Case records of the Massachusetts General Hospital. Case 36-2006. A 35-year-old pregnant woman with new hypertension.
Explore the source record for details and available documents.
Adrenal Cortex Neoplasms↗
Biomedical subjects
Anne Klibanski
Publications and source records attributed to Anne Klibanski.
The effects of SOM230 on cell proliferation and adrenocorticotropin secretion in human corticotroph pituitary adenomas.
CONTEXT: There is no tumor-directed medical therapy available for Cushing's disease. OBJECTIVE: The objective was to determine the in vitro effect of the somatostatin analog pasireotide (SOM230) on cell proliferation in human corticotroph tumors. DESIGN/METHODS: Expression of somatostatin receptors (SSTR 1-5) was determined by quantitative RT-PCR in 13 human corticotroph tumors and by immunohistochemistry (IHC) in 12 of the 13 tumors. SOM230 effects on cell proliferation and ACTH release were evaluated in vitro using primary cultures of six of the 13 human corticotroph adenomas. RESULTS: In our series, we found expression of SSTR subtypes 1, 2, 4, and 5 in human corticotroph tumors by quantitative RT-PCR. All receptor subtypes were detected by IHC, with SSTR subtype 5 having the highest IHC score in 83% (10 of 12) of the cases. Significant suppression of cell proliferation was observed in all tumors cultured (percent suppression range: 10-70%; P = 0.045-0.001). SOM230 inhibited ACTH secretion in five of the six tumors cultured (percent suppression range: 23-56%; P = 0.042-0.001). CONCLUSION: Corticotroph tumors express multiple SSTR subtypes. SOM230 significantly suppressed cell proliferation and ACTH secretion in primary cultures of human corticotroph tumors. These in vitro results support the hypothesis that SOM230 may have a role in the medical therapy of corticotroph tumors.
ACTH-Secreting Pituitary Adenoma↗
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↗
Cyclic AMP stimulates MEG3 gene expression in cells through a cAMP-response element (CRE) in the MEG3 proximal promoter region.
MEG3 is a human maternally expressed gene that potentially acts as a non-coding RNA. Our laboratory found that a cDNA isoform of MEG3, MEG3a, inhibits cell proliferation. MEG3 is highly expressed in the normal human pituitary but not expressed in clinically non-functioning pituitary tumors, suggesting that this imprinted gene may be involved in pituitary tumorigenesis. Previously we demonstrated that hypermethylation of the MEG3 promoter region is associated with the loss of MEG3 expression in pituitary tumors, potentially by blocking the binding of transcription factors to their cis-elements. To further investigate the cis- and trans-factors that are important for the regulation of MEG3, we have characterized the human MEG3 promoter. A single transcription initiation site was identified by 5' RACE. Up to 5kb of the 5'-flanking region of MEG3 gene was cloned into a reporter plasmid. Deletion and mutation analysis suggest that a cAMP response element (CRE), located between -69 and -49 of the MEG3 proximal promoter region, is critical for promoter activity. Consistent with this finding, Northern blot analysis demonstrate that elevated intracellular cAMP levels stimulate MEG3 expression in human fibroblasts in culture. Furthermore, gel shifting, ChIP analysis, and co-transfection experiments show that CREB directly binds to the CRE site and stimulates MEG3 promoter activity. Therefore, MEG3 is a downstream target gene of cAMP. Together with the anti-proliferative function of cAMP, our data suggest that MEG3 may interact with the cAMP-dependent signaling pathway to be involved in the control of cell proliferation and other cAMP-related physiological functions.
Base Sequence↗
Regional cerebral brain metabolism correlates of neuroticism and extraversion.
Factor-analytic approaches to human personality have consistently identified several core personality traits, such as Extraversion/Introversion, Neuroticism, Agreeableness, Consciousness, and Openness. There is an increasing recognition that certain personality traits may render individuals vulnerable to psychiatric disorders, including anxiety disorders and depression. Our purpose in this study was to explore correlates between the personality dimensions neuroticism and extraversion as assessed by the NEO Five-Factor Inventory (NEO-FFI) and resting regional cerebral glucose metabolism (rCMRglu) in healthy control subjects. Based on the anxiety and depression literatures, we predicted correlations with a network of brain structures, including ventral and medial prefrontal cortex (encompassing anterior cingulate cortex and orbitofrontal cortex), insular cortex, anterior temporal pole, ventral striatum, and the amygdala. Twenty healthy women completed an (18F)FDG (18F-fluorodeoxyglucose) positron emission tomography (PET) scan at rest and the NEO-FFI inventory. We investigated correlations between scores on NEO-FFI Neuroticism and Extraversion and rCMRglu using statistical parametric mapping (SPM99). Within a priori search territories, we found significant negative correlations between Neuroticism and rCMRglu in the insular cortex and positive correlations between Extraversion and rCMRglu in the orbitofrontal cortex. No significant correlations were found involving anterior cingulate, amygdala, or ventral striatum. Neuroticism and Extraversion are associated with activity in insular cortex and orbitofrontal cortex, respectively.
Adult↗
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↗
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↗
Fear conditioning and extinction: influence of sex and menstrual cycle in healthy humans.
Although sex differences have been demonstrated in behavioral paradigms of fear conditioning, the findings have been inconsistent, and fear extinction has been little studied. The present study investigated the influence of sex and menstrual cycle phase on the recall of fear extinction. Three groups of healthy adult participants were studied: women at 2 different phases of the menstrual cycle (early follicular [early cycle] and late follicular [midcycle]) and men. Participants underwent a 2-day fear conditioning and extinction protocol. The paradigm entailed habituation, fear conditioning, and extinction learning on Day 1 and extinction recall and fear renewal on Day 2. Skin conductance served as the dependent variable. During fear acquisition on Day 1, men showed significantly larger conditioned responses relative to women; early cycle and midcycle women did not differ. No significant group differences were found during extinction learning. On Day 2, men and early cycle women expressed greater extinction memory than midcycle women. These data confirm sex differences in conditioned fear acquisition and suggest that midcycle hormones attenuate extinction recall.
Adult↗
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↗
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↗
Serum prolactin levels among outpatients with major depressive disorder during the acute phase of treatment with fluoxetine.
OBJECTIVE: To determine changes in serum prolactin levels in outpatients with DSM-IV-diagnosed major depressive disorder (MDD) following a 12-week open-label trial of fluoxetine. METHOD: 87 outpatients enrolled in the trial had serum prolactin levels determined at baseline and during their final visit (week 12 or discontinuation visit). In addition, serum testosterone levels were measured in 44 of the 46 men during these 2 visits. Hyperprolactinemia was defined as a serum prolactin level greater than 16.5 ng/mL or 18.9 ng/mL for men and women, respectively. The study was conducted from September 1997 to March 2002. RESULTS: Of 80 patients with normal prolactin levels at baseline, 10 (12.5%) developed hyper-prolactinemia following fluoxetine treatment. Specifically, 2 (4.5%) of 44 men and 8 (22.2%) of 36 women with normal prolactin levels at baseline developed hyperprolactinemia following treatment with fluoxetine (p = .0174 for between-gender difference). In addition, there was a significant increase in mean +/- SD serum prolactin levels following treatment with fluoxetine in all patients with normal baseline prolactin levels (6.4 +/- 3.4 to 10.0 +/- 7.0 ng/mL, p = .002). There were no significant changes from baseline in testosterone levels in men following fluoxetine treatment (448.4 +/- 139.6 to 439.5 +/- 142.1 ng/dL, p > .05; normal above 245 ng/dL), while none of the 44 men developed low testosterone levels following fluoxetine treatment. CONCLUSION: 4.5% of men and 22.2% of women with MDD developed new onset hyper-prolactinemia following fluoxetine treatment.
Adult↗
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↗
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↗
Reciprocal changes in endogenous ghrelin and growth hormone during fasting in healthy women.
Ghrelin stimulates growth hormone (GH) secretion, but it is unknown whether there is a feedback of GH on ghrelin secretion. In this study, we characterized the relatedness of GH and ghrelin in a model of acute caloric deprivation in 10 healthy women (age 26.7 +/- 1.6 yr) during a 4-day fast in the early follicular phase. GH, ghrelin, and cortisol were assessed every hour over 24 h during an isocaloric diet and after a 4-day complete fast. Sampling during a normal diet at baseline demonstrated that ghrelin decreased 17.9% within 1 h after meals (P < 0.0001), but there was no meal effect on GH. BMI (22.3 +/- 0.4 vs. 21.5 +/- 0.4 kg/m2, P < 0.0001) and IGF-I (312 +/- 28 vs.124 +/- 22 ng/ml, P < 0.0001) decreased during fasting. Mean 24-h GH increased (2.6 +/- 0.5 vs. 5.6 +/- 0.5 ng/ml, P < 0.001), but ghrelin decreased (441.3 +/- 59.7 vs. 359.8 +/- 54.2 pg/ml, P = 0.012). The peak ghrelin level decreased from 483.5 to 375.6 pg/ml (P < 0.0001), and the time of the peak ghrelin changed from 0415 to 1715. In contrast, the diurnal pattern of GH was maintained, with increases in the nadir (1.1 to 3.4 ng/ml) and peak GH concentrations (4.1 to 7.9 ng/ml) from the fed to fasted state (P < 0.0001). The change in morning GH concentrations was inversely related to the change in ghrelin (r = -0.79, P = 0.012). During complete short-term caloric deprivation in healthy women, ghrelin decreases, even as GH rises, and these processes appear to be reciprocal, suggesting that GH exhibits feedback inhibition on ghrelin. Our data provide new evidence of the physiological relationship of GH and ghrelin in response to changes in protein-energy metabolism.
Adult↗
A critical analysis of pituitary tumor shrinkage during primary medical therapy in acromegaly.
CONTEXT: Somatostatin analogs have been successfully used to treat patients with GH-secreting pituitary adenomas because they are safe, effective, and usually well tolerated. The results of studies evaluating acromegaly treatment with the somatostatin receptor ligands (SRLs), octreotide and lanreotide, have supported the use of these agents for primary medical therapy before or as an alternative to traditional interventions of surgery and radiotherapy in selected cases. EVIDENCE ACQUISITION: We therefore undertook a systematic literature overview to characterize the results of studies involving primary therapy with somatostatin analogs and their effects on pituitary tumor size. Because most studies in which pituitary tumor shrinkage has been assessed involve uncontrolled, open-label, prospective trials or retrospective case series, the lack of a control arm does not permit pooling of data in a metaanalytic fashion to determine tumor size reduction. Therefore, this systematic review was designed to document and stratify data by study design, summarize therapeutic regimens and patient characteristics, assess the percentage of patients showing changes in tumor size, and calculate the weighted average effect on size reduction. EVIDENCE SYNTHESIS: Overall, for patients who experience significant shrinkage, an approximately 50% decrease in pituitary mass is achieved when a somatostatin analog is used exclusively or before surgery or radiotherapy. Fourteen studies (n = 424) provided a definition of significant tumor shrinkage, and the results showed that 36.6% (weighted mean percentage) of patients receiving primary SRL therapy for acromegaly experienced a significant reduction in tumor size. The weighted mean percent reduction in tumor size was 19.4% for those studies in which all patients received SRLs and change in tumor size was reported for all patients. CONCLUSIONS: Clinical implications are discussed for patients in whom tumor size control with SRLs is an important objective, typically those who have failed surgery or are being treated with primary medical therapy with large tumors.
Acromegaly↗
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↗
Medical findings in outpatients with anorexia nervosa.
BACKGROUND: Approximately 0.5% to 1% of college-aged women have anorexia nervosa and most of them live in the community. However, few clinical data exist regarding community-dwelling women with anorexia nervosa. The objective of this study was to determine the prevalences of common medical findings for these women. METHODS: Cross-sectional, community-based study of 214 women with anorexia nervosa as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Participants were recruited through advertisements and community-based referrals to a study investigating skeletal health in outpatients with anorexia nervosa. RESULTS: The prevalences of medical findings among the 214 participants were as follows: anemia, 38.6%; leukocytopenia, 34.4%; hyponatremia, 19.7%; hypokalemia, 19.7%; bradycardia, 41.3%; hypotension, 16.1%; hypothermia, 22.4%; elevation of alanine aminotransferase concentration, 12.2%; osteopenia, 51.7%; osteoporosis, 34.6%; and primary amenorrhea, 14.8%. Moreover, 30% of the women reported histories of bone fractures. Except for leukocytopenia (P = .01), bone loss (P = .04), and bradycardia (P = .01), the probability of specific medical findings could not be predicted by the degree of undernutrition. CONCLUSIONS: These results demonstrate a high prevalence of medical findings in community-dwelling women with anorexia nervosa. Therefore, women with anorexia nervosa should be carefully followed up with regular physical examinations and laboratory assessments. In addition, low weight, particularly in conjunction with the abnormalities reported, should prompt the consideration of a diagnosis of anorexia nervosa.
Absorptiometry, Photon↗
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↗