ACTA ENDOCRINOLOGICA (BUC)

Introduction. Pituitary adenomas (PA) are the third most common intracranial tumors, with an incidence rate of 10-15%. More than half are invasive, infiltrating adjacent structures. The primary objective of this project was to determine whether MGMT expression is associated with the invasiveness of PA. Material and Method. All patients who underwent surgical decompression consecutively between 2007- 2012 were included. All data were obtained from the case records. Formalin-fixed paraffin-embedded (FFPE) tissue specimens were stained with hematoxylin and eosin (HE) and then examined via light microscope. Paraffin blocks that lacked necrosis and hemorrhage were chosen for histologic examination. In addition to an immunoprofile battery that consisted of Ki-67 and p53, MGMT, S-100 and Pan-CK were evaluated as well. Results. The subjects included 25 women and 15 men. The mean age was 48.9 ± 14.5 years. Of these, 63% of cases involved the invasion of adjacent structures. Of the PA, 17 (42%) were non-functioning pituitary adenomas (NFPA). There was a statistically significant relationship between the invasiveness and Ki-67, p53, MGMT expression, and prolactinoma. Gonodotropinomas were mostly non-invasive. FPAs presented invasive features more frequently than NFPAs. Pan-CK was positive in GH-secreting adenomas but negative in FSH- and LH-secreting adenomas. Conclusion. Ki-67 and p53 in lower expression level can be used for evaluating invasiveness but not for recurrence. MGMT expression can be a useful IHC indicator for invasiveness. However, Pan-CK cannot be used for invasiveness or aggressiveness.

recently. However, the nature of the signals that may connect body fat/muscle tissues with the central nervous system governing energy homeostasis remains to be elucidated. Objective. The present study was designed to investigate the effects of peripheral kisspeptin-10 administration on irisin release in human males. Subjects and methods. Kisspeptin-10 was administered to normal weight (n=8) and obese (n=8) men. Sequential blood sampling was performed for 30 minutes pre and 210 minutes post kisspeptin injection at 30 minutes interval. ELISA kit was used to detect plasma irisin levels. Results. There is a significant (P<0.0001) effect of Kisspeptin-10 administration on irisin release in both normal weight and obese participants. Mean irisin levels (96.24 ± 1.351 ng/mL) at 210 minutes were significantly (P<0.0001) enhanced as compared to pre-kisspeptin (59.18 ± 4.815 ng/ mL) in normal weight subjects. In obese subjects mean irisin levels (75.76 ± 4.06 ng/mL) were significantly (P<0.0001) elevated at 180 minutes post-kisspeptin when compared with pre-kisspeptin irisin levels (41.28 ± 2.89 ng/mL). Conclusion. Our findings suggest that kisspeptin may have a novel therapeutic potential to induce irisin release in humans which may have anti-obesity effects.

Introduction. Subtypes of nonfunctioning pituitary adenomas which may differentiate into functioning adenomas are silent corticotroph adenomas (SCA). These are pituitary tumors positive on immunohistochemical staining for ACTH, but without clinical evidence of Cushing’s disease. Case report. FG, a 50 years old man was twice operated for compressive non secreting pituitary macroadenoma (NFPA). After the first surgery he developed hypopituitarism and needed replacement therapy for all the hormonal lines. After the second surgery he rapidly developed the clinical features of Cushing’s syndrome. Hormonal dosages showed: the absence of the circadian rhythm of cortisol, high ACTH level and the lack of suppression at 1 mg overnight and high dose Dexamethasone suppression tests. The immunohistochemistry of the previously resected pieces confirmed the diagnosis of a silent corticotroph adenoma. The patient was referred for conventional antitumoral radiotherapy associated with Cabergoline, then with Ketoconazole treatment. As the high levels of cortisol recurred, he was subjected to bilateral adrenalectomy. Conclusions. We present the rare case of a silent corticotroph macroadenoma which became hypersecreting after two pituitary adenomectomies. SCA may represent another entity in the spectrum of Cushing’s syndrome that must be evoked in the cases of pituitary macroadenomas thought to be non-functional.

treatment of postmenopausal osteoporosis. It has estrogen agonist effects on bone and on surrogate markers of cardiovascular risk, but estrogen antagonist effects on breast and endometrium. It inhibits bone resorption and decreases bone turnover, increases bone mineral density and reduces the risk of vertebral fractures in postmenopausal women.\r\nObjectives: The main endpoint of our study was to evaluate the effect of raloxifene therapy (60 mg/day) on biochemical markers of bone turnover in romanian osteoporotic postmenopausal women. Secondary endpoints were the effect on bone mineral density (BMD), body mass composition and lipid profile.\r\nMaterials and methods: We performed a longitudinal, prospective, open study, investigating 29 postmenopausal white women with osteoporosis (Group 1) aged 56.9?7.8 years (mean ? SD) and in addition a control group of 29 premenopausal healthy white women (Group 2) with a mean age of 35.10 ? 7.8 years. The diagnosis of osteoporosis was established by dual-energy x-ray absorptiometry. We appreciated in both groups the bone turnover, measuring a marker of bone resorption: serum beta CrossLaps and a marker of bone formation: serum osteocalcin. We determined also the lipid profile: plasma cholesterol (mg/dL), HDL cholesterol (mg/dL), LDL cholesterol (mg/dL) and triglycerides (mg/dL) in all patients. Osteoporotic women received raloxifene 60 mg/day for one year. Biochemical bone markers, lipid profile and body composition have been evaluated at 3, 6 and 12 months of treatment and BMD was performed at 6 and 12 months of therapy.\r\nResults: Postmenopausal osteoporotic women showed an increased bone turnover in comparison with premenopausal women, with statistically significant increased serum values of both resorption and formation biochemical bone markers: respectively 0.48?0.2 vs 0.23?0.1 ng/mL for beta CrossLaps and 27.94?12.1 vs 17.30?8.9 ng/mL for osteocalcin, p<0.001. Raloxifene therapy for three months reduced significantly both bone resorption and formation: 0.36 ? 0.2 vs 0.48 ? 0.2 ng/mL, p< 0.005 for beta CrossLaps and 22.03 ? 10.1 vs 27.94 ?12.1 ng/mL, p< 0.001 for osteocalcin. After 3, 6 and 12 months of therapy with raloxifene the bone markers were statistically significant reduced: -21.2%, -20.4% and respectively -31.6% for osteocalcin and -25%, -39.6% and respectively -50% for beta CrossLaps (p< 0.01). After six months of therapy, serum levels of beta CrossLaps were reduced to premenopausal range (0.29 ? 0.1 vs. 0.23 ? 0.1 ng/mL, p=ns). Total cholesterol and LDL-C were reduced after 12 months (p< 0.03), with no increase in triglycerides and at the same time body mass composition was unchanged.\r\nConclusions: Our results suggest that raloxifene reduces as early as three months the bone turnover in postmenopausal osteoporosis. It reduces bone turnover in premenopausal range after only six months of therapy, for the bone resorption (beta CrossLaps) and after 12 months for bone formation (osteocalcin). In addition raloxifene treatment has favorable effects on BMD and lipid profile, proving safety and a stable body mass composition.

Background. Cerebral vein and sinus thrombosis (CVT) is less encountered, compared to arterial stroke. Commonly witnessed symptoms are headache, nausea, vomiting, confusion, aphasia, seizures, cranial nerve dysfunction and motor or sensorial deficits. The diagnosis is accurately determined by the help of MRI and MR venography. Multiple risk factors associated with CVT are present. Venous thrombosis tends to occur when there is an imbalance between prothrombotic and thrombolytic processes.\r\nCase report. In this report, a patient with CVT extending from left transverse and sigmoid sinuses to jugular vein and diagnosed with diabetes mellitus (DM) during this period\r\nwas discussed in light of literature. The 55-year-old man was evaluated in the neurology clinic with the complaints of headache, nausea, vomiting and blurred speech. On neurologic examination, he was diagnosed with sensorial aphasia and consequently, with DM over the hospital stay. On the cranial MR venography, CVT thrombosis was detected, extending from transverse and sigmoid sinuses to internal jugular vein. Decreased level of protein C and shortage of aPTT were\r\nfound. Anticoagulant treatment was carried out. All complaints were improved.\r\nConclusion. In our subject, the existence of decreased protein C and shortage of APTT, along with DM, is a situation to increase hypercoagulability and the risk of cerebral vein and sinus thrombosis.

Aims. To investigate the changes in the miRNAs and mRNAs expressed in the liver upon induction of “hyperresistinemia”. Methods. We identified mRNA and miRNAs that were differentially expressed between normal and resistin-treated liver tissue using microarrays. Expression was validated using quantitative RT-PCR (qRT-PCR). The putative targets and pathways of the differentially expressed miRNAs and mRNAs were investigated, respectively, using various computational algorithms. In addition, the interactions between differentially expressed miRNAs and mRNAs were analyzed. Results. After the filtration of the signals below the threshold level, we identified 34 miRNAs and 875 genes with expression levels different by more than 1.5-fold and 2.0-fold, respectively, between the two groups. These observations were confirmed by qRT-PCR. Bidirectional prediction analyses showed that the differentially expressed miRNAs may be inversely regulated by their predicted targets. Conclusion. Hyperresistinemia results in changes in the miRNAs and mRNAs expressed in the liver.

Immunotherapy in Oncology, a fundamental distinctive treatment in cancer patients, needs molecules with different mechanisms: immune checkpoint inhibitors (ICIs) who attenuate the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and the programmed cell death 1 (PD-1)/ligand 1 (PD-L1) pathways, depriving cancer cells of a key strategy of evasion from immunosurveillance. Although their success in improving overall patient survival, unfortunately, superior clinical response of immunotherapy is often associated with treatment toxicity. European Society of Medical Oncology (ESMO) published in 2021 a comprehensive review of qualitatively resynthesized information on endocrinopathies after cancer immunotherapy with ICIs with practical recommendations for screening and management. Endocrinopathy such as thyroid dysfunctions, hypophysitis, primary adrenal insufficiency, type 1 diabetes mellitus, central diabetes insipidus, or hypoparathyroidism were reported and called immune-related adverse effects (irAEs). Practical guidelines for monitoring, diagnosis, and treatment of ICIs related endocrine toxicities are constantly updated. Given the increasing use of ICIs, cooperation between oncologists and endocrinologists is crucial in the management of oncologic patients.

Increased body mass index (BMI) is considered a risk factor for breast cancer. Moreover, it is associated with an unfavorable prognosis of the disease. Overweight and obesity are a global public health problem. Objective. We aimed to describe the risk factor of high BMI in breast cancer patients through an observational study of patients diagnosed with mammary neoplasm. Patients and Methods. The study was performed on a sample of 172 women with breast cancer with a mean age of 58.8 (±SD) years and a control sample of 217 women without breast cancer with a mean age of 54 (±SD) years. Data collection was performed by questionnaires and by anthropometric measurements, during 2017-2021. Statistical analysis used numerical descriptive methods: mean, standard deviation, etc. and graphical methods. Results. The sample of women with breast cancer compared to the control sample showed differences in BMI (26.27 vs. 24.45 kg/m2), p=0.001. Conclusion. Obesity is a risk factor for breast cancer. This risk factor for breast cancer could be altered by the quality of the diet and by the adoption of an active lifestyle.

Context. Inflammation-related markers may predict cardiovascular diseases. Objective. In this study, it was aimed to assess pentraxin-3 (PTX-3) levels and its relationship with carotid intima-media thickness (CIMT) and high-sensitive C-reactive protein (hsCRP) in patients with subclinical hypothyroidism. Design. Prospective cross-sectional study Methods. This study included 60 patients (aged 30-60 years) with subclinical hypothyroidism and 30 healthy volunteers as controls. The demographic characteristics and anthropometric measurements were performed in all patients and controls. In addition, sonographic carotid artery examination, thyroid functional tests, lipid profile, hsCRP, and PTX-3 levels of the participants were investigated. Results. The PTX-3, hsCRP levels and CIMT were higher in patients with subclinical hypothyroidism when compared to controls (p=0.008, p=0.001, p<0.001, respectively). The PTX-3 level was strongly correlated with hsCRP (r=0.865; p<0.001), but no such correlation was detected with CIMT (r=-0.255; p=0.50). In binominal logistic regression analysis, it was found that CIMT and serum uric acid levels were independent parameters associated with subclinical hypothyroidism. In ROC analysis, a cut-off value of >3.75 ng/mL for serum PTX-3 level predicted subclinical hypothyroidism with a sensitivity of 60% and specificity of 60.7% (AUC: 0.672, p=0.004). Conclusion. Showing inflammation and endothelial dysfunction, the PTX-3 may be a helpful marker in patients with subclinical hypothyroidism associated with increased risk for cardiovascular disease.

Purpose. Short chain fatty acids (SCFAs) play a major regulatory role in adipocyte function and metabolism. The aim of this study was to investigate the effects of SCFAs on adiponectin and leptin expression in adipocytes, and also to determine whether the effects of SCFA treatment in visceral adipocytes obtained from healthy subjects are different relative to the effects in adipocytes from patients with type 2 diabetes. Materials and Methods. Human pericardiac preadipocytes and human pericardiac preadipocytes type 2 diabetes were differentiated into adipocytes for 21 days in 48-well plates. After differentiation, two kinds of mature adipocytes, human pericardiac adipocytes (HPAd) and human pericardiac adipocytes-type 2 diabetes (HPAd-T2D) were incubated with or without 1 mM of acetic acid (AA), butyrate acid (BA), and propionic acid (PA). After 48 hours of incubation, intracellular lipid accumulation was measured using oil red staining. In addition, mRNA levels of adiponectin, leptin and Peroxisome Proliferator-Activated Receptor γ (PPARγ) were determined by Real-Time PCR system. Results. In HPAd, SCFA supplementation did not inhibit lipid accumulation. By contrast, both AA (p<0.01) and PA (p<0.01) significantly inhibited lipid accumulation in HPAd-T2D. Regarding mRNA levels of adiponectin, no significant changes were found in HPAd, while all three types of SCFAs significantly increased (p<0.05) adiponectin expression in HPAd-T2D. Leptin mRNA expression levels were significantly increased by treatment with all three types of SCFAs in both HPAd (p<0.05) and HPAd-T2D (p<0.05). Conclusion. SCFAs inhibited lipid droplet accumulation and increased mRNA expression of adiponectin and leptin in T2D-derived adipocytes.