Biomedical subjects

Madhusmita Misra

Publications and source records attributed to Madhusmita Misra.

At least 19 recordsLinked to original sources

PubMed2006

Determinants of skeletal loss and recovery in anorexia nervosa.

CONTEXT: Anorexia nervosa (AN) is complicated by severe bone loss. The effects of persistent undernutrition and consequent neuroendocrine dysfunction on bone mass and the factors influencing skeletal recovery have not been well characterized. OBJECTIVE: The objective of the study was to determine the rate of bone loss at the spine and hip in women with AN and whether resumption of menstrual function and/or improvement in weight are determinants of skeletal recovery in AN. DESIGN: The study had a longitudinal design. SETTING: The study was conducted at a clinical research center. STUDY PARTICIPANTS: Participants included 75 ambulatory women with AN. MAIN OUTCOME MEASURES: Bone mineral density (BMD) and body composition were measured with dual x-ray absorptiometry. RESULTS: In women not receiving oral contraceptives, those who did not improve weight or resume menses had a mean annual rate of decline of 2.6% at the spine and 2.4% at the hip. Those who resumed menses and improved weight had a mean annual increase of 3.1% at the posteroanterior spine and 1.8% at the hip. Women who recovered menses demonstrated a mean increase of posteroanterior spine but not hip BMD, independent of weight gain. Women who improved weight, regardless of whether they recovered menstrual function, demonstrated a mean increase of hip, but not spine, BMD. Increase in fat-free mass was a more significant determinant of increased BMD than weight or fat mass gain. In women receiving oral contraceptives, there was no increase in BMD at any site despite a mean 11.7% weight increase. CONCLUSIONS: These data suggest that rapid bone loss, at an average annual rate of about 2.5%, occurs in young women with active AN. Resumption of menstrual function is important for spine BMD recovery, whereas weight gain is critical for hip BMD recovery. We did not observe an increase in BMD with weight gain in women receiving oral contraceptives. Therefore, improvements in reproduction function and weight, with increases in lean body mass a critical component, are both necessary for skeletal recovery in women with AN.

Absorptiometry, Photon↗

PubMed2006

Anorexia nervosa and osteoporosis.

Anorexia nervosa (AN), a condition of severe undernutrition, is associated with low bone mineral density (BMD) in adults and adolescents. Whereas adult women with AN have an uncoupling of bone turnover markers with increased bone resorption and decreased bone formation markers, adolescents with AN have decreased bone turnover overall. Possible contributors to low BMD in AN include hypoestrogenism and hypoandrogenism, undernutrition with decreased lean body mass, and hypercortisolemia. IGF-I, a known bone trophic factor, is reduced despite elevated growth hormone (GH) levels, leading to an acquired GH resistant state. Elevated ghrelin and peptide YY levels may also contribute to impaired bone metabolism. Weight recovery is associated with recovery of BMD but this is often partial, and long-term and sustained weight recovery may be necessary before significant improvements are observed. Anti-resorptive therapies have been studied in AN with conflicting results. Oral estrogen does not increase BMD or prevent bone loss in AN. The combination of bone anabolic and anti-resorptive therapy (rhIGF-I with oral estrogen), however, did result in a significant increase in BMD in a study of adult women with AN. A better understanding of the pathophysiology of low BMD in AN, and development of effective therapeutic strategies is critical. This is particularly so for adolescents, who are in the process of accruing peak bone mass, and in whom a failure to attain peak bone mass may occur in AN in addition to loss of established bone.

Androgens↗

PubMed2006

Uncoupling of cardiovascular risk markers in adolescent girls with anorexia nervosa.

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.

Adolescent↗

PubMed2006

Nutrient intake in community-dwelling adolescent girls with anorexia nervosa and in healthy adolescents.

BACKGROUND: Adolescence is a common time for the onset of anorexia nervosa (AN), a condition associated with long-term medical and hormonal consequences. OBJECTIVE: The objective was to compare the nutrient intakes of community-dwelling girls with AN with those of healthy adolescents and to describe the associations between specific nutrient intakes and nutritionally dependent hormones. DESIGN: Nutrient intakes in 39 community-dwelling girls with AN and 39 healthy adolescents aged 12.1-18.7 y were determined by using 4-d food records. Fasting adiponectin, leptin, ghrelin, insulin, and insulin-like growth factor I (IGF-I) concentrations were measured. Indirect calorimetry was used to assess respiratory quotient and resting energy expenditure. RESULTS: In contrast with the control group, the AN group consumed fewer calories from fats (P < 0.0001) and more from carbohydrates (P = 0.0009) and proteins (P < 0.0001). Intake of individual fat components was lower and of dietary fiber higher in the AN group. No significant between-group differences were observed in dietary intakes of calcium, zinc, and iron; however, total intake was greater in the AN group because of greater supplement use (P = 0.006, 0.02, and 0.01, respectively). The AN group had greater intakes of vitamins A, D, and K and of most of the B vitamins, and significantly more girls with AN met the Dietary Reference Intake for calcium (P = 0.01) and vitamin D (P = 0.02) from supplement use. Fat intake predicted ghrelin, insulin, and IGF-I concentrations; carbohydrate intake predicted adiponectin. Resting energy expenditure was lower (P < 0.0001) and leisure activity levels higher in the AN group. CONCLUSIONS: Despite outpatient follow-up, community-dwelling girls with AN continue to have lower fat and higher fiber intakes than do healthy adolescents, which results in lower calorie intakes. Nutritionally related hormones are associated with specific nutrient intakes.

Adiponectin↗

PubMed2006

Role of cortisol in menstrual recovery in adolescent girls with anorexia nervosa.

Neuroendocrine abnormalities in anorexia nervosa (AN) include hypercortisolemia, hypogonadism, and hypoleptinemia, and neuroendocrine predictors of menstrual recovery are unclear. Preliminary data suggest that increases in fat mass may better predict menstrual recovery than leptin. High doses of cortisol decrease luteinizing hormone (LH) pulse frequency, and cortisol predicts regional fat distribution. We hypothesized that an increase in fat mass and decrease in cortisol would predict menstrual recovery in adolescents with AN. Thirty-three AN girls 12-18 y old and 33 controls were studied prospectively for 1 y. Body composition [dual energy x-ray absorptiometry (DXA)], leptin, and urinary cortisol (UFC) were measured at 0, 6, and 12 mo. Serum cortisol was measured overnight (every 30 min) in 18 AN subjects and 17 controls. AN subjects had higher UFC/cr x m2 and cortisol area under curve (AUC), and lower leptin levels than controls. Leptin increased significantly with recovery. When menses-recovered AN subjects were compared with AN subjects not recovering menses and controls, menses-recovered AN subjects had higher baseline cortisol levels and greater increases in leptin than controls and greater increases in fat mass than AN subjects not recovering menses and controls (adjusted for multiple comparisons). In a logistic regression model, increasing fat mass, but not leptin, predicted menstrual recovery. Baseline cortisol level strongly predicted increases in the percentage of body fat. We demonstrate that 1) high baseline cortisol level predicts increases in body fat and 2) increases in body fat predict menses recovery in AN.

Adipose Tissue↗

PubMed2006

Intermittent growth attenuation: is this a sign of craniopharyngioma?

We present two young children eventually diagnosed with large craniopharyngiomas, who had a normal growth velocity for several years following an initial short period of growth attenuation. These cases suggest the need for a low threshold to undertake hormonal evaluation of patients who present with a past history of growth attenuation.

Age Determination by Skeleton↗

PubMed2005

Elevated peptide YY levels in adolescent girls with anorexia nervosa.

BACKGROUND: Peptide YY (PYY) is an intestinally derived anorexigen that acts via the Y2 receptor, and Y2 receptor deletion in rodents increases bone formation. Anorexia nervosa (AN) is associated with a deliberate reduction in food intake and low bone density, but endocrine modulators of food intake in AN are not known. In addition, known regulators of bone turnover, such as GH, cortisol, and estrogen, explain only a fraction of the variability in bone turnover marker levels. HYPOTHESES: We hypothesized that PYY may be elevated in AN compared with controls and may contribute to decreased food intake and bone formation. METHODS: Fasting PYY was examined in 23 AN girls and 21 healthy adolescents 12-18 yr old. We also examined GH, cortisol, ghrelin, and leptin (overnight frequent sampling) and fasting IGF-I, estradiol, total T3, and bone markers. Macronutrient intake and resting energy expenditure (REE) were measured. RESULTS: AN girls had higher PYY levels compared with controls (17.8 +/- 10.2 vs. 4.8 +/- 4.3 pg/ml; P < 0.0001). Predictors of log PYY were nutritional markers, including body mass index (r = -0.62; P < 0.0001), fat mass (r = -0.55; P = 0.0003), and REE (r = -0.51; P = 0.0006), and hormones, including GH (r = 0.38; P = 0.004) and T3 (r = -0.59; P = 0.0001). Body mass index, fat mass, REE, GH, and T3 explained 68% of the variability of log PYY. Log PYY predicted percentage of calories from fat (r = -0.56; P = 0.0002) and independently predicted osteocalcin (r = -0.45; P = 0.003), bone-specific alkaline phosphatase (r = -0.46; P = 0.003), N-telopeptide/creatinine (r = -0.55; P = 0.0003), and deoxypyridinoline/creatinine (r = -0.52; P = 0.001) on regression modeling. CONCLUSION: Elevated PYY may contribute to reduced intake and decreased bone turnover in AN.

Adolescent↗

PubMed2005

Ghrelin and bone metabolism in adolescent girls with anorexia nervosa and healthy adolescents.

CONTEXT: Anorexia nervosa (AN) in adolescents is associated with low bone mineral density (BMD) and increases in ghrelin secretion, an orexigenic GH secretagogue that stimulates osteoblast proliferation in vitro. OBJECTIVE: We hypothesized that ghrelin may have independent effects on bone in AN adolescents. STUDY DESIGN, SUBJECTS, AND OUTCOME MEASURES: Frequent sampling was performed overnight every 30 min for 12 h in 23 adolescent AN girls aged 12-18 yr and 21 controls of comparable maturity. Ghrelin, leptin, cortisol, and GH secretion were examined using Cluster and deconvolution. We measured BMD and body composition (dual-energy x-ray absorptiometry) and carboxy-terminal peptide of type I procollagen and N-telopeptide levels. RESULTS: In healthy adolescents, ghrelin secretion strongly predicted BMD; secretory burst mass being the strongest predictor of lumbar spine (LS) bone mineral apparent density (BMAD) (r = 0.66, P = 0.003), LS BMAD z-scores (BMAD-z) (r = 0.59, P = 0.01), hip BMD (r = 0.55, P = 0.02), and hip BMD-z (r = 0.52, P = 0.03). When body composition measures (body mass index, lean and fat mass), and hormonal predictors (GH, IGF-I, cortisol, leptin, and estradiol) were entered into a regression model with ghrelin secretion to determine independent BMD predictors, ghrelin was the strongest predictor of LS BMAD, BMAD-z, hip BMD, and hip BMD-z, contributing to 43, 30, 26, and 19% of the variability, respectively, independent of GH or cortisol effects. Conversely, in AN, ghrelin secretion did not predict LS BMAD or hip-z and weakly predicted LS BMAD-z and hip BMD. Ghrelin did not predict carboxy-terminal peptide of type I procollagen or N-telopeptide/creatinine, which were predicted by GH and cortisol. CONCLUSION: Ghrelin secretion predicts bone density independent of body composition, the GH-IGF-I axis, cortisol, or estradiol in healthy girls but not in those with AN.

Absorptiometry, Photon↗

PubMed2005

Secretory dynamics of leptin in adolescent girls with anorexia nervosa and healthy adolescents.

Leptin, an adipocytokine that suppresses appetite and may regulate neuroendocrine pathways, is low in undernourished states like anorexia nervosa (AN). Although leptin exhibits pulsatility, secretory characteristics have not been well described in adolescents and in AN, and the contribution of hypoleptinemia to increased growth hormone (GH) and cortisol in AN has not been explored. We hypothesized that hypoleptinemia in AN reflects decreased basal and pulsatile secretion and may predict increased GH and cortisol levels. Sampling for leptin, GH, cortisol, and ghrelin was performed every 30 min (from 2000 to 0800) in 23 AN and 21 controls 12-18 yr old, and data were analyzed using Cluster and deconvolution methods. Estradiol, thyroid hormones, and body composition were measured. AN girls had lower pulsatile and total leptin secretion than controls (P < 0.0001) subsequent to decreased burst mass (P < 0.0001) and basal secretion (P = 0.02). Nutritional markers predicted leptin characteristics. In a regression model including BMI, body fat, and ghrelin, leptin independently predicted GH burst interval and frequency. Valley leptin contributed to 56% of the variability in GH burst interval, and basal leptin and fasting ghrelin contributed to 42% of variability in burst frequency. Pulsatile leptin independently predicted urine free cortisol/creatinine (15% of variability). Valley leptin predicted cortisol half-life (22% of variability). Leptin predicted estradiol and thyroid hormone levels. In conclusion, hypoleptinemia in AN is subsequent to decreased basal and pulsatile secretion and nutritionally regulated. Leptin predicts GH and cortisol parameters and with ghrelin predicts GH burst frequency. Low leptin and high ghrelin may be dual stimuli for high GH concentrations in undernutrition.

Adolescent↗

PubMed2005

Secretory dynamics of ghrelin in adolescent girls with anorexia nervosa and healthy adolescents.

Ghrelin is an orexigenic peptide and a growth hormone (GH) secretagogue. Secretory dynamics of ghrelin have not been characterized in adolescents with anorexia nervosa (AN). We hypothesized that, compared with healthy adolescents, girls with AN would have increased ghrelin concentrations measured over 12 h of nocturnal sampling from increased basal and pulsatile secretion, and endogenous ghrelin would independently predict GH and cortisol. We examined ghrelin concentration and secretory dynamics in 22 girls with AN and 18 healthy adolescents 12-18 yr old. Associations between ghrelin, various hormones, and measures of insulin resistance were examined. On Cluster analysis, girls with AN had higher ghrelin concentrations than controls, including total area under the curve (AUC) (P = 0.002), nadir (P = 0.0006), and valley levels (P = 0.002). On deconvolution analysis, secretory burst amplitude (P = 0.03) and burst mass (P = 0.04) were higher in AN, resulting in higher pulsatile (P = 0.05) and total ghrelin secretion (P = 0.03). Fasting ghrelin independently predicted GH burst frequency (r = 0.44, P = 0.005). The nutritional markers body mass index and body fat predicted postglucose and valley ghrelin but not fasting levels. Ghrelin parameters were inversely associated with fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), leptin, and IGF-I. HOMA-IR was the most significant predictor of most ghrelin parameters. Valley ghrelin independently predicted cortisol burst frequency (52% of variability), and ghrelin parameters independently predicted total triiodothyronine and LH levels. Higher ghrelin concentrations in adolescents with AN are a consequence of increased secretory burst mass and amplitude. The most important predictor of ghrelin concentration is insulin resistance, and ghrelin in turn predicts GH and cortisol burst frequency.

Adolescent↗

PubMed2005

Hormonal determinants of regional body composition in adolescent girls with anorexia nervosa and controls.

We have previously demonstrated that girls with anorexia nervosa (AN) have higher levels of GH and cortisol and lower levels of estradiol than healthy adolescents. The effects of endocrine alterations on regional body composition in AN, however, have not been reported. We, therefore, enrolled 23 adolescent girls with AN and 20 healthy girls of comparable maturity in a study examining regional body composition. Levels of estradiol and IGF-I, as well as measures of GH and cortisol concentration (using cluster analysis of data obtained from frequent sampling q30' for 12 h overnight) were examined to determine hormonal determinants of regional body composition in adolescent girls with AN and controls. Girls with AN were followed for 1 yr and examined again at weight recovery (10% increase in body mass index) (n = 11). Percent trunk fat and trunk to extremity fat ratio (T/E fat) were significantly reduced in girls with AN compared with healthy adolescents (P = 0.001 and 0.01, respectively). Percent trunk lean mass and trunk to extremity lean mass ratio (T/E lean) were higher in AN than in controls (P = 0.01 and 0.009); percent extremity lean mass was lower in AN (P = 0.009). In healthy controls, total area under the curve (AUC) for GH correlated inversely with percent trunk fat and T/E fat (r = -0.66, P = 0.002 and r = -0.62, P = 0.003). Similar correlations were observed between other measures of GH concentration (mean and nadir) and percent trunk fat and T/E fat. No relationship was observed between GH concentration and regional lean mass or between cortisol concentration and regional body composition. In contrast, GH concentration did not predict regional body composition in adolescents with AN on regression analysis. However, nadir cortisol concentration correlated inversely with percent extremity lean mass (r = -0.49; P = 0.02) and positively with percent trunk lean mass and T/E lean (r = 0.48, P = 0.03; and r = 0.49, P = 0.02) in girls with AN. A similar trend was observed between other measures of cortisol concentration (mean cortisol and AUC) and percent trunk lean mass and T/E lean in AN. Trunk fat was lowest in girls with AN who had high GH but low cortisol levels (based on median values), whereas some preservation of trunk fat was observed in girls with low GH and high cortisol levels. Weight recovery occurred in seven of 11 girls with low GH and high cortisol values; however, only two of the nine girls with high GH and low cortisol recovered weight. High GH with lower cortisol levels may thus be a marker of greater severity of AN. Our results suggest that in healthy controls, GH concentration predicts regional body composition and favors a redistribution of body fat such that T/E fat ratio decreases. In AN, however, high levels of GH and cortisol have contrasting associations with fat mass. High cortisol levels in AN predict a redistribution of lean body mass such that extremity lean mass decreases. Further studies are necessary to better understand the implications of these data.

Adolescent↗

PubMed2004

Growth hormone and ghrelin responses to an oral glucose load in adolescent girls with anorexia nervosa and controls.

Anorexia nervosa (AN) is associated with high levels of GH and low levels of IGF-I suggestive of a nutritionally acquired lack of GH action or GH resistance. The suppression of GH levels after administration of inhibitors of GH secretion such as oral glucose is the definitive test to distinguish normal from pathological states of GH excess, such as acromegaly. However, suppression of GH by glucose has not been well characterized in states of adaptive GH excess, such as AN, especially in a younger adolescent population with relatively higher GH levels, compared with adults. In this study, we investigated GH suppression after a 100-g oral glucose load over a 1-h period in 19 adolescent girls with AN and 20 healthy controls of similar chronologic and bone age. We also compared nocturnal GH secretion characteristics by deconvolutional analysis in both groups to determine differences in secretory patterns between adolescents whose GH values suppressed vs. those whose values did not after oral glucose. Fasting levels of ghrelin, a GH secretagogue, and suppression of ghrelin with oral glucose were also determined to assess whether GH suppression or nonsuppression could be related to ghrelin values at respective time points. At 0 min (0') of the oral glucose tolerance test, girls with AN had significantly lower levels of glucose (P = 0.009) and higher levels of GH (P = 0.04) than controls. Nadir GH values were higher in AN than in controls (2.0 +/- 1.8 vs. 0.5 +/- 0.5 ng/ml, P = 0.001). Only 31.6% of girls with AN suppressed their GH values to 1 ng/ml or less vs. 85.0% of healthy adolescents (P = 0.0005). All healthy controls had nadir postglucose GH values of 2 ng/ml or less. Nadir GH concentrations during the oral glucose tolerance test correlated directly with all measures of GH secretion [basal (r = 0.37, P = 0.02), pulsatile (r = 0.56, P = 0.0002), and total (r = 0.57, P = 0.0002)]. Adolescent girls who did not suppress their GH values to 1 ng/ml or less had significantly higher levels of ghrelin at 0', 30', and 60' (P = 0.02, 0.004, and 0.008), significantly higher GH at 0' (P = 0.001), and higher nocturnal basal (P = 0.002), pulsatile (P = 0.05), and total GH secretion (P = 0.03) than those who did suppress below this level. Ghrelin values were higher in AN than in controls at each time point (P = 0.02, 0.0002, and 0.01 at 0', 30', and 60') but did not predict GH values at these time points. Adolescent girls with AN fail to adequately suppress their GH values after a 100-g oral glucose load. This lack of suppression may be related to the higher GH secretion seen in adolescents with this disorder. In contrast, all healthy adolescents suppress their GH values to 2 ng/ml or less but not 1 ng/ml or less after a glucose load. Although ghrelin values are higher in AN than in controls, we could not demonstrate a relationship between ghrelin and GH values. The inability of healthy girls to uniformly suppress GH levels to 1 ng/ml or less, a normal level defined for adults, may be related to higher GH secretion in the pubertal years, compared with adult life. Further studies are needed to define GH suppression in an adolescent population.

Administration, Oral↗

PubMed2004

Hormonal and body composition predictors of soluble leptin receptor, leptin, and free leptin index in adolescent girls with anorexia nervosa and controls and relation to insulin sensitivity.

Anorexia nervosa (AN) is associated with very low levels of leptin, a cytokine secreted by adipose tissue and known to suppress appetite. Leptin may play a permissive role in onset of puberty and in resumption of gonadal function in conditions of undernutrition. The soluble leptin receptor (sOB-R) is the main leptin binding protein, and the ratio of serum leptin to sOB-R provides a measure of the free leptin index (FLI), which may be a more accurate determinant of leptin function. Determinants of sOB-R and FLI have not been examined in an adolescent population. We examined levels of sOB-R, leptin, and FLI, and body composition and hormonal determinants of these variables in 23 adolescent girls with AN and 21 healthy adolescent girls of comparable maturity prospectively over 1 yr. Measures of insulin resistance and adiponectin were also examined. We determined changes in levels of sOB-R, leptin, and FLI with weight recovery (defined as an increase in body mass index of >/=10%, n = 11), and with resumption of menstrual cycles (n = 13). Girls with AN had significantly higher levels of sOB-R (P = 0.0008) and significantly lower levels of leptin and FLI (P < 0.0001 for both) than healthy controls, and levels of FLI were reduced more than levels of leptin in girls with AN compared with controls. An inverse correlation was noted between levels of leptin and sOB-R for the group as a whole (r = -0.64, P < 0.0001) but not in girls with AN considered alone. The most important predictor of levels of sOB-R was cortisol in the group as a whole (r = 0.61, P < 0.0001) and in girls with AN considered alone (r = 0.66, P = 0.0008). Other independent predictors of sOB-R levels for the entire group were percent body fat (r = -0.44, P = 0.003) and levels of IGF-I (r = -0.37, P = 0.01). The most important predictors of leptin and FLI were body mass index and percent body fat. An inverse relationship was noted between measures of insulin resistance and sOB-R levels, whereas a positive association was noted between these measures and leptin and FLI. Adiponectin values did not differ in girls with AN compared with healthy controls and did not correlate with sOB-R, leptin, or FLI. Weight recovery resulted in significant decreases in levels of the sOB-R (24.7 +/- 1.7 to 17.6 +/- 1.2 U/ml, P = 0.004), and increases in levels of leptin (4.4 +/- 1.0 to 13.7 +/- 2.9 microg/liter, P = 0.02). Resumption of menstrual function, but not weight recovery alone, was associated with significant increases in FLI (0.19 +/- 0.04 to 0.50 +/- 0.09 microg/U x 10(-3), P = 0.02).We demonstrate an increase in levels of sOB-R and a decrease in the FLI in adolescent girls with AN, and also demonstrate that cortisol is the most important predictor of levels of sOB-R in this condition. Levels of leptin and FLI, conversely, are primarily predicted by body composition. Weight recovery is associated with a decrease in sOB-R and an increase in leptin. Resumption of menses is associated with significant increases in the FLI, suggesting that free leptin may be an important determinant of menstrual recovery.

Adipose Tissue↗

PubMed2004

Alterations in cortisol secretory dynamics in adolescent girls with anorexia nervosa and effects on bone metabolism.

Anorexia nervosa (AN) is associated with low bone density in adolescents and adults. Hypercortisolemia has been reported in adults with this disorder and has been hypothesized to be a factor in bone loss. However, the secretory dynamics of cortisol in adolescents with AN and the contribution of alterations in cortisol secretion to bone metabolism in AN have not been examined. We examined the dynamics of cortisol secretion by Cluster and deconvolutional analysis in 23 girls with AN and 21 healthy adolescents of comparable age and maturity. Cortisol sampling was performed every 30 min for 12 h overnight. Twenty-four-hour urinary free cortisol (UFC) and creatinine (cr) were obtained for all subjects. The surface area (SA) of the subjects was calculated. Markers of bone turnover (type 1 procollagen, osteocalcin, and N-telopeptide) were examined. Subjects with AN were prospectively followed over 1 yr, and those who recovered weight (defined as a 10% increase in body mass index) were again studied. On Cluster analysis, girls with AN had significantly higher mean cortisol (8.6 +/- 2.0 vs. 5.9 +/- 1.1 microg/dl; P < 0.0001), nadir cortisol (5.5 +/- 2.3 vs. 3.4 +/- 1.2 microg/dl; P = 0.0008), valley mean cortisol (7.0 +/- 2.7 vs. 4.7 +/- 1.5 microg/dl; P = 0.001), peak amplitude (12.6 +/- 4.4 vs. 7.8 +/- 3.0 microg/dl; P = 0.0004), peak area (652 +/- 501 vs. 340 +/- 238 microg/dl; P = 0.02), and total area under the curve (6112 +/- 1467 vs. 4117 +/- 802 microg/dl; P < 0.0001) than healthy adolescents. On deconvolutional analysis, the frequency of nocturnal secretory bursts (7.0 +/- 1.2 vs. 5.8 +/- 1.3 /12 h; P = 0.001), total nocturnal pulsatile cortisol secretion (69.3 +/- 14.7 vs. 53.9 +/- 11.1 microg/dl; P = 0.0003), and total cortisol secretion (89.6 +/- 18.8 vs. 71.2 +/- 17.6 microg/dl; P = 0.002) were significantly higher in girls with AN than in healthy controls. Cortisol half-life trended higher in girls with AN. However, basal cortisol secretion and approximate entropy did not differ between the groups. UFC/cr and UFC/cr.SA were significantly higher in girls with AN than in controls [0.050 +/- 0.028 vs. 0.036 +/- 0.017 (P = 0.04) and 0.035 +/- 0.020 vs. 0.023 +/- 0.012 (P = 0.03)]. Six of 23 girls with AN had UFC/cr.SA values that were more than 2 sd above those in healthy controls. An inverse correlation was noted between measures of cortisol concentration as well as pulsatile secretion and measures of nutritional status (body mass index, fat mass, leptin, insulin, and IGF-I). An oral glucose load suppressed cortisol levels in healthy adolescents, but not in AN patients. Weight recovery was associated with a significant decrease in the number of secretory bursts. In girls with AN, strong inverse correlations were noted between levels of cortisol (mean, nadir, and total area under the curve) and levels of markers of bone formation (C-terminal propeptide of type 1 procollagen and osteocalcin). Conversely, in healthy controls, cortisol values did not predict levels of markers of bone turnover. Adolescent girls with AN have significantly higher serum cortisol concentrations and UFC/cr.SA values than healthy adolescents. This increased cortisol concentration is a function of increased frequency of secretory bursts, resulting in increased pulsatile secretion. Hypercortisolemia appears to be a direct consequence of undernutrition and is associated with a decrease in markers of bone formation. Therefore, high cortisol values in AN may contribute to the low bone density observed in adolescents with this disorder by decreasing bone formation.

Adolescent↗

PubMed2004

Effects of anorexia nervosa on clinical, hematologic, biochemical, and bone density parameters in community-dwelling adolescent girls.

OBJECTIVE: Anorexia nervosa (AN) is an eating disorder that leads to a number of medical sequelae in adult women and has a mortality rate of 5.6% per decade; known complications include effects on hematologic, biochemical, bone density, and body composition parameters. Few data regarding medical and developmental consequences of AN are available for adolescents, in particular for an outpatient community-dwelling population of girls who have this disorder. The prevalence of AN is increasing in adolescents, and it is the third most common chronic disease in adolescent girls. Therefore, it is important to determine the medical effects of this disorder in this young population. METHODS: We examined clinical characteristics and performed hematologic, biochemical, hormonal, and bone density evaluations in 60 adolescent girls with AN (mean age: 15.8 +/- 1.6 years) and 58 healthy adolescent girls (mean age: 15.2 +/- 1.8 years) of comparable maturity. Nutritional and pubertal status; vital signs; a complete blood count; potassium levels; hormonal profiles; bone density at the lumbar and lateral spine; total body, hip, and femoral neck (by dual-energy x-ray absorptiometry) and body composition (by dual-energy x-ray absorptiometry) were determined. RESULTS: All measures of nutritional status such as weight, percentage of ideal body weight, body mass index, lean body mass, fat mass, and percentage of fat mass were significantly lower in girls with AN than in control subjects. Girls with AN had significantly lower heart rates, lower systolic blood pressure, and lower body temperature compared with control subjects. Total red cell and white cell counts were lower in AN than in control subjects. Among girls with AN, 22% were anemic and 22% were leukopenic. None were hypokalemic. Mean age at menarche did not differ between the groups. However, the proportion of girls who had AN and were premenarchal was significantly higher compared with healthy control subjects who were premenarchal, despite comparable maturity as determined by bone age. Ninety-four percent of premenarchal girls with AN versus 28% of premenarchal control subjects were above the mean age at menarche for white girls, and 35% of premenarchal AN girls versus 0% of healthy adolescents were delayed >2 SD above the mean. The ratio of bone age to chronological age, a measure of delayed maturity, was significantly lower in girls with AN versus control subjects and correlated positively with duration of illness and markers of nutritional status. Serum estradiol values were lower in girls with AN than in control subjects, and luteinizing hormone values trended lower in AN. Levels of insulin-like growth factor-I were also significantly lower in girls with AN. Estradiol values correlated positively with insulin-like growth factor-I, a measure of nutritional status essential for growth (r = 0.28). All measures of bone mineral density (z scores) were lower in girls with AN than in control subjects, with lean body mass, body mass index, and age at menarche emerging as the most important predictors of bone density. Bone density z scores of <-1 at any one site were noted in 41% of girls with AN, and an additional 11% had bone density z scores of <-2. CONCLUSIONS: A high prevalence of hemodynamic, hematologic, endocrine, and bone density abnormalities are reported in this large group of community-dwelling adolescent girls with AN. Although a number of these consequences of AN are known to occur in hospitalized adolescents, the occurrence of these findings, including significant bradycardia, low blood pressure, and pubertal delay, in girls who are treated for AN on an outpatient basis is of concern and suggests the need for vigilant clinical monitoring, including that of endocrine and bone density parameters.

Adolescent↗

PubMed2004

Effects of psychiatric disorders and psychotropic medications on prolactin and bone metabolism.

OBJECTIVE: Osteoporosis occurs in common psychiatric conditions and causes significant morbidity. Many neuroleptic medications can cause hyperprolactinemia, which can then potentially be associated with bone loss. Few reviews have thus far addressed this issue. We have consolidated information from studies that examined effects of psychiatric conditions and their treatment on bone metabolism. DATA SOURCES: We searched PubMed for original articles and reviews published between 1976 and 2004 that described changes in bone metabolism in psychiatric disorders and examined prolactin elevations with neuroleptic medications. Keywords used were major depressive disorder, bipolar disorder, schizophrenia, bone density, bone metabolism, hyperprolactinemia, typical antipsychotics, and atypical antipsychotics. STUDY SELECTION AND DATA EXTRACTION: 160 articles published in peer-reviewed journals were identified and are summarized, with greater emphasis given to data from larger, controlled studies. DATA SYNTHESIS: Schizophrenia and major mood disorders are often associated with perturbations in bone metabolism related to factors including nutritional alterations, smoking, and hypogonadotropic hypogonadism, with or without medication-induced hyperprolactinemia. Polydipsia can contribute to bone loss in schizophrenia, whereas hypercortisolemia is often associated with low bone density in depression. Lithium in bipolar disorder and thyroid-stimulating hormone-suppressive doses of L-thyroxine have a negative impact on bone health. Mood stabilizers such as carbamazepine and valproate can also affect bone density. Hyperprolactinemia may lead to bone loss only if associated with untreated amenorrhea in women or testosterone deficiency in men. Some atypical neuroleptics, by causing lesser elevations in prolactin, may therefore have a less marked impact on bone than typical neuroleptics. CONCLUSIONS: Because significant morbidity is associated with low bone density and many psychiatric conditions may have a negative impact on bone metabolism, bone density evaluation should be considered an integral component of chronic medical care of these disorders, and risk factors should be identified and addressed.

Adult↗

PubMed2003

MIS/AMH in the assessment of cryptorchidism and intersex conditions.

Mullerian inhibiting substance (MIS), also known as anti-Mullerian hormone (AMH), causes Mullerian duct involution during male sexual differentiation and also has a postnatal regulatory role in the gonads. Serum MIS/AMH has a gonad specific pattern of expression and its concentrations are sexually dimorphic in children; hence measurement of serum MIS/AMH helps in the evaluation of children with gonadal disorders. In boys with cryptorchidism (non-palpable gonads), serum MIS/AMH correlates with testicular tissue. A measurable value is predictive of undescended testes while an undetectable value is highly suggestive of anorchia. In minimally virilized phenotypic females, MIS/AMH helps differentiate between gonadal and non-gonadal causes of virilization. In children with intersex conditions, MIS/AMH values assist differential diagnosis: a value above the normal female range is predictive of testicular tissue, while an undetectable value is suggestive of absent testicular tissue. Thus, MIS/AMH is useful for delineating gonadal pathology and facilitates the differential diagnosis and management of children with diverse gonadal disorders.

Adolescent↗

PubMed2003

Regional body composition in adolescents with anorexia nervosa and changes with weight recovery.

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.

Abdomen↗