ACTA ENDOCRINOLOGICA (BUC)

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. 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.

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.

We report the case of a 55-year-old-male with a large cell metastatic pancreatic neuroendocrine carcinoma treated for 14 months with lanreotide autogel having a stable disease (SD) and not responding to chemotherapy. The somatostatin analogues (SSA) were introduced after an episode of diarrhea and controlled the disease. Progression-free survival (PFS) as determined by Computerized Tomography (CT) scans was obtained for 14 months. After more than a year, the patient’s health state deteriorated along with progressive disease. The capecitabine-temozolomide regimen was challenged, but after three cycles, a rapid clinical decline was noted. Conclusion. This unexpected event (diarrhea) in the course of the disease could represent the beginning of carcinoid syndrome. While the lanreotide autogel helped the episode of diarrhea pass, it also helped gain control over the disease itself.

We studied the incidence, risk factors, presentation, treatment and prognosis of calcific uremic arteriolopathy (CUA) in 140 of our hemodialysis patients. Methods. Patients with CUA in the past 3 years have been compared to controls in a cross-sectional survey of 140 hemodialysis patients. Results. Prevalence of CUA was 6/140 (4.28%); common presentation was ulcerated acral necrosis. Age, sex ratio, BMI, prevalence of diabetes were similar in case (n=6) and control (n=134) patients. CUA patients had higher serum calcium (9.58?1.25 mg/dL vs. 8.50?1.03 mg/dL, p=0.01), calcium-phosphate product (71.06?19.67 mg2/dL2 vs. 58.73?17.20 mg2/dL2, p=0.01) and parathormone levels (1854?1407 pg/mL vs. 654?776 pg/mL, p=0.0002). Differences in ingestion of calcium, active vitamin D and non-calcium containing phosphate binders in the year prior to the assessment were not significant. CUA patients had higher CRP values in the 6 preceding months than non CUA patients (6.61?9.68 mg/dL vs. 1.97?4.20 mg/dL, p=0.01); logistic regression disclosed CRP as the only predictive factor for CUA (p=0.03). 4 (66%) of the CUA patients died due to sepsis, as compared to 3(2.23%) of the control group (p=0.001). 2 of 3 parathyroidectomised patients survived. In conclusion, this is, to our knowledge, the first series of CUA reported from Eastern Europe. In our center acral, ulcerated forms of CUA in patients with severe hyperparathyroidism are predominant.

The qualitative influence of free fatty acids (FFAs) on glucose metabolism is well documented while there is no data quantifying this relationship. An attempt to measure this correlation was made by employing a prospective, cross-sectional study involving 21 patients grouped in 5 categories established after a standard 2h Oral Glucose Tolerance Test (OGTT): normal glucose tolerance (N); insulin resistant (IR; IR2); impaired glucose tolerance (IGT) and diabetes (D). Two OGTTs were performed for each patient, separated by two weeks during which dietary supplements were taken along with restriction of saturated fat ingestion; levels of FFAs, aminoacids, etc., were measured on both patient visits. Glucose metabolism was quantified as the area under the curve and named glucose metabolic index (GMI). FFAs influence on GMI was dependent on their degree of saturation, with saturated and monounsaturated fats impairing glucose tolerance and polyunsaturated fats (especially tetraenoic and hexaenoic acids) improving it. Short chain FFAs (up to 14 C) had a negative effect; 16 and 18 C were weakly correlated and 20-26 C had a positive effect on glucose tolerance. Levels of aminoacids and metabolic intermediaries suggested involvement of aminoacids in energy production and showed mitochondrial energy overproduction. Glucose and energy metabolism were altered in IR, IGT and D patients in a similar fashion; those alterations were more pronounced in D than in the IR while none was present in the N group. Glucose tolerance was improved upon restriction of saturated fats intake along with administration of antioxidants in D, IGT and IR groups.

Objective. To describe an unusual case of lymphocytic hypophysitis in a man,\r\npresenting with an elevated serum Insulin like growth factor-1(IGF-1) level.\r\nCase report. We report the case of a 27 year old male presenting with a 2 week history\r\nof severe headaches. Magnetic resonance imaging of the head showed an adenoma-like\r\npituitary. The physical examination was normal, laboratory tests revealed secondary\r\nhypothyroidism and hypogonadism along with an elevated IGF-1. Complete\r\ntranssphenoidal resection of the pituitary mass was done. Tissue analysis was diagnostic for\r\nlymphocytic hypophysitis. No evidence of a somatotroph adenoma was found. After surgery\r\nthe patient developed panhypopituitarism and diabetes insipidus.\r\nDiscussion. IGF-1 is a sensitive disease related marker in acromegaly and corresponds\r\nto disease activity. However, it should not be used as the sole marker for diagnosis of\r\ndisease. Inflammatory lesions of the pituitary gland, such as lymphocytic hypophysitis, can\r\nclinically and radiologically mimic tumors of the sellar region.\r\nConclusion. We report an index case of a young male who presented with elevated\r\nserum IGF-1 level in the setting of lymphocytic hypophysitis. This case illustrates the\r\ndilemma associated with reliance on the IGF-1 levels for diagnosis of acromegaly, since an\r\nelevated IGF-1 level in the presence of a pituitary mass may not always be a somatotroph\r\ntumor. We propose the differential diagnosis should also include autoimmune hypophysitis.