Publications by authors named "Mara Carsote"

34 Publications

Predictors of early and sustained virological response of viral hepatitis C.

Rom J Morphol Embryol 2020 Oct-Dec;61(4):1185-1192

Department of Bacteriology-Virology-Parasitology, Department of Cardiology, University of Medicine and Pharmacy of Craiova, Romania;

Due to complex interplay between host and viral factors, pathogenesis of chronic hepatitis C (CHC) is considered a challenging issue. Infection with hepatitis C virus (HCV) is not confined only to liver but can induce disturbances in many other organs and systems. Our primary aim for this study was to evaluate biological response rates and sustained virological response (SVR) in patients diagnosed with CHC, treated with Interferon-alpha (IFN-α), Pegylated (PEG)-IFN-α2a or -α2b plus Ribavirin. The second aim of the study was the identification of predictive factors for a favorable response to antiviral therapy in patients diagnosed with CHC. We enrolled in this study 210 patients diagnosed with CHC who have accomplished all inclusion and exclusion criteria, treated with PEG-IFN plus Ribavirin. Patients' recovery progress has been evaluated by determining: age, gender; biochemical tests: alanine aminotransferase (ALT), aspartate aminotransferase (AST); serological assays - detect anti-HCV antibody and molecular assays - detect, quantify and/or characterize hepatitis C viral load (ribonucleic acid) (HCV-RNA); liver histopathological (HP) examination. According to their response to treatment, they were classified into responders (n=145) and non-responders (n=65). Liver biopsies were histopathologically evaluated for necroinflammatory grade and fibrosis stage according to the modified Ishak and Metavir scoring systems for chronic hepatitis. Demographic, laboratory, and HP results were introduced in statistical analysis. These parameters were included in area under curve (AUC) analysis in order to estimate their degree of influence on getting early virological response (EVR) and SVR. Our study demonstrates that factors connected to treatment failure in CHC are linked to older age, high hepatitis C viral load, and impaired glucose tolerance at beginning of treatment [high fasting glucose and insulin, high homeostatic model assessment of insulin resistance (HOMA-IR) index] and also to liver histology features (high fibrosis score, liver steatosis, iron infiltration, and more or less high necroinflammatory activity). Analyzing results of our study shows that HOMA-IR index, serum insulin levels, baseline HCV-RNA, baseline mean blood glucose and HP score like Ishak fibrosis score, steatosis score and liver iron score may have a predictive value for obtaining an EVR in patients diagnosed with CHC.
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http://dx.doi.org/10.47162/RJME.61.4.20DOI Listing
June 2021

Vitiligo and chronic autoimmune thyroiditis.

J Med Life 2021 Mar-Apr;14(2):127-130

Department of Endocrinology, Clinical County Hospital, Cluj-Napoca, Romania.

Vitiligo, the discoloration of the skin, has different autoimmune mechanisms reflected by many biomarkers as shown by skin histology, staining for CD4 and CD8 T lymphocytes, chemokine ligand 9 or circulating cytokines such as interleukin (IL)-1 beta, interferon (IFN)-gamma, transforming growth factor (TGF)-beta, antibodies, markers of oxidative stress, chemokines, and others. In this narrative review, we aim to overview vitiligo in relationship with chronic autoimmune thyroiditis. Regarding vitiligo, more than 50 different genetic loci have been associated with this disease, and the heritability is high. There is a 20% risk of an environmental connection which may also act as a trigger; moreover, the association with human leukocyte antigen (HLA) expression is well recognized. The specific lesions display CD8+ tissue-resident memory T cells as continuous key activators of melanocytes. The association with chronic thyroiditis is based on common autoimmune background and excessive reactive oxygen species that destroy melanocytes and thyrocytes (oxidative stress hypothesis) with thyroxine and melanin as target molecules, thus sharing a common origin: tyrosine. Moreover, common epigenetic anomalies or mutations of the Forkhead transcription factor D3 (FOXD3) have been described. Since vitiligo affects up to 1-2% of the population worldwide and 34% of patients have positive thyroid antibodies, apart from common autoimmunity background and oxidative stress toxicity, the association is clinically relevant for different practitioners.
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http://dx.doi.org/10.25122/jml-2019-0134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169145PMC
June 2021

Anorexia nervosa: COVID-19 pandemic period (Review).

Exp Ther Med 2021 Aug 26;22(2):804. Epub 2021 May 26.

Department of Endocrinology, Clinical County Hospital, 400000 Cluj-Napoca, Romania.

Anorexia nervosa is an eating disorder characterized by restrictive eating and an intense fear of gaining weight. It is a disease with an increasing incidence during the last few decades, and represents a complex psychiatric condition which includes secondary amenorrhea, nutritional and metabolic damage, and impaired endocrine panel up to bone loss as well as cardiac, gastrointestinal and hematological complications. This is a narrative review which includes an update on this eating disorder from the perspective of an endocrine panel of anomalies, especially of the skeleton, considering the pressure of the recent global COVID-19 pandemic changes. Practically affecting every organ, anorexia nervosa needs to be taken into consideration during the pandemic period because of the higher risk of relapse due to new living conditions, social distancing, self-isolation, changes in food access, more intense use of social media platforms, disruption of daily habits, and more difficult access to healthcare practitioners. The lack of physical activity in addition to vitamin D deficiency related to low sun exposure or to the use of facial masks may also be connected to further bone damage related to this disease.
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http://dx.doi.org/10.3892/etm.2021.10236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170656PMC
August 2021

COVID-19-related thyroid conditions (Review).

Exp Ther Med 2021 Jul 13;22(1):756. Epub 2021 May 13.

Departament of Obstetrics and Gynecology, 'Carol Davila' University of Medicine and Pharmacy, 050474, Bucharest, Romania.

In patients who were not previously diagnosed with any thyroid conditions, the scenario of COVID-19-related anomalies of the hypothalamus-pituitary-thyroid axes may include either: A process of central thyroid stimulating hormone (TSH) disturbances via virus-related hypophysitis; an atypical type of subacute thyroiditis which is connected to the virus spread or to excessive cytokine production including a destructive process with irreversible damage of the gland or low T3 (triiodothyronine) syndrome (so called non-thyroid illness syndrome) which is not specifically related to the COVID-19 infection, but which is associated with a very severe illness status. Our objective here was to briefly review thyroid changes due to the COVID-19 infection. Ongoing assessment of the effects of the COVID-19 pandemic will reveal more information on coronavirus-induced thyroid conditions. Routine thyroid assays performed in patients with severe infection/at acute phase of COVID-19 are encouraged in order to detect thyrotoxicosis. After recovery, thyroid function should be assessed to identify potential hypothyroidism. There remain unanswered questions related to the prognostic value of interleukin-6 in infected patients, especially in cases with cytokine storm, and the necessity of thyroid hormone replacement in subjects with hypophysitis-related central hypothyroidism.
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http://dx.doi.org/10.3892/etm.2021.10188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8135141PMC
July 2021

Somatostatin receptors in normal and acromegalic somatotroph cells: the U-turn of the clinician to immunohistochemistry report - a review.

Rom J Morphol Embryol 2020 Apr-Jun;61(2):353-359

Department of Endocrinology, Carol Davila University of Medicine and Pharmacy, C. I. Parhon National Institute of Endocrinology, Bucharest, Romania;

This is a narrative review of literature introducing somatostatin receptors (SSTRs) as part of understanding the somatotroph cells since they are positive in normal cells but also in tumoral cells as seen in somatotropinoma, a growth hormone (GH)-producing neoplasia, which causes acromegaly. They are five subtypes of SSTRs (1 to 5), which are immunohistochemically positive in different proportions in somatotropinomas. SSTR types 2 and 5 are most frequent in GH-secreting adenomas and they are both targeted by medical therapy with somatostatin analogues (SSTAs) like first generation Octreotide and Lanreotide (mainly targeting SSTR2) and second generation Pasireotide (with highest affinity for SSTR5), thus heterogeneous SSTRs configuration into the tumor explains different pattern of response to treatment and it might predict it once the SSTRs immunostaining is performed. Monoclonal antibodies are used for immunohistochemical detection of SSTRs; currently, a lack of standardization is presented, and scoring systems, such as Volante, H-score or human epidermal growth factor receptor 2 (HER2)-score, are applied. Immunoreactive markers like SSTRs are the U-turn in clinical practice regarding somatotropinomas since the configuration of subtypes 2 and 5 explains the responsiveness to medical therapy like SSTA. Further achievement of disease control is imperiously necessary because acromegaly has an increased rate of morbidity and mortality.
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http://dx.doi.org/10.47162/RJME.61.2.05DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864306PMC
February 2021

Glucocorticoids and Trabecular Bone Score.

J Med Life 2020 Oct-Dec;13(4):449-453

Department of Endocrinology, Clinical County Hospital, Cluj-Napoca, Romania.

TBS (Trabecular Bone Score) is the latest tool for clinicians to evaluate bone micro-architecture based on a pixel greyscale, which is provided by lumbar dual-energy X-ray absorptiometry (DXA). Its use enhances fracture prediction in addition to DXA-BMD (Bone Mineral Density). This is independent of fracture risk assessment (FRAX) and DXA results. We present a narrative review regarding the connection between TBS and Glucocorticoids (GC), either as a drug used for different conditions or as a tumor-produced endogenous excess. TBS is a better discriminator for GC-induced vertebral fractures compared to DXA-BMD. This aspect is similarly available for patients with osteoporosis diagnosed by DXA. TBS is inversely correlated with the cumulative dose of GC (systemic or inhaled), with disease duration, and positively correlated with respiratory function in patients with asthma. Low TBS values are found in females with a T-score at the hip within the osteoporosis range, with diabetes mellitus, or who use GC. Lumbar TBS is a screening tool in menopausal women with type 2 diabetes mellitus. TBS is an independent parameter that provides information regarding skeleton deterioration in diabetic patients receiving GC therapy in a manner complementary to DXA-BMD. TBS might become an essential step regarding the adrenalectomy decision in patients with adrenal incidentaloma in whom autonomous cortisol secretion might damage bone micro-architecture. TBS currently represents a standard tool of fracture risk evaluation in patients receiving GC therapy or with endogenous Cushing's syndrome, a tool easy to be applied by different practitioners since GCs are largely used.
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http://dx.doi.org/10.25122/jml-2019-0131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803323PMC
January 2021

Glucagonoma: From skin lesions to the neuroendocrine component (Review).

Exp Ther Med 2020 Oct 3;20(4):3389-3393. Epub 2020 Jul 3.

Department of Gynecology, Emergency University Hospital, 050098 Bucharest, Romania.

Glucagonoma is a hormonally active rare pancreatic neuroendocrine tumour causing an excess of glucagon. This is a narrative review based on a multidisciplinary approach of the tumour. Typically associated dermatosis is necrolytic migratory erythema (NME) which is most frequently seen at disease onset. Insulin-dependent diabetes mellitus, depression, diarrhoea, deep vein thrombosis are also identified, as parts of so-called 'D' syndrome. Early diagnosis is life saving due to potential aggressive profile and high risk of liver metastasis. NME as paraneoplastic syndrome may be present for months and even years until adequate recognition and therapy; it is remitted after successful pancreatic surgery. Thus the level of practitioners' awareness is essential. If surgery is not curative, debulking techniques may improve the clinical aspects and even the outcome in association with other procedures such as embolization of hepatic metastasis; ablation of radiofrequency type; medical therapy including chemotherapy, targeted therapy with mTOR inhibitors such as everolimus, PRRT (peptide receptor radiotherapy), and somatostatin analogues (including combinations of medical treatments). Increased awareness of the condition involves multidisciplinary practitioners.
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http://dx.doi.org/10.3892/etm.2020.8966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465236PMC
October 2020

Somatostatinoma: Beyond neurofibromatosis type 1 (Review).

Exp Ther Med 2020 Oct 3;20(4):3383-3388. Epub 2020 Jul 3.

Department of Gynecology, Emergency University Hospital, 050098 Bucharest, Romania.

Somatostatinoma is a tumour mainly originating from pancreas or duodenum; overall with an incidence of 1/40 million persons. We introduce a narrative review of literature of somatostatinoma including the relationship with neurofibromatosis type 1. Clinical presentation includes: Diabetes mellitus, cholelithiasis, steatorrhea, abdominal pain, and obstructive jaundice while papillary tumour may cause acute pancreatitis. The neoplasia may develop completely asymptomatic or it is detected as an incidental finding during an imaging or a surgical procedure. It may be sporadic or associated to genetic backgrounds especially for duodenal localisation as neurofibromatosis type 1 ( gene with malfunction of RAS/MAPK pathway) or Pacak-Zhuang syndrome ( gene encoding HIF). Surgery represents the central approach if feasible but the prognostic depends on location, and grading as indicated by WHO 2017 classification of neuroendocrine tumours. Previously known as Von Recklinghausen disease, neurofibromatosis type 1, the most frequent neurocutaneous syndrome, is an autosomal dominant disorder including: Café-au-lait spot, skin fold freckling on flexural zones, and neurofibromas as well as tumours such as gliomas of optic nerve, gastrointestinal stromal tumours (GISTs), iris hamartomas and brain tumours. Duodenal somatostatinoma is associated with the syndrome which actually involves more often a duodenal tumour of GIST type than a somatostatin secreting neoplasia. Other neuroendocrine tumours are reported: Gastrointestinal NENs at the level of rectum or jejunum and pheocromocytoma. Overall, one quarter of subjects have gastrointestinal tumours of different types. Somatostatinoma, when not located on pancreas but in duodenoum, may be registered in subjects with neurofibromatosis type 1 most probably in addition to other tumours. Overall, this type of neuroendocrine tumour with a challenging presentation has a poor prognosis unless adequate radical surgery is promptly offered to the patient.
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http://dx.doi.org/10.3892/etm.2020.8965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465002PMC
October 2020

New oral anticoagulants - possible extension to other indications (Review).

Exp Ther Med 2020 Sep 5;20(3):2401-2405. Epub 2020 May 5.

'Carol Davila' University of Medicine and Pharmacy, Internal Medicine Department, Clinical Emergency Hospital of Bucharest, 014461 Bucharest, Romania.

Anticoagulant treatment is necessary in various conditions, with curative or preventive purposes. Until recently, the only oral anticoagulants available have been vitamin K antagonists. To overcome the disadvantages of the antivitamin K oral anticoagulants, new oral anticoagulants (NOACs) have been developed and included in clinical trials. After more than 60 years of using vitamin K antagonists, the introduction of NOACs represent a medical breakthrough, with promising prospects. Due to their promising results and better safety profile, NOACs have become an appealing alternative to vitamin K antagonists in a short period of time. NOACs have been approved for the prevention and treatment of venous thromboembolism and for the prevention of stroke in patients with nonvalvular atrial fibrillation. Starting with postoperative venous thromboprophylaxis after hip replacement surgery, NOACs have been approved also for other clinical situations. Rivaroxaban is the first oral anticoagulant approved to be used in combination with an antiplatelet agent to prevent atherothrombotic events in adults with coronary artery disease and/or peripheral artery disease. However, further investigation is needed to establish which group of patients would benefit most from this medical approach. Furthermore, preliminary studies have shown that NOACs seem to be a reasonable choice of anticoagulation for patients with cancer, but further studies are expected.
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http://dx.doi.org/10.3892/etm.2020.8713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401725PMC
September 2020

Metabolic and cardiovascular benefits of GLP-1 agonists, besides the hypoglycemic effect (Review).

Exp Ther Med 2020 Sep 5;20(3):2396-2400. Epub 2020 May 5.

Internal Medicine Department, Clinical Emergency Hospital of Bucharest, 'Carol Davila' University of Medicine and Pharmacy, 014461 Bucharest, Romania.

Patients with type 2 diabetes exhibit higher cardiovascular risk than normal individuals. Optimal blood glucose levels are rarely achieved in diabetic patients. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as a new antidiabetic drug class with multiple metabolic effects. Some trials have evaluated their safety, but it has been recently demonstrated that this new class has cardiovascular benefits, through other mechanisms than glycemic control. The use of GLP-1RAs was associated with a significant reduction of cardiovascular and all-cause mortality, with a safe profile related to pancreatitis or thyroid cancer, as compared with placebo. This review presents the cardiovascular and metabolic benefits of GLP-1 RAs versus placebo, in patients with type 2 diabetes. Semaglutide and liraglutide demonstrated a reduction in cardiovascular events, with similar rates on cardiovascular mortality. Ongoing trials assess the cardiovascular benefits and side effects of dulaglutide treatment. Exenatide and liraglutide demonstrated the decrease of blood pressure values, weight reduction and improvement of dyslipidemia. Liraglutide induced, both and , an improvement of blood circulation, increasing the nitric oxide level and inhibiting the adhesion and procoagulant factors. Also, liraglutide demonstrated beneficial effects on cardiac remodeling after myocardial infarction, but more large trials are required. However, the international guidelines recommend using GLP-1 RAs as first-line therapy in type 2 diabetes patients with high cardiovascular risk or as first-line agents in patients intolerant to metformin.
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http://dx.doi.org/10.3892/etm.2020.8714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401476PMC
September 2020

Abdominal wall endometriosis (a narrative review).

Int J Med Sci 2020 10;17(4):536-542. Epub 2020 Feb 10.

Department of Cellular and Molecular Biology and Histology, "Carol Davila" University of Medicine and Pharmacy, 050474, Bucharest, Romania; "C.I. Parhon" National Institute of Endocrinology, 011863, Bucharest, Romania.

One of the rarest forms of endometriosis is abdominal wall endometriosis (AWE), which includes caesarean scar endometriosis. AWE remains a challenging condition because some issues related to this topic are still under debate. The increasing number of caesarean sections and laparotomies will expect to increase the rate of AWE. The current incidence in obstetrical and gynaecological procedures is still unknown. The disease is probably underestimated. The pathogenic mechanism involves local environment at the implant site including local inflammation and metalloproteinases activation due to local growth factors, estrogen stimulation through estrogen receptors and potential epigenetic changes. However, the underlying mechanisms are not fully explained, and we need more experimental models to understand them. The clinical presentation is heterogeneous; the patient may be seen by a gynaecologist, an endocrinologist, a general surgeon, an imaging specialist, or even an oncologist. No particular constellation of clinical risk factors has been identified, and the histological report is the major diagnostic tool for confirmation. Surgery is the first line of therapy. Further on we need protocols for multidisciplinary investigations and approaches.
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http://dx.doi.org/10.7150/ijms.38679DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7053307PMC
December 2020

Ovarian Sertoli cell tumours: practical points.

J Pak Med Assoc 2020 Jan;70(1):129-133

Department of Endocrinology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.

Rarity of Sertoli cell tumours contributes to a low index of suspicion and therefore a thorough knowledge of the clinicopathological and immunological characteristics of such tumours is essential to diagnosis and proper management of the treatment and follow-up. The current narrative review of literature was planned to focus on ovarian Sertoli cell tumours that arise from the sex cords cells, which are typically benign unilateral neoplasia incidentally detected, or associated with hormonal hyperactivity, in women of reproductive age. A priory unpublished case of a 35-year old female is also introduced as the base of discussion Abdominal massrelated syndrome and vaginal bleeding anomalies have been reported. Genetic background, if presented, is mostly related to Peutz-Jeghers syndrome caused by STK11/LKB1 mutation. The tumour displays a microscopic tubular pattern and rarely displays cords or trabecular, retiform, spindles, diffuse or areolar structures. Although immunohistochemistry can be helpful in establishing the diagnosis, the results are sometimes inconclusive and the current results require new research to establish a specific immunological panel.
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http://dx.doi.org/10.5455/JPMA.1381DOI Listing
January 2020

Post-thyroidectomy Hypocalcemia - Risk Factors and Management.

Chirurgia (Bucur) 2019 Sept-Oct;114(5):564-570

The complications of thyroidectomy vary from hypocalcemia and recurrent laryngeal nerve lesions to injury of vocal folds, local hematoma, cysts, granuloma. Post-operative hypocalcemia has an incidence of 1.2-40%. Permanent hyoparathyroidism is registered in 3% of cases. This is a brief narrative review focusing on the levels of calcium after performing a thyroidectomy and the need of calcium supplements under these circumstances. This complication, even it seems rather harmless at first, in fact it represents an important contributor to hospitalization delay and, especially for severe forms, to poor quality of life, including the risk of life threatening episodes. Devascularisation of parathyroid glands in addition to injury or dissection causes hypoparathyroidism. Hypocalcemia risk differs with sex (females have a higher risk), lymph node dissection (it increases the risk), it differs with type of thyroidectomy (larger dissections have a higher risk; also the intervention for recurrent goitre and second intervention for post-operatory bleeding increase the risk of hypocalcemia; while Basedow disease is probably at higher risk than multinodular goitre among benign conditions) and the duration of procedure. Pre-operatory low calcium, parathormon (PTH), 25-hydroxivitamin D increases the risk. The calcium drop rate matters as well: a decrease of 1 mg/dL calcium over 12 hours after surgery is independently correlated with the risk of symptomatic hypocalcemia. Early post-operatory PTH and calcium are best predictors for the need of oral calcium supplements. Routine post-operatory calcium and vitamin D supplementation statistically significant decreases the risk of developing transitory hypocalcemia and acute complications compare to calcium alone supplements or no supplements. In cases of hypoparathyroidism calcitriol is preferred.
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http://dx.doi.org/10.21614/chirurgia.114.5.564DOI Listing
November 2019

Metabolic and bone profile in postmenopausal women with and without type 2 diabetes: a cross-sectional study.

Rom J Intern Med 2019 Mar;57(1):61-67

"C.I. Parhon" National Institute of Endocrinology, Bucharest,Romania.

Introduction: Current studies support the implication of metabolic changes associated with type 2 diabetes in altering bone metabolism, structure and resistance.

Objective: We conducted a cross-sectional study on postmenopausal women aimed to analyze the differences in metabolic and bone profile in patients with and without type 2 diabetes Methods. We analyzed the metabolic and bone profile in postmenopausal women with and without type 2 diabetes (T2DM). Clinical, metabolic, hormonal parameters, along with lumbar, hip and femoral bone mineral density (BMD) and trabecular bone score (TBS) were evaluated.

Results: 56 women with T2DM(63.57±8.97 years) and 83 non-T2DM (60.21±8.77 years) were included. T2DM patients presented a higher value of body mass index (BMI) and BMD vs. control group (p = 0.001; p = 0.03-lumbar level, p = 0.07-femoral neck and p = 0.001-total hip). Also, BMI correlated positively with lumbar-BMD and glycated hemoglobin (HbA1c) (r = 0.348, p = 0.01; r = 0.269, p = 0.04), correlation maintained even after age and estimated glomerular filtration rate (eGFR) adjustment (r = 0.383, p = 0.005; r = 0.237, p = 0.08). Diabetic patients recorded lower levels of 25(OH)D(p = 0.05), bone markers (p ≤ 0.05) and TBS(p = 0.07). For the entire patient group we found a negative correlation between HbA1c level and bone markers: r = -0.358, p = 0.0005-osteocalcin, r = -0.40, p = 0.0005-P1NP, r = -0.258, p = 0.005-crosslaps.

Conclusions: Our results indicate the presence of altered bone microarchitecture in T2DZ patients according to the TBS score, combined with lower levels of bone markers, with a statistically significant negative correlation between HbA1c level and bone markers.
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http://dx.doi.org/10.2478/rjim-2018-0036DOI Listing
March 2019

Incidentaloma: from general practice to specific endocrine frame.

J Pak Med Assoc 2017 Jun;67(6):917-922

Department of Endocrinology, Iuliu Hatieganu University of Medicine and Pharmacy & Clinical County Hospital, Cluj-Napoca, Romania.

Incidentaloma, a modern concept connected to technology progress, represents an accidentally discovered tumour, usually used for hypophysis and adrenals, and rarely for thyroid, parathyroids, and ovaries. This is a narrative review based on PubMed research, between 2012 and 2016 focusing on general and endocrine approach and current controversies. Main dilemma is the terminology itself: randomly imagery finding is enough or non-functioning profile and low-growth rate (not requiring surgery) should be mandatory? The controversies refers to best time framing of re-scanning pituitary and adrenal incidentaloma and setting of clear criteria for subclinical Cushing's syndrome. The need for general practical guidelines is imperative so clinicians from different areas of medicine touse the same definition and protocols. Currently, the widely accepted part is represented by incidental finding. For restricted defined incidentaloma the best intervention is no intervention, while some cases may require surgery depending on tumours features, patient's age and preference.
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June 2017

Cystic adrenal lesions: focus on pediatric population (a review).

Clujul Med 2017 15;90(1):5-12. Epub 2017 Jan 15.

Endocrinology Department, Iuliu Hatieganu University of Medicine and Pharmacy & Clinical County Hospital, Cluj-Napoca, Romania.

Background And Aim: The cysts may potentially affect any organ; adrenals cysts are rare. This is a review of the literature regarding adrenal cysts, focusing on children and young adults.

General Data: Three major types have been described: pure cysts (endothelial, epithelial, and hemorrhagic or pseudocyst), parasitic (as hydatid) cysts and cystic part of a tumour (most frequent are neuroblastoma, ganglioneuroma, pheocromocytoma, and teratoma). The complications are: bleeding, local pressure effects; infection; rupture (including post-traumatic); arterial hypertension due to renal vessels compression. Adrenal hemorrhage represents a particular condition associating precipitating factors such as: coagulation defects as Factor IX or X deficiency, von Willebrand disease, thrombocytopenia; antiphospholipid syndrome; previous therapy with clopidogrel or corticosteroids; the rupture of a prior tumour. At birth, the most suggestive features are abdominal palpable mass, anemia, and persistent jaundice. Adrenal insufficiency may be found especially in premature delivery. The hemorrhage is mostly self-limiting. Antenatal ultrasound diagnosis of a cyst does not always predict the exact pathology result. The most important differential diagnosis of adrenal hemorrhage/hemorrhagic cyst is cystic neuroblastoma which is highly suggestive in the presence of distant metastases and abnormal catecholamine profile. The major clue to differentiate the two conditions is the fact that the tumor is stable or increases over time while the adrenal hemorrhage is expected to remit within one to two weeks.

Conclusion: Pediatric adrenal cysts vary from simple cysts with a benign behavior to neoplasia- related lesions displaying severe prognosis as seen in cystic neuroblastoma. A multidisciplinary team is required for their management which is conservative as close follow-up or it makes necessary different surgical procedures in cases with large masses or if a malignancy suspicion is presented. Recently, laparoscopic approach is regarded as a safe procedure by some authors but generally, open surgery is more frequent used compare to adults; in most cases the preservation of normal gland is advisable.
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http://dx.doi.org/10.15386/cjmed-677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5305088PMC
January 2017

From syncope episode to the diagnosis of ovarian dermoid cyst associated with a cystadenoma.

J Pak Med Assoc 2016 Mar;66(3):354-6

Department of Endocrinology, C.I.Parhon National Institute of Endocrinology, Bucharest, Romania & Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.

Ovarian teratoma has various presentations. We present a 28-year female diagnosed with a tumour after a fainting episode. Medical history was non-contributory except for mild intermittent pelvic pain. Cardiologic and neurological evaluation found no cause of syncope. Abdominal ultrasound revealed a right ovarian tumour that was laparoscopically removed. The menses continued to be normal. The pathological exam showed an encapsulated tumour of 8 cm with hair and small bone parts (mature teratoma with a cystadenoma). Immunohistochemistry was positive for CK34beta E12 in stratified squamous epithelium of skin glands; positive CK7 in kidney tubular parts; positive actin in smooth muscle. The endocrine profile was normal and the patient remained asymptomatic. The challenging in the pathological report was to differentiate a cystic part of a solid tumour to a teratoma associated cystadenoma. No apparent cause of syncope was found so a possible tumour related local pain and inflammation mechanism might be involved.
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March 2016

Vanishing testes syndrome-related osteoporosis and high cardio-metabolic risk in an adult male with long term untreated hypergonadotropic hypogonadism.

Arch Endocrinol Metab 2016 Feb;60(1):79-84

C.I. Parhon National Institute of Endocrinology, Bucharest, Romania.

The male hypogonadism-related bone mass loss is often under diagnosed. Peak bone mass is severely affected if the hypogonadism occurs during puberty and is left untreated. We present an interesting; almost bizarre case of a male with non-functional testes early during childhood and undiagnosed and untreated hypogonadism until his fifth decade of life. Forty six year male is referred for goitre, complaining of back pain. Phenotype suggested intersexuality: gynoid proportions, micropenis, no palpable testes into the scrotum, no facial or truncal hair. His medical history had been unremarkable until the previous year when primary hypothyroidism was diagnosed and levothyroxine replacement was initiated. Later, he was diagnosed with ischemic heart disease, with inaugural unstable angina. On admission, the testosterone was 0.2 ng/mL (normal: 1.7-7.8 ng/mL), FSH markedly increased (56 mUI/mL), with normal adrenal axis, and TSH (under thyroxine replacement). High bone turnover markers, and blood cholesterol, and impaired glucose tolerance were diagnosed. The testes were not present in the scrotum. Abdominal computed tomography suggested bilateral masses of 1.6 cm diameter within the abdominal fat that were removed but no gonadal tissue was confirmed histopathologically. Vanishing testes syndrome was confirmed. The central DXA showed lumbar bone mineral density of 0.905 g/cm2, Z-score of -2.9SD. The spine profile X-Ray revealed multiple thoracic vertebral fractures. Alendronate therapy together with vitamin D and calcium supplements and trans-dermal testosterone were started. Four decades of hypogonadism associate increased cardiac risk, as well as decreased bone mass and high fracture risk.
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http://dx.doi.org/10.1590/2359-3997000000127DOI Listing
February 2016

Effects of combination therapy: somatostatin analogues and dopamine agonists on GH and IGF1 levels in acromegaly.

Clujul Med 2015 1;88(3):310-3. Epub 2015 Jul 1.

Department of Endocrinology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania ; Department of Endocrinology, Cluj-Napoca Clinical County Hospital, Romania.

Background And Aims: Acromegaly is a complex endocrine disorder caused by excessive secretion of GH, secondary to a GH secreting pituitary adenoma or a mixed pituitary adenoma secreting GH and PRL.

Methods: The aim of this study was to evaluate the effects of combination therapy: dopamine agonist and somatostatin analogue on GH and IGF1 levels in a group of 30 patients with acromegaly. Cabergoline in a dose of 2 mg/week and 4 mg/week respectively was associated with Sandostatin LAR in a dose of 20 mg/month and 30 mg/months respectively. Eight patients were treated with Lanreotide 30 mg/week and Cabergoline 2 mg/week and 3 patients were treated with Bromocriptine 10 mg/day and Sandostatin LAR 30 mg/month.

Results: Combination therapy: Cabergoline and Sandostatin achieved normal levels of IGF1 in 32% of the patients, better results being obtained after 12 months of treatment in the group treated with 4 mg Cabergoline/week. In 37% of cases the levels of IGF1 decreased by 50% after 12 months of treatment. In the group treated with Cabergoline and Somatuline a normal level of IGF1 was achieved in 25% of patients after 12 months of treatment. The outcome for the group treated with Sandostatin and Bromocriptine was similar to that obtained under Cabergoline 2 mg/week. There was no significant correlation between the level of GH and the type or dose of dopamine agonist used.

Conclusions: In conclusion, combination therapy consisting of dopamine agonist and somatostatin analogue achieves a significant reduction of IGF1 levels in patients with mixed adenomas secreting GH and PRL. A decrease in IGF1 levels is directly correlated with the dose of Cabergoline used.
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http://dx.doi.org/10.15386/cjmed-435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4632888PMC
November 2015

Vitamin d deficiency in postmenopausal women - biological correlates.

Maedica (Bucur) 2014 Dec;9(4):316-22

"Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania ; Department of Physical Medicine and Rehabilitation, Elias Emergency Hospital, Bucharest, Romania.

Introduction: Low vitamin D (VD) is associated with secondary hyperparathyroidism and both contribute to deleterious consequences (reduced bone mineral density (BMD), risk of fractures and falls).

Objective: To study the VD status and biological correlates in a group of postmenopausal women.

Material And Methods: We studied 123 postmenopausal women evaluated in the C.I.Parhon National Institute of Endocrinology, the Pituitary and Neuroendocrine Diseases department. All cases had been reffered for the evaluation of BMD by the general practitioner. The evaluation included serum measurements of total and ionised calcium, phosphorus, alkaline phosphatase (ALP), 25 hydroxi vitaminD (25OHD), parathyroid hormone (PTH), osteocalcin, betacrosslaps. Central DXA osteodensitometry was performed.

Results: 91.9% of cases had 25OHD serum levels below 30 ng/ml (74.8% had VD deficiency, 17.1% VD insufficiency). Only 8.1% had sufficient VD levels. A history of fragility fractures was present in 45.83% of the osteoporotic patients, 27.27% of the osteopenic ones and 15.15% of the women with normal BMD. 32 women (26%) were on VD supplementation at the time of evaluation. Among these subjects, the 25OHD level was significantly higher in those with prior fragility fractures (p=0.018) and osteoporosis (p=0.008). 25OHD concentration negatively correlated with PTH, alkaline phosphatase (ALP) and osteocalcin. The bone markers evaluated had a significant inverse correlation with the radius BMD, T and Z scores (p=0.004). 27.17% of the cases with VD deficiency had secondary hyperparathyroidism. The 25OHD concentration was significantly lower in these cases (p=0.000).

Conclusions: VD insufficiency is widely prevalent but still under-recognized and under-treated, possibly leading to secondary hyperparathyroidism. The compliance to VD supplementation is lower in subjects without osteoporosis or fragility fractures. Primary prevention measures should be more actively implemented.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4316873PMC
December 2014

Well-differentiated neuroendocrine tumor and osteoporosis: incidental findings?

Rom J Morphol Embryol 2013 ;54(4):1169-71

"Constantin I. Parhon" National Institute of Endocrinology, Bucharest, Romania;

The neuroendocrine tumors (NETs) have an increased incidence related to the age. Secondary osteoporosis might be found in patients with bone metastases and in those with NETs associated Cushing's disease or primary hyperparathyroidism. Primary osteoporosis might be found in postmenopausal women, but in case with non-metastatic NET as G1 NET it is difficult to establish the NET contribution to the bone loss. We present the case of a 53-year-old female accidentally diagnosed with G1 lung NET after surgery of the tumor. The immunohistochemistry pointed positive reaction for CHROMO, SYN and negative for CK7 and TTF1, and a Ki67 of 1-2% (well-differentiated neuroendocrine tumor). The central Dual X-Ray Absorptiometry (DXA) showed osteoporosis based on a T-score of -3. The patient had normal neuroendocrine markers and she was asymptomatic. She remained so for one year and the only therapy provided was weekly alendronate with adequate vitamin D and calcium supplements. Based on the pathological and immunohistochemistry profile, the low risk NET was diagnosed. We encourage the skeletal status assessment as central DXA in postmenopausal women with NETs, regardless clinical evidence of bone loss. The future will provide more epidemiological and pathogenic connections between the two dynamic fields of medicine as neuroendocrine tumors and osteoporosis.
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July 2014

The poor prognosis factors in G2 neuroendocrine tumor.

Rom J Morphol Embryol 2013 ;54(3 Suppl):717-20

"Constantin I. Parhon" National Institute of Endocrinology, Bucharest, Romania;

Background: The G2 neuroendocrine tumors (NET) or well-differentiated neuroendocrine carcinomas (2010 WHO Classification of Tumours of the Digestive System) embrace different types of evolution despite the fact that they actually are included in the same group of prognosis based on mitotic count and the Ki-67 proliferation index.

Aim: We studied the pathological and clinical aspects in patients with G2 NET.

Materials And Methods: This is a retrospective pilot observational study in patients admitted between January 2008 and January 2013 in "Constantin I. Parhon" National Institute of Endocrinology, Bucharest, Romania. They were evaluated based on the pathological report, imagistic scan, and neuroendocrine markers.

Results: Nine patients (female/male ratio: 5/4) with G2 NET were included (mean age at diagnosis 54.11 years). Surgery was performed in 66.66% of cases. 44.44% of tumors had unknown origin. 22.22% of patients had negative immunostain for chromogranin A. Synaptophysin was positive in all cases. Neuronal specific enolase (NSE) was performed in 44.44% of cases and it was positive in all these situations. 88.88% of patients had high neuroendocrine markers. Multiple tumors were found in two cases (follicular thyroid adenoma, and a carcinoma of the port vein, respective bilaterally pheochromocytomas). The youngest patient (39-year-old) had atypical onset with bilateral adrenal tumors (positive for CHROMO, EMA, CK-19, CK-20, negative for SOMATO, CK-7, S-100, glucagon, CD57, and a Ki-67 of 15%). Death was registered in two cases, both with bone metastases.

Discussion: Some poor prognosis factors may be taken into account as lack of CHROMO immunostain, young age at diagnosis, genetic background, and lack of therapy options as surgery. Larger databases will provide more information.

Conclusions: It is possible that the G2 NET group of tumors actually includes some different subtypes or in fact, a late diagnosis of the tumor might be associated with a poor diagnosis.
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July 2014

MicroRNAs with Specific Roles in Diabetes and Psychiatric Diseases.

Clujul Med 2014 30;87(2):87-90. Epub 2014 May 30.

Carol Davila University of Medicine and Pharmacy, Bucharest, Romania ; C. I. Parhon National Institute of Endocrinology, Bucharest, Romania.

Diabetes mellitus is one of the most cited non communicable diseases and the most common metabolic disorder. Epigenetics represents the field of study of heritable changes in gene expression which are not directly related to DNA. Epigenetics is concerned, alongside histone modifications, short interfering RNAs etc., with microRNAs (miRNAs) as well. These are small noncoding RNAs, 21 to 23 nucleotides in length, which either inhibit translation or affect mRNA stability and degradation. At present, there are dozens of miRNAs which have been proven to be involved in the animal and human pathology of diabetes (type 1 or 2). This review focuses on the miRNAs which have been identified as playing a role in both psychiatric diseases and diabetes.
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http://dx.doi.org/10.15386/cjmed-288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4620849PMC
November 2015

Screening for secondary endocrine hypertension in young patients.

Maedica (Bucur) 2013 Jun;8(2):108-15

"Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania ; "C.I. Parhon" National Institute of Endocrinology, Bucharest, Romania.

Abstract:

Background: Secondary endocrine hypertension accounts for 5-12% of hypertension's causes. In selected patients (type 2 diabetes mellitus, sleep apnea syndrome with resistant hypertension, sudden deterioration in hypertension control), prevalence could be higher.

Objectives: To present etiology of endocrine secondary hypertension in a series of patients younger than 40 years at hypertension's onset.

Material And Methods: Medical records of 80 patients (39M/41F), aged 30.1 ± 8.2 years (range: 12-40 years), with maximum systolic blood pressure=190.4 ± 29.2 mm Hg, range: 145-300 mm Hg, maximum diastolic blood pressure=107.7 ± 16.9 mm Hg, range: 80-170 mm Hg) referred by cardiologists for endocrine hypertension screening were retrospectively reviewed. Cardiac and renal causes of secondary hypertension were previously excluded. In all patients, plasma catecholamines were measured by ELISA and plasma cortisol by immunochemiluminescence. Orthostatic aldosterone (ELISA) and direct renin (chemiluminescence) were measured in 48 patients.

Results: Secondary endocrine hypertension was confirmed in 16 out of 80 patients (20%). Primary hyperaldosteronism was diagnosed in 7 (4M/3F) out of 48 screened patients (14.6%). i.e. 8.75% from whole group: 5 patients with adrenal tumors (3 left/2 right), 2 patients with bilateral adrenal hyperplasia; all patients were hypokalemic at diagnostic (average nadir K+ levels = 2.5 ± 0.5 mmol/L); four patients were hypokalaemic on diuretic therapy (indapamidum); other 3 patients were hypokalaemic in the absence of diuretic therapy. Cushing's syndrome was diagnosed in 6 patients (7.5%): subclinical Cushing due to 4 cm right adrenal tumour - n = 1, overt ACTH-independent Cushing's syndrome due to: macronodular adrenal hyperplasia associated with primary hyperparathyroidism - n = 1; due to adrenal carcinoma - n = 1; due to adrenal adenomas - n = 2; Cushing's disease - n = 1). Pheochromocytomas were diagnosed in 3 patients (3.75%).

Conclusion: Primary hyperaldosteronism was the most frequent cause of secondary endocrine hypertension in our series, followed by Cushing's syndrome and pheochromocytomas. Screening of young hypertensive patients for secondary causes, especially primary hyperaldosteronism, is mandatory.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3865118PMC
June 2013

New Clues that May Link Osteoporosis to the Circulating Lipid Profile.

Bone Res 2013 Sep 25;1(3):260-6. Epub 2013 Sep 25.

College of Physicians and Surgeons, Columbia University , New York, NY USA.

Bone Mineral Density (BMD) is a gold standard for the diagnosis of osteoporosis and is also important in the assessment of fracture risk. Other risk factors have been identified that together make up fracture risk assessment tools such as FRAX. Another potential factor, circulating lipids, has been suggested because of reports linking statins to fracture risk reduction. We analyzed the lipid profile in a cohort of women diagnosed with postmenopausal osteoporosis based on bone density determination: 610 women with osteoporosis (mean lumbar spine T-score -3.16±0.81, mean yrs. since menopause 15.79±8.9) were grouped according to age at evaluation (< 50 years, 51-60 years, 61-70 years, > 70 years), the presence/absence of a history of a fragility fracture, statin and/or antiresorptive drug use. There was no correlation between BMD and Body Mass Index (BMI: P>0.05, r (2)<0.02). However, when BMD was correlated with both BMI and the lipid profile (Triglycerides, Cholesterol, LDLc, HDLc), significant correlations were found in 5 cohorts: 51-60 years with fractures (n=61, r (2)=0.14, P<0.01), 61-70 years (n=201, r (2)=0.09, P<0.01) with fractures (n=88, r (2)=0.14, P<0.01) or without fractures (n=113, r (2)=0.24, P=0.02) and over 70 years (n=247, r (2)=0.11, P<0.01).
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http://dx.doi.org/10.4248/BR201303004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4472105PMC
September 2013

Immature ovarian teratoma with unusual gliomatosis.

J Ovarian Res 2013 Apr 16;6(1):28. Epub 2013 Apr 16.

C,I,Parhon National Institute of Endocrinology, 34 Aviatorilor Blvd,, Bucharest 011853, Romania.

This study aimed to investigate an unusual case of immature ovarian teratoma with onset of mature glial cells implanted on the contralateral ovary, a challenge in the diagnosis of the second ovarian tumor. We report the case of a 31- yr-old woman, who developed at the age of 16 an immature teratoma in the right ovary that was surgically removed. Six years later mature glial implants were present on the left ovary and six months later at the level of peritoneum that relapsed after other six months. The patient suffered three surgical resections after the initial one. Paraffin sections and immunohistochemical examinations using antibodies against glial and neuronal antigens were performed. In the teratoma, the neuroectodermal tissue expressed Glial fibrillary acidic protein (GFAP), S100 protein, Epithelial membrane antigen (EMA) and Cytokeratin 34 beta E12 (Ck34beta E12), wheares the implants expressed only GFAP and S100 protein. The immature teratoma is the rarest type of ovarian teratomas. Gliomatosis peritonei is an exceptional finding, expecially with onset on the contralaterally ovary. The implant of the mature glial cells has a high risk of relapse, as seen in our case, thus close follow-up of the patient is necessary.
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http://dx.doi.org/10.1186/1757-2215-6-28DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3637604PMC
April 2013

The dedifferentiation of neuroendocrine tumor metastases: myth or reality?

Rom J Morphol Embryol 2013 ;54(1):201-3

"Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania.

Dedifferentiation is a process that may be found in metastasis from the neuroendocrine tumors. We present the case of a female within the seventh decade of life incidentally diagnosed with a mature teratoma with element of cartilages, bronchia, mucinous glands, and a poorly differentiated neuroendocrine carcinoma (Ki67 of 30%). After six months of chemotherapy and another six months of disease free interval, a metastasis of the great omentum was removed. The dedifferentiation was diagnosed based on much higher Ki67 (of 70%). The loss of estrogen receptor of 40% from the initial site to 3% into metastasis indicates an exclusive neuroendocrine aggressive pattern. The ovarian carcinoid is a rare situation, and metastasis to the great omentum with dedifferentiation is even seldom.
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May 2014

The immunohistochemistry aspects in two cases of neurofibromatosis-associated abdominal tumors.

Rom J Morphol Embryol 2012 ;53(2):401-5

Carol Davila University of Medicine and Pharmacy, Bucharest.

Type 1 neurofibromatosis associates various abdominal tumors as gastrointestinal stromal tumors, duodenal or pancreatic carcinoid, and adrenal tumors like pheochromocytoma. We present the immunohistochemistry report in two cases with different profile regarding the evolution. One case is a 7th decade women diagnosed with unilateral pheochromocytoma and GISTs, with a good prognosis after surgery. The other case is a 41-year-old male diagnosed with duodenal metastatic somatostatinoma after an intestinal occlusive syndrome and later the hormonal profile leaded to the diagnosis of pheochromocytoma. The patient had a fulminate evolution within six months from diagnosis.
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January 2013

The value of the immunohistochemistry in a case of gastric neuroendocrine tumor and thyroid metastasis.

Rom J Morphol Embryol 2011 ;52(1):187-92

Department of Pathologic Physiology, University of Medicine and Pharmacy of Craiova, Romania.

Thyroid metastasis is atypical. We present a 70-year-old female case that was first diagnosed as gastric cancer after surgical approach. Two years later a thyroidectomy was performed and the immunohistochemistry (IHC) profile revealed a neuroendocrine tumor (NET): poorly differentiated neuroendocrine carcinoma (with small cells), with positive reaction for SYN, CROMO, negative for calcitonin, TTF1 and thyreoglobulin. The Ki-67 index was 25%. Considering the unusual metastasis, the IHC exam of the stomach tumor was performed pointing the same features as the thyroid findings. This proved that the thyroid tumor was a metastasis from a primary gastric neoplasia. This is an unusual case of NET because of the thyroid involvement. Nevertheless, the IHC exam played the major role in elucidating the diagnosis and the prognosis of the case.
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July 2011

Giant adrenal cyst: case study.

J Med Life 2010 Jul-Sep;3(3):308-13

Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.

One of the rarest situations regarding an adrenal incidentaloma is an adrenal cyst. We present the case of a 61-year-old male patient diagnosed with peritonitis. During surgery, a right adrenal tumor of 2 cm is discovered. The patient was referred to endocrinology. 6 months later the diameter of the tumor is 7 times bigger than the initial stage. It has no secretory phenotype, except for the small increase of serum aldosterone and the 24-h 17-ketosteroids. Open right adrenalectomy is performed and a cyst of 15 cm is removed. The evolution after surgery is good. The pathological exam reveals an adrenal cyst with calcifications and osteoid metaplasia. The immunohistochemistry showed a positive reaction for CD34 and ACT in the vessels and VIM in the stroma. The adrenal cysts are not frequent and represent a challenge regarding the preoperative diagnostic and surgical procedure of resection. The pathological exam highlights the major aspects.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3018989PMC
December 2010