI −1.04 to +1.92, P=.55). Parathyroid hormone decreased in the calcium- compared to the placebo-treated group (−0.71pmol/L, 95% CI −1.28 to −0.13).
The study took place at a research center, and its population was mostly women,
Dietary supplementation with 1500 mg/d of elemental calcium for 2 years had no statistically or clinically significant effects on weight in overweight and obese adults. Calcium supplementation is unlikely to have clinically significant efficacy as a weight gain preventive measure in such patients.
obesity; adipose tissue; weight; weight gain; dietary factors; calcium
Five of 6 HIV-infected children receiving TDF experienced absolute decreases in BMD. Two pre-pubertal subjects experienced greater than 6% BMD decreases. One was the smallest child and experienced a 27% decrease, necessitating withdrawal of TDF. Subsequently, her BMD recovered. Monitoring of HIV-infected children requiring treatment with TDF is warranted.
HIV; bone mineral density; children
Little is known about how simpler and more available methods to measure change in body fatness compare with criterion methods such as dual-energy X-ray absorptiometry (DXA) in children.
Our objective was to determine the ability of air-displacement plethysmography (ADP) and formulas based on triceps skinfold thickness (TSF) and bioelectrical impedance analysis (BIA) to estimate changes in body fat over time in children.
Eighty-six nonoverweight and overweight boys (n = 34) and girls (n = 52) with an average age of 11.0 ± 2.4 y underwent ADP, TSF measurement, BIA, and DXA to estimate body fatness at baseline and 1 ± 0.3 y later. Recent equations were used to estimate percentage body fat by TSF measurement (Dezenberg equation) and by BIA (Suprasongsin and Lewy equations). Percentage body fat estimates by ADP, TSF measurement, and BIA were compared with those by DXA.
All methods were highly correlated with DXA (P < 0.001). No mean bias for estimates of percentage body fat change was found for ADP (Siri equation) compared with DXA for all subjects examined together, and agreement between body fat estimation by ADP and DXA did not vary with race or sex. Magnitude bias was present for ADP relative to DXA (P < 0.01). Estimates of change in percentage body fat were systematically overestimated by BIA equations (1.37 ± 6.98%; P < 0.001). TSF accounted for only 13% of the variance in percentage body fat change.
Compared with DXA, there appears to be no noninvasive and simple method to measure changes in children’s percentage body fat accurately and precisely, but ADP performed better than did TSF or BIA. ADP could prove useful for measuring changes in adiposity in children.
Air-displacement plethysmography; bioelectrical impedance; skinfold thickness; dual-energy X-ray absorptiometry; DXA; adiposity; body fat mass; change; growth; children
Limited data suggest that psychological factors, including binge eating, dieting, and depressive symptoms, may predispose children to excessive weight gain. We investigated the relationship between baseline psychological measures and changes in body fat (measured with dual-energy x-ray absorptiometry) over time among children thought to be at high risk for adult obesity.
A cohort study of a convenience sample of children (age: 6–12 years) recruited from Washington, DC, and its suburbs was performed. Subjects were selected to be at increased risk for adult obesity, either because they were overweight when first examined or because their parents were overweight. Children completed questionnaires at baseline that assessed dieting, binge eating, disordered eating attitudes, and depressive symptoms; they underwent measurements of body fat mass at baseline and annually for an average of 4.2 years (SD: 1.8 years).
Five hundred sixty-eight measurements were obtained between July 1996 and December 2004, for 146 children. Both binge eating and dieting predicted increases in body fat. Neither depressive symptoms nor disturbed eating attitudes served as significant predictors. Children who reported binge eating gained, on average, 15% more fat mass, compared with children who did not report binge eating.
Children’s reports of binge eating and dieting were salient predictors of gains in fat mass during middle childhood among children at high risk for adult obesity. Interventions targeting disordered eating behaviors may be useful in preventing excessive fat gain in this high-risk group.
child; disturbed eating behaviors; depression; adiposity; overweight
Few studies have quantified the prevalence of weight-related orthopedic conditions in otherwise healthy overweight children. The goal of the present investigation was to describe the musculoskeletal consequences of pediatric overweight in a large pediatric cohort of children that included severely overweight children.
Medical charts from 227 overweight and 128 nonoverweight children and adolescents who were enrolled in pediatric clinical studies at the National Institutes of Health from 1996 to 2004 were reviewed to record pertinent orthopedic medical history and musculoskeletal complaints. Questionnaire data from 183 enrollees (146 overweight) documented difficulties with mobility. In 250, lower extremity alignment was determined by bilateral metaphyseal-diaphyseal and anatomic tibiofemoral angle measurements made from whole-body dual-energy x-ray absorptiometry scans.
Compared with nonoverweight children, overweight children reported a greater prevalence of fractures and musculoskeletal discomfort. The most common self-reported joint complaint among those who were questioned directly was knee pain (21.4% overweight vs 16.7% nonoverweight). Overweight children reported greater impairment in mobility than did nonoverweight children (mobility score: 17.0 ± 6.8 vs 11.6 ± 2.8). Both metaphyseal-diaphyseal and anatomic tibiofemoral angle measurements showed greater malalignment in overweight compared with nonoverweight children.
Reported fractures, musculoskeletal discomfort, impaired mobility, and lower extremity malalignment are more prevalent in overweight than nonoverweight children and adolescents. Because they affect the likelihood that children will engage in physical activity, orthopedic difficulties may be part of the cycle that perpetuates the accumulation of excess weight in children.
obesity; fractures; valgus deformity; child; quality of life
We evaluated the accuracy with which the Hologic QDR-4500A and QDR-2000 densitometers measure fat mass (FM) in 95 children. FM was derived from total body water measured by deuterium dilution (DD) in all children, by QDR-4500A in 50, and by QDR-2000 in 45 children. Compared with DD, both instruments underestimated FM (QDR-4500A: 3.35 ± 2.5 kg, P < 0.0001; QDR-2000: 1.05 ± 1.5 kg, P < 0.0001). Both absorptiometers showed magnitude biases relative to DD (QDR-4500: r = +0.70, P < 0.001; QDR-2000: r = −0.51, P < 0.001). We conclude that neither densitometer is equivalent to DD for estimation of children’s FM. The QDR-4500A’s current calibration seems to provide an even greater underestimate of FM than the QDR-2000.
children; body composition; fat mass; dual-energy x-ray absorptiometry; calibration
Endoscopic devices distort the image of a region under examination. The current inability of endoscopes to precisely measure the area of esophageal involvement by Barrett's metaplasia precludes an accurate assessment of the natural history of the disease. A method to accurately measure the extent of involvement has been derived. An endoscopic image was digitized and transformed into a flat image by digitally “unrolling” the region. In order to test this models of an esophagus were constructed and photographed endoscopicly. Comparisons were then made between the surface areas of the computer generated images and the model. Surface areas generated by the computer were linearly correlated with actual area (r>.96) and the difference in measured area varied between 0.5% and 8.5% (5.2±0.7%, mean±SEM).
Serum immunoreactive parathyroid hormone (IPTH) was measured by radioimmunoassay in 54 patients with primary hyperparathyroidism and in 18 consecutive patients with ectopic hyperparathyroidism due to nonparathyroid cancer without apparent skeletal metastasis. Although serum calcium concentration was higher in the group with ectopic hyperparathyroidism, serum IPTH was lower (rank sum test, P < 0.001) and was undetectable in eight. A second anti-PTH antiserum also differentiated between IPTH in the two groups, although IPTH was undetectable in only 1 of 14 sera. When IPTH values in serial dilutions were plotted, slopes for the two patients with ectopic hyperparathyroidism who had relatively high IPTH were less (P < 0.001) than slopes for standard hyperparathyroid sera. By using differences in either IPTH rank or slope of the dilutional curve of sera, primary hyperparathyroidism could be excluded as a cause of the hypercalcemia in 16 of the 18 patients with ectopic hyperparathyroidism. The data are interpreted as indicating that PTH-like material in the serum of these patients with ectopic hyperparathyroidism is immunologically different from the PTH in the serum of patients with primary hyperparathyroidism.
An inverse relationship between major depressive disorder (MDD) and bone mineral density (BMD) has been suggested, but prospective evaluation in premenopausal women is lacking.
Participants of this prospective study were 21 to 45 year-old premenopausal women with MDD (n = 92) and healthy controls (n = 44). We measured BMD at the anteroposterior lumbar spine, femoral neck, total hip, mid-distal radius, trochanter, and Ward's triangle, as well as serum intact parathyroid hormone (iPTH), ionized calcium, plasma adrenocorticotropic hormone (ACTH), serum cortisol, and 24-hour urinary-free cortisol levels at 0, 6, 12, 24, and 36 months. 25-hydroxyvitamin D was measured at baseline.
At baseline, BMD tended to be lower in women with MDD compared to controls and BMD remained stable over time in both groups. At baseline, 6, 12, and 24 months intact PTH levels were significantly higher in women with MDD vs. controls. At baseline, ionized calcium and 25-hydroxyvitamin D levels were significantly lower in women with MDD compared to controls. At baseline and 12 months, bone-specific alkaline phosphatase, a marker of bone formation, was significantly higher in women with MDD vs. controls. Plasma ACTH was also higher in women with MDD at baseline and 6 months. Serum osteocalcin, urinary N-telopeptide, serum cortisol, and urinary free cortisol levels were not different between the two groups throughout the study.
Women with MDD tended to have lower BMD than controls over time. Larger and longer studies are necessary to extend these observations with the possibility of prophylactic therapy for osteoporosis.
ClinicalTrials.gov NCT 00006180
Hutchinson–Gilford progeria syndrome is a rare, sporadic, autosomal dominant syndrome that involves premature aging, generally leading to death at approximately 13 years of age due to myocardial infarction or stroke. The genetic basis of most cases of this syndrome is a change from glycine GGC to glycine GGT in codon 608 of the lamin A (LMNA) gene, which activates a cryptic splice donor site to produce abnormal lamin A; this disrupts the nuclear membrane and alters transcription.
We enrolled 15 children between 1 and 17 years of age, representing nearly half of the world's known patients with Hutchinson–Gilford progeria syndrome, in a comprehensive clinical protocol between February 2005 and May 2006.
Clinical investigations confirmed sclerotic skin, joint contractures, bone abnormalities, alopecia, and growth impairment in all 15 patients; cardiovascular and central nervous system sequelae were also documented. Previously unrecognized findings included prolonged prothrombin times, elevated platelet counts and serum phosphorus levels, measured reductions in joint range of motion, low-frequency conductive hearing loss, and functional oral deficits. Growth impairment was not related to inadequate nutrition, insulin unresponsiveness, or growth hormone deficiency. Growth hormone treatment in a few patients increased height growth by 10% and weight growth by 50%. Cardiovascular studies revealed diminishing vascular function with age, including elevated blood pressure, reduced vascular compliance, decreased ankle–brachial indexes, and adventitial thickening.
Establishing the detailed phenotype of Hutchinson–Gilford progeria syndrome is important because advances in understanding this syndrome may offer insight into normal aging. Abnormal lamin A (progerin) appears to accumulate with aging in normal cells.