Bone: A Neglected Endocrine Organ?

Bone has traditionally been viewed in the context of its structural contribution to the human body. Foremost providing necessary support for mobility, its roles in supporting calcium homeostasis and blood cell production are often afterthoughts. Recent research has further shed light on the ever-multifaceted role of bone and its importance not only for structure, but also as a complex endocrine organ producing hormones responsible for the autoregulation of bone metabolism. Osteocalcin is one of the most important substances produced in bone tissue. Osteocalcin in circulation increases insulin secretion and sensitivity, lowers blood glucose, and decreases visceral adipose tissue. In males, it has also been shown to enhance testosterone production by the testes. Neuropeptide Y is produced by various cell types including osteocytes and osteoblasts, and there is evidence suggesting that peripheral NPY is important for regulation of bone formation. Hormonal disorders are often associated with abnormal levels of bone turnover markers. These include commonly used bone formation markers (bone alkaline phosphatase, osteocalcin, and procollagen I N-propeptide) and commonly used resorption markers (serum C-telopeptides of type I collagen, urinary N-telopeptides of type I collagen, and tartrate-resistant acid phosphatase type 5b). Bone, however, is not exclusively comprised of osseous tissue. Bone marrow adipose tissue, an endocrine organ often compared to visceral adipose tissue, is found between trabecula in the bone cortex. It secretes a diverse range of hormones, lipid species, cytokines, and other factors to exert diverse local and systemic effects.

Association of Obesity and Bariatric Surgery on Hair Health.

Obesity and obesity-related conditions today constitute a public health problem worldwide. Obesity is an "epidemic" chronic disorder, which is defined by the WHO as normal or excessive fat accumulation that may impair health. It is also defined for adults as a BMI that is greater than or equal to 30. The most common obesity-related diseases are type 2 diabetes mellitus, cardiovascular diseases, metabolic syndrome, chronic kidney disease, hyperlipidemia, hypertension, nonalcoholic fatty liver disease, and certain types of cancer. It has been also proven that obesity can have a negative effect on hair. It can lead to hair thinning. Patients with obesity can undergo bariatric surgery if they meet the inclusion criteria. The four common types of weight loss surgery include a duodenal switch with biliopancreatic diversion, laparoscopic adjustable gastric banding, Roux-en-Y gastric bypass, and sleeve gastrectomy. Bariatric surgery can affect skin and hair and is associated with telogen effluvium due to weight loss, microelement deficiency, anesthesia, low calorie intake, and low protein intake. Patients who undergo bariatric surgery can experience post-bariatric surgery depression. Hair loss can have a major impact on self-esteem, negatively affecting one's self-image. The purpose of this narrative review is to critically review how obesity, obesity-related diseases, and bariatric surgery affect hair health in general and the hair development cycle, and how they influence hair loss.

Association of Mitochondrial Variants with the Joint Occurrence of Polycystic Ovary Syndrome and Hashimoto's Thyroiditis.

BACKGROUND: The prevalence of Hashimoto's thyroiditis (HT) among women with polycystic ovary syndrome (PCOS) is higher than in the general female population, but the factors predisposing to the coexistence of these disorders remain unclear. This study employed whole genome sequencing of mitochondrial DNA to identify genetic variants potentially associated with the development of PCOS and HT and predisposing to their joint occurrence. RESULTS: A total of 84 women participated, including patients with PCOS, HT, coexisting PCOS and HT (PCOS + HT) and healthy women. Both Fisher's exact and Mann-Whitney U statistical analyses were performed to compare the frequency of variants between groups. Ten differentiating variants were common to both analyses in PCOS + HT vs. PCOS, one in PCOS + HT vs. HT, and six in PCOS + HT vs. control. Several variants differentiating the PCOS + HT group from PCOS and controls were identified, located both in the mitochondrial genes (including the MT-CYB, MT-ND1, MT-ND2, MT-ND4, MT-ND6, MT-CO1, MT-CO3) and the D-loop region. Only two variants differentiated PCOS + HT and HT groups. One variant (13237a in MT-ND5) was common for all three comparisons and underrepresented in the PCOS + HT group. Functional enrichment analysis showed 10 pathways that were unique for the comparison of PCOS + HT and PCOS groups, especially related to ATP production and oxidative phosphorylation, and one pathway, the NADH-quinone oxidoreductase, chain M/4, that was unique for the comparison of PCOS + HT and control groups. Notably, nine pathways shared commonality between PCOS + HT vs. PCOS and PCOS + HT vs. control, related to the biogenesis and assembly of Complex I. CONCLUSION: This study provides novel insights into the genetic variants associated with oxidative stress in women with coexisting PCOS and HT. Mitochondrial dysfunction and oxidative stress appear to play a role in the pathogenesis of both conditions. However, more mitochondrial variants were found to differentiate women with both PCOS and HT from those with PCOS alone than from those with HT alone.

Autoimmune polyendocrine syndromes associated with autoimmune rheumatic diseases.

Autoimmune polyendocrine syndromes (APSs), also called autoimmune polyglandular syndromes, are a group of autoimmune diseases characterized by the co-occurrence of dysfunctions of several (at least two) endocrine glands. They develop under the influence of environmental factors in genetically predisposed people. Autoimmune polyendocrine syndromes may accompany autoimmune rheumatic diseases and worsen their course - APS-2 and APS-3 are the most common. The APS-2 includes the coexistence of, e.g. Hashimoto's disease, celiac disease and rheumatoid arthritis (RA). In APS-3, rheumatic diseases such as RA, systemic lupus erythematosus, and Sjögren's syndrome may coexist with Hashimoto's disease, type 1 diabetes and hypogonadism or other endocrinopathies. Undiagnosed endocrine diseases may be the reason for the intensification of metabolic disorders observed in the course of rheumatic diseases, cause the ineffectiveness of rheumatological treatment and also increase the frequency of bone fractures due to osteoporosis, cardiovascular complications and even miscarriages when coexistent, e.g. Hashimoto's disease with hypothyroiditis, which increases the risk of pregnancy loss. It is important to be able to conduct an extensive interview, paying attention to the symptoms of possible endocrinopathy as well as the features of other autoimmune disorders in the physical examination (e.g. vitiligo or darkening of the skin in Addison's disease). Depending on the history and physical examination, screening for various APSs is advised.

Exome sequencing to explore the possibility of predicting genetic susceptibility to the joint occurrence of polycystic ovary syndrome and Hashimoto's thyroiditis.

A large body of evidence indicates that women with polycystic ovary syndrome (PCOS) have a higher risk of developing Hashimoto's thyroiditis (HT) than healthy individuals. Given the strong genetic impact on both diseases, common predisposing genetic factors are possibly involved but are not fully understood. Here, we performed whole-exome sequencing (WES) for 250 women with sporadic PCOS, HT, combined PCOS and HT (PCOS+HT), and healthy controls to explore the genetic background of the joint occurrence of PCOS and HT. Based on relevant comparative analyses, multivariate logistic regression prediction modeling, and the most informative feature selection using the Monte Carlo feature selection and interdependency discovery algorithm, 77 variants were selected for further validation by TaqMan genotyping in a group of 533 patients. In the allele frequency test, variants in RAB6A, GBP3, and FNDC7 genes were found to significantly (padjusted < 0.05) differentiated the PCOS+HT and PCOS groups, variant in HIF3A differentiated the PCOS+HT and HT groups, whereas variants in CDK20 and CCDC71 differentiated the PCOS+HT and both single disorder groups. TaqMan genotyping data were used to create final prediction models, which differentiated between PCOS+HT and PCOS or HT with a prediction accuracy of AUC = 0.78. Using a 70% cutoff of the prediction score improved the model parameters, increasing the AUC value to 0.87. In summary, we demonstrated the polygenic burden of both PCOS and HT, and many common and intersecting signaling pathways and biological processes whose disorders mutually predispose patients to the development of both diseases.

Binge Eating Disorder-The Point Prevalence among Polish Women with Polycystic Ovary Syndrome and Validity of Screening Tool for This Population.

BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders which is associated with an increased risk of metabolic dysregulation. The elevated prevalence of obesity has been observed in women with PCOS. Since obesity is commonly associated with eating disturbances, including the binge eating disorder (BED), and since the hormonal changes in PCOS patients could influence the food intake model, we decided to estimate the prevalence of BED in PCOS patients and to assess the sensitivity and specificity of the Questionnaire for Binge Eating Screening (QBES) in PCOS patients. METHODS: A total of 122 hospitalized women with PCOS aged 16-45 (M = 26; SD = 5.22) took part in the study. Binge eating disorder (BED) was diagnosed according to the DSM-5 diagnostic criteria. QBES was used as a screening tool for BED. RESULTS: The point prevalence of BED in PCOS women according to DMS-5 criteria was 51 (42%). At least two positive answers to four QBES items had 100% sensitivity and 91% specificity. Positive answers to even only the first two questions from QBES had 98% sensitivity and 85% specificity. CONCLUSIONS: Women with polycystic ovary syndrome are at a very high risk of binge eating behaviors. Screening for eating disorders should be a routine procedure in women with PCOS. The first two questions from QBES are a brief and relatively reliable screening tool that may be used in everyday practice with POSC patients.

Anti-Müllerian Hormone in Pathogenesis, Diagnostic and Treatment of PCOS.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among reproductive-aged women. It is characterized by chronic anovulation, hyperandrogenism, and the presence of polycystic ovary in ultrasound examination. PCOS is specified by an increased number of follicles at all growing stages, mainly seen in the preantral and small antral follicles and an increased serum level of Anti-Müllerian Hormone (AMH). Because of the strong correlation between circulating AMH levels and antral follicle count on ultrasound, Anti-Müllerian Hormone has been proposed as an alternative marker of ovulatory dysfunction in PCOS. However, the results from the current literature are not homogeneous, and the specific threshold of AMH in PCOS and PCOM is, therefore, very challenging. This review aims to update the current knowledge about AMH, the pathophysiology of AMH in the pathogenesis of PCOS, and the role of Anti-Müllerian Hormone in the treatment of this syndrome.

Chronic Low Grade Inflammation in Pathogenesis of PCOS.

Polycystic ovary syndrome (PCOS) is a one of the most common endocrine disorders, with a prevalence rate of 5-10% in reproductive aged women. It's characterized by (1) chronic anovulation, (2) biochemical and/or clinical hyperandrogenism, and (3) polycystic ovarian morphology. PCOS has significant clinical implications and can lead to health problems related to the accumulation of adipose tissue, such as obesity, insulin resistance, metabolic syndrome, and type 2 diabetes. There is also evidence that PCOS patients are at higher risk of cardiovascular diseases, atherosclerosis, and high blood pressure. Several studies have reported the association between polycystic ovary syndrome (PCOS) and low-grade chronic inflammation. According to known data, inflammatory markers or their gene markers are higher in PCOS patients. Correlations have been found between increased levels of C-reactive protein (CRP), interleukin 18 (IL-18), tumor necrosis factor (TNF-α), interleukin 6 (IL-6), white blood cell count (WBC), monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1α (MIP-1α) in the PCOS women compared with age- and BMI-matched controls. Women with PCOS present also elevated levels of AGEs and increased RAGE (receptor for advanced glycation end products) expression. This chronic inflammatory state is aggravating by obesity and hyperinsulinemia. There are studies describing mutual impact of hyperinsulinemia and obesity, hyperandrogenism, and inflammatory state. Endothelial cell dysfunction may be also triggered by inflammatory cytokines. Many factors involved in oxidative stress, inflammation, and thrombosis were proposed as cardiovascular risk markers showing the endothelial cell damage in PCOS. Those markers include asymmetric dimethylarginine (ADMA), C-reactive protein (CRP), homocysteine, plasminogen activator inhibitor-I (PAI-I), PAI-I activity, vascular endothelial growth factor (VEGF) etc. It was also proposed that the uterine hyperinflammatory state in polycystic ovary syndrome may be responsible for significant pregnancy complications ranging from miscarriage to placental insufficiency. In this review, we discuss the most importance evidence concerning the role of the process of chronic inflammation in pathogenesis of PCOS.

Takayasu's arteritis: a rare disease in Poland.

INTRODUCTION: Takayasu's arteritis (TA) is a rare and potentially life-threatening granulomatous large-vessel vasculitis that involves mostly in the aorta and its proximal branches, and occurs most commonly in young females. This study measures the incidence and prevalence of TA, and assesses the gender distribution and territorial differences in the occurrences of this disease in Poland over a five-year period. To the best of our knowledge, this is the first evaluation of this rare disease in Poland based on a hospital morbidity database. MATERIAL AND METHODS: Analyses were performed with population-based administrative data obtained from a national hospital morbidity study carried out between January 2011 - December 2015 by the Polish National Institute of Public Health. Yearly incidence rates and prevalence of TA were calculated using the number of TA patients and corresponding census data for the overall Polish population. RESULTS: Data included 660 hospitalization records. The final study sample comprised 177 patients: 154 female (87%) and 23 male (13%) with first-time hospitalization for TA. The mean age was 45.4years (95% CI: 42.9-47.8; SD 16.8; range 4-81 years), median 47. The incidence rate of TA was estimated at 0.92 per million per year (95% CI: 0.68-1.16). Five-year TA prevalence was estimated to be 4,6 per million. Incidence rates of TA did not vary significantly between more urban and more rural regions. CONCLUSIONS: The incidence of TA in Poland was similar or lower to data reported by other European countries. The study provides epidemiological data on TA in Poland that may be useful while comparing it with other geographical regions.

Prostate specific antigen (PSA) in diagnosis of polycystic ovarian syndrome - a new insight.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is the commonest endocrine disorder and cause of androgen excess in women. Prostate specific antigen (PSA) could be a new marker of hyperandrogenism in PCOS. OBJECTIVE: The aim of the study was to assess the concentration PSA (total PSA - TPSA and free PSA - fPSA) in 165 patients with PCOS and 40 healthy female controls, the relationship between PSA (TPSA and fPSA) and hormonal parameters and to determine the performance of PSA in diagnosis of PCOS. RESULTS: Total PSA was higher in PCOS group versus controls. The fPSA was below the lower detection levels among all patients. The median value of FAI was 4.31 in PCOS patients versus 1.79 in controls, p < 0.001. There was a correlation of TPSA and tT (r= 0.173, p = 0.027) and TPSA and FAI (r = 0.2603, p = 0.001). AUC for FAI was 82.1%, threshold 2.56 nmol/l, for tT AUC 80.5%, threshold 0.54 ng/ml, for TPSA AUC 66.3%, threshold 0.005 ng/ml. The ROC analysis for A AUC 62.7%, threshold 3.95 ng/ml. CONCLUSION: PCOS women have higher serum concentration of TPSA than controls. TPSA positively correlate with T and FAI, which is the best marker for hyperandrogenic states and has better accuracy for tT and total PSA serum levels in diagnostic of PCOS.