ACTA ENDOCRINOLOGICA (BUC)

We aim to describe a patient diagnosed with a rare and aggressive metastatic pattern of an ileal neuroendocrine tumor (NET). A 53-year-old male patient was referred to our cancer care center following the diagnosis of an ileal NET for further evaluation. As part of the initial diagnostic workup, 68Ga-DOTATOC positron emission tomography/computed tomography was conducted. The scan revealed a fulminant metastatic pattern of somatostatin-positive lesions affecting the axial and peripheral skeleton, liver, and a few lesions involving the brain leptomeninges and right extra-orbital eye muscle. Despite the prompt diagnosis and systematic therapeutic approach offered according to institutional guidelines, the patient did not achieve an optimal clinical response, resulting in his demise 18 months after his initial diagnosis. This case is shared with the primary aim of raising awareness of such an unreported aggressive metastatic pattern and encouraging further clinical investigations for patients with similar aggressive metastatic patterns to achieve optimal therapy and care.

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Context. Pancreatic neuroendocrine tumours (PanNETs) are rare pancreatic neoplasms. PanNETs can be treated by multimodal approach including surgery, locoregional and systemic therapy. Objective. The aim of the present study is to evaluate predictive factors of overall survival in patients with PanNETs surgically treated at a single center. Subjects and methods. The study group consisted of 120 patients with PanNETs who had undergone surgery at the Center of Digestive Diseases and Liver Transplantation of Fundeni Clinical Institute, Bucharest, Romania. Surgical resection of the primary tumor was performed in 110 patients. Results. Tumor size > 2 cm (p=0.048) (90% CI) lymph node involvement (p=0.048), ENET grade (p<0.001), distant metastases (p<0.001), Ki 67 index (<2%, 2-5%, 5-10%, 10-20%, >20%) (p<0.001) were identified as significant prognostic factors for OS on univariate analysis. Using multivariate Cox proportional regression model we found that distant metastases and Ki 67 index were independent risk factors for the survival outcome. Conclusions. Surgery with curative intent should be considered in all cases if clinically appropriate and technically feasible. High grade (Ki67 index ≥10%) tumours were associated with a 2- fold increase in risk of death as compared to those with a Ki67 <10%

Context. Alimentary supplements may have beneficial effects on retinal microvasculature in diabetic patients. Objective and Design. State-of-the-art imaging techniques were used to assess retinal microcirculation in diabetic patients in an observational study before and after 3 months treatment with a multinutrient complex including resveratrol, vitamins D3, C, E, essential fatty acids, trace elements (zinc and copper) and macular pigments (lutein and zeaxanthin)-Resvega. Subjects and Methods. Fifteen subjects were included in this study. Adaptive optics ophthalmoscopy was used to measure the parameters of temporal retinal arterioles. Optical coherence tomography angiography was employed to assess foveal avascular zone and vessel densities of the superficial capillary plexus, deep capillary plexus and choricapillary plexus. Results. After 3 months of treatment, there was a statistically significant median decrease in wall-to-lumen ratio (p=0.0001). The same tendencies were noticed for wall thickness values (p=0.008) and wall cross sectional area values (p=0.001). On the other side, no significant changes were noticed concerning the OCTA parameters. Conclusions. Resvega seems to have a beneficial effect on the retinal arterioles in diabetic patients.

We highlight here in a human pituitary prolactinoma, by double immunohistochemistry, clusters of cells with strong reactivity for Sox2 and prolactin The colocalization was mainly distributed at the periphery of the tumor. In contrast, in the central part of the same tumor, only\r\nisolated cells expressed Sox 2 colocalised with prolactin. To the best of our knowledge, this is the first microscopic evidence of Sox2 positivity in prolactin secreting cells from human pituitary and from such type of human pituitary adenoma.

accepted. Such an intrinsec system of the pineal gland was revealed by Rumanian scientists, which found a high renin like biological activity in the rat pineal, after nephrectomy, and also de novo production of isorenin by the monolayer cultured pineal cells; angiotensin I (A I) - immunoreactivity -was also found in the rat pineal at much higher concentration than in the brain structures. In this paper we add morphological evidences regarding components of the RAS in the bovine pineal gland. Bovine pineals were processed by immunohistochemistry for angiotensinogen, angiotensins I and II, as well as for renin. Frozen pineals were processed by "in situ" hybridization for angiotensinogen and renin mRNAs. Angiotensin converting enzyme(ACE), aminopeptidase A and angiotensin III (AIII) were not investigated. Our data showed that a number of pinealocytes stains for angiotensins (AI and AII), but the renin staining was negative. No nerve fibres were stained with AI or AII. The angiotensins-positive cells were dispersed in the pineal parenchyma, without a particular distribution in relation to the blood vessels. The angiotensinogen immunohistochemistry showed sparse positive cells. The "in situ" hybridization data showed the signal for angiotensinogen mRNA located over pinealocytes, while the renin mRNA was absent. The local synthesis of angiotensinogen in the bovine pineal cells, as a substrate for generation of AI and AII are supported by our data. However, at least the first enzyme involved in this cascade is different from the typical renin. The presence of an angiotensin system without renin in the pineal gland is an additional argument to the evidence that angiotensin II and related peptides can be formed by renin- and ACE- independent protease pathways.

A 52-year old women was diagnosed with acromegaly 5 years ago, and transseptal transsphenoidal pituitary microsurgery has been performed. Later the patient did not come to controls and the complaints prior to operation growth of the hands and feet, headache, sweating and resistant hypertension have continued. She was referred to our clinic with the same complaints. Physical examination showed typical acromegalic features without typical Cushingoid features. Magnetic resonance imaging of the brain revealed the presence of a pituitary macroadenoma. Basal plasma levels of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels were high. GH suppression was not observed in 75 gr oral glucose suppression test. Due to refractory hypertension and central obesity hypothalamo-pituitaryadrenal (HPA) axis was evaluated. HPA showed a lack of circadian rhythm of adrenocorticotropic hormone (ACTH) and cortisol, non-suppressibility to 1 mg overnight and classical 2 day low-dose dexamethasone, but suppressibility to high-dose (8 mg) dexamethasone. The tumour resected by transsphenodial surgery was histopathologically consistent with the diagnosis of adenoma. Immunostaining showed GH and ACTH producing cells. After surgery plasma GH and IGF-1 levels decreased to normal along with normalization of HPA axis. Hypertension disappeared without medical treatment after removal of the pituitary tumour. This is a very rare case of GH-producing pituitary adenoma causing typical acromegaly with concomitant production of ACTH causing subclinical Cushing’s disease.

Context. Subacute thyroiditis, a manifestation of Autoimmune/inflammatory syndrome induced by adjuvants that may develop after vaccination. Objective. The aim of this study is to determine the importance of vaccination against COVID-19 in the etiology of subacute thyroiditis. Design. This case reports/series is an observational, descriptive research design. Subjects and Methods. Five of the thirty patients who applied to our clinic with subacute thyroiditis in the last 6 months had a history of inactivated and mRNA vaccines in the last four weeks, after exclusion of infection and comorbidities. We present three cases of mRNAbased vaccination and two cases of inactive SARS-CoV-2 vaccination that met ASIA criteria. Results. Our findings suggest that subacute thyroiditis may be a complication of vaccination against COVID-19. Conclusion. Vaccine administration may led to autoimmune manifestation induction as well as autoantibody production. Adjuvant-induced autoimmune/inflammatory syndrome, an abnormal autoimmune response as a result of exposure to an adjuvant such as vaccine, appears likely in our cases.