ACTA ENDOCRINOLOGICA (BUC)

Background. Thyroid nodules stiffness may predict thyroid malignancy. Objectives. The purpose of the study was to investigate the diagnostic value, interobserver agreement and reliability of real time ultrasound elastography (USE) when assessing solid thyroid nodules. Design. A prospective, observational study in a tertiary center. Subjects and Methods. In 49 patients scheduled for thyroidectomy, a senior radiologist and two radiologists in training independently assessed 81 solid thyroid nodules with USE using a 6600 Hitachi machine. Pathology results were used as a reference standard. Nodule stiffness was evaluated using the Asteria scoring system. The diagnostic ability of the elastography scores for the assessment of the thyroid solid nodules was evaluated using AUROC (area under the receiver operating characteristic curve) analysis. The Cohen’s kappa (k) values were used for interobserver agreement evaluation and interclass correlation coefficient (ICC) was used as a measure of reliability. Results. Pathology results revealed 20 papillary carcinomas and 61 benign nodules. The elastography identification of malignant nodules by the senior radiologist was performed with an AUROC of 0.84 [95% Confidence interval (CI) 0.74-0.91], with Sensitivity= 100%, and Specificity= 68.85%. When performed by ultrasound operators in training, the diagnostic performance slightly decreased. With no statistically significant difference between the diagnostic performance of the three readers, USE demonstrated good inter-observer agreement and good reliability (ICC= 0.81). Conclusion. USE may be an accurate tool of assessment for solid thyroid nodules, identifying with high sensitivity the malignant ones, particularly micronodules. USE is reproducible and reliable when used both by experienced operators and medical professionals in training.

Objective. To study the effect of diethylhexyl phthalate (DEHP) alone or in combination with genistein (GEN) on the reproductive system of offspring rats, focus on the induction of reproductive outcomes. Method. 180 Wistar rats were divided in 6 groups (30 animals per group): DEHP 250 mg/kg/day group, DEHP 1000 mg/kg/day group, DEHP 2500 mg/kg/day group treated with DEHP 2500 mg/kg/day, DEHP (2500 mg/kg) + GEN (50 mg/kg) group, DEHP (2500 mg/kg) + GEN (500 mg/kg) group and control group treated with the same quantity of corn oil. The differences in sperm quality and reproductive organs were observed. Results. After DEHP administration we observed an increase in rat’s abestrus, metaestrus and all estrus cycle (P < 0.05), a decrease in rat testicle’s organ coefficient and relative energy of testis Sertoli cells and an increase in the early, late and total apoptotic rate of testicular Sertoli cells in a dose dependent manner (P < 0.05). When combine DEHP with GEN the sperm density, sperm quality, the cell activity rate and testis tissue’s changes will decrease compared with the group that receive only DEHP in a dose dependent manner. Conclusion. DEHP exposure induces cryptorchidism in offspring rats and this is aggravated by adding GEN.

Context. Retinal microvascular dysfunction differs in macular edema lesions in the two eyes of the same patient with diabetic retinopathy. Objective. To evaluate the relationship between central macular thickness (CMT) and metabolic/systemic factors including anthropometric and laboratory findings, in patients with regressed diabetic retinopathy and a history of pars plana vitrectomy (PPV) combined with internal limiting membrane peeling in one eye. Subjects and Methods. Forty-two eyes with PPV and the same patients’ fellow 42 eyes (without PPV) included this study. Fasting blood samples of these 42 diabetics were collected to study adiponectin levels and other routine parameters. Results. The average hemoglobinA1c value was 7.3±1.3%. CMT of the vitrectomized eyes were significantly correlated with atherogenic index of plasma, total cholesterol, low density lipoprotein cholesterol and uric acid (UA). On the other hand, CMT of the nonvitrectomized fellow eyes significantly correlated with glucose levels and diabetes duration. Adiponectin, adiponectin/body mass index, adiponectin/fibrinogen were found significantly higher in the subgroup with CMT≥300µm in the vitrectomized eyes (P<0.05). UA levels were higher in the subgroup with CMT≥300µm in the fellow (nonvitrectomized) eyes (P<0.05). Conclusions. Although there was no relationship between CMT and hemoglobinA1c values, CMT seemed to be affected by atherogenicity, prooxidant chemical alterations in the course of inflammation, so determination of adiponectin and UA levels may be suggested before surgery to predict the atherosclerotic damage and the postoperative CMT value. Vitrectomy performed at the proper time may be helpful in metabolic remodeling process of the retinal tissue along with life style changes, well control of diabetes, and intraocular treatments.

This study evaluates the differences of radiotherapy in patients with pituitary tumors, in relation to gonadotropin immunoreactivit.\r\nDesign. It is a longitudinal, retrospective study of 117 patients submitted to pituitary surgery and high voltage radiotherapy. The excised tumors were 70 non-functioning adenomas (NFA) and 47 GH-secreting adenomas producing active acromegaly (ACM). They were evaluated before and after pituitary surgery, before radiotherapy as baseline, then at 3 different intervals at 0 - 2, 2 - 5 and > 5 years after baseline.\r\nMethods and patients. Computer tomography was used for measuring the tumor size and specific immunoassays were used for FSH, LH and nadir GH during 75 g oral glucose load. Immunohistochemistry (IHC) was performed with avidin-biotine method. High voltage conformational radiotherapy used a linear accelerator of 10 meV, with a 50 Gy on target tumor. For statistics, student&#8217; t test was used. Data before surgery (tumor volume and hormonal sexretion) were available in 70 unselected patients (31 NFA and 39 ACM from the above group). Postsurgery we defined following groups: NFA-A1 exposed to radiotherapy (n=21) and NFA-C1 unexposed to radiotherapy (n=22); ACM-A2 exposed to radiotherapy (n=20) and ACM-C2 unexposed to radiotherapy (n=10).\r\nResults. Immunohistochemistry for NFA showed 27 immunopositive for FSH or/and LH (GD+) and 40 immunonegative for FSH and LH (GD-), 3 undetermined, while for ACM were 12 GD+, 33 GD-, 2 undetermined. Immunohistochemistry data on defined groups was as follows: NFA-A1 (n=21: 12 GD+, 9 GD-) and NFA-C1 (n=22: 6 GD+, 16 GD-); ACM-A2 (n=20: 4 GD+, 16 GD-) and ACM-C2 (n=10: 3 GD+, 7 GD-). In patients with NFA presented before therapy, there are not significant differences of tumor sizes or of the levels of FSH/LH between GD+ and GD- adenomas. In ACM, before any therapy, the GD+ patients showed a significantly higher FSH levels (20.7+11.4 U/L, n=6) than GD- patients (FSH 6.6+1.6 U/L, n=22, p< 0.05) and a nonsignificant lower serum GH levels (15.1+3.5 ng/mL, n=8 versus 33.5+8.9 ng/mL, n=30 p=0.06), although the tumor size was similar between the two groups. Radiotherapy upon NFA: GD+ adenomas did not decrease their volume after radiotherapy (cranio-caudal diameter 1.63+0.79 cm, before and 1.54+0.68 cm at 2 - 5 years post-radiotherapy n=6, p= NS), in contrast with GD- tumors in which a slightly, but significant decrement in volume could be demonstrated (from 2.79+0.53 cm to 2.43+0.31 cm at 2 - 5 years, n=5, p= 0.01). Radiotherapy in ACM resulted in a decrement of serum GH level and tumor size, as compared with the control group without radiotherapy. The effect was maximal at the interval of 2-5 years. The ACM, GD- tend to respond better to radiotherapy, (i.e. GH levels decreased from 15.1+5.4 to 6.6+2.4 ng/ml at 2-5 years, p=0.05), while in patients with ACM, GD+ the GH level did not show a significant decrease (serum GH was 7.3+3.3 ng/ml before and 5.1+4 ng/mL at 2-5 years post-radiotherapy, p = NS). The CC diameter of GD- decreased from 1.1+0.3 to 0.7+0.2 at 2-5 years, p=.059, while in GD+: from 1.64+0.4 to 1.2+0.3 ng/mL at 2-5 years, p = NS.\r\nConclusion. Pituitary adenomas, both NFA and ACM that contain gonadotropin immunoreactive cells tend to be more radioresistant than those without gonadotroph cells.

Background: Salivary monitoring of hormone levels has many advantages over the more conventional serum/plasma analysis. Salivary free metanephrines (MN) and normetanephrines (NMN) could precise biochemical diagnosis of pheochromocytoma (PHEO) as an alternative to plasma metabolites.\r\nSubjects and methods: The prospective case-control study included a group of 30 patients confirmed with PHEO an age-matched control group of 70 normotensive subjects. The PHEO diagnosis was suspected on clinical ground and confirmed by imaging studies and classical neuroendocrine markers. Free plasma and salivary NMN and MN were assayed using enzyme immunoassay for both metabolites.\r\nResults: In tumor cases all metabolites were increased. As expected, values for all 4 parameters (mean?SEM) differed significantly in tumor group vs. normal group: free plasma\r\nnormetanephrines (NMNp): 1514.16 ? 282.97 pg/mL vs 47.82?2.52 pg/mL; free salivary normetanephrines (NMNs):\r\n663.63?168.47 pg/mL vs 44.98? 2.47 pg/mL; free plasma metanephrines (MNp): 445.20 ? 99.92 pg/mL vs 18.87?1.03\r\npg/mL; free salivary metanephrines (MNs):206.60?91.48 pg/mL vs 14.47?0.72 pg/mL with significant correlations in all\r\n100 subjects. Passing & Bablok regression showed no significant deviation from linearity in Elisa assay of NMNs vs NMNp; a significant deviation from linearity existed\r\nin Elisa assay of MNs vs MNp. Cut-off values, sensitivity and specificity for all 4 parameters were calculated by ROC\r\nanalysis. Plasma and salivary normetanephrines proved similar sensitivity (100%) and specificity (100%). Pairwise\r\ncomparison of ROC curves areas showed no significant differences between NMNp vs NMNs and MNp vs MNs. Ten cases were investigated post-surgery. All 4 parameters\r\nshowed no significant differences vs. control group.\r\nConclusions: Salivary free normetanephrines could be used as a nonstressful marker for diagnosis purpose in pheochromocytoma proving similar sensitivity and specificity as plasma free normetanephrines.

Background. If not diagnosed at birth, congenital hypothyroidism (CH) can cause deleterious, irreversible neurodevelopmental sequels. The importance of thyroid newborn screening (NBS) is therefore well established. Objective. To evaluate the efficacy of NBS for CH in North-East Romania. Methods. Retrospective, descriptive study involving 271662 newborns screened between 2010 and 2019 for CH and phenylketonuria in maternities from six Romanian NorthEastern counties by measuring neonatal TSH (neoTSH) in the whole blood extracted from the heel between days 3 and 5 after birth. Values found higher than a cut-off level of 10 mIU/L were followed by serum evaluation of TSH and fT4 for the confirmation of CH. Thyroid ultrasound was further performed at children found with CH. Results. NeoTSH was found elevated in 417 newborns, but CH was subsequently confirmed in only 57 cases (1/4766 newborns). Mean age at the time when diagnosis was communicated was of 37.2 ± 15 days (between 9 and 157 days). Mean age when therapy was started was of 44.2 ± 17.9 days (between 13 and 160 days) with a mean delay of one week from diagnosis (between 0 and 62 days). Thyroid ultrasound revealed athyreosis in only 3 cases, atrophic thyroid gland in other 10 cases, whereas the thyroid was described as present in the remnant 44 cases. The number of first year follow-up visits greatly varied from 0 to 5, with an average of 2. Conclusions. NBS allowed rapid diagnosis of CH in North East Romania. The communication of diagnosis to families and therapy onset were however often delayed. Diagnosis and therapy onset before the age of two weeks, as well as a tighter follow-up should be assured by the healthcare system. Etiological diagnosis should be more accurate, for a better prognosis of disease severity, as well as the possibility of genetic advice in selected cases.

Introduction: During the past thirty years bone biopsy has been used as an invasive diagnostic and research investigation of bone structure and metabolism. Quantitative bone histomorphometry parameters offer information on both bone mass and bone quality.\r\nObjectives: This study aimed to establish the value of routine qualitative bone biopsy evaluation in subjects with unexplained primary osteoporosis. Patients in whom low bone mineral density was not adequately explained by risk factors or patients in whom therapy\r\nwas not followed by BMD changes according to evidence-based data on treatment of osteoporosis were referred to bone biopsy. One-hundred seventy patients (73 men and 97 women), aged 54.29?0.95 years, were included in the study. The diagnosis was based on clinical data, lumbar spine and hip dual X-ray absorptiometry (DXA) evaluation and routine laboratory measurements. Bone biopsy was performed by horizontal approach, using an electric drill. Qualitative bone biopsy evaluation was performed in one single department by trained pathologists. Quantitative bone histology assessment (histomorphometry) was not available.\r\nResults: Of the 170 bone samples, secondary causes of low bone mineral density were identified in 19 patients (mastocytosis, multiple myeloma, myeloproliferative syndrome, sarcoidosis and osteomalacia). In 21 subjects with osteoporosis as defined by WHO criteria qualitative histological evaluation found no pathological changes. Accelerated bone resorption as expressed by the daily urinary levels of deoxypyridinoline (D-Pyr) and longterm sodium fluoride therapy were associated with relevant osteoidosis as assessed by qualitative evaluation of bone samples. Bone biopsy changes were not related to serum thyroid hormone, parathyroid hormone or 25-hydroxyvitamin D3 levels.\r\nConclusions: Qualitative bone biopsy evaluation may offer valuable information in the diagnosis of metabolic bone diseases in subjects with unexplained causes of low bone mineral density or in non-responders to anti-fracture agents. Despite of lack of quantitative information on bone mass and the degree of mineralization of bone tissue, few patients with osteoporosis may benefit from this diagnostic routine procedure.

Detecting the primary tumours in carcinoid malignancies is a critical challenge. We report the case of a 25 year old male patient with a typical clinical carcinoid syndrome. Metastatic carcinoid malignancy was easily diagnosed by very high plasma chromogranin, plasma serotonin and urinary 5-Hydroxy-Indol Acetic Acid levels, and the detection of multiple liver metastases by ultrasound. Somatostatin receptor scintigraphy (SRS) failed to detect the primary lesion, as did upper and lower gastrointestinal (GI) tract endoscopy, bronchoscopy, total body CT, MRI, and GI video tract endoscopy; only F-DOPA PET-scan ascertained and accurately localized the primary ileal tumor. Surgery confirmed the localisation, and pathology revealed a 3 cm highly differentiated carcinoid tumor with low proliferation grade (Ki67<2). The therapy with short and long acting somatostatin analogues was started before surgery and continued after surgical intervention. There was a regression of the clinical carcinoid syndrome and a numerical involution of liver metastases, but the levels of chromogranin A and serotonin remained elevated. Other therapeutical option should be discussed.

Published data sustain the involvement of diet on pathogenesis of immune-mediated diseases.\r\nAim. To determine if the high fat diet (HFD), in the absence of obesity, could modulate the altered pulmonary arteries\r\nreactivity associated to allergic lung diseases.\r\nMaterials and Methods. Obese resistant rats were divided into 2 groups: standard chow diet and HFD. Randomly chosen rats from both groups were sensitized against ovalbumin. The histological aspect and reactivity of pulmonary arteries were comparatively assessed. Taking into account the involvement of adipokines on obesity associated vascular reactivity alteration we also studied the vasomotor effects of few adipokines on pulmonary vessels.\r\nResults. Lung histological examination revealed that HFD aggravated the remodelling of pulmonary arteries and\r\ninflammation of lung parenchyma. The HFD amplified the phenylephrine - induced contractions. Angiotensinogen amplified and apelin inhibited the Phe contractile effects on sensitized HFD fed rats.\r\nConclusion.These effects could be at least mediated, by both the alteration of adipokines vasomotor effects and\r\ninflammation associated to pulmonary allergic disease.

Prader Willi syndrome is a complex disease caused by the lack of expression of paternally inherited imprinted genes on chromosome 15q11.2-q13. Typical clinical features are hypotonia and feeding difficulties in infancy, followed by hyperphagia and progressive obesity, distinctive dysmorphic features, intellectual disability and behavioural problems. In this paper we present clinical, metabolic and endocrine aspects in five genetically confirmed patients with PWS. Data about thyroid dysfunction, GH deficiency, adrenal insufficiency, and LH/FSH disorder caused by hypothalamic dysfunction in PWS were collected and analyzed. Cardiovascular metabolic profile was also assessed, based on plasma lipids, blood glucose, HbA1c values, and measurements of body weight and blood pressure. Clinical features present in all our patients were marked hypotonia and feeding difficulties in infancy, obesity, dysmorphic face, viscous saliva, small hands and feet, intellectual disability and characteristic behaviour. Adrenal function appeared to be normal in all patients; mild hypothyroidism was identified in one patient; sex development abnormalities were present in three patients and GH levels were within lower normal range in all patients. GH therapy was initiated in two patients, both with unevolutive skeletal anomalies, with good results and no side-effects. Only one patient had a normal lipid profile, underlying the importance of early detection and treatment of cardiovascular risk factors. Our study also illustrates the challenges raised by some features very rarely described in PWS (Blount disease and multiple allergies).