Sudden 'cure' of type two diabetes due to pancreatic insulinoma: A case report.

Insulinomas are rare tumors of the islet cells of the pancreas and are the most common cause of endogenous hyperinsulinism. Although they usually present with symptoms of hypoglycemia, sometimes they can have vague symptoms. We present the case of a 62-year-old diabetic female who was diagnosed with a large insulinoma after being investigated for the 'cure' of her diabetes. We also review the literature regarding insulinomas in patients with diabetic. A 62-year-old, obese woman with type 2 diabetes mellitus was initially investigated for an unexplained normalization of her blood glucose levels after the cessation of antidiabetic medication due to an episode of severe hypoglycemia. She remained without antidiabetics for three months maintaining normoglycemia, and thereafter, she started experiencing frequent but less severe hypoglycemic episodes. She did not change her diet habits or level of activity and did not lose any weight. The patient underwent further investigation with a supervised 72 h fasting test, which resulted in the biochemical diagnosis of endogenous hyperinsulinism. Imaging studies revealed the presence of a large insulinoma in the head of the pancreas. Finally, the patient underwent a pylorus preserving Whipple procedure, which reversed the aforementioned 'normalization' of glucose levels and the underlying diabetes mellitus reappeared. Insulinomas are rare tumors causing hypoglycemia. Even more rarely are found in diabetic patients, making the diagnosis more challenging and probably delayed, as the symptoms are masked by the presence of diabetes, thereby leading to a more advanced disease diagnosis.

Association Between hsa-miR-30e Polymorphisms and Sporadic Primary Hyperparathyroidism Risk.

BACKGROUND/AIM: Almost 15% of patients with sporadic primary hyperparathyroidism (sPHPT) present with multiple gland disease (MGD). The aim of this study was to investigate the potential role of two polymorphisms of the hsa-miR-30e, in sPHPT tumorigenesis. PATIENTS AND METHODS: One-hundred twenty sPHPT patients, 77 presenting a single adenoma and 43 with MGD, and 54 healthy controls were genotyped. The SNPs were identified using the allele-specific PCR methodology, while the hsa-miR-30e expression was analyzed by real-time quantitative reverse transcriptase PCR. RESULTS: Hsa-miR-30e expression was found to be significantly higher in patients with MGD compared to patients with single adenomas (p=0.0019), but no differences were found regarding specific genotype carriers. The genotype frequencies for ss178077483 and rs7556088 were significantly different between patients and healthy controls. CONCLUSION: Although the polymorphisms cannot be used as biomarkers for the differential diagnosis of MGD, hsa-miR-30e expression could potentially serve as a biomarker for this purpose.

Immunohistochemical expression patterns of S100, synaptophysin, chromogranin A and neuron specific enolase in predicting malignant behaviour in paragangliomas.

PURPOSE: The purpose of this study was to evaluate the role of immunohistochemical markers in the prediction of malignancy in paragangliomas. METHODS: Our institute's patient records between 1990-2012 were retrieved in order to identify patients who were treated for paragangliomas. Size and location of the tumour, existence of concurrent metastatic disease, patient demographics and survival were recorded. Haematoxylin-eosin stained slides were reviewed and all tumours were stained specifically for neuron specific enolase (NSE), chromogranin, synaptophysin and S100 protein positivity. Positivity and expression patterns of the above markers were evaluated and compared between malignant and benign tumours. Malignant behaviour was defined when patient had concurrent or subsequent lymph node involvement, local recurrence and/or metastases. RESULTS: A total of 22 patients with a diagnosis of paraganglioma were treated in our institutes. Female to male ratio was 1.75: 1. The mean age was 43.5 and 51.6 years for women and men, respectively. In 5 patients the tumors had malignant clinical behavior. Their mean size was 3.65 cm for benign and 4.56 cm for malignant neoplasms. NSE expression was diffuse in 47.1% and 0% for benign and malignant tumors, respectively (p=0.10). S100 expression in the periphery of the tumour was typical in 88.2% and 0% for benign and malignant tumors, respectively (p<0.001). CONCLUSION: Immunohistochemical profile from the combination of NSE, synaptophysin chromogranin and S100 staining patterns can serve as a cheap and valuable tool for correctly distinguishing between malignant and benign paragangliomas with high diagnostic accuracy.

Visceral adiposity index for the diagnosis of nonalcoholic fatty liver disease in premenopausal women with and without polycystic ovary syndrome.

OBJECTIVE: Visceral adiposity index (VAI), initially developed for the assessment of cardiometabolic risk, has been also proposed for the detection of nonalcoholic fatty liver disease (NAFLD); however, its diagnostic performance for NAFLD is still under investigation. We evaluated VAI as a marker of NAFLD and compared its diagnostic performance with that of three other NAFLD indices - fatty liver index (FLI), lipid accumulation product (LAP) and hepatic steatosis index (HSI) - in premenopausal women with and without polycystic ovary syndrome (PCOS) assessed for NAFLD by ultrasonography. DESIGN: Cross-sectional case-control study. METHODS: Anthropometric measurements, biochemical testing and abdominal ultrasonography after excluding causes of secondary liver disease were performed in 145 premenopausal women with PCOS (Rotterdam criteria) and 145 healthy control women within the same age range and matched for body mass index (BMI). The diagnostic performance of the four indices was assessed with receiver operating characteristic (ROC) analysis. RESULTS: NAFLD by ultrasonography was detected in 132 of the total sample of 290 women (45.5%). VAI, FLI, LAP and HSI values were significantly higher in women with NAFLD than those without. The areas under the curve (AUROCs) for VAI, FLI, LAP and HSI were 0.77 ±â€¯0.03, 0.87 ±â€¯0.02, 0.84 ±â€¯0.02 and 0.83 ±â€¯0.02, respectively, in the whole group, showing an adequate discriminatory ability for NAFLD of the four indices. AUROCs of the four indices calculated separately for PCOS and control women showed a similar performance of all indices in the two groups. CONCLUSIONS: These data show that VAI is useful for detecting NAFLD in premenopausal women with and without PCOS. However, VAI had a lower diagnostic performance in this cohort than FLI, LAP and HSI.

Diagnosis, management, histology and genetics of sporadic primary hyperparathyroidism: old knowledge with new tricks.

Primary hyperparathyroidism (pHPT) is a common endocrinopathy resulting from inappropriately high PTH secretion. It usually results from the presence of a single gland adenoma, multiple gland hyperplasia or rarely parathyroid carcinoma. All these conditions require different management, and it is important to be able to differentiate the underlined pathology, in order for the clinicians to provide the best therapeutic approach. Elucidation of the genetic background of each of these clinical entities would be of great interest. However, the molecular factors that control parathyroid tumorigenesis are poorly understood. There are data implicating the existence of specific genetic pathways involved in the emergence of parathyroid tumorigenesis. The main focus of the present study is to present the current optimal diagnostic and management protocols for pHPT as well as to review the literature regarding all molecular and genetic pathways that are to be involved in the pathophysiology of sporadic pHPT.

Diabetic cardiomyopathy: a clinical entity or a cluster of molecular heart changes?

BACKGROUND: Although the increasing rate of cardiovascular mortality in patients with diabetes is thought to be due to the coronary atherosclerosis caused mainly by compounding factors such as dyslipidaemia and hypertension, it is now well documented that diabetes alone can lead to a vast array of molecular changes in the heart. DESIGN: The aim of this article was to comprehensively review the pathophysiological and molecular changes leading to diabetic cardiomyopathy (DCM), as well as to critically analyse the literature that offers evidence in favour and against the existence of the overt clinical expression of this entity. RESULTS: We included in the discussion studies that have revealed the existence of diabetic cardiomyopathy with unique remodelling pattern when compared to other types of cardiomyopathies. On the other hand, several studies debate the existence of clinically discernible cardiomyopathy caused only by diabetes and were also presented and discussed in details. CONCLUSION: Clinicians should be aware of DCM when facing patients with diabetes in order both to recognize on time relevant symptoms and to intensively look for and treat other compounding factors, apart from optimal glucose control. Furthermore, the elucidation of the pathophysiological mechanisms leading to DCM could provide new therapeutic targets for heart disease, which will be wonderful for the good of our patients.

Investigating the KNDy Hypothesis in Humans by Coadministration of Kisspeptin, Neurokinin B, and Naltrexone in Men.

CONTEXT: A subpopulation of hypothalamic neurons colocalize three neuropeptides, namely kisspeptin, neurokinin B (NKB), and dynorphin, collectively termed KNDy neurons. Animal studies suggest they interact to affect pulsatile GnRH release (KNDy hypothesis); kisspeptin stimulates, NKB modulates, and dynorphin (an opioid) inhibits. OBJECTIVE: To investigate the KNDy hypothesis in humans, we assessed for the first time the effects of the coadministration of kisspeptin-54, NKB, and an opioid receptor antagonist, naltrexone, on LH pulsatility (surrogate marker for GnRH pulsatility) and gonadotropin release. DESIGN, SETTING, AND PARTICIPANTS: This was an ethically approved prospective, single-blinded, placebo-controlled study. Healthy male volunteers (n = 5/group) attended our research facility for eight study visits. INTERVENTION AND MAIN OUTCOME MEASURE: After 1 hour of baseline blood sampling, participants received a different intervention at each visit: oral 50 mg naltrexone, 8-hour iv infusions of vehicle, 2.56 nmol/kg · h NKB, 0.1 nmol/kg · h kissspeptin-54 (KP) alone and in combination. Frequent blood sampling to measure plasma gonadotropins and sex steroids was conducted and LH pulsatility was determined using blinded deconvolution analysis. RESULTS: All kisspeptin and naltrexone containing groups potently increased LH and LH pulsatility (P < .001 vs vehicle). NKB alone did not affect gonadotropins. NKB+KP had significantly lower increases in gonadotropins compared with kisspeptin alone (P < .01). Naltrexone+KP was the only group to significantly increase LH pulse amplitude (P < .001 vs vehicle). CONCLUSIONS: Our results suggest significant interactions between the KNDy neuropeptides on LH pulsatility and gonadotropin release in humans. This has important implications for improving our understanding of GnRH pulse generation in humans.

Birth weight and polycystic ovary syndrome in adult life: is there a causal link?

OBJECTIVES: Several studies have demonstrated associations of birth weight with metabolic and reproductive abnormalities in adults. The aim of this study was to investigate the birth weight in women with PCOS and its correlation with clinical and biochemical characteristics of the syndrome. MATERIALS AND METHODS: We studied 288 women with PCOS according to the NIH criteria and 166 women with normal cycle and without clinical hyperandrogenism. Birth weight and anthropometric characteristics were recorded, and levels of serum androgens, SHBG, insulin and fasting glucose were measured. RESULTS: Birth weight data were available for 243/288 women with PCOS and age- and BMI-matched 101/166 controls. No differences were found (p> 0.05) in birth weight among women with PCOS and normal controls. Birth weight of PCOS women was negatively correlated with DHEAS levels (p = 0.031, r = -0.143) and positively correlated with waist circumference (p <0.001, r = 0.297) and body mass index (BMI) (p = 0.040, r = 0.132). Birth weight of controls was negatively correlated with SHBG levels (p = 0.021, r = -0.234). Women from both groups were further divided in 6 categories according to birth weight (A. <2.500 gr, B. 2.501-3.000 gr, C. 3.001-3.500 gr, D. 3.501-4.000 gr, E. 4.001-4.500 gr, F. > 4.500 gr). No statistically significant differences were observed in the distribution percentages between PCOS women and controls. (A. 7% vs 7.9%, B. 26.8% vs 20.8%, C. 39.1% vs 48.5%, D. 21.4% vs 20.8%, E. 4.9% vs 2%, F. 0.8% vs 0%), (in all comparisons, p> 0.05). CONCLUSIONS: Women with PCOS do not differ from controls in birth weight distribution. However, birth weight may contribute to subtypes of the syndrome that are characterized by adrenal hyperandrogenism and central obesity.

The menace of endocrine disruptors on thyroid hormone physiology and their impact on intrauterine development.

The delivery of the appropriate thyroid hormones quantity to target tissues in euthyroidism is the result of unopposed synthesis, transport, metabolism, and excretion of these hormones. Thyroid hormones homeostasis depends on the maintenance of the circulating 'free' thyroid hormone reserves and on the development of a dynamic balance between the 'free' hormones reserves and those of the 'bound' hormones with the transport proteins. Disturbance of this hormone system, which is in constant interaction with other hormone systems, leads to an adaptational counter-response targeting to re-establish a new homeostatic equilibrium. An excessive disturbance is likely to result, however, in hypo- or hyper- thyroid clinical states. Endocrine disruptors are chemical substances forming part of 'natural' contaminating agents found in most ecosystems. There is abundant evidence that several key components of the thyroid hormones homeostasis are susceptible to the action of endocrine disruptors. These chemicals include some chlorinated organic compounds, polycyclic aromatic hydrocarbons, herbicides, and pharmaceutical agents. Intrauterine exposure to endocrine disruptors that either mimic or antagonize thyroid hormones can produce permanent developmental disorders in the structure and functioning of the brain, leading to behavioral changes. Steroid receptors are important determinants of the consequences of endocrine disruptors. Their interaction with thyroid hormones complicates the effect of endocrine disruptors. The aim of this review is to present the effect of endocrine disruptors on thyroid hormones physiology and their potential impact on intrauterine development.

The hypothalamic-pituitary-adrenal and the hypothalamic- pituitary-gonadal axes interplay.

Vertebrates respond to stress with activation of the hypothalamic-pituitary-adrenal (HPA) axis, the adrenergic and the autonomic nervous systems. The principal central nervous system regulators of the HPA axis are corticotropin releasing hormone (CRH) and antidiuretic hormone (AVP). Apart from in the central nervous system, CRH has been found in the adrenal medulla, ovaries, myometrium, endometrium, placenta, testis and elsewhere. The activation of the HPA axis during stress affects all body systems. The reproductive axis is inhibited by the HPA axis for the sake of saving energy. The changes to the hypothalamic-pituitary-gonadal (HPG) axis during stress are species-specific, and depend on the type and duration of the stimulus. Several conditions may be associated with altered regulation of the HPA axis. Polycystic ovary syndrome, anorexia nervosa and pregnancy in the third trimester are all characterized by HPA axis activation. In contrast, during the postpartum period, HPA axis suppression is implicated in the "postpartum blues". The actions of CRH are also essential in fetal development and neonatal survival.