ACTA ENDOCRINOLOGICA (BUC)

Context. Aromatase is a key enzyme in local estrogen production by androgen conversion, especially in women post-menopause. There have been controversies concerning aromatase localization in breast carcinomas and its association with current histopathological variables. Material and Methods. Using polyclonal antibody immunohistochemistry we assessed (by intensity and percentage scores) the immunolocalization of aromatase in 70 tissue samples, and described particularities within the molecular subtypes of breast cancer. Results. Aromatase was found in all tissue compartments: tumor (95.7%), stroma (58.6%) and adipose tissue (94.3%). Aromatase expression in tumor cells correlated inversely with tumor grading (p=-0.361, p=0.027), and positively with estrogen receptor status (ER, p=0.143, p<0.001). Dividing the study group by intrinsic subtypes, a strongly inversely association between tumor aromatase and grading (p=-0.486, p<0.001), and between stromal aromatase and Ki67-index (p=-0.448, p=0.048) was observed in luminal A breast cancer. Tumor aromatase and ER percentage scores had stronger correlations in luminal B HER2 negative (p=0.632, p=0.002), and positive (p=0.324, p=0.026) tumors. In contrast, in triple negative tumors, a positive association stromal aromatase and Ki67 index (p=- 0.359, p=0.007) was observed. Conclusion. Local aromatase was linked to better tumor differentiation and proliferation in luminal breast subtypes, and not in triple negative cases, suggesting a potential prognostic role of aromatase in breast carcinomas.

Background. In most type 1 and mixed forms of amiodarone-induced thyrotoxicosis (AIT), after restoration of euthyroidism and whether amiodarone can be withdrawn, an ablative therapy (thyroidectomy or radioiodine) is required. Radioiodine ablation of the thyroid was reported to prevent recurrence of AIT after amiodarone reintroduction.\r\nAims. To assess the efficacy and safety of radioiodine treatment in type 1 and mixed forms of AIT.\r\nPatients and methods. 9 patients (6M/3F) with type 1 and mixed form of AIT, mean age 62.2 ? 13.3 years (range: 50-85 years), pretreated with methimazole, received radioiodine treatment. The underlying thyroid disease was Graves disease (n= 5), toxic multinodular goiter (n= 3) and toxic adenoma (n=1). TSH, total T3, total T4, free T4, TPOAb were measured by radioimmunoassay; radioiodine uptake, thyroid ultrasonography, color flow Doppler ultrasonography were performed.\r\nResults. Multiple radioiodine doses were required in 4 out of 9 patients. Pretreatment 24 hours radioiodine uptake exceeded 10% in 12 out of 16 doses. Mean cumulative dose was 23.17 ? 17.48 mCi 131I (range 6-50 mCi). The period between amiodarone withdrawal and 131I administration was 11.72 ? 12.45 months (range: 2-41 months). Mean cumulative 131I dose was higher in AIT due to toxic multinodular goiter and toxic adenoma (30.25 ? 20.09, range: 11-50 mCi) versus Graves disease (17.5 ? 14.76, range: 6.5-40 mCi). In one patient with toxic adenoma, thyroidectomy was contraindicated due to a comorbidity-central core disease - a non-progressive congenital myopathy, associated with an increased risk for malignant hyperthermia. Hypothyroidism occurred in all patients but one (euthyroid), within 14 ? 3 months (range: 5-27) after the first radioiodine dose. Sinus rhythm was restored in 3 out of 5 patients. One case of radiation thyroiditis occurred after a single 6.5 mCi 131I dose.\r\nConclusion. Radioiodine ablation therapy is an effective and safe alternative in patients with type 1 and mixed forms of amiodarone-induced thyrotoxicosis. Since amiodarone should need sometimes to be restarted, post radioiodine hypothyroidism should be viewed as a goal rather than a complication.

Background. Idiopathic hypercalciuria is a risk factor for nephrolithiasis. Both renal stones and hypercalciuria are associated with lower bone mineral density (BMD), but the relationship between these modifications is not completely understood. Aims. To evaluate some metabolic particularities possibly related to relapsing nephrolithiasis (RN) in young male patients. Methods. We performed a crosssectional study including a group of 30 young male patients with RN and a group of 30 healthy, age and BMI (body mass index) matched controls (CTR). We evaluated calcium and phosphate metabolism, bone remodeling markers alkaline phosphatase (AP) and osteocalcin in serum and 24-hour urine samples, and lumbar and hip BMD. Results. We observed higher values of serum calcium (P<0.05) and 24 hour urinary calcium (P<0.001) in the RN group. Parathyroid hormone (PTH) and AP were also higher in the RN group (P<0.01), whereas serum 25OH-D3 was lower (P<0.01). BMD, T and Z scores were lower in the RN group in both the lumbar (P<0.01) and hip (P<0.05) regions. Conclusions. Young male patients with hypercalciuric RN have lower BMD and higher bone turnover. Higher PTH levels related to vitamin D deficiency may contribute to bone demineralization in certain cases.

Context. Endothelial and vascular muscle dysfunctions are incriminated in the pathogenesis of diabetes mellitus (DM)-related vascular complications. However, the time-course of these changes remains unclear. Objective. We aimed to assess the time-dependency of changes that occur in vascular reactivity in aortic rings of rats with streptozotocin (STZ)-induced DM with shortversus long-term DM durations and in age-matched controls. Design. Wistar rats were assigned to young control (n=6), young DM (n=9), aging control (n=6), and aging DM (n=8) groups. DM was induced at 11 weeks of age using STZ (60 mg/kg, i.p.). Methods. At the end of the study (15 weeks of age for young controls and diabetics and 38 weeks of age for aging controls and diabetics), KCl - and phenylephrineinduced vascular contractility, and acetylcholine - and sodium nitroprusside (NTP)-induced relaxation were studied to assess endothelium-dependent and –independent vasodilation. Results. Young and aging controls presented similar vascular reactivity parameters. Acetylcholineinduced vasodilation was reduced in both young and aging diabetics compared to age-matched controls. Furthermore, acetylcholine-induced relaxation was significantly lower in aging compared to young diabetics. Meanwhile, NTPinduced vasodilation and both KCl- and phenylephrineinduced vasoconstriction were only diminished in aging diabetics. Conclusions. These results suggest that endothelial dysfunction is an early, progressive, event in the large arteries of diabetic rats that precedes the dysfunction of vessel musculature. The lack of any change in aortic reactivity in aging controls indicates that the changes observed in aging diabetics are probably due to prolonged, severe hyperglycemia, with a negligible participation, if any, of the advancing age.

The prerequisite for developing methods for type 1 diabetes mellitus prevention is to know its pathogenic mechanisms. The aim of this work was to characterize a group of children with type 1 diabetes mellitus regarding pancreatic antibody positivity and fasting C peptide concentrations. The study group enrolled 117 children, 61 boys (52.1%), mean age 12.7?3.1 years. Islet cell antibodies, glutamic acid decarboxylase antibodies (GADA), IA-2 antibodies (IA-2A) and fasting C peptide were measured. Sensitivity for GADA and IA-2A tests was 85% and 75%, respectively. Specificity for the tests was 87.1% and 98%, respectively. The threshold for pancreatic antibody positivity was considered the 97.5th percentile, and normal values for fasting C peptide were between the 5th and 95th percentiles from a control group (n=73), matched for age and gender. Thirty-nine patients (33.3%) were positive for 1 antibody, 10 (8.6%) were positive for 2 and 2 (1.7%) were positive for all 3 antibodies. The positivity for pancreatic antibodies and for islet cell antibodies was significantly lower in patients with diabetes duration>2 years, compared with the rest: 32% vs. 52.2% (p=0.03) and 6% vs. 20.9% (p=0.03), respectively. Mean fasting C peptide and the percentage of patients with normal C peptide decreased significantly one year after the diagnosis of diabetes: 0.20?0.40 ng/ml vs. 0.44?0.57 ng/ml (p=0.03) and 9.5% vs. 27.3% (p=0.02), respectively. In conclusion, in children with type 1 diabetes mellitus, pancreatic autoimmunity is more intense in the first two years of the disease and insulin secretion decreases one year after the diagnosis.

Gastrointestinal effects of estrogens are emerging as an important topic in colorectal cancer management. Current research demonstrated the link between inflammation and this malignancy, so important estrogen dependent mediators of the inflammatory response have been identified. Radioresistance and chemoresistance still represent an important cause of therapeutic failure in colorectal cancer and lead to further studies of colorectal carcinogenesis and predictive markers.

Context. Non-psychogenic polydipsia-induced hyponatremia is a rare clinical finding. The effects of severe hyponatremia on the electrical activity of the heart in this setting are far from clear. Case report. Resting ECG and 24-h ambulatory ECG monitoring performed in an 80-year-old hypertensive female accusing nonspecific symptoms of confusion, lethargy, disorientation, nausea, and palpitations, demonstrated significant intraatrial and atrioventricular conduction disorders and numerous atrial tachyarrhythmia episodes. Laboratory analysis revealed severe hyponatremia (108 mEq/L) as only significant disorder. Extensive endocrine, neurological, cardiology, and pulmonary examinations excluded the most common causes of hyponatremia, including the inappropriate antidiuretic hormone secretion syndrome. Careful history revealed excessive voluntary water intake of up to 6 L/day and low sodium intake, associated with long-term thiazidelike diuretic treatment. Correction of sodium levels was associated with complete resolution of both atrial arrhythmias and conduction disorders. Conclusions. This report presents the first case of severe hyponatremia caused by combined non-psychogenic polydipsia and thiazide-like diuretic use complicated with reversible cardiac conduction disorders and atrial arrhythmias. The close temporal relationship between the fully reversible cardiac electric abnormalities and severe hyponatremia strongly indicates hyponatremia as key feature in the pathogenesis of these electric abnormalities.

Recent studies suggest that osteopontin (OPN) could be used as an early marker for the diagnosis of bone disorders. Considering the contradictory opinions in the literature, the objective of this systematic review is to analyse the current information regarding the relationship between OPN and bone mineral density (BMD), which represents an important process in the development of osteoporosis. We performed a literature search of clinical trials using the PubMed database, published between 1999-2020, and identified 7 studies that were eligible for analysis. The eligibility criteria were based on studies that analysed the relationship between osteopontin and bone mineral density on human subjects. Conclusion: serum OPN levels might be used as a biomarker of the early diagnosis of osteoporosis in postmenopausal women, with or without osteoporotic vertebral fractures.