ACTA ENDOCRINOLOGICA (BUC)

Introduction. Diagnosing Cushing Syndrome (CS) remains challenging due to its diverse symptoms and the complexity of its subtypes. This study aimed to optimize diagnostic cut-off values for differentiating CS subtypes using the 1 mg dexamethasone suppression test (DST) in a cohort of 237 patients. Materials and Methods. Retrospective data from patients diagnosed with non-functional adrenal adenomas (NFA), mild autonomous cortisol secretion (MACS), adrenal CS, and pituitary CS at the Dokuz Eylül University Endocrinology and Metabolism Clinic (2005–2016) were analyzed. Sensitivity and specificity of morning cortisol levels after DST were evaluated using receiver operating characteristic (ROC) curve analysis. Results. The analysis identified optimal morning cortisol cut-off levels: 2.14 μg/dL (59.04 nmol/L) for MACS, 2.3 μg/dL (63.4 nmol/L) for adrenal CS, and 2.33 μg/dL (64.28 nmol/L) for pituitary CS. Conclusion. These optimized thresholds demonstrated high sensitivity and specificity, significantly improving diagnostic precision over the conventional threshold of 1.8 μg/dL (50 nmol/L). The findings underscore the importance of tailored cut-off values to address subtype-specific diagnostic challenges, reducing delays and mitigating long-term complications. Personalized diagnostic approaches, incorporating patient demographics and disease-specific characteristics, are essential for enhancing diagnostic accuracy and facilitating timely interventions.

Context. Regulatory T cells (Tregs) have critical roles in preventing autoimmune diseases such as Hashimoto’s thyroiditis (HT). Forkhead box P3 (Foxp3), the master transcription factor of Tregs, plays a pivotal role in Treg function. Objective. Herein, we investigated the association of two single nucleotide polymorphisms (SNPs) of the Foxp3 gene with HT development. Methods and study design. A total of 129 HT patients and 127 healthy subjects were genotyped for rs3761548 (-3279 A/C) and rs3761549 (-2383 C/T) in the Foxp3 gene, using polymerase chain reaction-restriction fragment length polymorphism. Results. Genotypic and allelic distribution of rs3761548 SNP showed a significant association with HT. The CC genotype was observed in 37.2% of patients versus 22.1% of the controls [P<0.008, odds ratio (OR): 2.1; 95% confidence interval (CI): 1.2-3.6] and the AC genotype in 41.1% of patients compared to 54.3% of the controls (P<0.025, OR: 2.1; CI: 1.2-3.6). In addition, higher frequency of C allele in patients compared to controls (P=0.05, OR: 1.4; 95% CI: 0.9-2) suggested that patients with the CC genotype and C allele had increased susceptibility to HT. There were significantly higher serum levels of anti-thyroid peroxidase (ATPO) antibody in patients with the rs3761548 CC genotype (1156±163 IU/mL) compared to the other genotypes (≈582-656 IU/mL; P<0.004). We observed a greater frequency of the AC genotype in patients who had decreased ATPO antibody levels (P=0.02). Conclusions. The association of the rs3761548 SNP with risk of HT and its influence on ATPO antibody levels suggested an important role for Foxp3 in the biology and pathogenesis of HT.

The aim of this study is to analyze and identify the main predictors that may indicate multifocal growth of PTC. Materials and methods. The main and control groups included patients with the category of malignant multifocal process T1-3mN0Mx (n=109) and unifocal T1- T3N0Mx (n=50) respectively, who underwent thyroidectomy with lymphadenectomy. Ultrasound characteristics of the nodes, tissue changes of the thyroid gland were taken into account. Results. Fibrous changes can be considered as one of the risk factors of the presence of additional PTC lesion. Discussion. There is no unambiguity in the definition of predictors of multifocal PTC growth. Conclusions. No clear predictors of multifocal PTC have been identified. It is advisable to improve the quality of ultrasound, to focus on single-focus PTC in patients with fibrinous changes in the thyroid gland at normal levels of TSH.

Context. The grey mullet, Mugil cephalus, is an edible fish of high economic importance. Breeding biology with reference to hormonal/growth factor regulation of oocyte maturation needs to be known for its commercial production. Objective. The present study was conducted to examine the potency of maturation inducing hormones, chorionic gonadotropin (hCG), bovine-insulin, and insulin like growth factor1 (h-IGF-1) I on ovarian steroidogenesis and oocyte maturation. Design. The role of hormones and growth factors on steroidogenesis and oocyte maturation was investigated using specific inhibitors, Wortmannin for phosphatidylinositol-3 (PI3) kinase, trilostane for 3β-hydroxysteroid dehydrogenase, 1-octanol and 1-heptanol for gap junctions, actinomycin D for transcription and cycloheximide for translation of signal molecules. Methods. Actions of hormonal and growth factors were examined for steroidogenesis, by radioimmunoassay and oocyte maturation by germinal vesicle breakdown (GVBD). Specific inhibitors were used to determine the cell signaling pathways, PI3 kinase. Results. All the inhibitors attenuated the hCGinduced oocyte maturation (GVBD%), steroidogenesis including transcription, translation, gap junctions and PI3 kinase signaling. These inhibitors failed to inhibit h-IGF-I and b-insulin-induced oocyte maturation, steroidogenesis, translation and PI3 kinase signaling. Conclusion. hCG induces oocyte maturation via steroid dependent pathway involving gap junctions, transcription, translation and PI3 kinase signaling, unlike h-IGF-I and b-insulin in the mullet.

Context. Obesity is a complex and heterogeneous disorder with multiple phenotypes described. Although metabolomic biomarkers of obesity have been extensively studied, biomarkers of obesity phenotypes and differences between these phenotypes and normal-weight (NW) persons have been less investigated. Objective. The objective of this cross-sectional analysis was to investigate serum amino acids (AA) as markers of metabolic alterations in obesity phenotypes and NW. Design. Cross-sectional Subjects and Methods. By targeted metabolomics we analyzed serum samples of 70 women using ultrahighperformance liquid chromatography/mass spectrometry. Participants were divided into 3 groups: NW, metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUHO). Results. Five AAs were significantly different between study groups: cysteine, methionine, asparagine, glutamine, and lysine (p-value <0.05 and variable importance in the projection >1). Cysteine increased linearly with metabolic unwellness from NW to MUHO. Lysine and glutamine were significantly higher, and asparagine was significantly lower in NW and MHO than in MUHO. Conclusions. By trend and group analysis we identified specific changes in serum AAs along with the progression of metabolically unwellness.

Context. Childhood cancer survival has increased substantially over the past few decades. However, long-term side effects associated with cancer treatment have also risen. Especially thyroid gland disorders are common. Objective and Design. The present retrospective cross-sectional study aimed to investigate risk factors of long-term TD in survivors of leukemia-lymphoma. Subjects and Methods. The study included 44 acute lymphoblastic leukemia (ALL) and 26 Hodgkin lymphoma survivors (HL). Abnormal laboratory and pathological ultrasonographic findings of the thyroid gland were accepted as a thyroid disorder. The possible causes of thyroid disorders were investigated. Results. Long-term thyroid disorder was found in 40% of the patients. This rate was higher in HL patients than in ALL (65% vs. 25%). Thyroid disorder was significantly more common in patients who received radiotherapy to the neck (57% vs. 17%). Radiotherapy to the neck area was the only significant determinant for thyroid disorders in the regression models [OR 33.17, 95% CI (2.76-398.9) p = 0.006]. However, HL remained significantly associated with TD in the logistic model performed using cancer type [OR 19.25, 95% CI (2.39-155.3) p = 0.006]. Conclusions. The study showed that radiotherapy applied to the neck was an essential risk factor for long-term TD in the average 6-year follow-up of cancer survivors. However, we recommend that childhood cancer survivors should be followed closely for a long time since long-term endocrine side effects were reported during longer than six years follow-up periods.

Background. An increasing number of studies suggest that hypothyroidism may lead to hepatorenal toxicity. This study examined whether thymoquinone (TQ), the main active Nigella sativa constituent, could prevent the detrimental influences of hepatorenal toxicity of hypothyroidism during the juvenile period in rats. Methods. The male rats were randomly divided into four groups (n = 7), including control, propylthiouracil (PTU), PTU-TQ 5 mg/kg, and PTU-TQ 10 mg/kg. PTU was dissolved in drinking water at a concentration of 0.05% and administered for six weeks. In the PTU-TQ5 and PTU-TQ10 groups, animals received PTU plus 5 mg/kg and 10 mg/kg of the TQ (i.p.) for six weeks, respectively. The rats were evaluated after TQ treatment by measuring serum markers of liver and kidney function tests as well as oxidative stress biomarkers in liver and kidney tissues. Results. Administration of TQ (5 and 10 mg/ kg) decreased oxidative stress damage in liver and kidney tissue in hypothyroidism rats with improvement in activities of antioxidant enzymes and a decrease in MDA in both liver and kidney homogenates. Furthermore, TQ treatment significantly inhibited the elevation of serum biochemical markers of liver and kidney function associated with this hepatorenal toxicity. Conclusion. These results suggest that the protective effect of TQ in hypothyroidism-induced hepatorenal toxicity in rats is attributed to its ability to reduce oxidative stress in hepatic and renal tissues. However, more studies are recommended to investigate the exact mechanism (s) for the effect of TQ on hepatorenal outcomes of hypothyroidism in human subjects.

Background. We aimed to evaluate whether a high carbohydrate or a high fat diet differs in alteration of the inflammatory and metabolic risk factors in cardio-renal metabolic syndrome in rats. Methods. Twelve male Wister rats were randomly divided into two groups: one received diet 1 standard pellet rat diet (D1) containing 10% fat, 50% carbohydrate, 25% protein and another group received diet 2 (D2) containing 59% fat, 30% carbohydrate and 11% protein for 16 weeks. Weight was recorded weekly. FSG and insulin levels were measured using an enzymatic spectrophotometric and a standard ELISA kit respectively. Inflammatory parameters including TGF-β, MCP-1, TNF-α, IL-1β, IL-6 in the renal and cardiac tissues of rats were evaluated by ELISA technique. Result. Food intake in D1 and D2 groups increased in the study period, however food intake in D2 group was significantly higher compared with D1 group. FSG, HOMA and TG concentrations in D2 group were significantly higher compared to D1 group. Moreover, TGF-β and MCP- 1 concentrations in the renal tissues of D2 group and TNF-α in the cardiac tissues of D1 group were significantly higher compared with D1 group (P<0.05). Positive associations between IL-1β and TG and between HOMA, FSG with TGF-β and MCP-1 in the renal tissue of animals were also identified.

Context. Some adrenal tumors, such as pheochromocytoma, can be life-threatening. Therefore it is crucial to distinguish them from other lesions, especially prior to surgery. Chromogranin A (CgA) seems to potentially be a good marker for tumors of chromaffin origin. Objective. To assess the differentiating value of CgA in the diagnostic work-up of pheochromocytoma. Design. Retrospective study of operated patients with adrenal incidentaloma with lesions > 10 Hounsfield’s units (HU) on CT. Subjects and Methods. Thirty patients (11 males, 19 females; aged 61.5±21 years) were enrolled in the study. Patients using medications interfering with the assessment of CgA and metanephrines were excluded. Two groups were formed: those with pheochromocytoma (Ph, n=16) and those with non-pheochromocytoma (N-Ph, n=14) lesions. Data included radiological features of masses, serum CgA and 24-hour urine metanephrines (24 - HUM) concentrations. Results. No difference in 24-HUM level nor tumor size or density was found between groups Ph and N-Ph. Median serum CgA concentration was higher in Ph group compared to the N-Ph: 99.35 (68.12-172.73) vs. 52.92 (34.37-101.26) ng/mL, respectively (P=0.04). In Ph group, the size of the lesion correlated negatively with density (r= -0.53, P=0.042). No significant correlation in CgA, 24-HUM, density or size of the lesion was found. Performed curve receiver operating characteristic (ROC) showed AUC=0.7232 for CgA. Taking into account CgA serum value of ≤ 50 ng/mL (sensitivity: 93.75%, specificity: 50.00%, P=0.012), we proposed an algorithm for management of lesions > 10 HU on CT. Conclusion. CgA level ≤ 50 ng/mL might be useful in initial screening evidence for the exclusion of pheochromocytoma. It is crucial to eliminate factors interfering with the measurements.

Context. It is unclear whether treatment is necessary for transient moderate hypocalcaemia occurring after total thyroidectomy; if it is present, it is unclear which treatment modality should be preferred. Objective. To investigate both the necessity and effectiveness of different treatment approaches of oral and/ or intravenous calcium treatment in patients with transient, postoperative, moderate hypocalcaemia. Design. This is a case control study made between June 2014 and June 2015. Subjects and Methods. Forty-five patients who had serum calcium levels 6 hours after total thyroidectomy between 7.5-8 mg/dL were divided into three equal groups: an oral calcium administration group, an intravenous calcium administration group and a no-treatment group. Serum calcium and parathyroid hormone levels were measured preoperatively and on postoperative days 1, 2, 5 and 10. Results. For post-thyroidectomy patients with serum calcium 7.5-8 mg/dL in the early postoperative period, no significant difference in serum calcium or parathyroid hormone was detected between groups. Conclusions. Follow-up without treatment seems to be the most effective approach for moderate hypocalcaemia occurring in the early period following total thyroidectomy; this suggests that intravenous treatment should be avoided.