Leptin, ghrelin, and adiponectin in the metabolic adjustment to burn injury in children.

OBJECTIVE: Leptin, adiponectin, and ghrelin have diverse roles in the control of inflammation and metabolism in a normal state as well as in a chronic disease state. The aim of this study was to evaluate their role in the extreme metabolic and proinflammatory state after burn injury and during the initial weeks of recovery. METHODS: A prospective descriptive study in a tertiary care center was undertaken. Patients were comprised of 5 children aged 20-108 months with severe burn injury; burn size ranged from 15%-36% of total body surface area. Early enteral feeding, according to estimated energy expenditure, was initiated as 150% of the recommended dietary allowance and in accordance with the patients' nitrogen balance. Seven blood samples were collected sequentially, approximately 5 days apart, during the first 65 days after the burn injury. Samples were tested for leptin, ghrelin, and adiponectin. RESULTS: Leptin, ghrelin, and adiponectin had a similar trajectory of concentration over time: low levels at the beginning, increasing until 2-3 weeks post-burn, where they reached a plateau at 5 weeks post-injury. The typical inverse correlations of ghrelin and adiponectin with leptin were absent. Interleukin-6 was negatively associated with ghrelin and adiponectin and was not associated with leptin. Insulin-like growth factor-1 (IGF-1) had a positive association with the 3 hormones; however, their profiles differ in their relationship to the expected concentration based on a literature review. Ghrelin and adiponectin were higher, leptin and IGF-1 were lower than expected. CONCLUSIONS: In the early weeks after burn injury, the hypermetabolic state and inflammation have a major effect on leptin, ghrelin, and adiponectin. The concurrent and similar change of the 3 hormones serves the parallel anabolic and catabolic processes during the recovery from burn injury. .

Evaluation of leptin levels among fibromyalgia patients before and after three months of treatment, in comparison with healthy controls.

BACKGROUND: Leptin, an adipocyte-produced cytokine, interacts with various hormones, including those of the hypothalamic-pituitary-adrenal axis. Fibromyalgia is a syndrome characterized by widespread pain accompanied by tenderness. The pathogenesis involves a disturbance in pain processing and transmission by the central nervous system, leading to a general increase in pain perception. OBJECTIVES: To analyze potential changes in leptin levels among female fibromyalgia patients compared with healthy controls, and to evaluate the changes in leptin levels during treatment. METHODS: Sixteen female fibromyalgia patients were recruited. Patients underwent clinical evaluation, physical examination, including manual dolorimetry, and were evaluated regarding quality of life, pain, fatigue, anxiety and depression. Plasma leptin levels were determined by ELISA. Patients were offered standard treatment for fibromyalgia. Clinical evaluation and leptin determination were repeated after three months. RESULTS: No significant difference was observed between leptin levels among fibromyalgia patients and controls; no significant correlation was observed between leptin levels and clinical parameters reflecting fibromyalgia severity; and no significant change was observed in leptin levels over three months of treatment. These results did not change after adjustment of leptin levels for body mass index values. CONCLUSIONS: The results of the present study do not support the existence of a significant relationship between leptin and fibromyalgia pathogenesis. Increasing the sample size or examining the interaction between leptin and additional hormones/mediators of metabolism and body weight control may yet uncover significant information in this field.

Leptin locally synthesized in carotid atherosclerotic plaques could be associated with lesion instability and cerebral emboli.

BACKGROUND: Unstable carotid plaques cause cerebral emboli. Leptin promotes atherosclerosis and vessel wall remodeling. We hypothesized that carotid atherosclerotic lesion instability is associated with local leptin synthesis. METHODS AND RESULTS: Carotid endarterectomy plaques from symptomatic (n=40) and asymptomatic patients with progressive stenosis (n=38) were analyzed for local expression of leptin, tumor necrosis factor (TNF)-α, and plasminogen activator inhibitor type 1. All lesions exhibited advanced atherosclerosis inclusive of thick- and thin-cap fibroatheromas or lesion rupture. Symptomatic lesions exhibited more plaque ruptures and macrophage infiltration (P=0.001 and P=0.05, respectively). Symptomatic plaques showed preferential leptin, TNF-α, and plasminogen activator inhibitor type 1 transcript (P=0.03, P=0.04, and P=0.05, respectively). Leptin mRNA and antigen in macrophages and smooth muscle cells were confirmed by in situ hybridization and immunohistochemistry. Plasma leptin levels were not significantly different between groups (P=1.0), whereas TNF-α was significantly increased in symptomatic patients (P=0.006). Human aortic smooth muscle cell culture stimulated by TNF-α, lipopolysaccharide, or lipoteichoic acid revealed 6-, 6.7-, and 6-fold increased secreted leptin antigen, respectively, at 72 hours (P<0.05). CONCLUSIONS: Neurologically symptomatic patients overexpress leptin mRNA and synthesize leptin protein in carotid plaque macrophages and smooth muscle cells. Local leptin induction, presumably by TNF-α, could exert paracrine or autocrine effects, thereby contributing to the pathogenesis of lesion instability. CLINICAL TRIAL REGISTRATION: URL: www.Clinicaltrials.gov. Unique identifier: NCT00449306.

Cord blood adiponectin and infant growth at one year.

OBJECTIVE: The aim of this study was to determine the association between cord blood adiponectin and leptin and early infant growth at one year in small for gestational age (SGA) and appropriate for gestational age (AGA) infants. STUDY DESIGN: In this prospective study adiponectin and leptin concentrations were determined in cord blood of (i) AGA newborns (n = 44) and (ii) SGA newborns (n = 24). At one year of age, height and weight were measured. Linear regression analysis was used to determine which factors were associated with anthropometric measurements at the age of one year. RESULTS: (i) SGA neonates had a significantly lower median cord blood adiponectin and leptin than AGA neonates; (ii) among SGA neonates, cord blood adiponectin concentrations were negatively correlated with body weight at one year, weight gain after one year and with BMI at one year; and (iii) among AGA neonates cord blood adiponectin concentrations were negatively correlated with body weight at one year, weight gain after one year and with BMI at one year. CONCLUSION: The disparity in cord blood adiponectin and leptin concentrations between SGA and AGA neonates suggests a role for adipokines in fetal growth.

Insulin sensitivity in late gestation and early postpartum period: the role of circulating maternal adipokines.

OBJECTIVE: Early postpartum period is characterised by a dramatic decrease in insulin resistance and significant metabolic alterations. The aims of this study were to determine the changes in circulating maternal concentrations of total adiponectin, adiponectin multimers, leptin and resistin before and after the delivery and to explore their relationship with insulin sensitivity. METHODS: Twenty-seven normal pregnant women at term were included in this longitudinal study. Blood samples were taken before and 4 days after elective caesarean section. Total adiponectin, adiponectin multimers, leptin, resistin, glucose, insulin and prolactin were measured in maternal serum. Adiponectin multimers were measured before and after the delivery in eight women. RESULTS: (1) The mean maternal serum total adiponectin concentration was significantly higher before than after delivery while the relative distribution of circulating maternal adiponectin multimers did not change after delivery; (2) the median maternal serum concentration of leptin was significantly higher in the antepartum than in the postpartum period; (3) the median maternal serum resistin concentration was comparable before and after delivery; (4) multiple linear regression analysis revealed that antepartum insulin sensitivity was associated with maternal low body mass index, and low glucose concentrations in glucose challenge test, as well as with maternal age and increased leptin concentrations. Postpartum insulin sensitivity was associated with decreased circulating resistin concentrations. CONCLUSIONS: Despite increase in insulin sensitivity, early postpartum period is characterised by a decrease in maternal circulating total adiponectin and by steady concentrations of resistin and adiponectin multimers compared to the late third trimester.

Serologic bone markers for predicting development of osteonecrosis of the jaw in patients receiving bisphosphonates.

PURPOSE: Osteonecrosis of the jaw is a well-documented side effect of bisphosphonate (BP) use. Attempts have recently been made to predict the development of bisphosphonate-related osteonecrosis of the jaw (BRONJ). We prospectively investigated the predictive value of serum levels of C-terminal telopeptide of collagen I (CTX), bone-specific alkaline phosphatase, and parathyroid hormone for the development of BRONJ. PATIENTS AND METHODS: Data on the demographics, comorbidities, and BP treatment were collected from 78 patients scheduled for dentoalveolar surgery. Of the 78 patients, 51 had been treated with oral BPs and 27 had been treated with frequent intravenous infusions of BPs. Blood samples for CTX, bone-specific alkaline phosphatase, and parathyroid hormone measurements were taken preoperatively. Surgery was performed conservatively, and antibiotic medications were prescribed for 7 days. RESULTS: Of the 78 patients, 4 patients taking oral BPs (7.8%) and 14 receiving intravenous BPs (51.8%) developed BRONJ. A CTX level less than 150 pg/mL was significantly associated with BRONJ development, with an increased odds ratio of 5.268 (P = .004). The bone-specific alkaline phosphatase levels were significantly lower in patients taking oral BPs who developed BRONJ. The parathyroid hormone levels were similar in patients who did and did not develop BRONJ. CONCLUSION: The incidence of BRONJ after oral surgery involving bone is greater among patients receiving frequent, intravenous infusions of BPs than among patients taking oral BPs. Although the measurement of serum levels of CTX is not a definitive predictor of the development of BRONJ, it might have an important role in the risk assessment before oral surgery.

Total and high molecular weight adiponectin are elevated in patients with Laron syndrome despite marked obesity.

OBJECTIVE: Patients with Laron syndrome (LS; primary GH insensitivity) caused by molecular defects of the GH receptor gene, are characterized by dwarfism, profound obesity, and hyperlipidemia. The aim of the current study was to evaluate adiponectin levels in LS, as obesity is known to be associated with low adiponectin. DESIGN AND METHODS: We studied nine untreated LS adult patients (5 males, 4 females) and six girls with LS receiving once-daily treatment by IGF1. Total and high molecular weight (HMW) adiponectin levels, adiponectin multimers distribution, and metabolic indices were analyzed in serum samples obtained during several years of follow-up. RESULTS: Adiponectin levels in the severely obese adult LS patients (percent body fat; females 61.0+/-2.5%, males 40.6+/-8.1%) were two- to three-fold higher than those reported for subjects of corresponding age, gender and degree of adiposity. Total adiponectin was significantly higher in females compared with males (21.4+/-3.5 vs 10.2+/-4.6 microg/ml, P<0.001). The elevated adiponectin in LS subjects was associated with an increased abundance of the HMW isoform, and positively correlated with body fat percentage (r=0.65, P=0.017) and leptin (r=0.65, P=0.012). There was no correlation between adiponectin levels (total and HMW) and the degree of insulin resistance in LS subjects or their blood lipids levels. Adiponectin was also high in young girls with LS (22.9+/-7.4 microg/ml) and did not change during long-term IGF1 replacement therapy. CONCLUSION: Adiponectin hypersecretion in LS, despite profound obesity, suggests that GH activity may negatively impact adiponectin secretion from adipocytes.

Maternal depression and anxiety across the postpartum year and infant social engagement, fear regulation, and stress reactivity.

OBJECTIVE: To examine the effects of maternal depression on infant social engagement, fear regulation, and cortisol reactivity as compared with maternal anxiety disorders and controls and to assess the role of maternal sensitivity in moderating the relations between maternal depression and infant outcome. METHOD: Using an extreme-case design, 971 women reported symptoms of anxiety and depression after childbirth and 215 of those at the high and low ends were reevaluated at 6 months. At 9 months, mothers diagnosed with a major depressive disorder (n = 22) and anxiety disorders (n = 19) and matched controls reporting no symptoms across the postpartum year (n = 59) were visited at home. Infant social engagement was observed during mother-infant interaction, emotion regulation was microcoded from a fear paradigm, and mother's and infant's cortisol were sampled at baseline, reactivity, and recovery. RESULTS: The infants of depressed mothers scored the poorest on all three outcomes at 9 months-lowest social engagement, less mature regulatory behaviors and more negative emotionality, and highest cortisol reactivity-with anxious dyads scoring less optimally than the controls on maternal sensitivity and infant social engagement. Fear regulation among the children of anxious mothers was similar to that of the controls and their stress reactivity to infants of depressed mothers. Effect of major depressive disorder on social engagement was moderated by maternal sensitivity, whereas two separate effects of maternal disorder and mother sensitivity emerged for stress reactivity. CONCLUSIONS: Pathways leading from maternal depression to infant outcome are specific to developmental achievement. Better understanding of such task-specific mechanisms may help devise more specifically targeted interventions.

Patterns and prognostic value of troponin, interleukin-6, and leptin after pediatric open-heart surgery.

PURPOSE: Leptin and interleukin-6 (IL-6) are inversely correlated and associated with decreased survival in critically ill patients. We investigated changes in leptin, IL-6, and troponin in children undergoing open-heart surgery, hypothesizing that IL-6 and troponin will increase after cardiopulmonary bypass (CPB) and will be negatively correlated with leptin. PATIENTS AND METHODS: Serial blood samples were collected from 21 patients 24 hours before and up to 48 hours after surgery. RESULTS: Leptin levels decreased by 50% during CPB (P < .001), then gradually increased, reaching baseline levels 12 hours after surgery. The IL-6 levels increased (P < .001) during CPB, peaking 2 hours after surgery and remaining slightly elevated at 24 hours after surgery (P < .001). Leptin and IL-6 were negatively correlated (R = -0.448, P < .001). Troponin levels increased during CPB (P < .001). Postoperative leptin and troponin were inversely correlated (r = -0.535, P < .001). Patients with modest elevations in troponin levels (<20 microg/L) had a shorter aortic clamp and CPB time (P < .01), lower IL-6 peak levels (P = .03), and shorter duration of ventilation and inotropic support compared with patients with peak troponin levels greater than 20 microg/L. CONCLUSIONS: Lower leptin and higher IL-6 levels correlated with troponin, a marker of myocardial injury. Because leptin may have cardioprotective effects, the postoperative drop in its levels may further contribute to myocardial dysfunction.

Adiponectin levels in adolescent girls with polycystic ovary syndrome (PCOS).

OBJECTIVE: To determine serum adiponectin concentrations in adolescent girls with and without polycystic ovary syndrome (PCOS) and to assess possible correlations of adiponectin levels with insulin and androgen levels. DESIGN: Prospective case-control study. SETTING: Endocrine clinics in the community. PATIENTS: Forty-four adolescent girls were grouped as follows: 14 were overweight [body mass index (BMI) standard deviation score >1.645] with PCOS; 16 were lean (BMI SDS <1.036) with PCOS; and 14 were lean (BMI SDS <1.036) without PCOS. Intervention Blood samples were collected from all girls between 8 and 11 am, after an overnight fast. MAIN OUTCOME MEASURES: Serum levels of adiponectin, leptin, insulin, Müllerian-inhibiting substance, luteinizing hormone, follicle-stimulating hormone, testosterone, 17-alpha-hydroxyprogesterone, androstendione, dehydroepiandrosterone sulphate (DHEAS) and 17beta-oestradiol. RESULTS: Adiponectin concentrations were significantly decreased in obese adolescents with PCOS (10.5 +/- 5.5 mug/ml) compared with that in lean girls with or without PCOS (16.9 +/- 8.64 and 18.0 +/- 7.4 mug/ml respectively). Leptin levels were significantly elevated in obese adolescents with PCOS compared with the levels in normal weight adolescents with PCOS, and compared with that in normal weight controls. Insulin levels were markedly higher in obese adolescents with PCOS compared with that in normal weight adolescents (12.3 +/- 12.2 vs. 4.5 +/- 2.9, P < 0.05), and compared with that in normal weight PCOS adolescents (7.4 +/- 4.9); however, this difference was not statistically significant. Insulin levels did not differ between normal weight adolescents with PCOS and normal controls. Adiponectin concentrations correlated inversely with BMI, leptin and insulin. CONCLUSIONS: Hypoadiponectinaemia is evident only in obese adolescents with PCOS and therefore does not seem to be involved in the pathogenesis of PCOS in this age group.

Adiponectin and leptin concentrations in dichorionic twins with discordant and concordant growth.

CONTEXT: Discordant twin gestation, in which one fetus is growth restricted, is a unique model that can elucidate the mechanism(s) by which the intrauterine environment affects fetal growth. OBJECTIVE: The objective of the study was to determine the cord blood adiponectin and leptin concentrations and evaluate their association with birth weight in dichorionic twins, with and without growth discordance. DESIGN, SETTING, PARTICIPANTS, AND MAIN OUTCOME MEASURE: In this cross-sectional study, arterial cord blood adiponectin and leptin concentrations were determined in two groups of newborns: 1) discordant twins, in which one of the twins is growth restricted (small for gestation age and abnormal umbilical arteries Doppler) and the other is appropriate for gestation age (AGA) (n = 14 pairs); and 2) concordant twins, in which both twins are AGA (n = 15 pairs). RESULTS: Results were: 1) within the discordant twins group, the median adiponectin concentration was significantly lower in the growth-restricted newborns than in their cotwins (P = 0.004); 2) within the concordant twin group, there was no significant difference in the median cord blood adiponectin concentration between the two AGA twins; 3) the median leptin concentration did not differ between the twins pairs in both study groups; 4) a positive correlation between cord blood adiponectin concentrations and both birth weight (r = 0.7, P < 0.001) and gestational age (r = 0.6, P < 0.02) was found only in the small-for-gestational-age newborns; 5) linear regression model revealed that birth weight is independently associated with circulating adiponectin concentration. CONCLUSIONS: Low circulating adiponectin concentrations, previously reported in adults, children, and infants who were born small for gestational age, characterize fetuses with growth restriction and are independently associated with birth weight.

Determining the source of fetal adiponectin.

OBJECTIVE: To determine whether maternal, placental or fetal compartment contributes to the high levels of cord blood adiponectin. STUDY DESIGN: Serum adiponectin levels were compared from 62 newborns and their mothers as well as 32 newborns at delivery and 4 days postpartum. In addition, human placental tissues were tested for the presence of adiponectin mRNA by reverse transcriptase polymerase chain reaction. RESULTS: Cord blood serum adiponectin levels were significantly higher and did not correlate with maternal adiponectin levels (32.5 +/- 7.5 vs. 11.0 +/- 3.6 microg/mL, p < 0.001). Cord blood and day 4 serum adiponectin did not differ significantly (32.6 +/- 7.6 vs. 29.5 +/- 8.4 microg/mL, p < 0.3). In addition, adiponectin mRNA was not expressed in the placenta. CONCLUSION: These findings preclude the possibility of a placental or maternal origin of cord adiponectin. Thus, the high cord adiponectin levels may be attributed to fetal tissues.

Suppression of amyloidogenesis in a mouse model by corticosteroid intervention.

Steroid treatment of amyloidosis was studied previously in human and murine models of reactive amyloidosis but with limited success and with conflicting results. To determine whether steroids may inhibit amyloidogenesis, and to study factors that may play a role in this effect, the authors induced amyloidosis in Swiss male mice, using the enhanced protocol with a single intravenous injection of amyloid-enhancing factor (AEF) and 3 successive daily subcutaneous AgNO(3) injections. Suppression of amyloid formation by various commonly used steroid preparations was evaluated from the amount of splenic amyloid, using the crush-and-smear technique. All steroid preparations examined were found to suppress amyloidogenesis but with differences between them in the degree and duration of inhibition. In general, hydrocortisone and dexamethasone had the highest suppressive effect, whereas methylprednisolone displayed lower activity for shorter duration. Single-dose experiments revealed that steroid effect is limited to the onset of amyloidogenesis. These experiments show that corticosteroids may significantly suppress amyloidogenesis but only briefly and, therefore, discourage a long-term and late use of steroid supplement in different anti-amyloid treatment protocols.

Modulation of adiponectin and leptin during refeeding of female anorexia nervosa patients.

CONTEXT: Several studies assessed adiponectin levels in anorexia nervosa (AN) patients, however, data regarding the dynamics of changes in adiponectin levels during refeeding of these patients is limited and contradicting. OBJECTIVE: Our objective was to assess adiponectin levels and the distribution of its different isoforms in AN patients before and after long-term refeeding, and to relate them to alterations in body mass index, leptin, insulin sensitivity, and additional endocrine parameters. DESIGN, SETTING, AND PARTICIPANTS: We conducted a longitudinal controlled study of 38 female adolescent malnourished AN inpatients, with 13 young, lean, healthy women serving as controls. Blood samples were obtained upon admission and thereafter at 1, 3, and 5 months (at target weight). MAIN OUTCOME MEASURES: Changes in body mass index, leptin, adiponectin, insulin sensitivity, and adiponectin multimeric forms were measured. RESULTS: At admission, leptin levels of AN patients were significantly lower, whereas insulin sensitivity (assessed by homeostasis model assessment-insulin resistance), adiponectin levels, and the ratio of high molecular weight (HMW) adiponectin to total adiponectin were significantly higher compared with controls. During weight recovery, leptin levels and homeostasis model assessment-insulin resistance increased significantly, whereas adiponectin and HMW adiponectin/total adiponectin ratio decreased significantly, to levels similar to controls. An initial increase in adiponectin levels was observed after 1 month of refeeding. There was no correlation between adiponectin and either T(4) or cortisol levels. CONCLUSIONS: Our study demonstrates hyperadiponectinemia, increased adiponectin HMW isoform, and increased insulin sensitivity in adolescent AN female patients and reversal of these findings with weight rehabilitation. We hypothesize that increased adiponectin levels may have a protective role in maintaining energy homeostasis during extreme malnourishment.

Adiponectin, ghrelin, and leptin in cancer cachexia in breast and colon cancer patients.

BACKGROUND: The hormone ghrelin and the adipocytokines leptin and adiponectin participate in body weight regulation. In response to weight loss, ghrelin and adiponectin levels increase and leptin decreases. Cancer cachexia is a complex metabolic state, characterized by loss of muscle mass and adipose tissue together with anorexia. The authors hypothesized that responses of these hormones may be attenuated in cancer cachexia. METHODS: Fasting plasma ghrelin, adiponectin, and leptin levels, as well as weight loss, were determined in 40 cancer patients: 18 of them suffered from cancer-induced cachexia, and 22 served as a comparison group. Hormone levels were measured before administration of cancer therapy. RESULTS: A similar distribution of age, gender, and diagnosis was observed in both study groups, but the cachectic patients had higher rates of metastatic disease and lower albumin levels. No significant correlation was observed between plasma adiponectin levels and weight loss. Mean plasma ghrelin levels were higher among cachectic compared with noncachectic patients. Notably, the association between ghrelin levels and weight loss was only modest, and in a third of the cachectic patients, ghrelin levels were equal to or lower than those in the noncachectic group. Plasma leptin levels showed gender-dependent associations, and significantly lower levels were found among cachectic women but not among cachectic men. CONCLUSIONS: Results suggested a gender-dependent attenuation of expected physiologic responses to weight loss among cancer cachexia patients. Thus, impaired response of adiponectin, ghrelin, and leptin may play a role in the pathogenesis of cancer cachexia syndrome.

Cord blood adiponectin in large-for-gestational age newborns.

OBJECTIVE: The purpose of this study was to disclose the relationship between adiponectin and birth weight in a large group of newborns with normal and aberrant growth ("overweight"). STUDY DESIGN: Eighty-one healthy, term newborns were divided into 2 groups: 20 in the large-for-gestational age (LGA; 4297 +/- 207 g), and 61 newborns in the appropriate-for-gestational age (AGA; 3384 +/- 368 g). Cord blood was analyzed for adiponectin, leptin, and insulin levels. RESULTS: Mean adiponectin level was significantly lower in LGA newborns (29.4 +/- 13.8 vs 35.0 +/- 9.9 microg/mL, P < .04). Both leptin and insulin levels were higher in LGA than AGA newborns, and leptin levels positively correlated with birth weight in both groups. Insulin levels positively correlated with birth weight in AGA newborns. CONCLUSION: The results of this study imply that adiponectin may have a role in fetal growth and support the notion of negative feedback exerted by adipose tissue on adiponectin levels, as previously shown in adults.

Adiponectin in human cord blood: relation to fetal birth weight and gender.

Adiponectin is an adipocyte-derived plasma protein with insulin-sensitizing and antiatherosclerotic properties. The aim of this study was to examine whether adiponectin is present in human fetal blood, to define its association with fetal birth weight, and to evaluate whether dynamic changes in adiponectin levels occur during the early neonatal period. Cord blood adiponectin levels were extremely high (71.0 +/- 21.0 microg/ml; n = 51) compared with serum levels in children and adults and positively correlated with fetal birth weights (r = 0.4; P < 0.01). No significant differences in adiponectin levels were found between female and male neonates. In addition, there was no correlation between cord adiponectin levels and maternal body mass index, cord leptin, or insulin levels. Cord adiponectin levels were significantly higher compared with maternal levels at birth (61.1 +/- 19.0 vs. 17.6 +/- 4.9 microg/ml; P < 0.001; n = 17), and no correlation was found between cord and maternal adiponectin levels. There were no significant differences between adiponectin levels at birth and 4 d postpartum (61.1 +/- 19.0 vs. 63.8 +/- 22.0 microg/ml; n = 17). These findings indicate that adiponectin in cord blood is derived from fetal and not from placental or maternal tissues. The high adiponectin levels in newborns compared with adults may be due to lack of negative feedback on adiponectin production resulting from lack of adipocyte hypertrophy, low percentage of body fat, or a different distribution of fat depots in the newborns.

Transient elevation of triiodothyronine caused by triiodothyronine autoantibody associated with acute Epstein-Barr-virus infection.

A unique 16-year old female patient presented after acute Epstein-Barr virus (EBV) infection with severe primary hypothyroidism. Her thyroid test results were thyrotropin level (TSH) of 198 mU/L (normal, 0.4-4 mU/L), free thyroxine [FT(4)], 2.5 pmol/L (normal, 10-25 pmol/L), total triiodothyronine (TT(3)) > 19.5 nmol/L (normal, 1.3-2.7 nmol/L), and free triiodothyronine (FT(3)), 0.77 pmol/L (normal, 3.3-6.3 pmol/L). She had high titers of thyroglobulin and thyroid peroxidase autoantibodies. In vitro triiodothyronine (T(3))-binding measured by radioimmunoprecipitation was 86% (normal, up to 8.5%) and thyroxine (T(4))-binding 8.2% (normal, 6.4%). Serum immunoglobulin G (IgG) absorption, achieved by protein-G Sepharose beads, decreased TT(3) toward normal. Levothyroxine treatment normalized the low baseline FT(4) and FT(3) values, and suppressed TSH to normal. However, TT(3) remained highly elevated and returned to normal after 20 months, while T(3 )binding gradually decreased. Thus, her severe hypothyroidism was masked by this unusual phenomenon. Thirty-four patients with EBV infection (15 with acute disease and 19 with previous infection) were tested for thyroid hormone levels. EBV antibodies (early antigen immunoglobulin M [IgM] and IgG and anti-Epstein-Barr virus nuclear antigen [EBNA] IgG) were measured by enzyme-linked immunosorbent assay (ELISA). In 15 patients with acute EBV the mean TT(3) level was 2.47 +/- 0.39 nmol/L (5 had TT(3) values above normal) compared to a mean TT(3) of 1.70 +/- 0.53 nmol/L in 19 subjects with previous infection (p < 0.0005; only 1 had a TT(3) result above normal), with no differences in FT(4) and TSH concentrations between the two groups. Acute EBV infection may be associated with transient mild to severe TT(3) elevation as a result of assay interference by anti-T(3) autoantibodies.

Familial partial 17,20-desmolase and 17alpha-hydroxylase deficiency presenting as infertility.

PURPOSE: Females with 17alpha-hydroxylase/17,20-desmolase deficiency normally present with amenorrhea, sexual infantilism, hypertension, and hypokalemia. We report on a new clinical presentation of this combined enzymatic defect. METHODS: Four Jewish women from two unrelated families presented with primary infertility. All patients exhibited a normal phenotype, blood pressure, and serum potassium levels with abnormally high follicular phase serum progesterone and low E2 levels. In order to characterize the underlying defect, the following steps were undertaken: 1) ovarian suppression by GnRH agonist, 2) adrenal suppression by dexamethasone, 3) ovarian stimulation by gonadotropins, 4) adrenal stimulation by ACTH, 5) hormonal assessment of follicular fluid aspirates, and 6) assessment of in vitro E2 production by luteinized granulosa cells. RESULTS: The clinical characteristics and endocrine testing results support the diagnosis of a partial deficiency in 17alpha-hydroxylase/17,20-desmolase activities, shared by the adrenal gland and the ovaries CONCLUSIONS: Female infertility can be the first and sole clinical manifestation of this enzymatic defect. Its exact nature and prevalence remain to be determined.

Elevated insulin-like growth factor-1 and insulin-like growth factor binding protein-2 in malignant pleural effusion.

Insulin-like growth factor-1 (IGF-1) and its binding proteins (IGFBPs) are produced by many tissues and are present in serum and other biological fluids. Alterations in sera of IGF-1 and 2 and IGFBPs were demonstrated in patients with malignancy, infection and other diseases causing pleural effusion. In this study the IGF-1 and IGFBP-2 content and the specific electrophoretic patterns of IGFBPs in samples of sera and pleural effusions of 25 patients with malignancy, infection and congestive heart failure were investigated. IGF-1 levels in exudative effusions of malignant solid tumors were significantly higher [(mean +/- SD), 20.9+/-7.5 nmol/L, n = 9] than in lymphoma (11.0+/-5.2 nmol/L, n = 5; p < 0.05), infection (11.4+/-6.5 nmol/L, n = 6; p < 0.05) and transudative effusion of congestive heart failure (4.3+/-3.3 nmol/L, n = 5; p < 0.02). IGFBP-2 was markedly increased in effusions of malignant solid tumors (2.14+/-0.82 mg/L, n = 9) compared with exudates of lymphoma, infection and transudates (1.10+/-0.70, 1.22+/-0.32 and 0.93+/-0.52 nmol/L, respectively, p < 0.05). Moreover, in effusion of solid tumors, IGFBP-2 levels were higher than those in corresponding sera, which suggests local production of this binding protein. The demonstration of IGFBP-2 in solid tumor cells by immunohistochemistry further supports this possibility. This work demonstrates the existence of the IGF-1/IGFBP system in pleural fluids from different etiologies and implies possible use of IGF-1 and IGFBP-2 as a potential marker of malignant effusions.