ACTA ENDOCRINOLOGICA (BUC)

Background. Phytoestrogens are a heterogenic chemical category in which are\r\nincluded: isoflavones (genistein, daitzein, glycitein, biochianin A, formononetin, equol),\r\nsome lignans from cereals, cumestrans, some components of volatile oils (anetol, scareol),\r\nsome steroid saponins (diosgenin) and some phytosterols (beta-sitosterol, stigmasterol).\r\nGenistein is the most discussed phytoestrogenic substance, because it is very well\r\nrepresented in the botanical sources - especially in Fabaceae (Leguminosae) species, and\r\nmainly in soybeans.\r\nAim. The actual study evaluates the quantity of genistein in soybeans\r\nMethods. We used three extraction techniques: extraction with hydrolysis, extraction\r\nwithout hydrolysis and, finally, extraction with hydrolysis and clean-up and HPLC\r\nidentification.\r\nResults The experimental results indicated the content of genistein /g soya using the\r\nextraction techniques described.\r\nConclusions. Our study shows that extraction without hydrolysis followed by HPLC\r\nchromatographic method detects the genistein from vegetal sources and offer a good\r\nmethod, proposed by us for the drug industry.

We report a case of an infant with syndromic 46,XY disorder of sexual development. The subject was born at term, to unrelated parents with no relevant medical history. At birth the infant was assigned female. Physical examination showed dysmorphic features and ambiguous external genitalia. Cytogenetic analysis of cultured peripheral blood lymphocytes revealed a male karyotype. The result of the chromosomal investigation showing male genetic sex, together with the ambivalent aspect of the external genitalia (Prader IV) and gonads that are exclusively testes led to the diagnosis of 46,XY disorder of sexual development. The clinical management will help the child and the family deal effectively with this condition A multidisciplinary approach to this problem involving pediatricians, specialists in the field of endocrinology, genetics, surgery and psychiatry is necessary in order to reach a prompt and correct diagnosis and treatment.

Thyroid hormones play a crucial role in the regulation of the mitochondrial oxidative\r\nmetabolism. Hyperthyroidism caused by the acceleration of the energy metabolism leads to\r\nthe occurrence of cellular oxidative stress.\r\nThe aim is to evaluate the pro-oxidant / antioxidant balance and the effect of vitamin\r\nE supplementation in damage caused by the excessive administration of thyroid hormones.\r\nMaterials and Methods. White, male Wistar rats were used in the study. Thirty male\r\nWistar rats were divided into three groups (1:control group, 2:animals treated with LThyroxine\r\n10 &#956;g/animal/day for 30 days, 3:L-Thyroxin treated rats protected with vitamin\r\nE 10 mg/animal/day). Malondialdehyde (MDA), the marker of lipid peroxidation, carbonyl\r\nproteins, SH groups, glutathione (GSH) and superoxide dismutase (SOD) were determined\r\nfrom the serum, while MDA, carbonyl proteins, SH groups and GSH were determined from\r\nthe thyroid tissue homogenates.\r\nThe results showed increased levels of carbonyl proteins (1.31?0.33 nmol/mg protein,\r\np=0.0001) in serum in thyrotoxic group versus control, while MDA levels did not differ\r\nsignificantly from the control. Significantly low values of the SH groups, GSH and SOD were\r\nfound (p<0.001) in the plasma of Thyroxin treated rats. Vitamin E supplementation\r\nsignificantly increased plasma MDA levels in the Thyroxin treated group as compared with\r\nthe control group (p=0.01) and with the animals treated only with Thyroxin (p=0.04).\r\nCarbonyl protein levels in plasma of the hyperthyroid supplemented rats were also increased\r\nas compared to controls (p=0.0002). Antioxidant capacity markers in plasma of group 3 were\r\ndecreased compared with group 1. The marker of lipid peroxidation (MDA) significantly\r\ndecreased in thyroid homogenates of the group 2 as compared with group 1 (p=0.004).\r\nSignificantly high levels of the SH groups (p=0.0006) and low levels of GSH (p=0.0001) were\r\nfound in thyroid homogenates of the L-Thyroxin treated group as compared with controls.\r\nThese results suggest that experimental hyperthyroidism is accompanied with\r\nincreased oxidative stress and with the consumption of antioxidant enzymes in induced\r\noxidative aggressions. No protective effects of vitamin E on oxidative stress induced by\r\nexcessive administration of thyroid hormones were detected.

Context. Permanent hypocalcemia is a rare but significant complication of thyroid surgery Objective. The aim of this study was to identify predictive factors of hypocalcemia and hypoparathyroidism after thyroidectomy . Design. Study included 134 total patients submitted to thyroidectomy from two endocrine units (January 2015 – August 2016). Methods. We measured total serum calcium (sCa) and intact PTH (iPTH) on postoperative day one and 1 month after surgery. Results. 118 patients were women with F/M ratio of 7.3/1 and a mean age of 51.8 years. 64 patients were included in group A (iPTH <12 pg/mL) and 70 patients in group B (iPTH >12 pg/mL). sCa and hypocalcemia symptoms were correlated with iPTH, measured 24 hours after surgery. The cut-off value was for sCa 8.05 mg/dL with a sensitivity of 85.29% and a specificity of 88.0% and for iPTH 11.2 pg/mL, with a sensitivity of 82.3% and a specificity of 71.0%. SCa (< 8.05 mg/dL) was a predictive factor with a 99 (IC95%:12.86- 761.58) and iPTH (<11.2 pg/mL) with a 10.77 higher risk (CI95%: 3.83-30.30) to be associated with symptoms. Conclusion. SCa and iPTH represent good predictive factors of early and safe hospital discharge and can predict the risk of prolonged and permanent hypoparathyroidism.

Introduction. Pseudoxanthoma elasticum (PXE) is a generalized progressive connective tissue disorder which affects elastic fibers and has multiple systemic manifestations. Case presentation. The patient, female, 39 years old, who was diagnosed in the teenage years with PXE, was hospitalized presenting asymptomatic nephrocalcinosis and increased plasma parathyroid hormone (PTH) levels. The laboratory data revealed: normal levels of calcium and phosphorus in serum, very low serum level of 25-hydroxycholecalciferol [25(OH)D] and low serum level of 1,25-dihydroxycholecalciferol [1,25(OH)2D3]. It was considered that our patient presented secondary hyperparathyroidism. The patient received therapy with alphacalcidol 0.5 μg/day and after 6 months of therapy, the evaluation of the plasma PTH level showed a normal value associated with an improvement of the serum level of the 25(OH)D (27.5 μg/L). Conclusions. Our case is original in terms of association of pseudoxanthoma elasticum with nephrocalcinosis and elevated plasma levels of PTH, which requires a differential diagnosis between normocalcemic primary hyperparathyroidism and secondary hyperparathyroidism. The very low level of 25(OH)D in serum associated with low levels of 1,25 (OH)2 D3 and a normal level of phosphorus led the diagnosis towards secondary hyperparathyroidism.

Background. Virilizing syndrome in a postmenopausal woman is a concerning matter, raising the suspicion of androgen-secreting tumour. Case report. A 65 years old woman presented with severe virilization features evolving rapidly over 4 years, accompanied by: severe polyglobulia, severe hypertension, dyslipidemia and uterine fibromatosis compressing both ureters, producing first degree hydroureteronephrosis. The hormonal dosages showed very high levels of both testosterone (15.5 ng/mL) and estradiol (299 pg/mL), meanwhile DHEAS level was normal, indicating an ovarian pathological secretion. The endovaginal ultrasound and computed tomography scan revealed an enlarged right ovary of 5.5/2.8 cm. A total hysterectomy and bilateral oophorectomy was performed. Pathological examination confirmed the diagnosis of right ovarian hilum Leydig cell tumour. After surgery, the testosterone and estradiol levels normalized (concordant to the age and menopausal status), the virilizing syndrome progressively improved and polyglobulia, hypertension and dyslipidemia remitted showing their secondary etiology. Conclusion. We present a very rare case of secreting ovarian Leydig cell tumour in a postmenopausal woman, showing besides the virilizing syndrome, four unusual features: severe polyglobulia, due to androgen excess, severe hypertension and dyslipidemia, all remitted after tumour removal, and severe compressive uterine fibromatosis that was the consequence of the estrogen excess.

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.

Background. Androgen receptor (AR) plays a crucial role in the homeostasis of\r\nmammary tissue. In the present study we investigated the immunohistochemical expression\r\nof AR in breast cancer and its relationships with clinico-pathological parameters of\r\nprognosis, hormone receptors status and HER2 overexpression.\r\nMethods. There were investigated 124 patients admitted with invasive breast cancer,\r\nand from these 48 had lymph node metastasis and 9 had distant metastasis. In all specimens\r\nthere were performed immunohistochemical staining for AR, estrogen receptors (ER),\r\nprogesterone receptor (PR) and HER2. Results were correlated with pathological findings\r\nand the molecular profile of the tumors.\r\nResults. The immunohistochemical expression for AR was found in 92 cases. A\r\nsignificant correlation was found between AR expression and pathological type, grade and\r\nlymph node status, but not with distant metastasis and the expression of ER, PR and HER2.\r\nAn inverse correlation was found between AR expression and triple negative breast cancers.\r\nConclusion. Our data suggest that AR is an individual factor of prognosis and is a\r\nuseful marker to stratify patients with triple negative tumors. AR could be a potential target\r\nfor specific therapy in individuals excluded from the conventional hormone therapy.

Background. Postoperative hypocalcemia after thyroid surgery has a high prevalence ( 16-55% in different series). Incidental parathyroidectomy (IP) is a less discussed complication of thyroidectomy with consequences not properly defined. The aim of our study was to find incidence, risk factors and how to prevent IP. Methods. Extensive search of English literature publications via PubMed was performed and 73 papers from 1980 to 2017 were analysed using the GRADE system/classification, quality of evidence was classified as “strong” when the result is highly unlikely to change existing recommendation and “weak” when opposite. Results. Incidence of IP is 3.7-24.9%, while prevalence of permanent hypoparathyroidism is less frequent 6-12%. Direct relation between IP and hypoparathyroidism/ hypocalcemia remains controversial. Female patients, ectopic parathyroids, small thyroids, Graves’, malignancy, redo surgeries and total thyroidectomy favour IP. Routine visualization of parathyroids, new hemostatic devices, magnifying instruments and fluorescence can prevent incidental removal of parathyroids. Incidence of IP during videoassisted or robotic thyroidectomies was similar to open procedures. High volume, experienced and younger surgeons have lower complication rates (including hypoparathyroidism). Conclusions. Incidental parathyroidectomy is more frequent than we might have expected. It should be avoided and parathyroid glands should be kept in situ. Majority of studies are retrospective (low degree of evidence according to previous mentioned GRADE classification) and further meta-analysis or randomized control studies are welcome in order to define the impact of incidental removal of parathyroids on postoperative outcome.

Background. The concept of NE differentiation in prostate carcinoma has two major aspects: prostate tumors with\r\nprimary NE differentiation and NE differentiation occurred during hormonal therapy for prostate adenocarcinoma, with\r\nthe extreme case of tumor dedifferentiation into a NE hormone resistant carcinoma.\r\nMaterial and method. The patient, 62 years old, with a history of poorly differentiated prostate adenocarcinoma,\r\nhormonally treated with the decrease and then constant maintenance of serum PSA level to 0.01 ng/mL was admitted in the hospital, 8 years after prostate tumor diagnosis, and 3 years after ceasing of hormone therapy, with multiple bone and liver metastases of unknown primary source.\r\nResults. The serum levels of CgA, NSE, CEA, CA19.9, serotonin were elevated. The histopathological examination\r\nof the needle biopsy fragment from a liver metastatic lesion revealed small cell neuroendocrine carcinoma. Despite the\r\nprompt chemotherapy, the disease has progressed, with the occurrence of brain metastases and the patient?s death\r\n6 months after detection of the metastatic disease.\r\nConclusions. The present case confirms the diagnostic difficulties in llymetastatic undifferentiated small cells\r\ntumors, and on the other hand, draws attention to the possibility of NE dedifferentiation as a result of hormone\r\ndeprivation in patients with prostate cancer.