Serum FGF21 in girls with anorexia nervosa - comparison to normal weight and obese female adolescents.

BACKGROUND: Fibroblast growth factor 21 (FGF21) is a hepatokine, myokine and adipokine of a potent influence to energy homeostasis. Data according its serum concentrations in AN are contradictory. OBJECTIVES: Analysis of serum FGF21 in girls with acute anorexia nervosa and comparison the results with normal weight and obese female adolescents considering their nutritional status, carbohydrate and lipid metabolism. METHODS: Serum FGF21 concentrations were evaluated using commercially available ELISA kit in 32 Polish girls with restrictive AN (AN), 29 girls with obesity (O) and 21 healthy controls (C). Anthropometric measurements (weight, height, BMI) and laboratory assays (serum fasting glucose, insulin, HOMA-IR, total cholesterol, HDL, LDL, triglycerides, C-reactive protein) were performed. RESULTS: Mean serum FGF-21 in the AN group was significantly lower, whereas in the O group it was significantly higher than in healthy controls. In all examined girls significant positive correlations between FGF21 and BMI were noted. We also observed significant positive relationships between serum FGF21 levels and fasting glucose, triglycerides, CRP, insulin and HOMA-IR. In all examined girls serum concentrations of this hormone correlated negatively with age and HDL-cholesterol levels. CONCLUSIONS: 1) Serum FGF21 concentrations are decreased in AN and elevated in obesity. They are independently and positively related to BMI and insulin resistance; 2) Decreased serum FGF21 in AN may support the maintenance of normal blood glucose through adjustment the insulin levels and insulin sensitivity; 3) Elevated FGF21 levels in obesity may be considered adaptive mechanism preventing insulin resistance and its metabolic consequences.

Genetic polymorphisms and serum concentrations of adiponectin and resistin in anorexia nervosa and healthy controls - pilot study.

BACKGROUND: A possible role of adipokines in the regulation of body weight in patients with anorexia nervosa (AN) has been proposed. Polymorphisms in genes encoding adiponectin and resistin in AN have not been widely assessed, yet. OBJECTIVES: 1) Assessment the frequency of ADIPOQ c.45T>G, ADIPOQ c.276G>T polymorphisms in adiponectin and RETN c.62G>A, RETN c.-180C>G in resistin genes in AN patients and control group (C) 2) Analysis of correlation between these polymorphisms and serum ADP or RETN. METHODS: We examined 67 AN girls and 38 C aged 11-18. Analyses of polymorphisms in ADIPOQ and RETN genes were performed using RFLP method and adiponectin and resistin serum levels - with commercially available ELISA kits. RESULTS: In AN subjects, TT genotype in ADIPOQ c.276 polymorphism as well as GG genotype of RETN c.-180 were significantly more frequent than in CG. In ADIPOQ c.45 polymorphic site, TT alleles were the most frequent in both examined groups. In RETN c.62 GA and GG alleles distribution did not differ between the groups and the most frequently observed genotype was GG. The mean serum adiponectin level in AN was significantly higher and resistin - lower than in controls. There were no statistically significant relationships between serum adiponectin and resistin levels and allele frequency in polymorphisms ADIPOQ c.276 as well as RETN c.-180 in the examined groups. CONCLUSION: Differences in genotype frequencies of ADIPOQ c.276 and RETN c.-180 suggest a need for studies on a larger cohort of patients with AN.

Serum adiponectin levels in adolescents and young adults with growth hormone deficiency.

INTRODUCTION: Adiponectin (APN) is adipose tissue-derived hormone influencing energy metabolism. Growth hormone deficiency (GHD) may contribute to the development of disturbances in the hormonal function of adipose tissue (AT), and many disorders observed in untreated patients with GHD coincides with these contributed to low serum APN levels. OBJECTIVES: The assessment of serum adiponectin levels in adolescents and young adults with severe or partial GHD and analysis of relationships between serum APN and GH/IGF-1 axis function impairment as well as cardiometabolic risk factors. DESIGN AND SETTING: Based on the results of insulin tolerance test (ITT) patients were qualified for one of the following groups: 1) severe GHD - SGHD (26 patients; 8 women and 18 men); 2) partial GHD - PGHD (22 patients, 7 women and 15 men); 3) normal GH status - NGHS (28 patients, 9 women and 19 men). The fourth examined group consisted of healthy individuals - H (46 participants; 15 women, 31 men). Anthropometric measurements (height, weight, BMI), analysis of body composition and serum glucose, lipids, insulin, IGF-1 and APN assays were performed in all participants. RESULTS: There were no significant differences in the concentrations of APN between groups. After calculation of the total APN content in extracellular fluids per unit of fat tissue mass (TAPN/FM), these values were significantly lower in the SGHD (p<0.001) and correlated with the degree of impairment of the GH/IGF-1 axis functioning. In patients with GHD positive correlations between APN and serum HDL cholesterol (r=0.39, p<0.05) have been demonstrated. In the subjects with normal GH secretion serum APN correlated positively with serum HDL cholesterol (r=0.28; p<0.05), and negatively with fasting blood glucose (r=-0.31; p<0.05). CONCLUSIONS: Severe, but not partial growth hormone deficiency impairs adiponectin production in the adipose tissue that is compensated by the increase of fat mass. The degree of GH/IGF-1 axis disruption is related to the TAPN/FM. This parameter may be potentially useful in diagnosing severe growth hormone deficiency in the adults.

Evaluation of the analgesic effect of morphine on models of acute nociceptive pain in rats with a central noradrenergic system lesion.

OBJECTIVES: Stimulation of some noradrenergic system receptors demonstrates a synergistic anti-nociceptive effect with the opioid system at the level of peripheral tissues, spinal cord, and supraspinal structures. Furthermore, opioids stimulate the noradrenergic descending pathways originating from the substantia nigra by presynaptic inhibition of the GABA neuron ends. It is thus important to determine whether a disruption to the adrenergic transmission obtained via DPS-4 administration to neonatal rats impacts the perception of noxious stimuli mediated by 5-HT3-serotonin receptors at the level of spinal cords or higher tiers of the central nervous system. DESIGN & SETTING: The studies were conducted with neonatal and adult rats, males of the Wistar strain in which a central noradrenergic system lesion was induced with DSP-4 on days 1 and 3 of life. Next, the evaluation of the analgesic effect of morphine was performed on 8- to 10-week-old animals using the following models of acute nociceptive pain: the hot plate test and the tail immersion test as models of acute nociceptive pain induced by a thermal stimulus, and the paw withdrawal test as a model of nociceptive pain caused by a mechanical stimulus. RESULTS: Morphine was found to produce a longer-lasting analgesic effect in the tail immersion test in the control group than in rats. Similarly, in the paw withdrawal test, this substance generated a strong analgesic effect (with over 200% of analgesia) in the control group, whereas its action in the rats with DSP-4 lesions was statistically significant. Morphine induced analgesia at about 13-14% in the control rats when examined with the hot plate test. CONCLUSIONS: The disruption to the central noradrenergic system in an early stage of development resulted in a reduction of the analgesic effect of morphine in the models of acute pain in which the mechanisms of supraspinal perception are involved.

The effect of central noradrenergic system lesion on dopamine (DA) and serotonin (5-HT) synthesis rate following administration of 5-HT3 receptor ligands in chosen parts of the rat brain.

INTRODUCTION: Since little has been known about the effect of the central noradrenergic system on the reactivity of serotonin 5-HT3 receptors, the aim of the current study was to find out whether this reactivity could be altered by chemical damage to the system in adult rats in early developmental stage. MATERIALS AND METHODS: Adult male Wistar rats with central noradrenergic lesion induced by DSP-4 on day 1 and 3 of life were injected with analgesic model substance - morphine, serotoninergic 5-HT3 receptor agonist (1-phenylbiguanide, PBG), 5-HT3 receptor antagonist (ondansetron) or both compounds jointly followed by decarboxylase inhibitor of aromatic amino acids (NSD-1050). After 30 min following NSD-1050 injection, the animals were decapitated using a guillotine. Chosen cerebral structures were dissected, and the contents of 5-hydroxytryptofan (5-HTP) and l-dihydroxyphenylalanine (l-DOPA) were determined using high-pressure liquid chromatography with electrochemical detection (HPLC/ED). RESULTS: Neither PBG nor morphine affected l-DOPA contents in the hippocampus in control rats; however, DSP-4 lesion caused a significant decrease in the synthesis rate of DA in this structure. Hippocampal contents of 5-HTP increased after morphine or PBG administration, and central noradrenergic lesion attenuated this effect. Morphine or PBG decreased cerebellar DA synthesis rate in control rats and DSP-4 lesion did not modify it. Cerebellar levels of 5-HTP increased after morphine or PBG challenge in control rats. DSP-4 lesion intensified the effect of morphine and attenuated that of PBG. Ondansetron abolished the effects mediated by PBG. We did not observe any impact of PBG or ondansetron on DA and 5-HT synthesis in the striatum. CONCLUSION: Damage to the central noradrenergic system in rat newborns, through altered reactivity of central 5-HT3 receptors, results in permanent disorders in serotoninergic transmission in hippocampus and cerebellum as well as dopaminergic transmission in hippocampus, which may attenuate the activity of the descending pathways that derive from these structures.

Serum alpha-klotho concentrations in girls with anorexia nervosa.

BACKGROUND: Soluble α-klotho may influence energy homeostasis. It also plays a role in calcium-phosphate and vitamin D3 metabolism regulation. Two so far published studies have demonstrated that serum α-klotho levels in patients with AN are decreased, but their relationships with BMI and metabolic disturbances in these patients remain unclear. OBJECTIVES: The aim of the study was to assess the association between serum soluble α-klotho levels and glucose, calcium-phosphorus and vitamin D3 metabolism in girls with acute AN. METHODS: Serum soluble α-klotho concentrations were evaluated using commercially available ELISA kit in 31 Polish girls with restrictive AN and 29 healthy controls (C). Moreover, anthropometric measurements (weight, height, BMI) and laboratory assays (serum fasting glucose, insulin, HOMA-IR, total calcium, phosphorus as well as 25-hydroxy vitamin D3 and calcitriol) were performed. RESULTS: The mean serum α-klotho concentrations in the AN group were significantly lower than in the C group even after adjustment for BMI. Significant correlations between serum α-klotho and body mass (r=0.54; p=0.009), BMI (r=0.48; p=0.02), serum calcitriol (r=0.48; p=0.03), insulin (r=0.49; p=0.008) and HOMA-IR (r=0.54; p=0.006) were observed in the AN, but not in healthy controls. CONCLUSIONS: Serum α-klotho concentrations in female adolescents with AN are decreased in comparison with normal weight girls and strongly associated with their nutritional status, insulin sensitivity and active vitamin D3 levels.

Chemerin serum levels in girls with anorexia nervosa.

BACKGROUND: The regulatory function of chemerin (CHEM) in the process of adipogenesis and the metabolism of adipocytes has been confirmed. Data from several studies have shown higher serum CHEM in obesity. To date, there are no available studies on serum CHEM concentrations in patients with anorexia nervosa (AN), which is recognized as a good biological model of the chronic atrophy of adipose tissue and energy metabolism disorders in humans. OBJECTIVES: The aim of the study was to assess serum CHEM concentrations in girls with AN in comparison to healthy and obese subjects and determine its relationship with body mass, BMI and insulin. METHODS: CHEM serum concentrations were evaluated using commercially available ELISA kit in 65 Polish girls with restrictive AN, in 39 healthy controls (H) and 64 girls with simple obesity (OB). RESULTS: The mean serum CHEM concentration in the AN group was significantly lower than in the H and OB groups. After adjusting for BMI, CHEM concentrations in the AN group were significantly lower than in the H group, but statistically higher than in the OB group. Significant correlations between serum CHEM and body mass (r=0.77), BMI (r=0.82), Cole index (r=0.81) and serum insulin (r=0.78) were observed.

Quality of life in transition phase in adolescents and young adults with severe and partial growth hormone deficiency.

BACKGROUND: Transition is a term used to describe the period of adolescence after which the final adult height during growth hormone (GH) treatment is achieved. According to re-evaluation results in insulin tolerance test (ITT) patients with severe and partial growth hormone deficiency (GHD) may be distinguished. OBJECTIVES: The aim of the study was to assess QoL in patients with different degrees of GHD in transition phase. METHODS: QoL was evaluated in 76 subjects aged 16-25 years with severe (SGHD, n=26), partial GHD (PGHD, n=22) and normal GH secretion (NGH, n=28) using SF-36 v.2™ Health Survey and the Quality of Life Assessment of Growth Hormone Deficiency in Adults (QoL-AGHDA) questionnaires. RESULTS: Physical Component Score (PCS), Physical Functioning (PF) and General Health (GH) results were significantly lower in patients with SGHD than in NGH group. SF-36 v.2™ Health Survey scores in PGHD were similar as in NGH patients. There were no statistically significant differences in QoL-AGHDA scores between the examined groups. We found positive correlations between peak GH in ITT and PF (r=0.29; p=0.02) or Role Emotional (r=0.37; p=0.002) scores. CONCLUSIONS: We demonstrated that the QoL in adolescents and young adults with severe GHD in transition period is disturbed mainly in terms of physical health and emotions. These changes were detected only by generic SF-36, but not by disease-specific QoL-AGHDA questionnaire. Therefore AGHDA-QoL assessment may not be applicable in GHD patients in transition period. QoL in the patients with partial GHD is unchanged in comparison to growth hormone sufficient subjects.

Serum resistin levels are elevated in schoolchildren with atopic asthma.

OBJECTIVES: There are limited data on the role of adipokines in atopic asthma. DESIGN AND SETTING: To determine serum levels of resistin in asthmatic children in relation to body weight, asthma severity and gender, serum resistin (RES) levels were measured using ELISA in 89 asthmatic children (61 boys and 28 girls, aged 7.0-17.0 years) and in 33 healthy children. Among examined asthmatics 59 (19 girls and 40 boys) had normal weight (ANW) and 30 (9 girls and 21 boys) were obese (AO). RESULTS: The mean serum levels of resistin were significantly (p<0.01) higher in all non-obese asthmatic children (4.11±0.1 ng/mL) than in healthy children (3.83±0.1 ng/mL). After stratifying by gender only ANW boys and AO boys had significantly higher RES levels than boys from control group. Both AO (4.4±0.2 ng/mL) and ANW girls (4.38±0.2 ng/mL) as well as girls from control (4.09±0.1) group showed significantly higher mean RES serum concentrations than boys from corresponding groups (3.99±0.1 ng/ml, 3.83±0.17 ng/ml and 3.44±0.06 ng/ml, respectively). No relationship between examined adipokine levels and asthma severity, spirometric parameters, degree of allergic sensitization, BMI, BMI-SDS was stated. CONCLUSION: Increased serum RES in children with atopic asthma suggest that this adipokine may be implicated in its pathogenesis.

Androgens concentrations and second-to fourth-digit ratio (2D:4D) in girls with congenital adrenal hyperplasia (21-hydroxylase deficiency).

OBJECTIVES: Excessive hyperandrogenism, though proper hydrocortisone supplementation is a frequent clinical problem in girls with congenital adrenal hyperplasia (CAH). This may result from autonomic regulation of androgen production established in prenatal life. It has been suggested that the length of the second finger relative to the length of the fourth finger (2D;4D ratio) is negatively related to prenatal testosterone concentration. DESIGN AND SETTING: The retrospective study aimed to establish the relationship between the level of androgenization in utero determined using 2D:4D ratio and serum androgen concentrations in treated girls with CAH (21-OH deficiency) has been performed on 19 girls with CAH (21-OH deficiency) at the age of 3.7-19 years (mean 13.8 ± 4.07 years). All subjects were adequately treated with hydrocortisone (10-19 mg/m2; mean 13.81 ± 4.07 mg/m2). Anthropometric measurements of digits length were performed in all girls on X-rays obtained for bone age estimation. Apart from it, serum androgens concentrations (testosterone, androstenedione, s-DHEA) and 17-OH-progesterone (17-OHP) were assayed. RESULTS: Mean androgens serum concentrations in examined group were: testosterone 150.21 ± 155.44 ng/ml; androstenedione 4.15 ± 5.32 ng/ml, s-DHEA 70.39 ± 85.52 µg/dl. Mean 2D:4D ratio was 0.96 ± 0.04. Analysis of correlation showed positive linear correlations between testosterone, s-DHEA and 2D:4D ratio (r=0.53, p=0.023 and r=0.53; p=0.019, respectively). CONCLUSIONS: 2D:4D ratio parameter may be a simple test in indentification of female CAH patients prone to excessive androgen secretion despite proper treatment. The autonomization of adrenal androgens production in foetal life may cause its elevated levels in female patients with CAH although treated adequately.

Assessment of serum levels resistin in girls with anorexia nervosa. Part II. Relationships between serum levels of resistin and thyroid, adrenal and gonadal hormones.

OBJECTIVES: Thyroid, adrenal glands and gonadal hormones play a role in maintaining metabolic homeostasis of the body via the receptors located in the adipose tissue. The correlations between serum resistin (RES) and function of other hormonal axes in patients with AN have not been established, yet. Therefore, the aim of this study is: 1) assessment of concentrations of thyroid hormones (FT4, TSH), adrenal hormones (ACTH, cortisol), sex hormones (LH, FSH, estradiol, testosterone); 2) establishing their relationship with BMI and 3) analysis of correlations between examined hormones and RES serum concentrations in adolescent female patients with AN. DESIGN AND SETTING: Serum RES (ELISA) and fT4, TSH, ACTH, LH, FSH, estradiol and testosterone (ECLIA) concentrations have been assayed in 195 adolescent girls: 87 with restrictive AN, 17 with not otherwise specified eating disorders (NOS), 30 with simple obesity (OB) and 61 healthy (H) subjects. RESULTS: Mean serum FT4, LH and estradiol concentrations were significantly lower (p=0.015; p<0.0001; p<0.0001, respectively) in AN than in OB group, and cortisol increased (p<0.001) compared to OB and H subjects. In all examined subjects BMI correlated positively (p<0.0001) with LH (r=0.61) and estradiol (r=0.30), and negatively with cortisol (r=-0.35; p=0.008). Also the significant positive relationship between serum RES and FT4 (r=0.34), LH (r=0.57) as well as estradiol (r=0.28) was observed, whereas serum cortisol correlated negatively with RES (r=-0.40). CONCLUSION: Changes in resistin serum concentrations in eating disorders may be involved in the altered regulation of hypothalamic-pituitary-adrenal, thyroid and gonadal axes.

Assessment of serum levels resistin in girls with anorexia nervosa. Part I. Relationship between resistin and body mass index.

OBJECTIVES: There are only few studies available on blood resistin (RES) levels in patients with anorexia nervosa (AN), which revealed scarce results, however it has been demonstrated that RES mRNA expression in adipose tissue of these patients is increased. The aim of this study is: 1) the evaluation of serum resistin levels in girls with AN and determination a threshold value differentiating these patients from healthy subjects; 2) analysis of the relationship between serum resistin levels and BMI in examined subjects. DESIGN AND SETTING: Serum RES concentration has been assayed using ELISA kit in 195 adolescent girls: 87 with restrictive AN (mean BMI-SDS: -2.65 ± 0.2), 17 with not otherwise specified eating disorders (NOS) (mean BMI-SDS: -1.4 ± 0.68), 30 with simple obesity (OB) (mean BMI-SDS: 6.91 ± 1.23) and 61 healthy (mean BMI-SDS: -0.18 ± 0.54). RESULTS: Mean serum RES concentration in AN (2.8 ± 0.6 ng/ml) and NOS (3.1 ± 0.9 ng/ml) were significantly lower (p<0.0001) than in OB and H groups (4.8 ± 0.5 and 4.1 ± 0.4 ng/ml respectively). After corrected for BMI, RES values in AN were similar as in H subjects, but significantly higher (p<0.005) in comparison to OB group. ROC curve analysis revealed that 3.87 ng/ml is the threshold value of RES serum concentration differentiating AN from H girls (specificity 100%, sensitivity 80%). No significant correlations between BMI and serum resistin concentration are found in AN group, although a significant positive correlation has been established for all examined subjects. CONCLUSION: Additional adaptive mechanisms may be involved in regulation of RES levels in adolescent girls with AN.

Effects of feminizing surgery for ambiguous genitalia - a novel scale for evaluation of cosmetic and anatomical results.

INTRODUCTION: Ambiguous genitalia always present diagnostic and therapeutic problem. Long-term results of feminizing operations are unsatisfactory in some cases and reports from follow-up after feminizing genitoplasty are rare in the literature. Systematic studies are needed to evaluate ultimate function of all girls undergoing feminizing surgery. In our opinion, the lack of worldwide-accepted scale for the assessment of long-term effects of feminizing genitoplasty, enabling the possibility of comparing outcomes between institutions and countries, may contribute to this deficit of reliable data. AIM: The aim of the study was the evaluation of the outcomes of surgical management of masculinization using a novel scale developed by the authors. MATERIAL AND METHODS: We examined 43 patients aged 3-24 years (mean age 15,4 years) operated due to ambiguous genitalia. Most of the patients were females with congenital adrenal hyperplasia (CAH) diagnosed in 38 of subjects (88.4%).The patients were operated at the age from 10 months - 15 years (mean age 4,5 years). Five patients had to be reoperated. The effects of surgical management in ambiguous genitalia were assessed using our own scale. We evaluated five anatomical and cosmetic parameters (general appearance, size of pudendal labia, symmetry of pudendal labia symmetry, size and position of clitoris, size of introitus and position of urethra opening), each of them was scored 0-2 points. RESULTS: In 36 of examined patients the result of the surgery was considered good, in 4 patients - satisfactory and in 3 - poor. The most common complication of feminizing genitoplasty in our patients was stenosed vagina (in 10 patients, 23.8%). Location of urinary coil in anterior wall of vagina was found in 6 patients (13.9%) and in 1 patient it was invisible (2.3%). Post-operational clitoral enlargement was found in 3 cases (6.9%). CONCLUSION: Taking into consideration controversial data about the results of feminizing genitoplasty, a standarized, well-defined and commonly accepted scale enabling comparison between methods and institutions is necessary. In our opinion scoring scale makes the evaluation more precise and the results are more comparable.

Effect of intrauterine infection and perinatal risk factors on serum concentrations of insulin like growth factor (IGF-I) in full-term and preterm newborns.

OBJECTIVES: IGF-I is believed to be a key factor in fetal growth dynamics It is widely known, that serious early-onset infection in the newborn is a risk factor for further developmental disturbances in a child. However, effect of congenital infection as well as an influence of infectious and non-infectious perinatal risk factors on circulating IGF-I concentrations in newborns has not been examined, yet. DESIGN: Thus, the aim of this study was: 1) evaluation of IGF-I venous blood serum concentration in full-term and premature infants considering their sex, occurrence of intrauterine infection and perinatal risk factors; 2) establishing the relationship between IGF-I serum concentrations and chosen anthropometric parameters values in infected and healthy newborns. SETTING: The study involved 112 newborns appropriate for gestational age. Taking into consideration occurrence of early onset infection and gestational age we divided examined children into 4 groups: I group--infected, full-term newborns; II group--infected premature newborns; III group--healthy full-term newborns; IV group--healthy premature newborns. In all infants immediately after birth anthropometric measurements were performed (birth weight, body length, circumference of head and circumference of chest) and serum IGF-I concentration was determined. RESULTS: We demonstrated that full-term infants with intrauterine infection have statistically significantly higher concentration of IGF-I in blood serum than infected premature infants and healthy full-term infants. Analysis of correlation revealed a significant positive linear correlations between IGF-I serum concentration and gestational age and anthropometric parameters values. CONCLUSIONS: We conclude that intrauterine infection increases serum IGF-I concentration in full-term infants, but not in preterm infants, that may be a result of immaturity. We suggest serum IGF-I concentration may be considered an additional element of developmental and nutritional state assessment in infected newborn.

Growth hormone therapy in boy with panhypopituitarism may induce pilomatricoma recurrence: case report.

Pilomatricoma is usually a solitary subcutaneous nodule. Recurrence of the nodule after surgical excision is very rare. Pilomatricoma occurrence in patients with growth hormone (GH) deficiency has not been reported, yet. We report a 14-year-old boy with pilomatricoma and panhypopituitarism. After GH therapy had been started, we observed two relapses of previously completely excised pilomatricoma in the same location and a new pilomatricoma formation on the chin.