ACTA ENDOCRINOLOGICA (BUC)

case of a young woman with cold intolerance is presented. Her thyroid function tests\r\nwere all within the normal range although both TSH and free T4 were in the low normal\r\nrange. The possibility of subclinical central hypothyroidism was raised and tests to confirm\r\nit were performed. The results could be consistent with the diagnosis and treatment with\r\nthyroid hormone was started with clinical improvement. However, with treatment, her TSH\r\nlevel decreased below the normal reference range. We discuss the question of having\r\nhypothyroid symptoms with normal thyroid function tests, should we treat it and how to\r\nevaluate the clinical and laboratory response to treatment in this patient.

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.

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.

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.

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.

Glycemic control can be impaired in active acromegaly and insulin sensitivity (IS) decreases with rising growth hormone (GH) levels.\r\nAim. To assess the short-term impact of transsphenoidal surgery for acromegaly on glycemic control. Methods. 11 patients with native active acromegaly due to pituitary macroadenoma were assessed before and after (2-3 months) transsphenoidal hypophysectomy. Serum glucose, GH and insulin levels were measured by immunoradiometric assay at 0, 30, 60 and 120 minutes during a 75 g OGTT before and after surgery. IGF-1 levels were measured by ELISA. Basal hepatic IS was assessed using HOMA-S% and QUICKI indexes and stimulated IS using OGTTISI. Basal and stimulated insulin secretion was assessed using HOMA-B% index and IGI respectively. Results. All patients had their acromegaly improved (mean?SD pretreatment nadir GH 34?24.7 ng/mL vs. 4.6?3.5 ng/mL postsurgery; p<0.001) but only one was cured (nadir GH<1 ng/mL, normal IGF- 1 level). Mean fasting serum glucose was lowered by 7.9 mg/dL (95% CI 1.3-14.4, p=0.03) and fasting serum insulin by 9.6 mU/mL (95% CI 1.0-18.1, p=0.02). IS increased after surgery as shown by HOMA-S% index which rose 0.25?0.18 to 0.5?0.36 (p<0.01), QUICKI which rose form 0.31?0.03 to 0.33?0.03 (p=0.001) and OGTTISI index which rose from 2.5?1.6 to 5.1 ? 3.5 (p=0.002). Insulin secretion was unchanged as shown by HOMA-B% index (313?229 presurgery vs. 227?139 postsurgery, p=NS) and IGI index (0.96 ? 0.86 presurgery vs. 0.55 ? 0.49, p=NS). Conclusions. Partial removal of the pituitary adenoma by transsphenoidal surgery in patients with acromegaly induces a significant increase in insulin sensitivity and an improvement in glycemic control at 3 months after surgery. This suggests that transsphenoidal surgery should be indicated even if complete removal of the pituitary adenoma is not achieved.

Background. Hashimoto thyroiditis (HT) is an autoimmune disease and the most common cause of hypothyroidism. The widespread lymphocyte infiltration in the thyroid gland and intolerance of the body against its thyroid antigens leads to the destruction of thyroid cells and impaired thyroid function. Granulysin (GNLY) is a cytolytic antimicrobial peptide that has been associated with a wide range of diseases such as various infections, cancer, transplantation, and skin problems. However, there are a few studies investigating the relationship between HT and granulysin. Aim. Our study aims to investigate whether granulysin levels and GNLY gene polymorphism contribute to the damaged immune response leading to HT. Material and Methods. 100 unrelated patients diagnosed with HT and 140 healthy individuals were included in our study. Frequencies of GNLY rs10180391 and rs7908 gene polymorphisms were determined using PCR- RFLP method and serum granulysin levels were determined using ELISA. Results. There is no statistical significance between patient and control groups in terms of genotype and allele frequencies of GNLY gene polymorphisms and serum levels of granulysin. Conclusion. In conclusion, granulysin and GNLY gene polymorphisms do not appear to relate to HT disease.

Objective. To investigate the effect of puerarin (Pue) on the proliferation and differentiation of osteoblasts and the expression of type I collagen(Coll I) mRNA in a high-glucose (HG) environment, and to provide evidence for the clinical treatment of diabetic osteoporosis(DOP). Subjects and Methods. The proliferation of osteoblasts from three groups – the control group, the HS group, and the HG+Pue (10-8-10-6 M) group – was cultivated for 72 h and evaluated using the methyl thiazolyltetrazolium (MTT) assay. Results. The MTT values and the ALP activities in all experimental groups were significantly lower than those in the control group, and the MTT values and the ALP activities in the HG+Pue group were significantly higher than those in the HS group. Coll I mRNA expression in all experimental groups was significantly lower than that in the control group, while that in the HG+Pue group was significantly higher than that in the HG group. Conclusions. The proliferation and differentiation of osteoblasts and the expression of Coll I mRNA were inhibited by high glucose, but Pue can increase the proliferation and differentiation as well as the expression of Coll I mRNA in the osteoblasts, indicating that Pue could be therapeutically beneficial against DOP.

Background. To evaluate the protective effect of Nigella sativa oil (NSO) on the myocardium in streptozotocin-induced diabetic rats. Materials and methods. Thirty-two 7–8-week-old female Wistar albino rats (300–350 g) were equally divided into 4 groups: nondiabetic untreated animals (control), diabetes mellitus (DM), NSO, and DM+NSO groups. For the induction of diabetes, 45 mg/kg streptozotocin was applied to the rats in the DM and DM+NSO groups as a single intraperitoneal dose. NSO (400 mg/kg) was orally administered through an intragastric catheter once a day over 21 days. Formalin-fixed, paraffin-embedded tissue sections of the myocardium were evaluated histopathologically and immunohistochemically. Results. Compared to the control, NSO, and DM+NSO groups, the myocardial tissue samples from the rats in the DM group had significantly higher myositis, hyaline degeneration, and Zenker’s necrosis. Moreover, the Bcl-2 expressions were significantly higher in the control, NSO, and DM+NSO groups than in the DM group. Conclusion. NSO has a protective effect on the myocardium of streptozotocin-induced diabetic rats, most likely via suppressing apoptosis.