Endocrine Immune-Related Adverse Events Are Independent Predictors of Survival in Patients with Lung Cancer.

Lung cancer (LC) is a serious health problem worldwide. Survival outcomes have improved over time due to the widespread use of novel therapeutic agents, including immune checkpoint inhibitors (ICIs). Endocrine immune-related adverse events (e-irAEs) are common in LC patients treated with ICIs. We performed a retrospective study of patients with LC who received treatment with ICIs at a tertiary referral center between January 2014 and October 2023. In total, 983 LC patients were included in the study. E-irAEs presented at a median time of 4.1 months and included hypothyroidism (15.6%), hyperthyroidism (4.3%), adrenal insufficiency (0.4%), hypophysitis (0.4%), and diabetes mellitus (0.2%). These toxicities were not related to the duration of treatment or the type of ICIs. Most (97.6%) e-irAEs were mild (grade 1-2). Median overall survival (OS) was higher in LC patients who experienced e-irAEs (31.6 months) compared to those who did not (10.8 months). The difference remained statistically significant in the 3-month (HR: 0.42) and 6-month landmark analysis (HR: 0.51). The OS advantage was observed in both patients with NSCLC (HR: 0.36) and SCLC (HR: 0.27). Additional research is needed to validate the role of e-irAEs as an independent predictor of survival outcomes in patients with LC.

Food Cravings and Obesity in Women with Polycystic Ovary Syndrome: Pathophysiological and Therapeutic Considerations.

Polycystic ovary syndrome (PCOS), the most common endocrine disorder in women of reproductive age, constitutes a metabolic disorder frequently associated with obesity and insulin resistance (IR). Furthermore, women with PCOS often suffer from excessive anxiety and depression, elicited by low self-esteem due to obesity, acne, and hirsutism. These mood disorders are commonly associated with food cravings and binge eating. Hypothalamic signaling regulates appetite and satiety, deteriorating excessive food consumption. However, the hypothalamic function is incapable of compensating for surplus food in women with PCOS, leading to the aggravation of obesity and a vicious circle. Hyperandrogenism, IR, the reduced secretion of cholecystokinin postprandially, and leptin resistance defined by leptin receptors' knockout in the hypothalamus have been implicated in the pathogenesis of hypothalamic dysfunction and appetite dysregulation. Diet modifications, exercise, and psychological and medical interventions have been applied to alleviate food disorders, interrupting the vicious circle. Cognitive-behavioral intervention seems to be the mainstay of treatment, while the role of medical agents, such as GLP-1 analogs and naltrexone/bupropion, has emerged.

Lung NETs and GEPNETs: One Cancer with Different Origins or Two Distinct Cancers?

Lung neuroendocrine tumors (LNETs) and gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are two distinct types of neuroendocrine tumors (NETs) that have traditionally been treated as a single entity despite originating from different sources. Although they share certain phenotypic characteristics and the expression of neuroendocrine markers, they exhibit differences in their microenvironment, molecular mutations, and responses to various therapeutic regimens. Recent research has explored the genetic alterations in these tumors, revealing dissimilarities in the frequently mutated genes, the role of EGFR in carcinogenesis, the presence of transcription factors, and the immunogenicity of the tumor and its microenvironment. Spread Through Air Spaces (STAS), a phenomenon unique to lung carcinomas, appears to play a crucial role in LNET prognosis. These distinctions are also evident in the cascade response of lung and GI tract neuroendocrine tumors to somatostatin analogs, Peptide Receptor Radionuclide Therapy (PRRT), chemotherapy, and immunotherapy. Identifying similarities and differences between the two groups may improve our understanding of the underlying mechanisms and facilitate the development of more effective treatment strategies.

The influence of environmental factors on premature ovarian insufficiency and ovarian aging.

Premature ovarian insufficiency and ovarian aging are complex conditions that affect women's reproductive health and overall well-being. They are both characterized by hypergonadotropic hypogonadism and infertility, and together affect about 1 in 100 women by the age of 40. This review explores the influence of environmental factors on the development and progression of premature ovarian insufficiency and ovarian aging. When referring to environmental factors, we include a wide range of external agents and conditions, including chemicals, socioeconomic factors and lifestyle choices. Through a review of the literature, we attempt to highlight the link between environmental factors and ovarian health. We examine the impact of endocrine-disrupting chemicals, such as bisphenol A and phthalates, on ovarian function and investigate the mechanisms by which these chemicals can disrupt hormone signaling pathways, leading to alterations in ovarian reserve, oocyte quality, and folliculogenesis. Moreover, we explore lifestyle factors like obesity, stress, smoking and alcohol in relation to their effects on ovarian aging. Epigenetic changes may play a crucial role in the prevalence of premature ovarian insufficiency. Understanding the impact of environmental factors on premature ovarian insufficiency and ovarian aging is very important in public and clinical health contexts. By identifying risk factors, healthcare providers can develop targeted and strategic prevention and intervention plans. Furthermore, this knowledge can promote reproductive health and minimize exposure to harmful environmental agents.

Dietary Approach of Patients with Hormone-Related Cancer Based on the Glycemic Index and Glycemic Load Estimates.

Hormone-related cancers, namely breast, endometrial, cervical, prostate, testicular, and thyroid, constitute a specific group of cancers dependent on hormone levels that play an essential role in cancer growth. In addition to the traditional risk factors, diet seems to be an important environmental factor that partially explains the steadily increased prevalence of this group of cancer. The composition of food, the dietary patterns, the endocrine-disrupting chemicals, and the way of food processing and preparation related to dietary advanced glycation end-product formation are all related to cancer. However, it remains unclear which specific dietary components mediate this relationship. Carbohydrates seem to be a risk factor for cancer in general and hormone-related cancers, in particular, with a difference between simple and complex carbohydrates. Glycemic index and glycemic load estimates reflect the effect of dietary carbohydrates on postprandial glucose concentrations. Several studies have investigated the relationship between the dietary glycemic index and glycemic load estimates with the natural course of cancer and, more specifically, hormone-related cancers. High glycemic index and glycemic load diets are associated with cancer development and worse prognosis, partially explained by the adverse effects on insulin metabolism, causing hyperinsulinemia and insulin resistance, and also by inflammation and oxidative stress induction. Herein, we review the existing data on the effect of diets focusing on the glycemic index and glycemic load estimates on hormone-related cancers.

Secondary diabetes mellitus in pheochromocytomas and paragangliomas.

Secondary diabetes mellitus (DM) in secretory pheochromocytomas and paragangliomas (PPGLs) is encountered in up to 50% of cases, with its presentation ranging from mild, insulin resistant forms to profound insulin deficiency states, such as diabetic ketoacidosis and hyperglycemic hyperosmolar state. PPGLs represent hypermetabolic states, in which adrenaline and noradrenaline induce insulin resistance in target tissues characterized by aerobic glycolysis, excessive lipolysis, altered adipokine expression, subclinical inflammation, as well as enhanced gluconeogenesis and glucogenolysis. These effects are mediated both directly, upon adrenergic receptor stimulation, and indirectly, via increased glucagon secretion. Impaired insulin secretion is the principal pathogenetic mechanism of secondary DM in this setting; yet, this is relevant for tumors with adrenergic phenotype, arising from direct inhibitory actions in beta pancreatic cells and incretin effect impairment. In contrast, insulin secretion might be enhanced in tumors with noradrenergic phenotype. This dimorphic effect might correspond to two distinct glycemic phenotypes, with predominant insulin resistance and insulin deficiency respectively. Secondary DM improves substantially post-surgery, with up to 80% remission rate. The fact that surgical treatment of PPGLs restores insulin sensitivity and secretion at greater extent compared to alpha and beta blockade, implies the existence of further, non-adrenergic mechanisms, possibly involving other hormonal co-secretion by these tumors. DM management in PPGLs is scarcely studied. The efficacy and safety of newer anti-diabetic medications, such as glucagon-like peptide 1 receptor agonists and sodium glucose cotransporter 2 inhibitors (SGLT2is), as well as potential disease-modifying roles of metformin and SGLT2is warrant further investigation in future studies.

Glycemic Index and Glycemic Load Estimates in the Dietary Approach of Polycystic Ovary Syndrome.

Polycystic ovary syndrome is a common endocrine disorder characterized by hormonal imbalances and various metabolic abnormalities linked to insulin resistance via a vicious cycle. Genetic and environmental factors underlie its pathogenesis and evolution. Nutrition, in terms of nutrient composition, dietary patterns, endocrine-disrupting chemicals, and food processing and preparation, has gained significant attention in the pathogenesis and the therapeutic approach of polycystic ovary syndrome. Carbohydrate intake seems to be a critical point in the diet assignment. Glycemic index and glycemic load constitute indexes of the impacts of dietary carbohydrates on postprandial glucose levels. Numerous studies have indicated that a high glycemic index and glycemic load diet may exacerbate insulin resistance, a key feature of the syndrome, and offer a risk for its development and its complications. Conversely, low-glycemic index and low-glycemic load diets seem to improve insulin sensitivity, regulate menstrual cycles, and mitigate the risk of comorbidities associated with polycystic ovary syndrome, such as obesity, alterations in body composition, type 2 diabetes, cardiovascular disease, and quality of life. This comprehensive review aims to explore the relevance of nutrition and more specifically, the association of glycemic index and glycemic load with the various aspects of polycystic ovary syndrome, as well as to assess the potential benefits of manipulating those indexes in the dietary approach for the syndrome.

Primary Adrenal Lymphomas with Cushing's Syndrome: Two Cases with Evidence of Endogeneous Cortisol Production by the Neoplastic Lymphoid Cells.

Primary adrenal lymphoma (PAL) is a rare entity that presents as unilateral or bilateral rapidly growing adrenal masses, with signs and symptoms most commonly related to adrenal insufficiency due to the mass effect on the surrounding tissues. Although steroeidogenesis has not been previously described in PAL, we herein report two cases of PAL presenting as adrenal incidentalomas (AIs) that demonstrated autonomous cortisol production. A 52-year-old woman presented with lumbar pain; a computed tomography (CT) scan demonstrated a left AI measuring 8.5 × 15 × 10 cm. Similarly, an 80-year-old woman presented with lumbar pain, demonstrating in a CT scan a bilateral AI (right: 9 × 6.5 cm, left: 3.6 × 3.2 cm). Both cases underwent a full hormonal evaluation according to the algorithm for the investigation of AIs, demonstrating increased 24-h cortisol excretion, suppressed fasting adrenocorticotropic hormone (ACTH) levels, and non-suppressed serum cortisol levels in both the overnight and the low-dose dexamethasone suppression tests, indicating autonomous cortisol secretion and Cushing's syndrome. In a relatively short time, both patients developed night sweats, and their clinical picture deteriorated, while the CT scans showed increased dimensions of the masses with radiological characteristics compatible to lymphoma. Both patients underwent ultrasound-guided biopsies (FNBs), revealing infiltration of the left adrenal by diffuse large B-cell lymphoma in the first case, whereas bilateral adrenal infiltration from the same histological type was noted in the second case. Subsequently, they were treated with immunochemotherapy, but the second patient died from an infection shortly after the initiation of the treatment. To our knowledge, this is the first report of PAL presenting with Cushing's syndrome due to autonomous cortisol production, indicating that neoplastic lymphoid cells in PAL might acquire the potential for steroidogenesis; therefore, more cases of PAL should be analyzed so as to further elucidate the complex pathogenesis and the natural course of this entity.

Secondary diabetes mellitus in acromegaly.

Secondary diabetes mellitus (DM) is a common complication of acromegaly, encountered in up to 55% of cases. Vice versa, the prevalence of acromegaly is markedly higher in cohorts of patients with type 2 DM (T2DM). The presence of secondary DM depends primarily on acromegaly status and is associated with increased cardiovascular morbidity, malignancy rate and overall mortality. The principal pathophysiologic mechanism is increased insulin resistance due to excessive lipolysis and altered fat distribution, reflected at the presence of intermuscular fat and attenuated, dysfunctional adipose tissue. Insulin resistance is ascribed to the direct, diabetogenic effects of growth hormone (GH), which prevail over the insulin-sensitizing effects of insulin-like growth factor 1 (IGF-1), probably due to higher glucometabolic potency of GH, IGF-1 resistance, or both. Inversely, GH and IGF-1 act synergistically in increasing insulin secretion. Hyperinsulinemia in portal vein leads to enhanced responsiveness of liver GH receptors and IGF-1 production, pointing towards a mutually amplifying loop between GH-IGF-1 axis and insulin. Secondary DM occurs upon beta cell exhaustion, principally due to gluco-lipo-toxicity. Somatostatin analogues inhibit insulin secretion; especially pasireotide (PASI) impairs glycaemic profile in up to 75% of cases, establishing a separate pathophysiologic entity, PASI-induced DM. In contrast, pegvisomant and dopamine agonizts improve insulin sensitivity. In turn, metformin, pioglitazone and sodium-glucose transporters 2 inhibitors might be disease-modifying by counteracting hyperinsulinemia or acting pleiotropically. Large, prospective cohort studies are needed to validate the above notions and define optimal DM management in acromegaly.

Optimal extent of initial parathyroid resection in patients with multiple endocrine neoplasia syndrome type 1: A meta-analysis.

BACKGROUND: Hyperparathyroidism is an almost universal feature of multiple endocrine neoplasia type 1 syndrome. We present a systematic review and meta-analysis of the postoperative outcomes of patients undergoing initial operative treatment of primary hyperparathyroidism complicating multiple endocrine neoplasia 1. METHODS: A comprehensive literature search was performed with a priori defined exclusion criteria for studies comparing total parathyroidectomy, subtotal parathyroidectomy, and less than subtotal parathyroidectomy. RESULTS: Twenty-one studies incorporating 1,131 patients (272 undergoing total parathyroidectomy, 510 subtotal parathyroidectomy, and 349 less than subtotal parathyroidectomy) were identified. Pooled results revealed increased risk for long-term hypoparathyroidism in total parathyroidectomy patients (relative risk 1.61; 95% confidence interval, 1.12-2.31; P = .009) versus those undergoing subtotal parathyroidectomy. In the less than subtotal parathyroidectomy or subtotal parathyroidectomy comparison group, a greater risk for recurrence of hyperparathyroidism (relative risk 1.37; 95% confidence interval, 1.05-1.79; P = .02), persistence of hyperparathyroidism (relative risk 2.26; 95% confidence interval, 1.49-3.41; P = .0001), and reoperation for hyperparathyroidism (relative risk 2.48; 95% confidence interval, 1.65-3.73; P < .0001) was noted for less than subtotal parathyroidectomy patients, albeit with lesser risk for long-term for hypoparathyroidism (relative risk 0.47; 95% confidence interval, 0.29-0.75; P = .002). CONCLUSION: Subtotal parathyroidectomy compares favorably to total parathyroidectomy, exhibiting similar recurrence and persistence rates with a decreased propensity for long-term postoperative hypoparathyroidism. The benefit of the decreased risk of hypoparathyroidism in less than subtotal parathyroidectomy is negated by the increase in the risk for recurrence, persistence, and reoperation. Future studies evaluating the performance of less than subtotal parathyroidectomy in specific multiple endocrine neoplasia 1 phenotypes should be pursued in an effort to delineate a patient-tailored, operative approach that optimizes long-term outcomes.

Tailoring treatment for PCOS phenotypes.

Introduction: Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies in reproductive-aged women. Hyperandrogenism, polycystic ovaries, chronic anovulation, and metabolic aberrations are its common features. The treatment approach focuses on the main aberrations, which characterize the different phenotypes. Areas covered: Management strategies targeting the metabolic phenotype include lifestyle modifications for weight loss and improvement of dietary habits, as well as medication, such as insulin-sensitizers. The treatment of hyperandrogenic phenotype includes cosmetic procedures and the combined oral contraceptives with or without antiandrogens. The therapeutic approach to reproductive phenotype includes diet and lifestyle modifications, clomiphene citrate, and aromatase inhibitors. Alternative treatments include dietary supplements, herbs, resveratrol, myo-inositol, and acupuncture. Expert opinion: New studies have shown that higher anti-Müllerian hormone levels, gut microbiome composition, and plasma metabolomics are new parameters that are related to the most severe phenotypes. The clinical phenotypes can change over the lifespan with weight gain and can coexist in the same individual. Individualized treatment remains the main approach but grouping the phenotypes and following therapeutic recommendations may prove to be also clinically appropriate.

Review of the Literature on Leiomyoma and Leiomyosarcoma of the Adrenal Gland: A Systematic Analysis of Case Reports.

BACKGROUND/AIM: To date few cases of smooth muscle-derived tumors of the adrenal gland have been reported and their treatment remains a medical challenge. The aim of this manuscript was to systematically review the literature and present the tumor characteristics and their management in order to provide a standardized approach to their diagnosis and management. MATERIALS AND METHODS: We searched five databases (PubMed, Scopus, Elsevier, ResearchGate, Google scholar) for relevant articles published until March 2020. RESULTS: Twenty-two cases of adrenal leiomyoma, four cases of adrenal smooth muscle tumor and forty-five cases of adrenal leiomyosarcoma were included. CONCLUSION: We present the demographic, clinical, radiological, pathological and oncological characteristics and prognosis of tumors of the adrenal gland arising from smooth muscle cells, as well as describe the common clinical investigations and therapeutic modalities that have been reported as part of their management.

Malignant Pheochromocytomas/Paragangliomas and Ectopic Hormonal Secretion: A Case Series and Review of the Literature.

Malignant pheochromocytomas (PCs) and paragangliomas (PGLs) are rare neuroendocrine neoplasms defined by the presence of distant metastases. There is currently a relatively paucity of data regarding the natural history of PCs/PGLs and the optimal approach to their treatment. We retrospectively analyzed the clinical, biochemical, imaging, genetic and histopathological characteristics of fourteen patients with metastatic PCs/PGLs diagnosed over 15 years, along with their response to treatment. Patients were followed-up for a median of six years (range: 1-14 years). Six patients had synchronous metastases and the remaining developed metastases after a median of four years (range 2-10 years). Genetic analysis of seven patients revealed that three harbored succinate dehydrogenase subunit B/D gene (SDHB/D) mutations. Hormonal hypersecretion occurred in 70% of patients; normetanephrine, either alone or with other concomitant hormones, was the most frequent secretory component. Patients were administered multiple first and subsequent treatments including surgery (n = 12), chemotherapy (n = 7), radionuclide therapy (n = 2) and radiopeptides (n = 5). Seven patients had stable disease, four had progressive disease and three died. Ectopic hormonal secretion is rare and commonly encountered in benign PCs. Ectopic secretion of interleukin-6 in one of our patients, prompted a literature review of ectopic hormonal secretion, particularly from metastatic PCs/PGLs. Only four cases of metastatic PC/PGLs with confirmed ectopic secretion of hormones or peptides have been described so far.

Denosumab in transfusion-dependent thalassemia osteoporosis: a randomized, placebo-controlled, double-blind phase 2b clinical trial.

Denosumab (DNM) is a fully human monoclonal antibody against the receptor activator of nuclear factor kappa-B ligand (RANKL) that has been licensed for the treatment of different types of osteoporosis. However, the prospective data for the evaluation of DNM efficacy on transfusion-dependent thalassemia (TDT)-induced osteoporosis are rather limited. Thus, we conducted a randomized, placebo-controlled, double-blind, phase 2b clinical trial to evaluate DNM in TDT osteoporosis. Patients were assigned to receive either 60 mg DNM (n = 32) or placebo (n = 31) subcutaneously on day 0 and 180 during a total of 12 months of follow-up. The percentage increase of L1-L4 bone mineral density was higher in the DNM group than the placebo group (5.92% ± 5.25% vs 2.92% ± 5.56%, respectively; P = .043), whereas the advantage of DNM regarding wrist bone mineral density was much higher compared with placebo (-0.26% ± 5.31% vs -3.92% ± 8.71%, respectively; P = .035). No grade 3 or 4 toxicity was observed. DNM reduced pain scores that remained unaltered in the placebo group. DNM showed a significant reduction of soluble RANKL (sRANKL), sRANKL/osteoprotegerin ratio, C-telopeptide of collagen type I, tartrate-resistant acid phosphatase isoform-5b, and bone-specific alkaline phosphatase between baseline and the 12th month (P < .01 for all comparisons) without changes in dickkopf-1, sclerostin, and osteocalcin. On the contrary, placebo patients showed an increase in sRANKL, osteoprotegerin, dickkopf-1, sclerostin, C-telopeptide of collagen type I, tartrate-resistant acid phosphatase isoform-5b, and bone-specific alkaline phosphatase during the study period (P < .01 for all comparisons). In conclusion, DNM increased lumbar spine and wrist bone mineral density and reduced pain and bone remodeling markers, and thus it is another valuable option for the management of TDT-induced osteoporosis. This trial was registered at www.clinicaltrials.gov as #NCT02559648.

MECHANISMS IN ENDOCRINOLOGY: Aging and anti-aging: a Combo-Endocrinology overview.

Aging and its underlying pathophysiological background has always attracted the attention of the scientific society. Defined as the gradual, time-dependent, heterogeneous decline of physiological functions, aging is orchestrated by a plethora of molecular mechanisms, which vividly interact to alter body homeostasis. The ability of an organism to adjust to these alterations, in conjunction with the dynamic effect of various environmental stimuli across lifespan, promotes longevity, frailty or disease. Endocrine function undergoes major changes during aging, as well. Specifically, alterations in hormonal networks and concomitant hormonal deficits/excess, augmented by poor sensitivity of tissues to their action, take place. As hypothalamic-pituitary unit is the central regulator of crucial body functions, these alterations can be translated in significant clinical sequelae that can impair the quality of life and promote frailty and disease. Delineating the hormonal signaling alterations that occur across lifespan and exploring possible remedial interventions could possibly help us improve the quality of life of the elderly and promote longevity.

High incidence of thyroid cancer among patients with acromegaly.

PURPOSE: Several studies have suggested that patients with acromegaly have an increased risk of thyroid, colorectal, breast and prostate cancers. In this study we determined the prevalence of malignant neoplasms in patients with acromegaly. METHODS: Cancer risk was evaluated in a cohort of 110 patients (M/F 48/62, age 58.63±13.8 years, range 30-86) with acromegaly. Mean age at diagnosis of acromegaly was 46.37±13.11 years. Mean period of time since diagnosis of acromegaly was 12.26+9.6 years. RESULTS: From 110 patients, cancer was diagnosed in 26 (23.6%) patients. Thyroid cancer was the most common cancer and was diagnosed in 13 patients (11.8%); other cancers encountered were gastric cancer (N=2), endometrial cancer (N-2), and breast cancer, colon cancer, prostate cancer (N-2), myelodysplastic syndrome, renal cell carcinoma, lung cancer and pancreatic carcinoma, one case each. Age, gender, age at the time of diagnosis of acromegaly, tumor size of pituitary adenoma and duration of disease were not associated with cancer development. CONCLUSIONS: This study suggests that patients with acromegaly have an increased risk of thyroid cancer and therefore they should undergo regular screening with hormonal and ultrasound evaluation of the thyroid and FNAB when required.

Acute Necrotizing Pancreatitis Following Olanzapine Treatment and 759C/T Polymorphism of HTR2C Gene: A Case Report.

Acute pancreatitis can be attributed to numerous potential causes, such as alcohol abuse, chololithiasis, infection, lesions, tumors, hypercalcemia, hyperlipidemia, and medications. Among psychotropic medications, the use of some atypical antipsychotics, such as clozapine, olanzapine, quetiapine and risperidone, has been implicated in the development of acute pancreatitis, although the underlying mechanism has not been clarified. We describe the case of a young man with no other major medical problems, alcohol abuse or predisposing factors, who developed acute necrotizing pancreatitis following olanzapine administration, possibly through severe elevation of serum triglycerides. A pharmacogenomic analysis revealed the presence of the 5-hydroxytryptamine (serotonin) receptor 2C, G protein-coupled (HTR2C) -759C genotype which is related to increased risk for metabolic syndrome.

NGAL and cystatin C: two possible early markers of diabetic nephropathy in young patients with type 1 diabetes mellitus: one year follow up.

OBJECTIVE: Diabetic nephropathy constitutes a major long-term complication in patients with type 1 diabetes mellitus (T1D) and its diagnosis is based on microalbuminuria. The aim of this observational follow-up study was to explore the role of neutrophil-gelatinase-associated lipocalin (NGAL) and cystatin C in unravelling early diabetic nephropathy even in patients with normoalbuminuria. DESIGN: Fifty-six euthyroid patients with T1D, with mean age 13.1 (SD: 3.2) years, and 49 healthy controls with mean age 12.8 (SD: 6.6) were recruited. Besides standard blood chemistry and urinary albumin excretion, serum NGAL (ELISA) and cystatin C (nephelometry) were measured at enrollment and after 12-15 months. GFR was calculated with the bedside Schwartz formula (eGFR) and the Lund strategy formula (L-eGFR). RESULTS: At baseline, mean NGAL levels were not significantly different between children with diabetes and controls. At re-evaluation, mean NGAL value and mean eGFR value in patients with diabetes were increased (p=0.032 and p=0.003 respectively). At both baseline and reevaluation, NGAL was positively correlated with cystatin C (r=0.41, p<0.001), systolic arterial pressure z-score (r=0.3, p=0.031) and creatinine (r=0.32, p=0.010). NGAL correlated negatively with eGFR (r=-0.26, p=0.049) and L-eGFR (r=-0.33, p=0.010). Cystatin C had a negative correlation to eGFR (r=-0.29, p=0.025) and a positive one with creatinine (r=0.35, p=0.009) at reevaluation. No statistically significant correlation was found between cystatin C and microalbuminuria (p=0.736). CONCLUSIONS: NGAL and cystatin C, known markers of renal injury, correlate with renal function decline in T1D, suggesting that they may be used as supplementary tests to urine albumin excretion in order to unmask early renal dysfunction.

The prevalence of glucose metabolism abnormalities in Greek women with polycystic ovary syndrome.

The prevalence of glucose metabolism abnormalities in PCOS women worldwide varies between 10 and 40% but there are no data in Greek PCOS women. In this retrospective study the prevalence of glucose abnormalities and the indices of insulin resistance (IR) and whole-body insulin sensitivity were estimated in a Greek population with PCOS. Impaired glucose tolerance (IGT), impaired fasting glucose (IFG) and type 2 diabetes mellitus (t2DM) were calculated. The prevalence of IGT, IFG and t2DM in our PCOS population was 7.6, 5.1 and 1.7%, respectively. The total prevalence of glucose abnormalities was estimated as 14.1%. The prevalence of t2DM was three- to four-fold higher than in the general Greek female population of the same age as this was estimated by 2, recently published studies. PCOS women with increased BMI and waist circumference and age greater than 30 years, present more severe IR and decreased whole-body insulin sensitivity. Our data indicates a relatively high prevalence of glucose intolerance and t2DM in a Greek population with PCOS. Obese women with PCOS are in higher risk to develop glucose abnormalities and probably t2DM later in life and therefore every woman diagnosed with PCOS should undergo a 2-h post load OGTT.

Primary mucosa-associated lymphoid tissue thyroid lymphoma: a rare thyroid neoplasm of extrathyroid origin.

Primary thyroid lymphoma is a rare malignancy, representing 2-8% of all thyroid malignancies and 1-2% of all extranodal lymphomas. The majority of cases concern non-Hodgkin's lymphoma of B cell origin, following by Hodgkin's disease, T cell lymphomas and rarely marginal zone B-cell mucosa-associated lymphoid tissue (MALT) lymphomas. MALT lymphomas have been associated with long-standing autoimmune Hashimoto's thyroiditis. We present the case of a 44-years-old woman with thyroid MALT lymphoma in the background of multinodular goiter of autoimmune origin.