DIAGNOSIS OF ENDOCRINE DISEASE: Drug-induced endocrinopathies and diabetes: a combo-endocrinology overview.

In the currently overwhelming era of polypharmacy, the balance of the dynamic and delicate endocrine system can easily be disturbed by interfering pharmaceutical agents like medications. Drugs can cause endocrine abnormalities via different mechanisms, including direct alteration of hormone production, changes in the regulation of the feedback axis, on hormonal transport, binding and signaling, as well as similar changes to counter-regulatory hormone systems. Furthermore, drugs can interfere with the hormonal assays, leading to erroneous laboratory results that disorientate clinicians from the right diagnosis. The purpose of this review is to cover a contemporary topic, the drug-induced endocrinopathies, which was presented in the monothematic annual Combo Endo Course 2018. This challenging part of endocrinology is constantly expanding particularly during the last decade, with the new oncological therapeutic agents, targeting novel molecular pathways in the process of malignancies. In this new context of drug-induced endocrine disease, clinicians should be aware that drugs can cause endocrine abnormalities via different mechanisms and mimic a variety of clinical scenarios. Therefore, it is extremely important for clinicians not only to promptly recognize drug-induced hormonal and metabolic abnormalities, but also to address the therapeutic issues for timely intervention.

Health benefits and consequences of the Eastern Orthodox fasting in monks of Mount Athos: a cross-sectional study.

BACKGROUND/OBJECTIVES: Greek Orthodox fasting (OF), which involves 180-200 days of fasting per year, is dictated by the Christian Orthodox religion. For the first time, this cross-sectional study examines the characteristics and the effects of OF on anthropometry, cardiometabolic markers and calcium homeostasis in Athonian monks (AMs). SUBJECTS/METHODS: Daily intakes of energy, macro- and micronutrients of a day during a weekend of Nativity Fast, defined as non-restrictive day (NRD), and a weekday during Great Lent, labeled as restrictive day (RD) were recorded. RESULTS: The daily energy intake of 70 AM (age=38.8±9.7 years) was low during both RD and NRD (1265.9±84.5 vs 1660±81 kcal, respectively, P<0.001). Paired samples t-test showed statistically significant difference between daily intakes in RD and NRD: carbohydrates (159.6±21.8 vs 294.3±23.4 g, P<0.0001) and saturated fat (12.7±0.0 vs 16.4±0.0 g, P<0.0001) were lower, whereas protein (89.2±1.3 vs 72.35±1.3 g, P<0.001) was higher during RD. A subsample of 50 monks (age=38.7±10.6 years) formed a study cohort for cardiometabolic and calcium homeostasis assessment. Body weight (74.3±12.9 kg) and body mass index (BMI; 23.8±4.1 kg/m2) were independent of level of physical activity. Optimal profiles for lipid and glucose parameters (total cholesterol: 183.4±41.7 mg/dl, LDL: 120.6±37.6 mg/dl, triglycerides: 72.2±31.3 mg/dl, HDL: 48.5±14.2 mg/dl and homeostasis model assessment of insulin resistance (HOMA-IR) 1.02±0.40) were found. Profound hypovitaminosis D (8.8±6.2 ng/ml), high parathyroid hormone (PTH): 115.5±48.0 pg/ml with normal serum calcium levels (8.9±3.2 mg/dl) was observed. CONCLUSIONS: Unaffected by variation in lifestyle factors, the results of this unique study offers clear evidence for the health benefits of the strict Athonian OF through optimal lipid and glucose homeostasis.

Prevalence of overweight and abdominal obesity in Greek children 6-12 years old: Results from the National Epidemiological Survey.

OBJECTIVE: To provide estimates of overweight (OW), obesity (OB) and abdominal obesity (AO) in a sample of children throughout the whole of Greece. MATERIAL AND METHODS: This epidemiological, cross-sectional survey examined 3,140 children aged 6-12 y (1,589 boys and 1,551 girls) who were selected by stratified sampling through household family members of Greek adolescents attending school. Participants reported data on height, weight and waist circumference (WC). BMI and Waist-to-Height ratio (WHtR) were calculated. AO was estimated using WC and WHtR. RESULTS: Overall prevalence of OW including OB was 31.2% in boys and 26.5% in girls, while OB prevalence was 9.4% and 6.4% respectively. The prevalence of AO based on WC (AO-WC), was similar in girls (14.2%) and boys (12.5%) while the prevalence of AO, based on WHtR (AO-WHtR), was higher in boys than in girls (25.6% vs 20.0%, p<0.0001). With increasing age, the prevalence of OW and OB decreases in both genders, and AO-WHtR only in girls. Rates of OW were significantly more prevalent in Greeks than in immigrants. CONCLUSIONS: Overweight and obesity in Greek children is very prevalent, particularly in boys, comparable with that reported for Mediterranean European countries. Abdominal obesity also appears high. Preventive and treatment strategies are urgently needed to combat this national epidemic.

Obesity, weight loss and conditional cardiovascular risk factors.

Obesity is a pathological condition aggregating a substantial number of proatherogenic factors, such as insulin resistance, type 2 diabetes mellitus, dyslipidaemia and hypertension. In addition to these classic cardiometabolic risk factors, atherosclerosis may be aggravated by other non-classic factors, which are characterized as conditional, including homocysteine, fibrinogen, lipoprotein(a), LDL particle size and high-sensitivity CRP. Some of these biomarkers are disturbed in obesity because of a combination of dietary factors, hypertrophic adipose tissue, low-grade inflammation, insulin resistance and other parameters under investigation. For the reduction of these risk factors, weight loss exceeding 10-20% of the initial body weight is probably necessary, achieved through either conventional lifestyle measures or more drastic interventions such as bariatric surgery. It has been shown that certain well-balanced diets, such as the Mediterranean diet, constitute a means of improving in a concerted manner the levels of CRP, fibrinogen, homocysteine and small dense LDL particles, regardless of weight loss. The significance of considering these factors in weight management intervention is an issue that needs further investigation.

Does the presence of metabolic syndome influence weight loss in obese and overweight women?

BACKGROUND: It is known that weight loss is beneficial for obese and overweight subjects with metabolic syndrome. Very few data exist, however, about whether the presence of metabolic syndrome and insulin resistance (IR) influence the response of these subjects to weight-reducing interventions. The current study intends to examine whether the presence of metabolic syndrome and its components could influence weight loss in obese and overweight women during a short-term, dietary-based intervention program. METHODS: A total of 107 women aged 49.1 +/- 13.5 years old, with a body mass index (BMI) greater than 25 were studied. The subjects were prescribed a low-fat diet plus weight-reducing drugs when necessary. RESULTS: After 3 months, the subjects with metabolic syndrome lost more weight than those without (6.62% vs. 4.50%; P < 0.05). There was a positive correlation between the percentage of weight loss and the number of the components of metabolic syndrome present at baseline (Spearman rho = 0.329; P < 0.01). Furthermore, patients in the quartile with the highest homeostasis model assessment index (HOMA-index) lost more weight than the remaining subjects (8.17% +/- 3.34 vs. 5.59% +/- 3.87; P < 0.05). These results were significant, even after adjustment for the medical treatment prescribed. CONCLUSIONS: Obese and overweight patients with metabolic syndrome showed a greater reduction of their body weight, compared to the patients without metabolic syndrome. The components of the metabolic syndrome present at baseline correlated positively with the percentage of the weight loss. Finally, the patients with the highest levels of HOMA-index at baseline lost significantly more weight than those with lower levels of this parameter.

Plasma phospholipid transfer protein (PLTP): review of an emerging cardiometabolic risk factor.

Plasma phospholipid transfer protein (PLTP) is a lipid transfer glycoprotein that binds to and transfers a number of amphipathic compounds. In earlier studies, the attention of the scientific community focused on the positive role of PLTP in high-density lipoprotein (HDL) metabolism. However, this potentially anti-atherogenic role of PLTP has been challenged recently by another picture: PLTP arose as a pro-atherogenic factor through its ability to increase the production of apolipoprotein B-containing lipoproteins, to decrease their antioxidative protection and to trigger inflammation. In humans, PLTP has mostly been studied in patients with cardiometabolic disorders. Both PLTP and related cholesteryl ester transfer protein (CETP) are secreted proteins, and adipose tissue is an important contributor to the systemic pools of these two proteins. Coincidently, high levels of PLTP and CETP have been found in the plasma of obese patients. PLTP activity and mass have been reported to be abnormally elevated in type 2 diabetes mellitus (T2DM) and insulin-resistant states, and this elevation is frequently associated with hypertriglyceridemia and obesity. This review article presents the state of knowledge on the implication of PLTP in lipoprotein metabolism, on its atherogenic potential, and the complexity of its implication in obesity, insulin resistance and T2DM.

Effects of a low-calorie diet associated with weight loss on lipoprotein-associated phospholipase A2 (Lp-PLA2) activity in healthy obese women.

INTRODUCTION: Platelet-activating factor acetylhydrolase (PAF-AH or Lp-PLA(2)) is a Ca(2+)-independent phospholipase A(2) primarily associated in plasma with low density lipoproteins (LDL), especially with small dense LDL (sdLDL) particles. Increased plasma Lp-PLA(2) levels have been associated with increased cardiovascular risk in large clinical trials. AIM: To assess the effects of weight loss on Lp-PLA(2) activity and to examine the association of Lp-PLA(2) activity changes with the alterations of sdLDL, the primary carrier of Lp-PLA(2) in plasma. METHODS: Twenty-eight obese, non-diabetic women participated in a weight reduction program. Anthropometric parameters were assessed and parameters of glucose metabolism, lipid profile, Lp-PLA(2) activity, and LDL phenotype (using a 3% polyacrylamide gel-tube electrophoresis method), were determined at baseline and after 4months of weight loss. RESULTS: A 10% diet-induced weight loss resulted in significant improvement in most parameters of lipid and glucose metabolism. Moreover, Lp-PLA(2) activity was significantly reduced (-10.2%, p<0.01). Mean LDL particle diameter did not change after the weight loss program. The cholesterol levels of very low-density lipoprotein (VLDL) and large-buoyant LDL particles were significantly reduced, but neither the cholesterol levels of sdLDL particles nor the % proportion of the sdLDL-cholesterol over the total LDL-cholesterol were changed after the intervention program. Interestingly, the changes in Lp-PLA(2) activity were correlated with the changes of VLDL-cholesterol (r=0.39, p<0.05), but not with the changes of anthropometric or other lipid variables. CONCLUSIONS: A low-calorie diet associated with weight loss in obese women resulted in the significant reduction of the plasma levels of Lp-PLA(2), the potentially new predictor for incident atherosclerotic disease.

First national epidemiological survey on the prevalence of obesity and abdominal fat distribution in Greek adults.

AIM: To provide estimates of the prevalence of obesity, overweight and body fat distribution among the adult population of Greece. DESIGN: Epidemiological, cross-sectional nationwide survey providing self-reported data. SUBJECTS: A total of 17,341 men and women aged from 20 to 70 years and classified into five 10-year age groups participated. The selection was conducted by stratified sampling through household family members of Greek children attending school. MEASUREMENTS: The participants reported data on weight, height, waist and hip circumference. BMI and waist-to-hip ratio were calculated. Abdominal obesity was defined as waist circumference > or = 102 cm in men and > or = 88 cm in women. RESULTS: In the total population, the mean BMI was 26.5 kg/m2, (27.3 in men, 25.7 in women). The overall prevalence of obesity was 22.5%, (26% in men, 18.2% in women) while that of overweight was 35.2% (41.1% in men, 29.9% in women). The percentages of obesity and overweight in men were similar in almost all age groups, while in women they progressively increased with age. Abdominal obesity was more frequent among women than men (35.8 vs. 26.6%, respectively), especially after the age of 50. CONCLUSIONS: Excess body weight is reaching epidemic proportions in Greece and obesity rates are among the highest, if not the highest, in Western society. The problem affects particularly men, and women after menopause. Interestingly, more women than men present with abdominal obesity. Preventive and treatment strategies are urgently needed to stop the obesity epidemic in this Mediterranean European country.

Changes in lipoprotein(a) levels and hormonal correlations during a weight reduction program.

BACKGROUND AND AIM: To examine the effects of a weight reduction program on serum lipoprotein(a) [Lp(a)] levels and investigate whether the hormonal modifications occurring during weight loss may explain the changes in Lp(a) levels. METHODS AND RESULTS: This longitudinal clinical intervention study of a low-calorie diet involved 62 healthy obese patients (21 men aged 32 +/- 9.6 years and 41 women aged 37 +/- 14.6 years). Their anthropometric parameters (weight, height, body mass index, waist-to-hip ratio), fasting serum lipid levels, hormones (total testosterone, estradiol, total triiodothyronine, insulin), sex hormone binding globulin (SHBG) and blood sugar levels were determined at baseline and after six weeks of dietary treatment. A 7.5% loss in initial body weight was achieved and there was a statistically significant decrease in serum total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides (p < 0.001). No changes in Lp(a) levels were observed in the study population as a whole, but there was a 17.6% (p < 0.05) reduction in the subjects with high pre-treatment Lp(a) values (> 20 mg/dL). The decrease in Lp(a) levels closely correlated with initial Lp(a) levels (r = 0.81 p < 0.001), but did not correlate with changes in anthropometric parameters or the hormonal modifications occurring during the weight loss. CONCLUSIONS: A low-calorie diet associated with weight loss in obese subjects may have beneficial effects on serum Lp(a) levels in patients with high pre-treatment Lp(a) concentrations. This effect seems to be independent of the hormonal changes observed during weight loss.

Prevalence and trends in overweight and obesity among children and adolescents in Thessaloniki, Greece.

Obesity is the most prevalent nutrition-related problem in Western societies. Childhood obesity is rapidly emerging as a global epidemic that will have profound public health consequences, as overweight children become overweight adults. The aim of this study was to investigate the prevalence of overweight and obesity among children and adolescents in the city of Thessaloniki, and evaluate the trends in Greece by comparing our results to those of other cross-sectional studies. Data concerning the height and weight of 2,458 schoolchildren aged 6 to 17 years (1,226 6-10 years, 1,232 11-17 years) of 27 primary and secondary public schools were collected. BMI was calculated from the two measurements. In the analyses, the estimations of the prevalence of overweight and obesity are based on recently established international BMI percentile curves and cut-off points from 2-18 years. To investigate the secular trends in obesity in Greece, data of schoolchildren from four successive surveys were used. In the younger group (6-10 yr), the prevalence of overweight and obesity were 25.3% and 5.6%, while for adolescents (11-17 yr) they were 19.0% and 2.6%, respectively. The prevalence was 25.9% and 5.1% for all males, and 19.1% and 3.2% for all females, respectively. As far as trends are concerned, an increase of BMI was found among males when the results of our survey were compared with those of the previous three. However, the trends for girls are different. An increase was found when the results of our study were compared with 1942. A decrease of BMI at most ages was found when the results of our study were compared with those of the 1982 survey, while an increase was recorded only for younger girls below 13 years compared to the 1984-5 study. This study demonstrates that the prevalence of overweight and obesity among schoolchildren is 22.2% and 4.1%, respectively, and has been increasing in the last decades, especially among boys.

Determinants of body mass index in Greek children and adolescents.

The aim of this study was to investigate the determinants of body mass index (BMI) among Greek children and adolescents, such as parental age and BMI, number of family members in the household, parents' educational status and occupation, physical activity and hours of television viewing and playing computer games by children per day. This cross-sectional study included 2,495 children aged 6-17 years from primary and high schools of Thessaloniki, capital of Northern Greece. Data were collected by questionnaires concerning age, height and weight of the parents, number of family members, and socioeconomic status as determined by occupation and educational status of the parents. Our results revealed that overweight in Greek children and adolescents is influenced positively by several determinant factors, such as parental age and obesity, hours of television viewing, and negatively by a high parental educational level. No significant association was found between children's BMI and physical activity. Intervention and prevention measures should be targeted at the reduction of sedentary activities, especially television viewing, and promotion of physical activity. These measures should be directed at families that are affected and/or concerned with obesity.

Changes in lipoprotein(a) levels in overt and subclinical hypothyroidism before and during treatment.

The aim of this prospective, follow-up study was to examine the influence of overt hypothyroidism (OHP) and subclinical (SHP), before and during thyroxine (T4) treatment, on lipoprotein(a) [Lp(a)], other lipoproteins, and apolipoproteins. Twenty-four patients (17 females, 7 males) with OHP, aged 54 +/- 11.1 years (group A) and 23 patients (females) with SHP aged 50.1 +/- 13.2 years (group B) were evaluated and compared to 34 and 38 controls, respectively. All patients received T4 therapy in a stepwise fashion until euthyroidism was reached. Thyrotropin (TSH), free thyroxine (FT4), and total triiodothyronine (TT3) levels were measured before T4 therapy and repeatedly every 4 weeks after the initiation of treatment until the euthyroid state was reached. Levels of Lp(a), total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDLc), high-density lipoprotein cholesterol (HDLc), apolipoprotein A1 (apoA1) and apolipoprotein B (apoB) were measured before and 4 months after the achievement of euthyroidism. Additionally, body mass index (BMI) was also evaluated. We found that in OHP patients, levels of TC, LDLc, and apoB were elevated before treatment and decreased significantly after the return to the euthyroid state. BMI and levels of triglycerides also decreased significantly; Lp(a) was higher in OHP patients in comparison with controls and decreased significantly by 14.56% (25.29% in men and 10.34% in women) during T4 treatment. In SHP patients, levels of all common lipoproteins, apolipoproteins, and Lp(a) did not differ significantly from controls before treatment and did not change after the euthyroid stage was reached. It is concluded that in overt hypothyroidism, Lp(a) levels and most of the lipoproteins were elevated before treatment and decreased significantly. In subclinical hypothyroidism, lipoproteins and Lp(a) levels were normal at baseline and did not change during treatment.

Leptin concentrations during oral glucose tolerance test (OGTT) in obese and normal weight women.

OBJECTIVE: To examine possible changes of leptin concentrations after the acute administration of glucose orally (OGTT). DESIGN: Seventy-five grams of glucose were administered per os in one group of obese and normal weight individuals and concentrations of glucose, insulin and leptin were measured at 0, 30, 60, 90 and 120 min. In an age matched control group of individuals with similar BMI water was given and leptin concentrations were measured before and after 30, 60, 90 and 120 min. SUBJECTS: Twenty-seven obese women aged 34+/-1.57 y with BMI 37.1+/-0.8 kg/m2 and 16 normal weight women, aged 32+/-1.13 y with BMI 23.6+/-0.3 kg/m2 formed the experimental group, while 10 obese and 10 normal weight females with similar age and BMI were used as controls. MEASUREMENTS: Weight, height, BMI, body fat, glucose, insulin and leptin at baseline and during OGTT. Variations of the above parameters were calculated from the area under the curve (AUC). RESULTS: Fasting leptin concentrations and AUC were higher in obese than in normal weight women. In obese women, leptin increased significantly in comparison to its basal concentrations 30 and 60 min after the glucose loading. Insulin was also increased, as expected. No correlation was found between insulin and leptin concentrations after glucose loading. Basal concentrations of leptin did not correlate with those of glucose and insulin. No changes in leptin concentrations were found in normal weight women after OGTT. However, a significant positive correlation was found between insulin and basal leptin. Finally, leptin concentrations did not change in obese and normal weight controls after water administration. CONCLUSION: A significant increase in leptin concentrations was found 30 and 60 min after glucose loading in obese individuals. No such increase was found in normal-weight women.