ACTA ENDOCRINOLOGICA (BUC)

Introduction. Non-diagnostic (ND) fine needle aspiration biopsy (FNAB) results are problematic for clinicians who want to accurately diagnose malignancy and avoid unnecessary thyroidectomies. In this study, we aimed to investigate the incidence of malignancy in nodules whose first FNAB result was ND, and ultrasonography (USG) findings affecting malignancy and the effectiveness of repetitive biopsies. Patients and Method. In our clinic, 156 consecutive nodules whose first FNAB were ND according to the Bethesda system and underwent thyroidectomy between 1 January 2011 and 1 January 2018, directly or after repeated biopsies, were retrospectively analyzed. Results. Malignancy was detected in 44 (28%) of 156 nodules that were ND in the first FNAB. Twenty-two (31%) of 72 nodules that underwent FNAB for the second time resulted in ND again. The malignancy rate of nodules with two consecutive ND results was 23%. Of the USG features, a significant correlation was found between malignancy and solid nodule structure (p<0.001), microcalcification (p=0.025), cervical lymphadenopathy (LAP) (p=0.004) and medium-high risk USG pattern (p=0.002). In multivariate analysis, only the solid nodule structure (p<0.002) and the presence of cervical LAP (p=0.013) resulted as independent predictive factors. Conclusion. Diagnostic thyroidectomy is an effective method for reaching the diagnosis in selected patients considering the USG findings.

Context. Primary hyperparathyroidism (PHPT) is often associated with thyroid disorders like nodular goiter, Hashimoto’s thyroiditis (HT) and Graves’ disease. Objective. Our aim was to explore whether the coexistence with HT affects bone metabolism in patients with PHPT. Design. This was a comparative cross-sectional study carried out in a tertiary inpatient endocrine center from January 2018 through December 2020. Subjects and Methods. A total of 234 patients were diagnosed with PHPT at our endocrine center. One hundred of them were included in the study - 50 with PHPT only and 50 with PHPT and HT. Two control groups were defined: 37 with HT and 37 without PHPT and HT. Serum markers of calcium-phosphate metabolism, bone markers (RANKL, Osteoprotegerin, β-CTX, Osteocalcin) and interleukin-17A were measured. Results. The frequency of HT among patients with PHPT was 37.6% (95% CI 31-43%) and did not differ significantly from that in the general population, 32.5% (95% CI 30-35%). Age, BMI, markers of calciumphosphate metabolism, bone markers and interleukin-17A weren’t significantly different in PHPT with and without HT or between the two control groups. The participants with PHPT had higher levels of interleukin-17A, β-CTX and Osteocalcin (p<0.05) than those without the PHPT. RANKL and Osteoprotegerin in these groups did not differ. Interleukin-17A correlated positively with serum calcium, PTH and RANKL and negatively with serum inorganic phosphate and 25(OH)D. Controlling for HT and age did not change the correlation. Conclusions. In our study, HT has not additional effect on bone metabolism in the patients with PHPT. Higher levels of interleukin-17A in PHPT suggest a possible role in the PTH-induced bone remodeling.

Context. Endothelial dysfunction and diabetic cardiomyopathy are critical complications of diabetes. Gallic acid (GA) plays a significant role in cardiovascular disorders resulted from diabetes. In addition, increased plasma miR-24, miR-126 associated with endothelial dysfunction. Aim. The current study was designed to assess the effects of GA on plasma miR-24, miR-126 levels in the diabetic rats. Animals and Methods. Adult male Sprague-Dawley rats were divided into three groups (n=8): control (C), diabetic (D) and diabetic group treated with GA (D+G, 25 mg/kg, by gavage) for eight weeks. The blood glucose level, body weight, lipid profile, blood pressure, plasma miR-24 and miR-126 levels, antioxidant and inflammatory biomarkers were measured. Results. The plasma levels of miR-24, miR-126, body weight, high-density lipoprotein cholesterol (HDL-c), total anti-oxidant capacity (TAC) and the systolic blood pressure significantly reduced and blood glucose, total cholesterol (TC), triglycerides (TG), very low-density lipoprotein cholesterol (VLDL-c), malondialdehyde (MDA), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and low-density lipoprotein cholesterol (LDL-c) significantly elevated among the diabetic rats compared with the control group. However, GA restored body weight, blood pressure, TC, TG, VLDL-c, TNF-α, miR- 126, blood glucose, HDL-c, MDA, TAC, miR-24 and IL-6 among the GA treated rats compared with the diabetic group. Conclusion. GA improves inflammation, oxidative stress and hypotension result from diabetes. These protective effects are probably mediated via increasing plasma miR-24 and miR-126 levels.

Aims: To assess if amiodarone maintains its antiarrhythmic efficacy in the presence of amiodarone-induced hyperthyroidism (AIT) and to identify the tri-iodothyronine (T3) threshold for atrial fibrillation in patients with AIT versus common hyperthyroidism.\r\nPatients and methods. Study group A consists in 49 patients (25 M/24 F) with AIT (220.83 ? 71.33 mg/day along 2.36 ? 2.25 years) and severe cardiopathies (9 valvulopathies, 40 ischaemic, dilatative and hypertensive cardiomyopathies), aged 57.87?12.63 years. Control group B consists in 51 hypothyroid (B1) or euthyroid patients (B2) treated with amiodarone (222.55 ? 68.78 mg/day along 2.67 ? 1.84 years) and also in 100 patients (23M/77F) with overt hyperthyroidism (B3), without major heart diseases, aged 52.74?12.85 years; TSH, total T3, total T4, free T4 were measured by radioimmunoassay. All were clinically, ECG and echocardiography evaluated.\r\nResults. Prevalence of arrhythmias recurrence was 59.2% (29/49 patients) in group A, significantly higher than in each control subgroups B: B1- 28% (7/25), B2- 15.45% (4/26) and B3- 20% (20/100), P< 0.001. Patients from study group A with AIT and T3 levels >250 ng/dL developed significantly more frequent atrial fibrillation (p= 0.04). However, in control group B3 with common hyperthyroidism, no T3 threshold for arrhythmias could be identified. Overall, there were no significant differences in total T3 levels with respect to the presence of atrial fibrillation in both study group A and subgroup B3 with common hyperthyroidism (p=ns).\r\nConclusion. Amiodarone antiarrhythmic efficacy is surpassed in AIT by the increased arrhythmic susceptibility of damaged myocardial tissue to minimally increased thyroid hormones levels. A tri-iodothyronine level > 250 ng/dL superimposed on preexistent proarrhythmic substrate in amiodarone-induced hyperthyroidism should be avoided.

Context. Hypothalamic-pituitary-adrenal (HPA) axis irregularities have been described both in bipolar disorder and suicidal behaviour, but few studies have examined the relationship between suicidal behaviours and cortisol levels in bipolar disorder. Objective. We compared HPA axis activity in bipolar I (BPD I) individuals with and without suicidal ideation and behaviour through multiple measurement of serum and salivary cortisol. Design. Cross-sectional, observational study. Subjects and Methods. 75 BPD I patients were assigned into 3 groups (no history of suicidal behaviour, history of suicidal ideation, history of suicide attempt), according to the C-SSRS. Socio-demographical and clinical data was obtained by using MINI 6.0 and a semi-structured questionnaire. Salivary samples were collected using Sarstedt Cortisol Salivette synthetic swab system for two consecutive days at 08:00, 16:00, 23:00 and salivary cortisol concentrations were determined by ELISA technique. A unique 1mg dose of dexamethasone was administered on the first day, at 23:00, after the collection of the saliva sample. Blood was collected on the first day at 8:00 AM and basal morning serum cortisol levels were determined by immunoassay with fluorescence detection. Results. Cortisol parameters in our BPD I sample did not vary significantly in respect to suicidal history. However, patients with a history of suicidal ideation have significantly higher total cortisol outputs than patients with no history of suicidal behaviour in the 18 to 40 age category compared with the above 40 age category. Conclusions. Total cortisol daily output varies significantly in an age-dependent manner in respect to suicidal thoughts in BPD I individuals.

Cinacalcet is used to treat tertiary hyperparathyroidism in renal failure. However, its use in pregnancy and hereditary hypophosphatemic vitamin D resistant rickets (HVDRR) has not been reported. In this study we describe the use of cinacalcet in a case of HVDRR with tertiary hyperparathyroidism diagnosed during pregnancy, in a tertiary care hospital in an academic center. A 29 year old woman with HVDRR was found to have tertiary hyperparathyroidism at week 15 of her second pregnancy: serum calcium 11.4 mg/dL, intact parathyroid hormone 307 pg/mL. Reductions in potassium phosphate and calcitriol were unsuccessful in restoring normocalcemia. Cinacalcet was started to avoid parathyroidectomy and to reduce the risk of hypercalcemia to the mother and fetus. After 10 weeks of treatment, calcium normalized but placental abruption prompted delivery at week 27 of gestation. A healthy live male was born with weight of 964 g and serum calcium of 9.0 mg/dL. After delivery cinacalcet was stopped. Eight months later, calcium was 10.0 mg/dL and intact parathyroid hormone 426 pg/mL. This case demonstrates the successful use of cinacalcet during pregnancy to manage hypercalcemia in a patient with HVDRR and treatment related tertiary hyperparathyroidism.

Background. Adverse effects of gasoline vapour (GV) on reproductive functions have been reported in experimental animals, including the female rats. Aim. Assessment of the ameliorative potencies of vitamins A, C and E against GV-induced toxicity on serum sex hormonal level in female rats. Animals and Methods. Five groups of adult female rats (n = 6) were daily treated respectively with distilled water (control), GV by inhalation (6 hr/day, 5 days /week) for 60 days, vitamins A (400 IU /kg) + GV, C (600 mg/kg) + GV and E (400 IU/ kg) + GV. The animals were sacrificed at the end of experiment, and serum sex hormonal (FSH, LH, estradiol and progesterone) levels were determined. Results. Exposure to GV significantly decreased (P ≤ 0.05) serum FSH, LH, estradiol and progesterone levels (2.26 ± 1.02 mIU/mL, 6.80 ± 1.62mIU/mL, 27.58± 4.27 ng/ mL and 18.82 ± 2.56 ng/mL, respectively), compared to control values (5.15 ± 2.54 mIU/ mL, 13.25 ± 3.30 mIU/mL, 54.02± 5.18 ng/ mL and 38.00 ± 3.56 ng/mL, respectively). The serum hormonal levels obtained for GVexposed rats treated with the vitamins (4.30 ± 2.62 mIU/mL, 12.38 ± 2.40mIU/mL, 52.06 ± 6.28 ng/mL and 36.26 ± 3.66 ng/mL, respectively for Vit. A; 4.66 ± 2.48 mIU/mL, 12.75 ± 2.92 mIU/mL, 53.80 ± 7.29 ng/mL and 36.78 ± 3.68 ng/mL, respectively for Vit. C; 5.62 ± 2.84 mIU/mL, 17.22 ± 2.92 mIU/ mL, 69.98 ± 5.66 ng/mL and 46.88 ± 4.0 ng/mL, respectively for Vit. E) were significantly higher (P ≤ 0.05) compared to the GV-exposed untreated rats. However, the hormonal levels obtained for vitamin E treated GV-exposed rats were significantly higher (P ≤ 0.05) than the levels for vitamins A and C treated GV-exposed rats, respectively. Conclusion. Vitamin E is more effective than A and C in ameliorating the adverse effect associated with exposure to GV on the female serum sex hormonal levels in rats.

The RET proto-oncogene is the most well-known gene involved in medullary thyroid cancer (MTC). The associations between specific RET mutations and the age of onset and aggressiveness of MTC and the presence or absence of other endocrine neoplasms such as pheochromocytoma or hyperparathyroidism have been well documented. When a new mutation is identified in the RET gene, defining that mutation’s codon-specific risk level is important in the management of patients with MTC. Case Report. Here, we present the first report of a patient with a germline variant of Ala641Thr, in the transmembrane domain of the RET gene. A 37-year-old female presented with an anterior neck mass, which was confirmed to be MTC by biochemical tests and pathologic findings. The patient had no identifiable family history of MTC or multiple endocrine neoplasia syndromes. Histology revealed a single unilateral MTC lesion (21 mm × 16 mm) in the right thyroid lobe without cervical lymph node metastasis. Genetic testing revealed a germline Ala641Thr missense mutation in the RET gene. The RET gene variant was inherited by one of her children. Conclusion. Although this novel variant has unknown clinical significance at present, the causative role of this genetic variant in MTC pathogenesis could be clarified by further molecular structure-function studies and additional clinical cases showing a genotype-phenotype relationship.

Objective. The mechanisms underlying the development of diabetic neuropathic pain (NeP) are still unknown. The aim of the study was to evaluate painful diabetic neuropathy in Type II diabetic patients with Leeds Assessment of Neuropathic Symptoms and Signs Scale (LANSS), thermal and vibratory Quantitative Sensory Testing (QST) and, EMG supported Diabetic Neuropathy Score (DNS) and to evaluate the differences in patients with and without neuropathic pain. Methods. Eighty three Type II diabetic patients (26 males, 57 females) were investigated. Patients with pain were assessed by the LANSS pain scale and a score of ≥12 was classified as NeP. All patients underwent nerve conduction studies (NCS) to obtain EMG supported diabetic neuropathy score (DNS). Cold and warm sensation thresholds and cold pain and heat pain thresholds were obtained for evaluation of A-delta and C type fibers. Vibratory perception thresholds were recorded for evaluation of thickly myelinated fibers. Results. The percentage of NeP (LANSS score ≥12) was 15.7 %. QST revealed significantly lower cold detection, higher warm detection and higher heat pain thresholds at the feet in patients with NeP compared with patients without NeP. Although small fiber dysfunction has been revealed in all patients with NeP, the percentages of the presence of small fiber neuropathy and EMG supported diabetic neuropathy were not significantly different among patients with NeP and without NeP. Conclusions. We concluded that QST is a useful and a noninvasive tool to detect small fiber dysfunction in Type II diabetic patients. QST revealed increased severity of small fiber dysfunction in patients with NeP. Although small fiber neuropathy has been revealed in all Type II diabetic patients with neuropathic pain the absence of pain does not predict preserved small fiber function.