ACTA ENDOCRINOLOGICA (BUC)

Context. Persistent inflammation and impaired neovascularization are important contributors to the development of diabetic retinopathy (DR). Gene polymorphisms of adiponectin (APN) were demonstrated to have an important role on the plasma level and activity of adiponectin. APN has anti-inflammatory, anti-diabetic and anti-atherogenic properties. Toll-Like Receptor 4 (TLR4) is a critical mediator of innate immunity. Polymorphisms in TLR-4 gene were shown to be associated with impaired inflammatory response in diabetes. Objective. The aim of the study was to analyze the association of +276G>T variant of APN gene and Asp299Gly and Thr399Ile of TLR-4 gene variants in relationship with T2DM and DR in an Eastern European population group. Design. The distribution of the mutant alleles in 198 T2DM patients with DR and 200 non-T2DM controls was examined. Genomic DNA from T2DM patients and healthy controls genotyped through the use of PCR-RFPL assay. Results. Genotype and allele frequencies of the Asp299Gly and Thr399Ile polymorphisms differed between T2DM patients and non diabetic subjects (P<0.001). Moreover, the presence of the minor alleles of these polymorphisms were significantly identified as protective factors against T2DM, under a dominant model of Fisher’s exact test (χ2=4.988, phi=0.745, OR=0.767, 95% CI=0.602-0.867, P<0.001; respectively χ2=5.254, phi=0.820, OR=0.487, 95% CI=0.211- 0.648, P<0.001). Genotype analysis for the adiponectin 276G>T gene polymorphism yielded no significant association with T2DM, but revealed a borderline significance for the association with DR (χ2=5.632, phi=0.423, OR =1.101, 95% CI=0.887-1.203, P=0.009). Conclusions. We found an association between the TLR4 Asp299Gly and Thr399Ile polymorphisms and protection for DR. The APN genetic polymorphism is not associated with T2DM.

Introduction. The aim of this study is to appreciate the visual and endocrine outcome and to determine the factors that may influence the outcome of patients with pituitary apoplexy. Material and Methods. Between January 2006 and March 2012, 81 pituitary tumors were treated at “N. Oblu” Clinical Emergency Hospital in Iasi. Investigations of 22 of these cases met the criteria for pituitary apoplexy (17 cases of non-secreting pituitary adenomas and 5 cases of secreting tumors (4 GH secreting adenomas with acromegaly and 1 prolactinoma). Twenty one patients underwent surgery. The mean follow-up duration was 21 months. Results. Distribution between sexes was 1:1, with a mean age of 55.0 years. In all cases pituitary apoplexy emerged in patients with macroadenomas (>1cm). 77.27% presented decreased visual acuity, cranial nerve palsy was found in 45.45%. Visual acuity improved after surgical decompression best results being obtained in patients operated within first 7 days from onset (p=0.005); 80% recovered the CN palsy after surgery (p=0.005), with no relation to delay of surgery (p=0.26) or cavernous sinus invasion (0.095); 18.18% presented with pituitary deficiency and maintained it after surgery, the rate of new pituitary deficiency was 27.77% significantly higher in patients operated using craniotomies (p=0.001). Conclusions. Clinical apoplexy emerged in patients with macroadenomas unrelated to the tumor type. Early surgical decompression (< 7 days) and high dose corticoids represent the main therapeutic approach for obtaining good recovery of visual function. CN palsy has a good prognostic not being related to the delay of surgery. Pituitary dysfunction at presentation is irreversible and has a high occurrence after surgical decompression, requiring lifelong hormone replacement.

Introduction. Surgery has lost a lot of ground as the main therapy of most prolactinomas as it is clear from the current guidelines in most prolactin secreting adenomas, even in the setting of optic compression. However, we believe that surgery is still an important part in the treatment of this type of adenomas. This study is aimed to define what is the role of pituitary surgery in the current setup of prolactinoma management. Material and methods. In this retrospective, single-center study we analyzed 12 consecutive patients who underwent primary endoscopic transsphenoidal surgery for prolactinomas, between 2013 and 2022. Surgical indication, previous dopamine agonist (DA) treatment, remission rates, surgical complications, pituitary function and imagistic appearance are presented. Results. Of the 12 patients included, 4 had giant PRL and 8 macroadenomas, while 9 of them had previous DA treatment. The main surgical indication was pituitary apoplexy in 5 patients followed by CSF leak after DA treatment, 3 cases, and DA resistance in 3 cases. The main surgical complications were transitory diabetes insipidus in 7 cases. Normalization of prolactin levels was achieved in 2 patients. Conclusions. Surgical intervention should be strongly considered in all patients with neurologic symptoms referable to the lesion, resistance to medical therapy, other treatment failure or with complications after DA treatment. The endoscopic endonasal surgery offers good surgical outcomes with low rates of surgical complications and should remain an open option for specific cases.

Context. Neuroendocrine tumors are tumors developing from primitive cells in the intestinal walls, but can also affect the lungs, liver, pancreas, ovaries. Objective. We aim to describe the clinical, imagistic and biologic aspect of neuroendocrine tumors with different localizations and present the evolution, treatment options and prognosis. Design. Four patients either with previously known neuroendocrine tumors or with newly discovered tumors were studied. Subjects and methods. The first patient was diagnosed with primary liver carcinoid with pulmonary metastases by abdominal and thoracic CT scan, liver biopsy and determination of serologic markers. The second patient was diagnosed with primary lung neuroendocrine tumor using thoracoscopy biopsy and serologic markers The third patient was diagnosed with a large gastric neuroendocrine tumor with liver and spleen metastases. using CT scan, MRI and biopsy from the abdominal mass. The fourth patient was diagnosed with primary liver carcinoid using imagistic methods (CT scan) and liver biopsy. Results. The first patient died after 4 months due to the extent of the disease and comorbidities. The second patient had a good evolution, as the tumor was diagnosed in a localized stage. The third patient had a decreased survival due to the dimensions of the primary tumor and the multiple liver metastases which later caused obstructive jaundice requiring external biliary drainage. The fourth patient has had a good evolution, the tumor masses in the liver are being kept under control using transarterial chemoembolization. Conclusion. Neuroendocrine tumors are very versatile both in location and clinical aspect. The diagnosis requires imagistic methods but it is imperative to perform biopsy of the lesions with special histologic stains in order to be sure of the diagnosis.

Anthracyclines are used in breast cancer both in early and advanced stages and their recommendation together with taxanes, either concurrently or sequentially, is debatable and individualized by phenotype. Circulating biomarkers have already been introduced in clinical practice for metastatic disease monitoring. We questioned whether it might be a role for these markers in neoadjuvant and adjuvant settings too and a general review was conducted. CK18 and CTC were found predictive for anthracycline related response in preoperative setting. Soluble E-cadherin is promising, a retrospective analysis showing a direct correlation with clinical response. CEA, CA 15-3 and HER2 ECD are not of interest for their predictive role.

Endogenous Cushing’s syndrome is rare, with an incidence of 0.7–2.4 per a million people a year. Clinical presentation of Cushing syndrome can be pleomorphic, and establishing diagnosis can be difficult. Early recognition and rapid control of hypercortisolaemia are necessary to decrease morbidity and mortality in these patients. We report a series of 6 endogenous Cushing’s syndromes of different etiologies (4 Cushing’s disease and 2 adrenal Cushing’s syndrome) assessed in our endocrine department over a decade (2009-2019). In order to highlight the diversity of clinical forms, diagnostic tools and specific management of this condition we labelled each case suggestively: the typical Cushing’s disease, the Pseudo Cushing’s, the elusive Cushing’s disease, the mild autonomous cortisol hypersecretion, Cushing’s syndrome in pregnancy and Cushing’s disease with thromboembolism. We discussed their particularities which were revelatory for the diagnosis, such as dermatologic, cardiovascular, musculoskeletal, neuropsychiatric, or reproductive signs, reviewing literature for each manifestation. We also discuss the commonalities and differences in laboratory and imagistic findings. Therapeutic approach can also differ with respect to the particular condition of each patient and the multiple choices of therapy will be reviewed.

Background. There are few cases of methimazole induced hepatitis. The mechanism is probably related to the fact that it is a hepatic- metabolised drug. Objective. To demonstrate the fact that an acute cholestatic hepatitis can be triggered by methimazole. Design. While dealing with a major cholestatic syndrome with cytolysis, we performed the following steps: correct and complete history, serum detection of acute viral hepatitis, an autoimmune cause and finally liver biopsy. Subjects and Methods. We present the case of an 80 year old woman, with a history of hyperthyroidism, in treatment with Methimazole. After a month, the patient developed jaundice, for which she was admitted to our clinic. On admission she presented an important cholestatic syndrome, with elevated transaminases (5 times normal). Results. None of the laboratory tests indicated a possible viral infection or autoimmune disease. Abdominal ultrasound revealed no possible obstruction of the biliary system. Ultimately we performed a liver biopsy, which revealed inflammatory infiltration and cholestasis. Conclusion. We conclude that the hepatitis was induced by methimazole. Corticotherapy was initiated, with a relatively slow but favourable evolution. I131- Radiation therapy was elected for the treatment of hyperthyroidism.

Despite several attempts to establish the role of QUS in clinical practice, issues such as definition of osteoporosis based on QUS, screening strategy and therapy efficacy for patients identified by QUS as having high risk of fracture remain a matter of debate. The present study aimed to evaluate the diagnostic agreement between two QUS techniques (heel QUS and proximal phalanges QUS) and DXA in an unselected population of Romanian women aged 24- 80 years, as well as to offer cut-off levels for QUS to distinct between women with or without osteoporosis identified by DXA. In women measured by both DXA and calcaneus QUS (c- QUS), bone mineral density (BMD) moderately correlated with stiffness index (SI) (L1-L4: r=+0.51, p<0.001; femoral neck: r=+0.53, p<0.001; hip: r=+0.57, p<0.001), while in women examined by both DXA and phalanx QUS (ph-QUS), BMD was positively related to amplitude-dependent speed of sound (Ad-SoS) (L1-L4: r=+0.47, p<0.001; femoral neck: r=+0.50, p<0.001; hip: r=+0.38, p<0.001) and ultrasound bone profile index (UBPI) (L1-L4: r=+0.44, p<0.001; femoral neck: r=+0.50, p<0.001; hip: r=+0.38, p<0.001). At a T-score cutoff level of -2.5SD, the high specificity but low sensitivity suggests a low false positive rate of c-QUS as a diagnostic test; still, several patients with the disease may not be correctly diagnosed. At the same cut-off level, ph-QUS showed higher sensitivity and lower specificity. Diagnostic agreement between DXA and QUS was poor, with k-scores ranging from 0.33 to 0.39 for c-QUS and from 0.14 to 0.29 for ph-QUS, respectively. Lowering c-QUS T-score cutoff for lumbar spine osteoporosis screening to -1.5SD and ph-QUS T-score cut-off to -1.9SD, respectively, improved sensitivity and had a minor effect on diagnostic agreement. Regardless of the evaluated site, neither c-QUS nor ph-QUS does represent an adequate predictor of BMD in Romanian women. Changing the diagnostic T-score threshold from -2.5 SD to -1.5 SD and -1.9 SD in subjects examined by c-QUS or ph-QUS, respectively, is followed by improved sensitivity and diagnostic agreement in the identification of patients with vertebral osteoporosis. Cut-off values may allow QUS to be used as a screening tool for spine and femur osteoporosis.

Context and objective. The new insights in the pathogenesis of osteoarthritis (OA) reveal the implications of adipocytokines. This study aims to analyze the correlations between the serum value of adiponectin and the clinical rehabilitation effects in patients diagnosed with knee OA, admitted and treated in the complex balneal resort of Techirghiol lake. Subjects and methods. The prospective randomized clinical study included 23 patients in the study group, diagnosed with knee OA according to ACR criteria, and a matching control group of 23 subjects. Serum level of adiponectin (using ELISA technique), uric acid, triglycerides, cholesterol, HDLcholesterol and clinical response using a visual analog scale (VAS) were evaluated in all patients on their admission day and after 10 days of balneal treatment. Control group benefited from the same procedures except for cold mud therapy and mineral water baths. Results. Plasma adiponectin levels (23.73±6.44 ng/dL) were statistically higher (p<0.05) in the study group compared to the control group (18.15±6.49 ng/dL). The mean VAS in both groups was decreased (p<0.005) compared to the initial moment. Conclusions. Cold peloidotherapy combined with physical therapy and balneal factors induces serum adiponectin elevation and improves knee pain in OA. Therapeutic properties of Techirghiol mud still need further research.

Context. Foetal asphyxia, a frequent birth complication, detrimentally impacts the immature brain, resulting in neuronal damage, uncontrolled seizure activity and long-term neurological deficits. Oxytocin, a neurohormone mediating important materno-foetal interactions and parturition, has been previously suggested to modulate the immature brain’s excitability, playing a neuroprotective role. Our aim was to investigate the effects of exogenous oxytocin administration on seizure burden and acute brain injury in a perinatal model of asphyxia in rats. Animals and methods. Asphyxia was modelled by exposing immature rats to a 90-minute episode of low oxygen (9% O2) and high CO2 (20% CO2). Control rats were kept in ambient room-air for the same time interval. In a third group of experiments, oxytocin (0.02 UI/g body weight) was nasally administered 30 minutes before the asphyxia episode. Seizure burden was assessed by the cumulative number of loss of righting reflex (LRR) over a two-hour postexposure period. Acute brain injury was assessed through hippocampal S-100 beta, a biomarker of cellular injury, 24-hours after exposure. Results. Asphyxia increased both LRR and hippocampal S-100 beta protein compared to controls, and these effects were significantly reduced by oxytocin administration. Conclusion. Oxytocin treatment decreased both seizure burden and hippocampal injury, supporting a potential neuroprotective role for oxytocin in perinatal asphyxia.