Assessment of Type 2 Diabetes Risk in Young Women with Polycystic Ovary Syndrome.

Women with polycystic ovary syndrome (PCOS) are at increased risk for dysglycemia and type 2 diabetes compared to healthy BMI-matched women of reproductive age: robust evidence exists supporting this notion. The presence of altered glycemic status in young women with the syndrome presents a distinct challenge for the clinician for several reasons. Firstly, the reported incidence of this disorder varies among the limited available studies. Furthermore, there is a lack of consensus on the best screening method, which women to screen, at what frequency, and which strategies need to be implemented to reduce the above risk. We provide data regarding the prevalence of dysglycemia in young women suffering from PCOS and the pathophysiological mechanisms underlying the disorder. In addition, we present evidence suggesting universal screening with the oral glucose tolerance test in young women with the syndrome, irrespective of age or BMI status, to identify and manage glycemic abnormalities in a timely manner. Regarding follow-up, oral glucose testing should be carried out at regular intervals if there are initial abnormal findings or predisposing factors. Finally, the efficacy of a well-balanced diet in conjunction with regular exercise and the use of non-pharmacologic agents in this specific population is discussed.

Methotrexate concentrations and associated variability factors in high dose therapy of children with acute lymphoblastic leukemia and non-Hodgkin lymphoma.

Monitoring and optimization procedures improved high dose methotrexate (HDMTX) treatment outcomes. However, there are still some concerns regarding unexplained concentration variability. The objective of this study was to evaluate drug concentrations and associated variability factors in pediatric patients with acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL) on HDMTX. Fifty patients (aged 1-18 years), receiving in total 184 HDMTX cycles of 3 or 5 g/m2/24 h infusion, were included in the study. Comparisons of MTX concentrations and concentrations to dose ratio between two dosing groups were conducted by Mann-Whitney U test. Regression analysis was performed with transformed data to assess relationship between MTX concentration to dose ratio and patient characteristics, biochemical analysis and therapy data. Statistically significant difference in concentrations between 3 and 5 g/m2 dosing groups was detected only at 24 h after the start of infusion (p < 0.001), but not at 48 and 72 h (p > 0.05). There was no difference between dose-normalized concentrations. Regression analysis showed that 73.9% of variability in dependent variable can be explained by included variables: time since dose, creatinine clearance (CrCl), hemoglobin and certain concomitant therapy. Our results highlight the importance of not only renal function and concomitant therapy, but also hemoglobin in reducing the variation in MTX concentrations. Therefore, monitoring of aforementioned biochemical parameters during HDMTX is important not only to assess toxicity, but also in predicting their impact on drug level.

Age, Body Mass Index, and Waist-to-Hip Ratio Related Changes in Insulin Secretion and Insulin Sensitivity in Women with Polycystic Ovary Syndrome: Minimal Model Analyses.

Insulin resistance is believed to be an integral component of the polycystic ovary syndrome (PCOS). Beta (ß) cell dysfunction is also found in PCOS. In the study, we determined the influence of age, body mass index (BMI), and waist-to-hip ratio (WHR) on insulin response to oral glucose load (OGTT) and on insulin sensitivity (Si) and ß-cell function in young women with PCOS. One hundred fourteen patients with PCOS and 41 controls with normal basal plasma glucose were studied. A 75-g OGTT was performed to determine glucose tolerance and insulin response. Insulin sensitivity and ß-cell function were studied using a modified frequently sampled IV glucose tolerance test (FISGTT) to determine the acute insulin response (AIRG), as well as Si by minimal model analysis. Si was decreased in PCOS women (2.49 0.18 vs. 3.41 ± 0.36, p < 0.05), but no difference in AIRG existed between the PCOS and control group (75.1 ± 4.6 vs. 63.4 ± 4.6, p < 0.05). BMI and WHR correlated negatively with Si (r = -0.43; r = -0.289, p < 0.001, respectively), but not with AIRG (r = 0.116; r = -0.02, p > 0.05, respectively). Increasing age correlated negatively with AIRG (r = -0.285, p < 0.001). There was a significant interaction between disease (PCOS), BMI, and WHR on Si as well as between age and PCOS on AIRG. Thus, patients below the age of 25 with PCOS showed enhanced AIRG (89.5 ± 7.1 vs. 65.1 ± 6.7, p < 0.05) and decreased Si (2.43 ± 0.25 vs. 4.52 ± 0.62, p < 0.05) compared to age-matched controls. In conclusion, these data suggest that not all patients with PCOS have basal and stimulated hyperinsulinemia, insulin resistance, and impaired glucose tolerance. Based on these data in young PCOS subjects, the development of insulin resistance and T2DM may be prevented with appropriate treatment strategies.

Reproductive outcomes after bariatric surgery in women.

The presence of obesity may significantly influence female fertility through various mechanisms. Impairment of the hypothalamic-pituitary-ovarian axis in obese women may induce anovulation and infertility. Obesity may have an effect on women's spontaneous and assisted conception rates, increased miscarriage rates, premature labor, stillbirth and perinatal risks, and menstrual irregularity. It has been suggested that weight loss improves reproductive outcomes due to fertility amelioration and an improvement in menstrual irregularity and ovulation. It is still not known which weight reduction procedures (changes in lifestyle, pharmacological management or bariatric intervention) result in optimal outcome on infertility. Currently, bariatric surgery is defined as the best available method for the management of obesity and its associated diseases.We have analyzed literature facts about effects of bariatric surgery on the function of the hypothalamic-pituitary-ovarian axis, polycystic ovary syndrome (PCOS), anti-Mullerian hormone (AMH) and sexual dysfunction in obesity and pregnancy in obesity. Immediate positive effects of bariatric surgery are evident at the moment, while for long-term outcomes more prolonged follow-up investigations should be done.

Five-Year Outcomes in Bariatric Surgery Patients.

Background and objectives: Obesity presents as a multifactorial, pandemic disease that arises as a consequence of unequal energy intake and energy consumption. Obesity adversely affects the quality of life, leading not only to disability, but also to various other disorders. Bariatric surgery is the most effective method for achieving significant and sustained weight loss in individuals with extreme obesity. The aim of this study was to examine how well surgically induced weight loss is maintained after five years of follow-up and its effects on cardiovascular risk factors and outcome. Materials and Methods: This is a retrospective cross-sectional study of 66 patients with morbid obesity, with body mass index (BMI) ≥ 40 kg/m2 or BMI ≥ 35 kg/m2 and obesity-related health conditions, aged 20 to 61 years, mostly women (77.3%) who underwent laparoscopic Roux-en-Y gastric bypass surgery. Results: Average follow-up was 6.42 years (95% CI 6.30-6.54 years) after surgery, with survival rate of 97% in operated individuals. There was a statistically significant reduction of weight and body mass index 6 months and 5 years after surgery in comparison to the initial values (p < 0.001). Of 62 patients who presented weight loss at the end of the follow-up period, 38 were able to maintain the amount of weight loss that was attained 6 months after surgery, while 24 patients regained weight compared to their postoperative weight at 6 months. Two patients reported no weight loss after treatment. Significant weight reduction was associated with better control of diabetes and increased self-reported physical activity at 6 months and 5 years after surgery, as well as with a reduction of the use of anti-diabetic and anti-hypertensive medications. Conclusions: Our research demonstrates a positive long-term impact of bariatric surgery on patients' health conditions, significant and sustained weight loss, and decrease in BMI, which were associated with a reduction of co-morbidities and risk factors for cardiovascular diseases.

Cardiovascular, renal and liver protection with novel antidiabetic agents beyond blood glucose lowering in type 2 diabetes: consensus article from the European Society of Hypertension Working Group on Obesity, Diabetes and the High-risk Patient.

: The prevalence of type 2 diabetes (T2D) has increased over the past few decades. T2D has a strong genetic propensity that becomes overt when a patient is exposed to a typical Western lifestyle, gain weight and becomes obese, whereas weight loss protects from the development of T2D. Except of lifestyle modifications, the choice of the appropriate treatment is essential in the management of patients with T2D and appears critical for the obese population with T2D. The new pharmacological approach for the treatment of T2D, sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists, seems to be effective not only in the management of T2D but also for weight loss, reduction of blood pressure and improvement of nonalcoholic fatty liver disease. Sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 analogues reduced cardiovascular risk, prevented cardiovascular disease and mortality, thereby playing an important role in the treatment of obese patients with hypertension and T2D.

The Amount of Weight Loss Six Months after Bariatric Surgery: It Makes a Difference.

BACKGROUND: Bariatric surgery, especially Roux-en-Y gastric bypass (RYGB), has become the most frequently used therapy for morbid obesity. OBJECTIVES: The aim of this study was to examine the effects of surgically induced weight loss on cardiopulmonary function 6 months after the procedure, as well as the effect of such an intervention on well-known risk factors for cardiovascular diseases. METHODS: This is a cross-sectional study on 66 morbidly obese patients (BMI ≥40 or ≥35 kg/m2 with present comorbidities), comparing their cardiopulmonary function prior to and 6 months after RYGB surgery. RESULTS: The substantial amount of weight loss (29.80 ± 13.27 kg) after RYGB surgery was associated with significant reduction of comorbidities, especially diabetes and sedentary lifestyle (p = 0.005 and p = 0.002, respectively). Regarding functional capacity, there was significant increase in peak oxygen uptake (VO2 peak, p = 0.003), duration of exercise testing, metabolic equivalents (exercise time and METs, p < 0.001), and in peak O2 pulse. These findings were particularly pronounced in a group of patients who had lost more than 18% of initial weight. CONCLUSIONS: Reduction of body weight after RYGB surgery is associated with significantly improved cardiorespiratory function 6 months after surgery, especially in patients who lost more than 18% of their initial body weight. In addition, substantial decreases in body weight were also associated with a reduction of cardiovascular risk factors such as diabetes, smoking, hypertriglyceridemia, and sedentary lifestyle.

Obesity and cardiovascular risk: a call for action from the European Society of Hypertension Working Group of Obesity, Diabetes and the High-risk Patient and European Association for the Study of Obesity: part B: obesity-induced cardiovascular disease, early prevention strategies and future research directions.

: Obesity predisposes for atrial fibrillation, heart failure, sudden cardiac death, renal disease and ischemic stroke, which are the main causes of cardiovascular hospitalization and mortality. As obesity and the cardiovascular effects on the vessels and the heart start early in life, even from childhood, it is important for health policies to prevent obesity very early before the disease manifestation emerge. Key roles in the prevention are strategies to increase physical exercise, reduce body weight and to prevent or treat hypertension, lipids disorders and diabetes earlier and efficiently to prevent cardiovascular complications.

Obesity and cardiovascular risk: a call for action from the European Society of Hypertension Working Group of Obesity, Diabetes and the High-risk Patient and European Association for the Study of Obesity: part A: mechanisms of obesity induced hypertension, diabetes and dyslipidemia and practice guidelines for treatment.

: Obesity is a key factor for cardiovascular diseases and complications. Obesity is associated with hypertension, dyslipidemia and type II diabetes, which are the major predictors of cardiovascular disease in the future. It predisposes for atrial fibrillation, heart failure, sudden cardiac death, renal disease and ischemic stroke that are the main causes of cardiovascular hospitalization and mortality. As obesity and the cardiovascular effects on the vessels and the heart start early in life, even from childhood, it is important for health policies to prevent obesity very early before the disease manifestation emerge. Key roles in the prevention are strategies to increase physical exercise, reduce body weight and to prevent or treat hypertension, lipids disorders and diabetes earlier and efficiently to prevent cardiovascular complications.Epidemiology and mechanisms of obesity-induced hypertension, diabetes and dyslipidemia will be reviewed and the role of lifestyle modification and treatment strategies in obesity will be updated and analyzed. The best treatment options for people with obesity, hypertension, diabetes and dyslipidemia will discussed.

Luteinizing hormone and insulin resistance in menopausal patients with adrenal incidentalomas: The cause-effect relationship?

OBJECTIVE: A high prevalence of insulin resistance (IR) has proven to manifest in patients with adrenal incidentalomas (AI). It has been demonstrated that an increase in IR is related to the size of tumourous masses; additionally, luteinizing hormone (LH)-dependent adrenal pathologies are well documented in patients with LH-responsive adrenal tumours occurring under conditions of physiologically elevated LH. We hypothesized that an association between LH and insulin might play a role in adrenal tumourigenesis and steroidogenesis. DESIGN: The aim of our study was to investigate the association between LH and IR; adrenal tumour size (ATS) and IR; LH and cortisol after the 1 mg overnight dexamethasone test (1 mg DST); and ATS and 1 mg DST cortisol in AI patients. This was a case-control study conducted in the Clinic for Endocrinology, Diabetes and Metabolic Diseases in Belgrade, Serbia. The total study group consisted of 105 menopausal women: 75 AI patients [27 with nonfunctional AI (NAI) and 48 with (possible) autonomous cortisol secretion ((P)ACS)] and 30 age-, BMI-, LH- and menopause duration-matched healthy control (HC) women. To estimate IR, we used homeostasis model assessment (HOMA-IR). RESULTS: Luteinizing hormone and ATS are in a significant positive correlation with HOMA-IR and 1 mg DST cortisol in menopausal patients with AI and (P)ACS. CONCLUSIONS: Our data point to a possible cause-effect relationship between LH and insulin in patients with AI and (P)ACS adding to the body of evidence of their involvement in adrenal tumourigenesis and steroidogenesis.

Obesity and Type 2 Diabetes: Two Diseases with a Need for Combined Treatment Strategies - EASO Can Lead the Way.

Obesity is a chronic metabolic disease affecting adults and children worldwide. It has become one of the leading causes of death, as obesity is known to be the main risk factor for a number of non-communicable diseases, in particular type 2 diabetes. This close relationship led to the connotation 'diabesity', highlighting the fact that the majority of individuals with diabetes are overweight or obese. Until today the BMI is still used to classify overweight and obesity. Since reduced muscle mass is highly prevalent throughout the BMI range, the measurement of body composition is strongly recommended. Moreover, it is essential for monitoring the course of weight reduction, which is part of every effective anti-obesity treatment. Weight reduction can be achieved via different weight loss strategies, including lifestyle intervention (diet and exercise), pharmacotherapy, or bariatric surgery. However, not all of these strategies are suitable for all patients, and any further needs should be considered. Besides, attention should also be drawn to concomitant therapies. These therapies may promote additional weight gain and further trigger the deterioration of blood glucose control. Thus, therapeutic strategies are warranted, which can be easily used for the management of obese patients with type 2 diabetes to achieve their glycemic and weight loss goals.

A Proposal of the European Association for the Study of Obesity to Improve the ICD-11 Diagnostic Criteria for Obesity Based on the Three Dimensions Etiology, Degree of Adiposity and Health Risk.

Diagnostic criteria for complex medical conditions caused by a multitude of both genetic and environmental factors should be descriptive and avoid any attribution of causality. Furthermore, the wording used to describe a disorder should be evidence-based and avoid stigmatization of the affected individuals. Both terminology and categorizations should be readily comprehensible for healthcare professionals and guide clinical decision making. Uncertainties with respect to diagnostic issues and their implications may be addressed to direct future clinical research. In this context, the European Association of the Study of Obesity (EASO) considers it an important endeavor to review the current ICD-11 Beta Draft for the definition of overweight and obesity and to propose a substantial revision. We aim to provide an overview of the key issues that we deem relevant for the discussion of the diagnostic criteria. We first discuss the current ICD-10 criteria and those proposed in the ICD 11 Beta Draft. We conclude with our own proposal for diagnostic criteria, which we believe will improve the assessment of patients with obesity in a clinically meaningful way.

The impact of thyroid autoimmunity (TPOAb) on bone density and fracture risk in postmenopausal women.

OBJECTIVE: Skeletal development, linear growth, cartilage biology and bone turnover are highly dependent on the activity of thyroid hormones. Thyroid dysfunction affects the skeleton, and autoimmune thyroid disease, manifesting as a chronic inflammatory condition, may be an important contributing factor to impaired bone quality in these patients. MATERIALS AND METHODS: Measurement of TSH, FT4, TPOAb and bone mineral density and FRAX score calculations were performed in 189 postmenopausal women (110 euthyroid women and 79 women diagnosed with subclinical hypothyroidism) divided into subgroups according to the presence of TPOAb. RESULTS: In multivariate logistic regression analysis only TPOAb were found to be significantly related to fracture, independently of TSH values (p=0.018; OR=7.800; 95% CI 1.424-42.721). Lower bone mineral density and FRAX score for hip and for major osteoporotic fractures were associated with the presence of TPOAb in euthyroid postmenopausal women in an unadjusted logistic regression model, as well as in a model adjusted for age, BMI and smoking. TSH was a better predictive factor for fractures in women with subclinical hypothyroidism (FRAX main p <0.001; 95% CI for SE 0.858-0.959 and FRAX hip p <0.001; 95% CI for SE 0.628-0.854). CONCLUSION: Autoimmune thyroid disease is associated with decreased bone mineral density at both spine and hip and risk of future fracture incidence in euthyroid postmenopausal women. Presence of TPOAb is a potential marker of higher fracture risk in these patients. However, in subclinical hypothyroidism, TSH is a better indicator of future fragility fractures than TPOAb.

Patterns of diabetes care in Slovenia, Croatia, Serbia, Bulgaria and Romania : An observational, non-interventional, cross-sectional study.

BACKGROUND: National guidelines for treating type 2 diabetes in the Balkans generally follow European guidelines. The current study was undertaken to estimate the rate of glycated hemoglobin (HbA1c) measurements and level of HbA1c control in diabetic patients treated in regular clinical practice settings in the Balkans and to evaluate if providing HbA1c measurements improves adherence to treatment guidelines. METHODS: This cross-sectional study enrolled type 2 diabetic patients treated by 79 primary care physicians and 102 specialists. The participants were provided with HbA1c measuring devices to measure HbA1c during regular office visits and a physician survey evaluated HbA1c the results feedback. Relevant clinical, demographic, drug treatment and specialist referral data were extracted from patient charts. Descriptive statistics and stepwise multivariate regression analysis were used. RESULTS: Among 1853 patients included (average age 63.5 ± 10.7 years, 51% male) the average diabetes duration was 8.9 ± 7.1 years, 40% of patients had HbA1c measured every 6 months and 34% every 12 months (or less frequently). The rate of 6­month measurement was higher among specialists (43%) vs. primary care physicians (32%, p < 0.01). The average HbA1c was 7.3 ± 1.5 and 35% of patients achieved the target HbA1c level of < 6.5%. Metformin monotherapy was prescribed to 28% of patients and metformin + sulphonylurea to 23%, 55% of patients on metformin monotherapy and 32% of patients on dual therapy metformin + sulphonylurea achieved the target HbA1c < 6.5%. Treatment remained unchanged in 91% and was stepped up in only 7.2% of patients. Physicians were not surprised (in 79% of patients) or were pleasantly surprised (in 11%) by the HbA1c results at the time of visit. Average diabetes duration and patient use of home glucometers were associated with the level of disease control. CONCLUSIONS: The rates of HbA1c measurements remain low in the Balkans, although higher among specialists. Over 60% of patients, mostly treated with traditional oral antidiabetics did not achieve disease control. Providing convenient HbA1c measurement devices was not associated with a marked change in diabetes management. Future research is needed to evaluate the impact of these treatment patterns on long-term outcomes and costs to society.

Downregulation of autophagy gene expression in endometria from women with polycystic ovary syndrome.

Autophagy, a process of controlled cellular self-digestion, could be involved in cyclic remodeling of the human endometrium. We investigated endometrial mRNA expression of 23 autophagy-related (ATG) genes and transcription factors in healthy controls (n = 12) and anovulatory polycystic ovary syndrome (PCOS) patients (n = 24), as well as in their subgroup (n = 12) before and after metformin treatment. The mRNA levels of transcription factor forkhead box protein O1 (FOXO1) and several molecules involved in autophagosome formation (ATG13, RB1-inducible coiled-coil 1), autophagosome nucleation (ATG14, beclin 1, SH3-domain GRB2-like endophilin B1), autophagosome elongation (ATG3, ATG5, γ-aminobutyric acid receptor-associated protein - GABARAP), and delivery of ubiquitinated proteins to autophagosomes (sequestosome 1), were significantly reduced in anovulatory PCOS compared to healthy endometrium. Free androgen index, but not free estrogen index, insulin levels, or body mass index, negatively correlated with the endometrial expression of ATG3, ATG14, and GABARAP in PCOS patients. Treatment of PCOS patients with metformin (2 g/day for 3 months) significantly increased the endometrial mRNA levels of FOXO1, ATG3, and UV radiation resistance-associated gene. These data suggest that increased androgen availability in PCOS is associated with metformin-sensitive transcriptional downregulation of endometrial autophagy.

Combined Administration of Ghrelin and Corticotropin-Releasing Hormone in the Diagnosis of Cushing's Disease.

BACKGROUND/AIMS: Exaggerated adrenocorticotropic hormone (ACTH) and cortisol responses to ghrelin in Cushing's disease (CD) have previously been reported, similarly to responses to corticotropin-releasing hormone (CRH). We assessed the ability of ghrelin to enhance ACTH and cortisol responses when added to CRH stimulation in CD patients. METHODS: In 21 CD patients (18 females, 3 males; age 49.8 ± 10.2 years; BMI 29.8 ± 0.8) and 8 healthy subjects (7 females, 1 male; age 40.6 ± 5.3 years; BMI 29.9 ± 1.2), we administered (1) ghrelin 100 µg i.v. bolus, (2) CRH 100 µg i.v. bolus, and (3) ghrelin + CRH combination. ACTH and cortisol were analyzed by commercially available kits from samples taken at 0, 15, 30, 45, 60, 90 and 120 min. ACTH and cortisol responses were calculated as peak and area under the curve (AUC0-120 min). RESULTS: ACTH and cortisol at baseline and stimulated with ghrelin and/or CRH (peak and AUC0-120 min) were significantly higher in CD patients compared to controls (p < 0.01). ACTH and cortisol responses to ghrelin or CRH were similar in CD patients. Combined ghrelin + CRH administration in CD patients produced the highest ACTH response (peak and AUC0-120 min) compared to ghrelin or CRH alone (p < 0.01). Cortisol responses after ghrelin + CRH were uncoupled with ACTH responses and similar to the response to ghrelin or CRH alone in both groups. ACTH and cortisol responses, during all three tests, were similar in CD patients with micro- or macroadenomas. CONCLUSION: Ghrelin administration causes exaggerated ACTH and cortisol responses in CD patients compared to healthy controls. In combination with CRH, it additionally enhances ACTH secretion without further additive effect on cortisol output.

European Guidelines for Obesity Management in Adults.

Obesity is a chronic metabolic disease characterised by an increase of body fat stores. It is a gateway to ill health, and it has become one of the leading causes of disability and death, affecting not only adults but also children and adolescents worldwide. In clinical practice, the body fatness is estimated by BMI, and the accumulation of intra-abdominal fat (marker for higher metabolic and cardiovascular disease risk) can be assessed by waist circumference. Complex interactions between biological, behavioural, social and environmental factors are involved in regulation of energy balance and fat stores. A comprehensive history, physical examination and laboratory assessment relevant to the patient's obesity should be obtained. Appropriate goals of weight management emphasise realistic weight loss to achieve a reduction in health risks and should include promotion of weight loss, maintenance and prevention of weight regain. Management of co-morbidities and improving quality of life of obese patients are also included in treatment aims. Balanced hypocaloric diets result in clinically meaningful weight loss regardless of which macronutrients they emphasise. Aerobic training is the optimal mode of exercise for reducing fat mass while a programme including resistance training is needed for increasing lean mass in middle-aged and overweight/obese individuals. Cognitive behavioural therapy directly addresses behaviours that require change for successful weight loss and weight loss maintenance. Pharmacotherapy can help patients to maintain compliance and ameliorate obesity-related health risks. Surgery is the most effective treatment for morbid obesity in terms of long-term weight loss. A comprehensive obesity management can only be accomplished by a multidisciplinary obesity management team. We conclude that physicians have a responsibility to recognise obesity as a disease and help obese patients with appropriate prevention and treatment. Treatment should be based on good clinical care, and evidence-based interventions; should focus on realistic goals and lifelong multidisciplinary management.

The Fracture Risk Assessment Tool (FRAX score) in subclinical hyperthyroidism.

BACKGROUND/AIM: The Fracture Risk Assessment Tool (FRAX score) is the 10-year estimated risk calculation tool for bone fracture that includes clinical data and hip bone mineral density measured by dual-energy x-ray absorptiometry (DXA). The aim of this cross-sectional study was to elucidate the ability of the FRAX score in discriminating between bone fracture positive and negative pre- and postmenopausal women with subclinical hyperthyroidism. METHODS: The bone mineral density (by DXA), thyroid stimulating hormone (TSH) level, free thyroxine (fT4) level, thyroid peroxidase antibodies (TPOAb) titre, osteocalcin and beta-cross-laps were measured in 27 pre- and postmenopausal women with newly discovered subclinical hyperthyroidism [age 58.85 +/- 7.83 years, body mass index (BMI) 27.89 +/- 3.46 kg/m2, menopause onset in 46.88 +/- 10.21 years] and 51 matched euthyroid controls (age 59.69 +/- 5.72 years, BMI 27.68 +/- 4.66 kg/m2, menopause onset in 48.53 +/- 4.58 years). The etiology of subclinical hyperthyroisims was autoimmune thyroid disease or toxic goiter. FRAX score calculation was performed in both groups. RESULTS: In the group with subclinical hyperthyroidism the main FRAX score was significantly higher than in the controls (6.50 +/- 1.58 vs. 4.35 +/- 1.56 respectively; p = 0.015). The FRAX score for hip was also higher in the evaluated group than in the controls (1.33 +/- 3.92 vs. 0.50 +/- 0.46 respectively; p = 0.022). There was no correlations between low TSH and fracture risk (P > 0.05). The ability of the FRAX score in discriminating between bone fracture positive and negative pre- and postmenopausal female subjects (p < 0.001) is presented by the area under the curve (AUC) plotted via ROC analysis. The determined FRAX score cut-off value by this analysis was 6%, with estimated sensitivity and specificity of 95% and 75.9%, respectively. CONCLUSION: Pre- and postmenopausal women with subclinical hyperthyroidism have higher FRAX scores and thus greater risk for low-trauma hip fracture than euthyroid premenopausal women. Our results point to the use of FRAX calculator in monitoring pre- and postmenopausal women with subclinical hyperthyroidism to detect subjects with high fracture risk in order to prevent further fractures.

Acquired Hypertrichosis Lanuginosa: Typical Presentation and Unusual Association.

Paraneoplastic syndrome might be the first clinical manifestation of malignancy. We present a menopausal female with the acquired hypertrichosis lanuginosa (AHL) as an initial clinical presentation of rectal adenocarcinoma, unusually associated with paraneoplastic cerebellar degeneration (PCD) and disseminated intravascular coagulation (DIC).