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Aims:: Lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) in the general population. However, such a role in patients with familial hypercholesterolemia (FH) is less documented. The purpose of this study was to evaluate the association between Lp(a) concentrations and ASCVD prevalence in adult patients with FH. Methods:: This was a cross-sectional study from the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH). Patients were categorized into 3 tertiles according to Lp(a) levels. Results:: A total of 541 adult patients (249 males) with possible/probable/definite FH heterozygous FH (HeFH) were included (mean age 48.5 ± 15.0 years at registration, 40.8 ± 15.9 years at diagnosis). Median (interquartile range) Lp(a) concentrations in the 1st, 2nd and 3rd Lp(a) tertile were 6.4 (3.0–9.7), 22.4 (16.0–29.1) and 77.0 (55.0–102.0) mg/dL, respectively. There was no difference in lipid profile across Lp(a) tertiles. The overall prevalence of ASCVD was 9.4% in the first, 16.1% in the second and 20.6% in the third tertile (p= 0.012 among tertiles). This was also the case for premature ASCVD, with prevalence rates of 8.5, 13.4 and 19.8%, respectively (p= 0.010 among tertiles). A trend for increasing prevalence of coronary artery disease (8.3, 12.2 and 16.1%, respectively; p= 0.076 among tertiles) was also observed. No difference in the prevalence of stroke and peripheral artery disease was found across tertiles. Conclusions:: Elevated Lp(a) concentrations are significantly associated with increased prevalence of ASCVD in patients with possible/probable/definite HeFH.

Purpose: Intraoperative imaging of parathyroid glands (PGs) has been developed in order to reduce the risk of unintentional parathyroidectomy during total thyroidectomy. This novel modality is based on their intrinsic characteristic of autofluorescence (AF) after near-infrared light exposure. The aim of this study was to assess the effect of this method on the risk of unintentional PG excision (total or partial) during total thyroidectomy. Methods: This was a single-blind, randomized-controlled trial including adult patients who underwent scheduled total thyroidectomy between December 2019 and March 2020. These patients were randomly allocated to two groups: one in which near-infrared autofluorescence imaging (NIRAF) was applied (NIR group) and one without NIRAF (NONIR group). Hormonal and biochemical assessment was performed pre- and 24-h postoperatively. AF findings and the number of PGs autotransplanted were recorded. Results: One-hundred and eighty patients were eligible. Unintentional (total or partial) PG excision rates during total thyroidectomy in the NONIR (n= 90) and NIR (n= 90) groups were 28.9% [95% confidence interval (CI) 19.8–39.4%] and 14.4% (95% CI 7.7–22.1%), respectively (p= 0.02). Furthermore, NIR reduced the risk of parathyroid tissue presence in the specimen sent for pathology (relative risk 0.51, 95% CI 0.28–0.92; p= 0.02). However, the number of PGs identified by NIR could not predict the risk of postoperative hypoparthyroidism. Conclusions: NIRAF imaging during total thyroidectomy led to a significant reduction in PG excision rates. However, this modality did not result in the reduction of postoperative hypoparathyroidism or hypocalcemia risk.

Purpose: The exact risk of type 2 diabetes mellitus (T2DM) in women with polycystic ovary syndrome (PCOS) is unknown. It is also unclear if obesity independently increases T2DM risk in this population. The aim of this study was to systematically review and synthesize the best available evidence regarding the association between PCOS and T2DM, stratified according to obesity status. Methods: A comprehensive search was conducted in PubMed, CENTRAL and Scopus databases up to October 31, 2020. Data are expressed as relative risk (RR) with 95% confidence interval (CI). The I2index was employed for heterogeneity. Results: The eligibility criteria were fulfilled by 23 studies (319,780 participants; 60,336 PCOS and 8847 type 2 diabetes cases). Women with PCOS demonstrated a higher risk of T2DM than those without PCOS (RR 3.45, 95% CI, 2.95–4.05, p< 0.001; I281.6%). This risk remained significant both in studies matched or unmatched for participants’ age. With regard to body mass index (BMI), the RR for developing T2DM in obese and non-obese PCOS women compared with their non-PCOS counterparts was 3.24 (95% CI 2.25–4.65; p< 0.001; I230.9%) and 1.62 (95% CI 0.14–18.50; p= 0.70; I289.9%), respectively. The RR for developing T2DM was 3.85 (95% CI 1.99–7.43; p< 0.001; I246.2%) in obese compared with non-obese women with PCOS. This was also the case for overweight compared with lean women with PCOS. Conclusions: Women with PCOS present an increased risk of T2DM compared with non-PCOS women only if they are obese/overweight.

Purpose: Statins are the mainstay of treatment for patients with familial hypercholesterolaemia (FH). However, their efficacy and safety in children and adolescents with FH has not been well-documented. The purpose of this study was to systematically investigate and meta-analyze the best available evidence from randomized-controlled trials (RCTs) regarding the efficacy and safety of statins in this population. Methods: A comprehensive search was conducted in PubMed, Scopus and Cochrane, up to 10 January 2020. Data were expressed as mean differences with 95% confidence intervals (CI). The I2index was employed for heterogeneity. Results: Ten RCTs were included in the qualitative and quantitative analysis (1191 patients, aged 13.3 ± 2.5 years). Compared with placebo, statins led to a mean relative reduction in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride and apolipoprotein B (apo-B) concentrations by −25.5% (95% CI −30.4%, −20.5%; I291%), −33.8% (95% CI −40.1%, −27.4%; I290%), −8.4% (95% CI −14.8%, −2.03%; I226%) and −28.8% (95% CI −33.9%, −23.6%; I283%), respectively. High-density lipoprotein cholesterol (HDL-C) was increased by 3.1% (95% CI 1.1%−5.2%; I20%). Statins were well-tolerated, with no significant differences in transaminase and creatine kinase levels or other adverse effects compared with placebo. Statins exerted no effect on growth or sexual development. Conclusion: Statins are quite effective in reducing TC, LDL-C, TG and apo-B and increasing HDL-C concentrations in children and adolescents with FH. No safety issues were seen with statin use.

Purpose: The increased experience of a thyroid surgeon reduces the risk of postoperative complications. However, whether it is also cost-effective is currently unknown. The aim of the present study was to compare cost-effectiveness of high-volume (HVS) with low-volume surgeons (LVS) when performing a total thyroidectomy. Methods: This was a retrospective study, comparing the mean cost of a total thyroidectomy per patient, between HVS and LVS. This included the cost of surgical procedure and pre- and post-operative inpatient hospitalization. A threshold of 25 thyroidectomies/year was used to discriminate between HVS and LVS. Results: Four-hundred and forty-one patients were classified into HVS and 342 into the LVS group. With regard to surgical complications, higher rates of temporary hypoparathyroidism and endangered airway were observed in the LVS than in the HVS group. The estimated total cost per patient was higher in the LVS compared with the HVS group [€1721 ± 396 ($1910 ± 439) versus €979 ± 68 ($1086 ± 487); p< 0.0001]. This cost remained higher when sub-analysis was performed for each surgical stage, involving either surgical procedure or pre- and post-operative inpatient hospitalization. Differences between LVS and HVS mainly involved the cost in surgical procedure (23% attributed to occupation of the operating room) and postoperative inpatient hospitalization (45% of the total thyroidectomy cost). Conclusion: Total thyroidectomy performed by a HVS seems to be cost-effective compared with the one conducted by LVS. This is mostly attributed to the lower rates of surgical complications, such as postoperative hypoparathyroidism and airway obstruction.

Polycystic ovary syndrome (PCOS) affects 6–15% of women of reproductive age. Nonalcoholic fatty liver disease (NAFLD) affects 25–30% of the general population and its prevalence increases in parallel with the epidemics of obesity and type 2 diabetes mellitus. A growing body of evidence suggests that NAFLD and PCOS quite often co-exist. The aim of this article is to summarize and critically appraise the literature regarding: (1) the rates of co-existence of the two entities, (2) the possible pathophysiological links, (3) the proper diagnostic assessment and (4) the appropriate management of women with NAFLD and PCOS. Data from clinical studies and meta-analyses indicate a higher prevalence of NAFLD in women with PCOS ranging from 34% to 70% compared with 14% to 34% in healthy women. Inversely, women with NAFLD are more often diagnosed with PCOS. Insulin resistance (IR) and hyperandrogenism are two main potential pathophysiological links between the two entities. In this regard, IR seems to interplay with obesity and hyperandrogenism, thus affecting NAFLD and PCOS and being affected by them. Women with PCOS, particularly those with IR and/or hyperandrogenism, are suggested to be screened for NAFLD, while premenopausal women with NAFLD is suggested to be screened for PCOS. Lifestyle recommendations with a change in dietary habits, weight loss and exercise, constitute currently the cornerstone of the management of both NAFLD and PCOS. Insulin sensitizers maybe used for the treatment of these women, while there are limited promising data for the use of liraglutide.

Purpose: Vitamin B12 deficiency has been associated with a plethora of metabolic abnormalities, such as hyperhomocysteinaemia, insulin resistance and defective synthesis of neurotransmitters and fatty acids. Inconsistency exists as to whether vitamin B12 deficiency is also associated with increased risk of gestational diabetes mellitus (GDM). The purpose of this study was to systematically review and meta-analyze the existing evidence for this association. Methods: A comprehensive search was conducted in PubMed, Scopus and Cochrane Central up to April 30, 2019. Data are expressed as odds ratio (OR) with 95% confidence interval (CI). The I2index was employed for heterogeneity. Results: Six studies (n?=?1810 pregnant women, 309 GDM cases) fulfilled the eligibility criteria for qualitative and two studies for quantitative analysis. In five studies providing data on vitamin B12 concentrations for both groups, women with GDM had lower vitamin B12 levels when compared with non-GDM women. Women with vitamin B12 deficiency were at higher risk for developing GDM when compared with those who were vitamin B12 sufficient: OR 1.81 (95% CI, 1.25–2.63, I2: 0%). Due to the small number of studies, the role of potential confounders could not be safely estimated. Conclusions: Vitamin B12 deficiency seems to be associated with increased risk of GDM. More studies are needed to further strengthen this finding and to clarify possible pathogenetic mechanisms.

The pathogenesis of Graves’ disease (GD) and orbitopathy (GO) is not completely elucidated. On the other hand, vitamin D receptor (VDR) gene polymorphisms have been associated with vulnerability to a plethora of chronic autoimmune diseases. The primary aim of this study was to synthesize evidence on the association between VDR gene polymorphisms and GD. Secondary aim was to investigate their association with GO. A comprehensive search was conducted in PubMed, CENTRAL and Scopus, up to December 8, 2018. Data were expressed as odds ratio (OR) with 95% confidence intervals (CI). Heterogeneity was quantified with I2index. Ten studies were included in the qualitative and quantitative analysis. TT subtype of TaqI polymorphism was associated with an increased risk of GD compared with Tt and tt polymorphisms (OR: 1.42; 95% CI, 1.05–1.94, p= 0.025), whereas tt was associated with a lower risk of GD, compared with TT and Tt polymorphisms (OR: 0.79; 95% CI, 0.62-0.99, p= 0.043). No association was found for ApaI, BsmI, and FokI polymorphisms. The bb subtype of BsmI polymorphism was associated with a lower risk in Asian, but with a higher GD risk in Caucasian populations, compared with BB/Bb subtypes. No eligible study was found regarding the association between VDR gene polymorphisms and the risk of GO. The TT subtype of the TaqI polymorphism was associated with a higher susceptibility for GD compared with Tt and tt. Regarding BsmI, the bb subtype was associated with increased GD risk in Caucasians, whereas it is protective in Asians.

Early menopause (EM, age at menopause < 45 years) and premature ovarian insufficiency (POI, age at menopause < 40 years) are associated with an increased risk of osteoporosis. However, their association with increased fracture risk has not been established, with studies yielding conflicting results. The primary aim of this systematic review and meta-analysis was to synthesize studies evaluating the association between age at menopause and fracture risk. The secondary aim was to evaluate this effect concerning the site of fractures. A comprehensive search was conducted in PubMed, CENTRAL and Scopus, up to 31 January 2018. Data were expressed as odds ratio (OR) with 95% confidence intervals (CI). The I2index was employed for quantifying heterogeneity. Eighteen studies were included in the qualitative and quantitative analysis (462,393 postmenopausal women, 12,130 fractures). Compared with women with age at menopause > 45 years, women with EM demonstrated higher fracture risk (OR 1.36, 95% CI 1.11–1.66, p< 0.002, I² 81.5%). Women with POI did not display any difference in fracture risk compared either with women with age at menopause > 40 (OR 1.23, 95% CI 0.72–2.09, p= 0.436, I² 62.5%) or >45 years (OR 0.54, 95% CI 0.22–1.29, p= 0.17, I20%). No difference was evident when a separate analysis was performed for vertebral, non-vertebral and hip fractures. This is the first meta-analysis showing that EM is associated with increased fracture risk compared with normal age at menopause, without any distinct effect on the site of the fracture.

Both type 1 (T1DM) and type 2 diabetes mellitus (T2DM) have been associated with bone fragility and increased fracture risk. However, little is known regarding the effect of anti-osteoporotic treatment on bone mineral density (BMD) and/or fracture risk in these patients. We aimed to systematically investigate the efficacy of anti-osteoporotic medications in patients with diabetes in comparison with non-diabetic subjects. MEDLINE and Scopus databases were searched (up to 31st October 2017). Nine studies fulfilled the pre-defined inclusion criteria [patients with T2DM (n= 8) or either T1DM or T2DM (n= 1)]. Regarding fracture risk, five studies were identified. Alendronate demonstrated comparable vertebral anti-fracture efficacy in patients with and without diabetes (n= 2), whereas non-vertebral fracture risk was either the same (n= 1) or higher in diabetic patients (n= 1). Raloxifene also demonstrated comparable vertebral anti-fracture efficacy in both groups (n= 2), without any effect on non-vertebral fractures in either group. In one study, diabetic patients exposed to raloxifene demonstrated the same vertebral and non-vertebral fracture risk with non-diabetic patients. Teriparatide (n= 1) demonstrated the same non-vertebral fracture rates in both patients with and without T2DM. Regarding BMD, equal increases in spine BMD were observed with alendronate (n= 4), risedronate (n= 1), and teriparatide (n= 1). With respect to hip BMD, similar increases were observed with teriparatide (n= 1), whereas data regarding alendronate were controversial (n= 3). No eligible study was found for zoledronic acid, ibandronate, strontium ranelate, denosumab, or bazedoxifene. The presence of diabetes does not alter anti-osteoporotic treatment response, regarding BMD increase and vertebral fracture risk reduction.

Thyroid nodularity has been associated with obesity, but data regarding associations of body composition parameters with specific ultrasound features of thyroid nodules are lacking. The aim of the present study was to assess associations between thyroid nodule ultrasound characteristics, lifestyle, and anthropometric parameters. This was a cross-sectional study in the general apparently healthy population of Northern Greece. Thyroid ultrasound data together with medical history, demographic, and anthropometric characteristics were individually recorded. Body composition was evaluated using bioelectrical impedance. Three hundred and six subjects [215 females (70.3%), aged 20–83 years] were included. Ultrasound revealed one or more thyroid nodules in 168 subjects (54.9%). Subjects with thyroid nodules were more frequently females (p= 0.033), older (p< 0.001) and had higher fat mass (p= 0.011), total body fat percentage (p< 0.001) and waist circumference (p= 0.045) than subjects without nodules. In logistic regression analyses, age and female gender were the only independent predictors of presence of thyroid nodules, as well as specific sonographic features. Additionally, total body fat percentage was positively correlated with nodule size (rho= 0.210, p= 0.006) and was the only independent predictor of hypoechoic thyroid nodule(s) and peripheral vascularity, while lack of exercise was predictive of internal vascularity. Body fat accumulation and lack of exercise, used as surrogate markers of sedentary lifestyle, influence thyroid nodule size and could predict some ultrasonographic characteristics, like hypoechoicity and internal vascularity. Therefore, routine thyroid examination of obese patients and promotion of active lifestyle may be warranted to prevent thyroid nodule formation and possibly progression to malignancy.

Several studies have shown that acromegaly is associated with increased psychological morbidity. However, it is not known whether this is attributed to acromegaly per se or to its chronicity as a debilitating disease affecting quality of life (QoL). The aim of this study was to assess psychological profile in acromegalics compared with those suffering from other serious chronic diseases and healthy controls. Secondary end points were QoL assessment and its association with mood disturbances. Comparative, cross-sectional study conducted in Northern Greece (2011–2012). The Greek versions of the Profile of Mood States (POMS) and AcroQoL questionnaires were used to assess psychological status and QoL, respectively. Forty acromegalics, 40 age- and sex-matched people with other chronic diseases and 80 healthy controls were included. No significant differences were identified between acromegalics and those suffering from other chronic diseases, regarding tension, anger, depression, confusion, fatigue and vigor. Compared with healthy controls, acromegalics suffered more from depression and anger, which remained significant after controlling for age, gender and marital status (p= 0.003 and p= 0.048, respectively). Negative predictors were female gender, macroadenomas and radiotherapy. AcroQoL scores were negatively associated with POMS subscales. Males had better QoL than females. Other than a negative association between AcroQoL-relationships subscale and disease duration, no association with other parameters was observed. Acromegaly has a negative impact on psychological status, which is worse than that of general population, but comparable to other chronic diseases. Mood disturbances are associated with impaired QoL, mainly in females and those with longer disease duration.

Antithyroid drugs (ATDs) remain the first-line therapy in patients with Graves’ disease (GD), despite a high relapse rate. The purpose of this study was to identify the predictors of remission in patients with GD treated with ATDs—retrospective study at an endocrine referral service in Northern Greece. Two-hundred and eleven patients met the study’s criteria. Females (p= 0.049), non-smokers (p= 0.017), patients without ophthalmopathy (p= 0.033), and those developing pharmaceutical hypothyroidism (p= 0.018) experienced longer duration of remission. Duration of remission was positively associated with therapy duration (rs= 0.151, p= 0.030), maximum TSH levels during (rs= 0.241, p= 0.001), at the end (rs= 0.280, p< 0.001) and 3 months after therapy (rs= 0.341, p= 0.003). There was a negative association with free T4 (FT4) (rs= −0.426, p< 0.001) and free triiodothyronine (FT3) (rs= −0.467, p= 0.038) levels at 6 months after ATDs discontinuation. In multiple-regression analysis, only duration of the first ATDs course for more than 24 months independently predicted duration of remission. Female gender, non-smoking, the absence of orbitopathy, treatment duration, pharmaceutical hypothyroidism, higher TSH levels during, at the end and 3 months after ATDs discontinuation, and lower FT4 and FT3 levels 6 months after therapy were associated with longer duration of remission. However, only duration of ATDs therapy for more than 24 months independently predicted predict long-term remission in GD.