P. S. Morpurgo

Fetal Plasma Leptin Concentrations: Relationship with Different Intrauterine Growth Patterns from 19 Weeks to Term

The relationship between in utero fetal growth and fetal leptin concentrations was investigated between 19 and 41 wk in 40 normal (appropriate for gestational age, AGA) fetuses, in 25 intrauterine growth-restricted (IUGR) fetuses, and in 18 fetuses from gestational diabetic mothers (GDM), representing different intrauterine growth patterns. Umbilical venous plasma leptin concentrations were determined at the time of either in utero fetal blood sampling or delivery. Plasma leptin was measurable as early as 19 wk of gestation. A significant difference was observed between umbilical venous and arterial plasma leptin concentrations (0.6 ± 0.6 ng/mL;p < 0.01). In AGA and in IUGR fetuses, significant positive relationships were found between fetal leptin concentrations and both gestational age (p < 0.001) and fetal weight (p < 0.001). Leptin concentrations were significantly higher in AGA than IUGR only after 34 wk (p < 0.05), but leptin per kilogram fetal weight (leptin/kg) was not significantly different. In IUGR with abnormal umbilical arterial Doppler velocimetry and fetal heart rate, leptin/kg significantly higher than in IUGR with normal biophysical and biochemical parameters was found (p < 0.05). Both circulating plasma leptin and leptin/kg were significantly higher in GDM than in normal fetuses (p < 0.001) and correlated with abdominal fat mass measured by ultrasound. No gender differences were observed in any group of fetuses. These findings indicate a clear relationship between fetal leptin concentrations and fetal fat mass. Data in severe IUGR suggest the presence of increased leptin concentrations associated with in utero signs of fetal distress.

Aminotransferase and gamma-glutamyltranspeptidase levels in obesity are associated with insulin resistance and the metabolic syndrome

Fatty liver at ultrasounds, with/without raised plasma levels of hepatic enzymes, is common in obesity. In most cases, it is the hallmark of non-alcoholic fatty liver disease (NAFLD), a potentially progressive disease associated with insulin resistance and the metabolic syndrome (MS). We tested the hypothesis that insulin resistance per se might be associated with hepatocellular necrosis. Alanine and aspartate aminotransferases (ALT and AST; no.=799) and gamma-glutamyltranspeptidase (GGT; no.=459) were analyzed in a group of treatment-seeking obese patients recruited in 12 Italian medical centers. Insulin resistance was calculated by the homeostasis model assessment method (HOMA-IR; no.=522). Median ALT and AST increased with increasing obesity class (p=0.001 and p=0.005) and exceeded normal limits in 21.0% of cases. Also HOMA-IR increased with the obesity class (p<0.0001), and was higher in subjects with elevated ALT (median, 4.93 vs 2.89; p<0.0001). A significant correlation was observed between HOMA-IR and ALT (R2=0.208; p<0.0001), as well as between HOMA-IR and AST or GGT (R2=0.112 and R2=0.080; p<0.0001). The correlation was maintained when cases with elevated enzyme levels were omitted from analysis. Diabetes and hypertriglyceridemia were the features of the MS most commonly associated with raised liver enzymes. In logistic regression, after correction for age, gender, BMI and features of the MS, HOMA-IR maintained a highly predictive value for raised ALT, AST and GGT. We conclude that in obesity insulin resistance is a risk factor for raised liver enzyme levels, possibly related to NAFLD.

Ghrelin secretion in severely obese subjects before and after a 3-week integrated body mass reduction program

Ghrelin, the endogenous ligand of GH-secretagogue receptors, has been implicated in the regulation of feeding behavior and energy balance. Aim of the study was to investigate ghrelin levels in fasting conditions and after a standard meal test in obese subjects before and after a 3-week integrated body weight reduction (BWR) program (consisting of energyrestricted diet, exercise training, psychological counselling and nutritional education). Weight, height, fat mass, fat free mass (by impedentiometry), circulating ghrelin, insulin and leptin levels were evaluated in 10 obese subjects (3 male, 7 female; mean age: 35±9.3 yr; body mass index BMI: 45.2±10.6 kg/m2) before and after weight reduction. At baseline, obese subjects showed significantly lower ghrelin levels than controls, which were negatively correlated with BMI, weight, insulin and leptin levels. Fasting ghrelin levels were not modified by standard meal test in obese subjects (from 110.8±69.7 to 91.8±70.2 pmol/l p=ns), while a significant reduction was observed in controls (from 352.4±176.7 to 199.0±105.2 pmol/l; p<0.01). After a 3-week integrated BWR program obese subjects significantly reduced weight, BMI and leptin levels, while no significant changes were found both in fasting ghrelin and in ghrelin response after the meal. In conclusion, 5% weight loss obtained after a short-term period of integrated BWR program is not sufficient to normalize fasting ghrelin levels nor to restore the normal ghrelin suppression after a meal in severely obese subjects.

Reduced levels of adiponectin in sleep apnea syndrome.

Background: To investigate adiponectin levels in an obese population with and without obstructive sleep apnea syndrome (OSAS) and the acute modifications in adiponectin after a whole-night control by auto continuous positive air pressure (CPAP). Methods: 46 obese subjects [22 males, 24 females, age 55.1±11.4 yr, body mass index (BMI) 38.9±6.5 kg/m2]: 11 OSAS with apnea/hypopnea index (AHI) from 10/h to 30/h, 14 OSAS with AHI >30/h and 21 without OSAS. Thirty-seven normal weight healthy subjects (20 males, 17 females, age 31.3±9.5 yr, BMI 21.5±1.8 kg/m2). Serum adiponectin levels, biochemical parameters, anthropometric measurements, pulmonary function, pulse-oxymetry and polisomnography. Results: The 3 groups of obese patients were comparable for gender, BMI, age, fat mass, fat free mass, hip and waist circumference, waist-to-hip ratio (WHR), systolic and diastolic blood pressure and glycometabolic parameters. Adiponectin levels were significantly reduced in obese patients compared to healthy normal weight subjects (8.1±3.5 vs 11.3±4.8 μg/ml p<0.001) In particular, adiponectin showed a trend to decrease according to the severity of OSAS. No differences in adiponectin levels were found after a whole-night control by Auto CPAP. Conclusions: OSAS is associated with reduced levels of adiponectin independently of insulin-resistance and BMI. These low adiponectin levels may contribute to the increased mortality seen in such patients.

Activin A serum levels and aging of the pituitary-gonadal axis: a cross-sectional study in middle-aged and elderly healthy subjects

Aim of the study was to investigate activin A serum concentration in healthy adult males and post-menopausal females over a wide age-range and its correlation to gonadotropins, inhibin B and testosterone concentrations. The study included 73 males (aged 30-101 years) and 42 postmenopausal females (aged 50-104 years). Blood samples were collected after an overnight fast to measure serum activin A, inhibin B, LH, FSH, and gonadal steroid levels. A significant increase in serum activin A levels over age in both genders, especially in the oldest age-groups, was observed. Serum inhibin B and testosterone concentrations showed a sharp decrease in male subjects, reflecting the age-related decrease of testicular function and by consequence serum FSH and LH significantly increased. In female subjects LH and FSH levels were very high in subjects in their 50s and showed a continuous decline due to pituitary aging. Simple and multivariable regression analyses demonstrated the lack of correlation between activin A and FSH in both males and females. In conclusion, a steep increase in activin A levels is present during aging in both genders, especially in the last decades of life. The physiologic role and site of production of activin A in old subjects remain to be clarified.

Ghrelin and adiponectin in patients with Cushing's disease before and after successful transsphenoidal surgery

background  Ghrelin, an endogenous ligand of the GH secretagogue receptor that exerts orexigenic activity, is negatively correlated with body mass index (BMI) and insulin resistance. Conversely, low levels of adiponectin (ApN), a circulating adipocytokine with antidiabetic, antiatherogenic and anti‐inflammatory properties, have been found in several insulin‐resistant conditions. Although Cushings syndrome causes several metabolic and hormonal changes leading to insulin resistance and central obesity, few data concerning the impact of glucocorticoid excess on ghrelin and ApN levels are so far available.

Different effects of short- and long-term recombinant hGH administration on ghrelin and adiponectin levels in GH-deficient adults.

objective  To evaluate circulating levels of ghrelin and adiponectin (ApN) in GH‐deficient (GHD) adults before and after short‐ and long‐term recombinant human GH (rhGH) administration.

Normal Range of Calcitonin in Children Measured by a Chemiluminescent Two-Site Immunometric Assay

Calcitonin (CT) assay is of considerable importance in the routine evaluation of thyroid nodules and for screening and follow-up of patients with medullary thyroid carcinoma and their relatives. Aim of this study was to assess the reference ranges for CT levels in healthy children and to evaluate possible differences in CT levels between sex and age. Serum CT levels were measured by a commercially available two-site chemiluminescence immunometric assay (sensitivity = 0.2 pg/ml). The ILMA recognizes the mature monomeric form of CT. We evaluated a cohort of 125 healthy children and compared these results with those from 98 healthy adult men and women. The ranges for human CT in children were <0.2–11.7 pg/ml and <0.2–17 pg/ml for female and male, respectively. No gender differences were observed in children population, though higher CT levels were observed in males. Serum CT levels did not correlate with age. Adult female had statistically significant lower CT levels than female children (p ≤0.05). In the adult population, males showed levels of CT higher than females. In conclusion, this study provide normal range for children population at different age with a sensible two-site chemiluminescent immunoassay. Since the normal range of serum CT levels is wider in healthy children than in adults, these data suggest establishing different normal range values in different age groups.

Ghrelin in human medullary thyroid carcinomas

Objective  Ghrelin is a novel gastrointestinal hormone involved in several metabolic functions. It has been identified previously in several normal and tumoral neuroendocrine tissues, including human medullary thyroid carcinomas (MTCs). The aim of the study was to evaluate ghrelin levels in patients with MTC and nontoxic goitre (NTG) with elevated calcitonin (CT) levels, as an additional marker of the disease.

In vitro release of activin A from human normal and pathological thyroid tissues

Activin A is a dimeric glycoprotein belonging to the transforming growth factor β (TGF-β) superfamily characterized by the ability to affect FSH secretion. Activin A was originally indicated as a gonadal product but the expression of activin A has been successively identified in several different tissues, including the thyroid gland. The aim of this study was to evaluate the release of activin A from human normal and pathological thyroid tissues in culture. Activin A concentration was evaluated in media obtained from primary culture of perinodular normal tissues (no.=2), hyperplastic hyperfunctioning thyroid tissues due to Graves’ disease (no.=3) and autonomous thyroid adenomas (no.=3). Detectable levels of activin A were found in the incubation media from all tissues, without significant differences between normal and pathological samples. We conclude that activin A is secreted by follicle thyroid cells in normal and pathological conditions.