Could Lipid Profile be Used as a Marker of Autonomous Cortisol Secretion in Patients with Adrenal Incidentalomas?

Adrenal incidentalomas (AIs) have been associated with an increased risk of metabolic syndrome and dyslipidemia, though evidence regarding the latter is limited. Lipid abnormalities in patients with AIs have been associated with subclinical hypercortisolism. The current study aims to test whether lipid profile in patients with AIs predicts "autonomous cortisol secretion" (ACS). Patients with AIs found on either computerized tomography (CT) or magnetic resonance imaging (MRI), were included in a prospective cohort study. All patients were followed up for at least three years. Alterations in their hormonal and lipid profiles were recorded. Ninety-four patients (69 women) harboring 111 AIs were included. There were no differences between patients with ACS and those without, with respect to their baseline lipid profile [total cholesterol, low-density-lipoprotein cholesterol (LDL-C), triglycerides, high-density lipoprotein cholesterol (HDL-C) and non-HDL-C] and blood pressure (systolic and diastolic). Non-HDL-C concentrations decreased over time (Repeated Measures ANOVA, p=0.013), despite patients' body mass index (BMI) remaining unchanged. Logistic regression analysis revealed that the only predictor of ACS was the size of AIs, as calculated by CT or MRI. The current study demonstrated that lipid profile at baseline or during follow-up cannot predict ACS in patients with AIs. However, larger AIs may have a greater probability of ACS.

Thyroid function and autoimmunity during ovarian stimulation for intracytoplasmic sperm injection.

The aim of the present study was to assess changes in thyroid function and thyroid autoimmunity (TAI) throughout ovarian stimulation (OS) for intracytoplasmic sperm injection (ICSI) and the association of these changes with ICSI outcome. A flexible gonadotrophin-releasing hormone (GnRH) antagonist protocol was used in 42 women and their thyroid function and TAI were assessed at baseline and five times during OS (Days 3 and 5 of the menstrual cycle, the day of hCG administration, the day of ovum pick-up and the day of the pregnancy test). The primary outcome measure was the change in thyroid function throughout OS. No overall change was recorded in thyrotropin-stimulating hormone (TSH) concentrations throughout OS (P=0.066). In women who became pregnant (n=8), an increase in TSH concentrations was noted on the day of the pregnancy test compared with Day 3 of the menstrual cycle (3.410±1.200 vs 2.014±0.950µIU mL-1, respectively; P=0.001; mean ± s.d.). TAI was present in 11 of 42 women. Biochemical pregnancy was negatively correlated with changes in TSH (r=-0.7, P=0.004). No such association was noted regarding the live birth rate. The present study provides evidence that TSH concentrations could increase during OS, especially in women who become pregnant.

Periostin and sclerostin levels in juvenile Paget's disease.

Juvenile Paget's disease (JPD) is a rare, autosomal recessive disorder featuring markedly increased serum alkaline phosphatase activity, indicative of greatly accelerated bone turnover throughout the skeleton. The main aim of this study was to evaluate circulating periostin and sclerostin levels in two adult patients with mild JPD (due to "Balkan" mutation). We measured periostin and sclerostin levels in a previously described woman and a newly diagnosed man with JPD, and 10 apparently healthy individuals, matched (1:5) to JPD patients for gender, age and body mass index. Sclerostin levels were similar between JPD patients and controls. Periostin levels were about 2.5 times higher in JPD patients. Periostin and sclerostin levels were negatively correlated (rs= -0.63; p=0.03). In conclusion, a trend towards higher periostin levels was observed in JPD patients, whereas sclerostin levels were similar to controls.

Thyroid function and IVF outcome: when to investigate and when to intervene?

PURPOSE OF REVIEW: To summarize the evidence regarding the need to assess thyroid function in women undergoing ovarian stimulation as well as the need to intervene when thyroid function is suboptimal. RECENT FINDINGS: There is now evidence that ovarian stimulation can influence thyroid function not only via hyperestrogenism but also directly, since thyroid-related receptors are present in human granulosa cells and in the endometrium. Prospective and retrospective observational studies, as well as a few clinical trials, have been conducted in an effort to clarify the association between ovarian stimulation and thyroid function with controversial results. SUMMARY: The need of thyroid function screening with thyroid stimulating hormone (TSH) in infertile women attempting pregnancy is recognized by many international societies. Since TSH is a simple, cheap screening tool and levothyroxine (LT4) supplementation is an easy to apply, cheap and well tolerated intervention, universal thyroid screening in women undergoing IVF represents a reasonable policy. In case of subclinical hypothyroidism, when TSH exceeds the threshold of 4.0 or 4.5 µIU/ml before IVF, LT4 replacement should be administered, while the same intervention might also be justified for women with TSH concentration more than 2.5 µIU/ml before IVF.

Genetic basis of familial isolated hyperparathyroidism: a case series and a narrative review of the literature.

Primary hyperparathyroidism is a heterogeneous clinical entity. In the clinical setting, the diagnosis and management of familial isolated hyperparathyroidism (FIHP) and other familial hyperparathyroidism (FHPT) forms continue to rely on clinical, laboratory, and histological findings, with careful examination of the family. In this article, we report a case series of FIHP in a four-generation Greek family, with no identifiable gene mutations. Clinical approach and long-term follow-up are discussed and a narrative review of the genetic basis of this entity has been performed.

Association of TSH concentrations and thyroid autoimmunity with IVF outcome in women with TSH concentrations within normal adult range.

BACKGROUND/AIMS: This study aimed to evaluate the association of thyroid-stimulating hormone (TSH) concentrations and presence of thyroid autoimmunity (TAI) with the live birth rate in euthyroid women undergoing in vitro fertilization (IVF). METHODS: This study of retrospective design included 158 euthyroid women (TSH 0.5-4.5 µIU/ml) who underwent IVF from January 2006 to December 2010. Thyroid parameters were measured on day 3 of the previous nontreatment cycle. Women were subgrouped and analyzed according to their TSH concentrations (low: 0.5-2.5 vs. high: 2.6-4.5 µIU/ml) and TAI (present vs. absent). RESULTS: No difference in the live birth rate was found between the TSH (low: 34.2% vs. high: 36.8%, p = 0.763) or TAI (present: 26.7% vs. absent: 34.3%, p = 0.568) subgroups. CONCLUSION: This study found no evidence that increased TSH concentrations or the presence of TAI determined before IVF affect the live birth rate in euthyroid women. A better insight into the role of thyroid function during application of IVF is needed.

Hypogonadism and nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD), recently proposed to be renamed to metabolic dysfunction-associated steatotic liver disease (MASLD), is a major global public health concern, affecting approximately 25-30% of the adult population and possibly leading to cirrhosis, hepatocellular carcinoma, and liver transplantation. The liver is involved in the actions of sex steroids via their hepatic metabolism and production of the sex hormone-binding globulin (SHBG). Liver disease, including NAFLD, is associated with reproductive dysfunction in men and women, and the prevalence of NAFLD in patients with hypogonadism is considerable. A wide spectrum of possible pathophysiological mechanisms linking NAFLD and male/female hypogonadism has been investigated. As therapies targeting NAFLD may impact hypogonadism in men and women, and vice versa, treatments of the latter may affect NAFLD, and an insight into their pathophysiological pathways is imperative. This paper aims to elucidate the complex association between NAFLD and hypogonadism in men and women and discuss the therapeutic options and their impact on both conditions.

Skin Microvascular Dysfunction in Type 2 Diabetes Mellitus Using Laser Speckle Contrast Analysis and Association with Carotid Intima-Media Thickness.

Background: It is established that diabetes mellitus (DM) is characterized by increased cardiovascular risk associated with subclinical atherosclerosis as well as microvascular alterations. Laser speckle contrast analysis (LASCA) is an innovative, non-invasive method for assessing skin microvascular function. Objectives: We sought to assess skin microvascular function in patients with type 2 DM and matched controls. Methods: Consecutive patients with DM and individuals matched for age, sex and BMI were included in the study. Skin microvascular perfusion was assessed, using LASCA, during baseline, a 5 min occlusion period and a 5 min reperfusion period. Carotid intima-media thickness (cIMT) was measured as a surrogate marker of macrocirculation. Results: In total, 18 patients with DM and 22 in the control group were enrolled. No statistically significant differences were observed in baseline flux, peak flux and percentage decrease during arterial occlusion. During reperfusion, individuals with DM exhibited a smaller peak magnitude compared to controls (147.0 ± 64.7% vs. 189.4 ± 46.0%, respectively; p < 0.05). Moreover, cIMT was higher in patients with DM compared to controls (0.68 ± 0.09 mm vs. 0.60 ± 0.08 mm, respectively, p < 0.01) and was negatively correlated with skin microvascular reactivity in the univariate analysis. In the multivariate analysis, glucose and office systolic blood pressure levels remained significant predictors of microvascular reactivity. Conclusions: Our study shows that patients with type 2 DM exhibit impaired skin microvascular function compared to controls. Furthermore, glucose levels and blood pressure play a key role in microvascular dysfunction. However, additional studies are needed to address the clinical significance of early microvascular changes in DM.

EMAS position statement: Thyroid disease and menopause.

INTRODUCTION: Thyroid diseases are common in women in their late reproductive years; therefore, thyroid disease and menopause may co-exist. Both conditions may present with a wide range of symptoms, leading to diagnostic challenges and delayed diagnosis. Aim To construct the first European Menopause and Andropause Society (EMAS) statement on thyroid diseases and menopause. MATERIALS AND METHODS: Literature review and consensus of expert opinion (EMAS executive board members/experts on menopause and thyroid disease). SUMMARY RECOMMENDATIONS: This position paper highlights the diagnostic and therapeutic dilemmas in managing women with thyroid disease during the menopausal transition, aiming to increase healthcare professionals' awareness of thyroid disorders and menopause-related symptoms. Clinical decisions regarding the treatment of both conditions should be made with caution and attention to the specific characteristics of this age group while adopting a personalized patient approach. The latter must include the family history, involvement of the woman in the decision-making, and respect for her preferences, to achieve overall well-being.

Ketone Bodies in Diabetes Mellitus: Friend or Foe?

In glucose-deprived conditions, ketone bodies are produced by the liver mitochondria, through the catabolism of fatty acids, and are used peripherally, as an alternative energy source. Ketones are produced in the body under normal conditions, including during pregnancy and the neonatal period, when following a ketogenic diet (KD), fasting, or exercising. Additionally, ketone synthesis is also augmented under pathological conditions, including cases of diabetic ketoacidosis (DKA), alcoholism, and several metabolic disorders. Nonetheless, diet is the main regulator of total body ketone concentrations. The KDs are mimicking the fasting state, altering the default metabolism towards the use of ketones as the primary fuel source. Recently, KD has gained recognition as a medical nutrition therapy for a plethora of metabolic conditions, including obesity and diabetes mellitus (DM). The present review aims to discuss the role of ketones, KDs, ketonemia, and ketonuria in DM, presenting all the available new evidence in a comprehensive manner.

Microvascular and Endothelial Dysfunction in Prediabetes.

Prediabetes is a significant metabolic status since there is high potential for future progression of diabetes mellitus (DM). People with prediabetes are at increased risk of cardiovascular disease (CVD) and mortality. Endothelial and microvascular dysfunction is considered a key step towards the development and progression of CVD. Importantly, endothelial and microvascular dysfunction can be detected and monitored using non-invasive procedures in peripheral organs and tissues, including the retina, kidney, skin and skeletal muscle. Structural and functional alterations of the microvasculature have been consistently documented in the above microvascular beds in patients with diabetes mellitus. In contrast, such alterations remain understudied in prediabetes, but are currently receiving attention as markers of subclinical and future CVD. The aim of this review is to summarize available evidence regarding the presence of subclinical microvascular and endothelial dysfunction in prediabetes and their impact on cardiovascular risk.

Diet Quality and Nutritional Risk Based on the FIGO Nutrition Checklist among Greek Pregnant Women: A Cross-Sectional Routine Antenatal Care Study.

The International Federation of Gynecology and Obstetrics (FIGO) nutrition checklist is a tool for everyday antenatal clinical practice, easy to use by most healthcare professionals, aiming to initiate a conversation regarding gestational weight gain (GWG) and nutrition and identify women who might require further assessment. The present cross-sectional study aimed to apply the FIGO nutrition checklist to pregnant women attending routine antenatal care and identify nutritional risk factors. Pregnant women (n = 200) were recruited from the outpatient pregnancy clinics of two hospitals in Thessaloniki and completed the checklist. The FIGO-diet quality score and the FIGO-nutritional risk score (NRS) were calculated. The results revealed that 99% of the women exhibited at least one nutritional risk factor based on the checklist. The median FIGO diet quality score of the sample was 4.0 (3.0-5.0), with 95% of the participants responding negatively to at least one question, indicating the need for improving diet quality. Improved diet quality was noted in cases of hyperemesis gravidarum and among those receiving vitamin D supplements. A large percentage of the participants (36%) exhibited five or more nutritional risk factors, as indicated by a total FIGO-NRS below 5. Women with low middle-upper arm circumference, indicative of protein-energy malnutrition (20.6% of the sample), exhibited more nutritional risk factors compared with the rest. On the other hand, being in the third trimester of pregnancy was associated with lower nutritional risk and, subsequently, better diet quality.

Metabolic, Oxidative and Psychological Stress as Mediators of the Effect of COVID-19 on Male Infertility: A Literature Review.

Over 300 million patients with coronavirus disease 2019 (COVID-19) have been reported worldwide since the outbreak of the pandemic in Wuhan, Hubei Province, China. COVID-19 is induced by the acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The effect of SARS-CoV-2 infection on the male reproductive system is unclear. The aim of this review is to assess the effect of SARS-CoV-2 infection on male fertility and the impact of possible mediators, such as metabolic, oxidative and psychological stress. SARS-CoV-2 infection aggravates metabolic stress and directly or indirectly affects male fertility by reducing seminal health. In addition, SARS-CoV-2 infection leads to excessive production of reactive oxygen species (ROS) and increased psychological distress. These data suggest that SARS-CoV-2 infection reduces male fertility, possibly by means of metabolic, oxidative and psychological stress. Therefore, among other consequences, the possibility of COVID-19-induced male infertility should not be neglected.

Seminal L-Carnitine In Infertile Oligoasthenoteratozoospermic Men with Varicocele.

Background: Few studies have investigated the relationship of seminal L-Carnitine (LC) with male infertility associated with varicocele. The purpose of this prospective cross-sectional study was to assess seminal plasma LC levels in infertile oligoathenoteratozoospermic (OAT) men with varicocele. Methods: Overall, 86 men were investigated. They were divided into infertile OAT men with varicocele (n=45), infertile OAT men without varicocele (n=21), and fertile men (n=20) as a control group. According to WHO guidelines, these men were subjected to history taking, clinical examination, and semen analysis. Seminal LC levels were evaluated by the colorimetric method. Statistical comparisons were done using Kruskal-Wallis and Mann-Whitney U tests and correlations were verified by the Pearson test. P-value<0.05 was set to be statistically significant. Results: The mean seminal plasma LC levels were significantly lower in infertile OAT men with varicocele (216.3±57.1 ng/ml) compared to infertile OAT men without varicocele (252.9±62.9 ng/ml, p=0.01), or fertile men (382.8±63.6 ng/ml, p=0.001). Besides, the mean seminal plasma LC level exhibited statistically significant decreases in infertile OAT men of varicocele grade III compared to varicocele grade II cases, and in infertile OAT men with bilateral varicocele compared with unilateral varicocele cases. Collectively, there was a statistically significant positive correlation between seminal LC levels with sperm concentration, motility, and normal morphology. Conclusion: Seminal LC levels are expressively reduced in infertile OAT men with varicocele and are influenced by an increase in varicocele grade and laterality.

Plasma Ceramide Concentrations in Full-Term Pregnancies Complicated with Gestational Diabetes Mellitus: A Case-Control Study.

Ceramides, a sphingolipid group that acts as a messenger in cellular differentiation, proliferation, apoptosis and senescence, have been associated with cardiovascular disease and type 2 diabetes. The evidence for an association between ceramides and gestational diabetes mellitus (GDM) is scarce. This case-control study aimed to compare women with GDM with healthy, pregnant women in terms of plasma ceramide concentrations at the time of delivery. Ninety-two pregnant women were included in this case-control study, 29 in the GDM group and 63 in the control group. All women were admitted to a tertiary academic hospital for a full-term delivery. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was applied for the quantification of four molecular ceramides, namely Cer d18:1/16:0 (Cer16:0), Cer d18:1/18:0 (Cer18:0), Cer d18:1/24:0 (Cer24:0) and Cer d18:1/24:1 (Cer24:1) in plasma samples. The raw chromatographic data obtained from the LC-MS/MS analysis were processed using Analyst SCIEX (AB Sciex Pte. Ltd., USA). In a univariate statistical analysis, Cer24:0 concentration was significantly lower in the GDM group compared with the control group (p = 0.01). The present study demonstrated lower Cer24:0 concentrations in pregnancies complicated by GDM. Further prospective studies are required to enhance the results of this study.

Neurofibromatosis Type 1 Has a Wide Spectrum of Growth Hormone Excess.

Overgrowth due to growth hormone (GH) excess affects approximately 10% of patients with neurofibromatosis type 1 (NF1) and optic pathway glioma (OPG). Our aim is to describe the clinical, biochemical, pathological, and genetic features of GH excess in a retrospective case series of 10 children and adults with NF1 referred to a tertiary care clinical research center. Six children (median age = 4 years, range of 3−5 years), one 14-year-old adolescent, and three adults (median age = 42 years, range of 29−52 years) were diagnosed with NF1 and GH excess. GH excess was confirmed by the failure to suppress GH (<1 ng/mL) on oral glucose tolerance test (OGTT, n = 9) and frequent overnight sampling of GH levels (n = 6). Genetic testing was ascertained through targeted or whole-exome sequencing (n = 9). Five patients (all children) had an OPG without any pituitary abnormality, three patients (one adolescent and two adults) had a pituitary lesion (two tumors, one suggestive hyperplasia) without an OPG, and two patients (one child and one adult) had a pituitary lesion (a pituitary tumor and suggestive hyperplasia, respectively) with a concomitant OPG. The serial overnight sampling of GH levels in six patients revealed abnormal overnight GH profiling. Two adult patients had a voluminous pituitary gland on pituitary imaging. One pituitary tumor from an adolescent patient who harbored a germline heterozygous p.Gln514Pro NF1 variant stained positive for GH and prolactin. One child who harbored a heterozygous truncating variant in exon 46 of NF1 had an OPG that, when compared to normal optic nerves, stained strongly for GPR101, an orphan G protein-coupled receptor causing GH excess in X-linked acrogigantism. We describe a series of patients with GH excess and NF1. Our findings show the variability in patterns of serial overnight GH secretion, somatotroph tumor or hyperplasia in some cases of NF1 and GH excess. Further studies are required to ascertain the link between NF1, GH excess and GPR101, which may aid in the characterization of the molecular underpinning of GH excess in NF1.

Dynamic endocrine test of inhibin B and anti-Müllerian hormone in men with non-obstructive azoospermia.

Although both serum inhibin B (Inh-B) and anti-Müllerian hormone (AMH) concentrations have been proposed as markers of spermatogenesis in men with subfertility, there are wide overlaps with fertile controls. The main aim of this study was to evaluate stimulated serum Inh-B and AMH concentrations in men with non-obstructive azoospermia (NOA). Thirty-seven men with NOA confirmed by testicular fine-needle aspiration and 17 fertile controls participated at this prospective, case-control study. All subjects underwent the Exogenous FSH SErtoli Reserve Test (EFSERT): estimation of serum Inh-B and AMH concentrations before, 24 and 48 hours after administration of 300 IU human recombinant FSH (hrFSH). Basal serum Inh-B and AMH concentrations, as well as Inh-B concentrations at 24 and 48 h were lower in men with NOA as compared to controls. No changes in Inh-B or AMH concentrations were recorded throughout the EFSERT in either men with NOA or controls nor when men with NOA were classified according to their clinical, hormonal and cytological diagnosis. Thus, stimulated serum concentrations of Inh-B and AMH, as obtained by an EFSERT, do not contribute to the diagnostic evaluation of the men with NOA, as the same information can be acquired by the basal serum concentrations of these hormones.

Exercise as a Therapeutic Intervention in Gestational Diabetes Mellitus.

Gestational Diabetes Mellitus (GDM) is defined as any degree of glucose intolerance with onset or first recognition during pregnancy. Regular exercise is important for a healthy pregnancy and can lower the risk of developing GDM. For women with GDM, exercise is safe and can affect the pregnancy outcomes beneficially. A single exercise bout increases skeletal muscle glucose uptake, minimizing hyperglycemia. Regular exercise training promotes mitochondrial biogenesis, improves oxidative capacity, enhances insulin sensitivity and vascular function, and reduces systemic inflammation. Exercise may also aid in lowering the insulin dose in insulin-treated pregnant women. Despite these benefits, women with GDM are usually inactive or have poor participation in exercise training. Attractive individualized exercise programs that will increase adherence and result in optimal maternal and offspring benefits are needed. However, as women with GDM have a unique physiology, more attention is required during exercise prescription. This review (i) summarizes the cardiovascular and metabolic adaptations due to pregnancy and outlines the mechanisms through which exercise can improve glycemic control and overall health in insulin resistance states, (ii) presents the pathophysiological alterations induced by GDM that affect exercise responses, and (iii) highlights cardinal points of an exercise program for women with GDM.

Nonalcoholic fatty liver disease in males with low testosterone concentrations.

AIMS: There are limited clinical data on the association between serum testosterone concentrations and nonalcoholic fatty liver disease (NAFLD) in men. The main aim of this study was to evaluate the association between testosterone concentrations and NAFLD in adult men, in terms of noninvasive indices of NAFLD and hepatic fibrosis. METHODS: In this cross-sectional study, 98 men were recruited on an outpatient basis and were divided into low-testosterone (<12 nmol/l or <346 ng/dl, n = 37) or high-testosterone groups (≥12 nmol/l or ≥346 ng/dl, n = 61). Serum testosterone concentrations were measured by immuno-chemiluminescence. Hepatic steatosis index (HSI) and Triglyceride-to-HDL-C ratio (THR), as non-invasive indices of NAFLD, as well as AST-to-Platelet Ratio Index (APRI), fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS), as non-invasive indices of hepatic fibrosis, were calculated based on standard formulas. RESULTS: Both the non-invasive indices of NAFLD (HSI and THR) were higher in low-testosterone compared with high-testosterone group (HSI: 47.5 ± 2.9 vs. 38.4 ± 1.0, p = 0.005; THR: 1.70 ± 0.16 vs. 0.98 ± 0.07, p < 0.001). On the contrary, none of the non-invasive indices of hepatic fibrosis was different between groups. HSI (p = 0.038), but not THR, remained inversely independently associated with serum testosterone, after adjustment for potential confounders, including sex hormone-binding globulin. CONCLUSIONS: Men with low testosterone concentrations have higher non-invasive indices of NAFLD (HSI and THR), but not of hepatic fibrosis (APRI, FIB-4, NFS), compared with counterparts of high testosterone concentrations. HSI was inversely and independently associated with testosterone concentrations.

Evidence for a manifold role of selenium in infertility.

This review aimed to assess the evidence from observational and interventional studies in humans and animals regarding the role of selenium (Se) in male and female infertility. As oxidative stress can seriously impair male, and possibly also female, reproductive functions, it can be speculated that the antioxidant properties of Se could constitute one of the pathways by which this element is involved in fertility. Specifically, there are strong indications that Se influences the growth, maturation, and replication of oocytes, though the precise mechanisms have not as yet been fully elucidated. Given that it is not clear at present which tissue sample (blood, serum, seminal plasma, sperm, or follicular fluid) renders the most accurate picture of Se concentration in terms of its role in reproduction, the data are still insufficient to recommend routine assessment of Se status in men and women seeking fertility. Nevertheless, the existing evidence, despite being of limited quantity and somewhat low quality, suggests that Se supplementation (< 200 µg/d) is possibly beneficial in men through its improvement of sperm motility. Well-designed, randomized control studies are needed to reveal the seemingly diverse protective/positive role of Se supplementation in men and women seeking fertility treatment.