Medullary Thyroid Carcinoma in Patients with Graves' Disease-A Case Series and Literature Review.

INTRODUCTION: Graves' disease (GD) is an autoimmune disorder affecting the thyroid gland, leading to systemic manifestations such as hyperthyroidism, Graves' orbitopathy, and pretibial myxedema. Contrary to previous beliefs that hyperthyroidism protects against thyroid cancer, recent studies reveal an increased incidence of thyroid malignancies in GD patients, particularly differentiated thyroid carcinomas and, in rare cases, medullary thyroid carcinoma (MTC). CASE SERIES: This case series presents three female GD patients diagnosed with MTC, highlighting the complexities of diagnosis and management. All patients exhibited thyroid nodules with suspicious ultrasonographic features, elevated plasma calcitonin levels, and required total thyroidectomy. Histological examination confirmed MTC. DISCUSSION: These cases underscore the importance of routine calcitonin screening in GD patients with thyroid nodules to facilitate early detection and improve prognosis. Our findings suggest that while the coexistence of GD and MTC is likely incidental, vigilant monitoring and comprehensive evaluation are crucial for timely intervention. CONCLUSIONS: This study advocates for integrating calcitonin testing into the standard diagnostic protocol for GD patients presenting with thyroid abnormalities.

Primary Thyroid Lymphoma: A Retrospective-Observational Study in a Single Institutional Center.

Background and Objectives: primary thyroid lymphoma (PTL) is a rare neoplasm, displaying a variety of histological features. It is often a challenge for pathologists to diagnose this tumor. Materials and Methods: this study is a retrospective analysis of clinical and pathological characteristics of a group of eleven patients (eight women and three men, mean age 68 years, range 50-80 years) diagnosed with PTL. Results: nine patients (81.81%) presented a tumor with progressive growth in the anterior cervical region, usually painless and accompanied by local compressive signs. Histologically, we identified six cases (55%) of diffuse large B-cell lymphoma, three cases (27%) of extranodal marginal zone lymphoma, one case (9%) of follicular lymphoma, and one case (9%) of mixed follicular-diffuse lymphoma. PTL was associated with microscopic Hashimoto autoimmune thyroiditis in ten cases (90.9%). Ten patients (90.9%) presented with localized disease (stage I-IIE). A percentage of 60% of patients survived over 5 years. We observed an overall longer survival in patients under 70 years of age. Conclusions: PTL represents a diagnosis that needs to be taken into account, especially in women with a history of Hashimoto autoimmune thyroiditis, presenting a cervical tumor with progressive growth. PTL is a lymphoid neoplasia with favorable outcome, with relatively long survival if it is diagnosed at younger ages.

A rare form of hyperthyroidism leading to the diagnosis of acromegaly: A case report.

Acromegaly is a rare disease, usually caused by a pituitary tumor. It typically exhibits slow evolution and can result in numerous complications. In the present case report, the patient presented with hyperthyroidism associated with ophthalmopathy and right nodular goiter. The laboratory tests revealed persistent high levels of phosphorus without an apparent cause. After ruling out common pathologies associated with this finding, a focus was placed on the clinical aspects associated with acromegaly, a rare cause of hyperphosphatemia. Laboratory tests and MRI confirmed the diagnosis. The patient underwent transsphenoidal surgery, but the disease remained active, thus medical treatment was initiated, to a poor initial response. Associated with acromegaly, two distinct thyroid pathologies were diagnosed: Toxic adenoma and Graves' disease. This case highlights the challenges in diagnosing and managing a rare endocrine pathology.

Can Routine Laboratory Tests Be Suggestive in Determining Suspicions of Malignancy in the Case of Thyroid Nodules?

Background and objectives: Thyroid nodules are a common finding in clinical practice and can be either benign or malignant. The aim of this study was to compare laboratory parameters between patients with malignant thyroid nodules and those with benign thyroid nodules. Materials and methods: A total of 845 patients were included, with 251 in the study group (malignant thyroid nodules) and 594 in the control group (benign thyroid nodules). Results: Our results show that there were statistically significant differences in several laboratory parameters, including FT3, FT4, ESR, fibrinogen, WBC, and lymphocyte percentage, between the two patient groups (p < 0.05). Conclusions: These findings suggest that certain laboratory parameters may be useful in differentiating between benign and malignant thyroid nodules and could aid in the diagnosis and treatment of thyroid cancer. However, further diagnostic tests such as fine-needle aspiration biopsy and imaging studies are typically required for an accurate diagnosis. Routine laboratory tests prove most effective when combined with other diagnostic methods to identify thyroid cancer. Although not conclusive on their own, these tests significantly suggest and guide physicians to suspect malignancy in thyroid nodules. This affirmative answer to our question, "Can routine laboratory tests be suggestive in determining suspicions of malignancy in the case of thyroid nodules?" aligns with the results of our study.

The Experience of a Single Tertiary Center Regarding Benign and Malignant Tumors in Acromegalic Patients.

Background and Objectives: Acromegaly is a rare disease associated with increased levels of growth hormones (GHs) that stimulates the hepatic production of insulin growth factor-1 (IGF-1). Increased secretion of both GH and IGF-1 activates pathways, such as Janus kinase 2/signal transducer and activator of transcription 5 (JAK2/STAT5), and mitogen-activated protein kinase (MAPK), involved in the development of tumors. Materials and Methods: Given the disputed nature of the topic, we decided to study the prevalence of benign and malignant tumors in our cohort of acromegalic patients. In addition, we aimed to identify risk factors or laboratory parameters associated with the occurrence of tumors in these patients. Results: The study group included 34 patients (9 men (25.7%) and 25 women (74.3%)). No clear relationship between the levels of IGF-1 or GH and tumor development could be demonstrated, but certain risk factors, such as diabetes mellitus (DM) and obesity, were more frequent in patients with tumors. In total, 34 benign tumoral proliferations were identified, the most common being multinodular goiter. Malignant tumors were present only in women (14.70%) and the most frequent type was thyroid carcinoma. Conclusions: DM and obesity might be associated with tumoral proliferation in patients with acromegaly, and findings also present in the general population. In our study we did not find a direct link between acromegaly and tumoral proliferations.

Subgaleal Lipoma: Imaging Findings.

Subgaleal lipoma is a benign tumor of adipose tissue. It should be suspected when a semi-spherical avascular mass with well-defined margins, iso- or hyperechoic in most cases, with thin internal echogenic lines parallel to the long axis of the tumor, is observed between the galea aponeurosis and periosteum of the cranial bone. We report a series of cases of three patients who underwent surgical lesion excision and whose histopathological examination findings confirmed the diagnosis of lipoma. MAIN TEACHING POINT: The presence of long continuous echogenic lines within a lens-shaped soft tissue mass located beneath the galea aponeurosis may suggest the diagnosis of subgaleal lipoma.

Long noncoding RNAs may impact podocytes and proximal tubule function through modulating miRNAs expression in Early Diabetic Kidney Disease of Type 2 Diabetes Mellitus patients.

Aims: Long noncoding RNAs (lncRNAs) play key roles in the pathophysiology of DKD involving actions of microRNAs (miRNAs). The aims of the study were to establish the involvement of selected lncRNAs in the epigenetic mechanisms of podocyte damage and tubular injury in DKD of type 2 diabetes mellitus (DM) patients in relation to a particular miRNAs profile. Methods: A total of 136 patients with type 2 DM and 25 healthy subjects were assessed in a cross-sectional study concerning urinary albumin: creatinine ratio (UACR), eGFR, biomarkers of podocyte damage (synaptopodin, podocalyxin) and of proximal tubule (PT) dysfunction (Kidney injury molecule-1-KIM-1, N-acetyl-D-glucosaminidase-NAG), urinary lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), nuclear-enriched abundant transcript 1 (NEAT1), myocardial infarction-associated transcript (MIAT), taurine-upregulated gene 1 (TUG1), urinary miRNA21, 124, 93, 29a. Results: Multivariable regression analysis showed that urinary lncMALAT1 correlated directly with urinary synaptopodin, podocalyxin, KIM-1, NAG, miRNA21, 124, UACR, and negatively with eGFR, miRNA93, 29a (p<0.0001; R2=0.727); urinary lncNEAT1 correlated directly with synaptopodin, KIM-1, NAG, miRNA21, 124, and negatively with eGFR, miRNA93, 29a (p<0.0001; R2=0.702); urinary lncMIAT correlated directly with miRNA93 and 29a, eGFR (p<0.0001; R2=0.671) and negatively with synaptopodin, KIM-1, NAG, UACR, miRNA21, 124 (p<0.0001; R2=0.654); urinary lncTUG1 correlated directly with eGFR, miRNA93, 29a, and negatively with synaptopodin, podocalyxin, NAG, miRNA21, 124 (p<0.0001; R2=0.748). Conclusions: In patients with type 2 DM lncRNAs exert either deleterious or protective functions within glomeruli and PT. LncRNAs may contribute to DKD through modulating miRNAs expression and activities. This observation holds true independently of albuminuria and DKD stage.

Detection of Vascular Reactive Oxygen Species in Experimental Atherosclerosis by High-Resolution Near-Infrared Fluorescence Imaging Using VCAM-1-Targeted Liposomes Entrapping a Fluorogenic Redox-Sensitive Probe.

Excessive production of reactive oxygen species (ROS) and the ensuing oxidative stress are instrumental in all phases of atherosclerosis. Despite the major achievements in understanding the regulatory pathways and molecular sources of ROS in the vasculature, the specific detection and quantification of ROS in experimental models of disease remain a challenge. We aimed to develop a reliable and straightforward imaging procedure to interrogate the ROS overproduction in the vasculature and in various organs/tissues in atherosclerosis. To this purpose, the cell-impermeant ROS Brite™ 700 (RB700) probe that produces bright near-infrared fluorescence upon ROS oxidation was encapsulated into VCAM-1-targeted, sterically stabilized liposomes (VLp). Cultured human endothelial cells (EC) and macrophages (Mac) were used for in vitro experiments. C57BL6/J and ApoE-/- mice were randomized to receive normal or high-fat, cholesterol-rich diet for 10 or 32 weeks. The mice received a retroorbital injection with fluorescent tagged VLp incorporating RB700 (VLp-RB700). After two hours, the specific signals of the oxidized RB700 and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-(7-nitro-2-1,3-benzoxadiazol-4-yl) (NBD-DSPE), inserted into liposome bilayers, were measured ex vivo in the mouse aorta and various organs by high-resolution fluorescent imaging. VLp-RB700 was efficiently taken up by cultured human EC and Mac, as confirmed by fluorescence microscopy and spectrofluorimetry. After systemic administration in atherosclerotic ApoE-/- mice, VLp-RB700 were efficiently concentrated at the sites of aortic lesions, as indicated by the augmented NBD fluorescence. Significant increases in oxidized RB700 signal were detected in the aorta and in the liver and kidney of atherosclerotic ApoE-/- mice. RB700 encapsulation into sterically stabilized VCAM-1-sensitive Lp could be a novel strategy for the qualitative and quantitative detection of ROS in the vasculature and various organs and tissues in animal models of disease. The accurate and precise detection of ROS in experimental models of disease could ease the translation of the results to human pathologies.

Collision tumor of the thyroid - a challenge during the COVID-19 pandemic.

Some of the patients with anaplastic thyroid carcinomas have a coexistent differentiated thyroid cancer, sustaining the hypothesis that this cancer may develop from more differentiated tumors. We describe a case with a collision tumor of the thyroid, defined as a neoplastic lesion composed of two distinct cell populations, with distinct borders. The patient presented during the COVID-19 pandemic with dysphonia, dyspnea, multinodular goiter and a painless, rapidly enlarging, left cervical swelling. She had been first time diagnosed with left nodular goiter in 2007, with an indication for surgery, which she declined. After partial excision of the left latero-cervical adenopathy, the pathological analysis showed massive lymph node metastasis from anaplastic thyroid cancer. A total thyroidectomy was done; the postoperative pathological exam identified a papillary thyroid microcarcinoma in the right lobe and an anaplastic thyroid cancer in the left lobe. Postoperatively, levothyroxine treatment was started and the patient was referred to radiotherapy. This case highlights the importance of urgent management of some cases with compressive multinodular goiter, even during the COVID-19 pandemic.

Pharmacological inhibition of histone deacetylase reduces NADPH oxidase expression, oxidative stress and the progression of atherosclerotic lesions in hypercholesterolemic apolipoprotein E-deficient mice; potential implications for human atherosclerosis.

NADPH oxidase (Nox)-derived reactive oxygen species (ROS) are instrumental in all inflammatory phases of atherosclerosis. Dysregulated histone deacetylase (HDAC)-related epigenetic pathways have been mechanistically linked to alterations in gene expression in experimental models of cardiovascular disorders. Hitherto, the relation between HDAC and Nox in atherosclerosis is not known. We aimed at uncovering whether HDAC plays a role in mediating Nox up-regulation, oxidative stress, inflammation, and atherosclerotic lesion progression. Human non-atherosclerotic and atherosclerotic arterial samples, ApoE-/- mice, and in vitro polarized monocyte-derived M1/M2-macrophages (Mac) were examined. Male ApoE-/- mice, maintained on normal or high-fat, cholesterol-rich diet, were randomized to receive 10 mg/kg suberoylanilide hydroxamic acid (SAHA), a pan-HDAC inhibitor, or its vehicle, for 4 weeks. In the human/animal studies, real-time PCR, Western blot, lipid staining, lucigenin-enhanced chemiluminescence assay, and enzyme-linked immunosorbent assay were employed. The protein levels of class I, class IIa, class IIb, and class IV HDAC isoenzymes were significantly elevated both in human atherosclerotic tissue samples and in atherosclerotic aorta of ApoE-/- mice. Treatment of ApoE-/- mice with SAHA reduced significantly the extent of atherosclerotic lesions, and the aortic expression of Nox subtypes, NADPH-stimulated ROS production, oxidative stress and pro-inflammatory markers. Significantly up-regulated HDAC and Nox subtypes were detected in inflammatory M1-Mac. In these cells, SAHA reduced the Nox1/2/4 transcript levels. Collectively, HDAC inhibition reduced atherosclerotic lesion progression in ApoE-/- mice, possibly by intertwined mechanisms involving negative regulation of Nox expression and inflammation. The data propose that HDAC-oriented pharmacological interventions could represent an effective therapeutic strategy in atherosclerosis.

Histone Acetyltransferase-Dependent Pathways Mediate Upregulation of NADPH Oxidase 5 in Human Macrophages under Inflammatory Conditions: A Potential Mechanism of Reactive Oxygen Species Overproduction in Atherosclerosis.

Histone acetylation plays a major role in epigenetic regulation of gene expression. Monocyte-derived macrophages express functional NADPH oxidase 5 (Nox5) that contributes to oxidative stress in atherogenesis. The mechanisms of Nox5 regulation are not entirely elucidated. The aim of this study was to investigate the expression pattern of key histone acetyltransferase subtypes (p300, HAT1) in human atherosclerosis and to determine their role in mediating the upregulation of Nox5 in macrophages under inflammatory conditions. Human nonatherosclerotic and atherosclerotic tissue samples were collected in order to determine the expression of p300 and HAT1 isoforms, H3K27ac, and Nox5. In vitro determinations were done on human macrophages exposed to lipopolysaccharide in the absence or presence of histone acetyltransferase inhibitors. Western blot, immunohistochemistry, immunofluorescence, real-time PCR, transfection, and chromatin immunoprecipitation assay were employed. The protein levels of p300 and HAT1 isoforms, H3K27ac, and Nox5 were found significantly elevated in human atherosclerotic specimens. Immunohistochemistry/immunofluorescence staining revealed that p300, HAT1, H3K27ac, H3K9ac, and Nox5 proteins were colocalized in the area of CD45+/CD68+ immune cells and lipid-rich deposits within human atherosclerotic plaques. Lipopolysaccharide induced the levels of HAT1, H3K27ac, H3K9ac, and Nox5 and the recruitment of p300 and HAT1 at the sites of active transcription within Nox5 gene promoter in cultured human macrophages. Pharmacological inhibition of histone acetyltransferase significantly reduced the Nox5 gene and protein expression in lipopolysaccharide-challenged macrophages. The overexpression of p300 or HAT1 enhanced the Nox5 gene promoter activity. The histone acetyltransferase system is altered in human atherosclerosis. Under inflammatory conditions, HAT subtypes control Nox5 overexpression in cultured human macrophages. The data suggest the existence of a new epigenetic mechanism underlying oxidative stress in atherosclerosis.

2D-Shear Wave Elastography in the Evaluation of Parathyroid Lesions in Patients with Hyperparathyroidism.

BACKGROUND AND AIMS: 2D-shear wave elastography (2D-SWE) is a relatively new elastographic technique. The aim of the present study is to determine the values of the elasticity indexes (EI) measured by 2D-SWE in parathyroid benign lesions (adenomas or hyperplasia) and to establish if this investigation is helpful for the preoperative identification of the parathyroid adenoma. MATERIAL AND METHODS: The study groups were represented by 22 patients with primary or tertiary hyperparathyroidism, diagnosed by specific tests, and 43 healthy controls, in whom the thyroid parenchyma was evaluated, in order to compare the EI of the thyroid tissue with those of the parathyroid lesions. RESULTS: The mean EI measured by 2D-SWE in the parathyroid lesions was 10.2 ± 4.9 kPa, significantly lower than that of the normal thyroid parenchyma (19.5 ± 7.6 kPa; p = 0.007), indicating soft tissue. For a cutoff value of 12.5 kPa, the EI assessed by 2D-SWE had a sensitivity of 93% and a specificity of 86% (AUC = 0.949; p < 0.001) for predicting parathyroid lesions. CONCLUSION: A value lower than 12.5 kPa for the mean EI measured by 2D-SWE can be used to confirm that the lesion/nodule is a parathyroid adenoma.

The absence of CD56 expression can differentiate papillary thyroid carcinoma from other thyroid lesions.

CONTEXT: The neural cell adhesion molecule CD56 is an antigen important for the differentiation of the follicular epithelium. Recent studies have reported low or absent expression of CD56 in papillary thyroid carcinoma (PTC) and its presence in normal thyroid tissue, benign thyroid lesions, and most follicular non-PTC tumors. AIM: We wish to estimate the value of CD56 in the differentiation of PTC (including follicular variant-PTC [FV-PTC]) from other nontumoral lesions and follicular thyroid neoplasias. SETTINGS AND DESIGN: This was a retrospective, case-control study. SUBJECTS AND METHODS: We analyzed the expression of CD56 in normal thyroid follicular tissue, 15 nonneoplastic thyroid lesions (nodular hyperplasia, Graves' disease, and chronic lymphocytic thyroiditis/Hashimoto), and 38 thyroid follicular cell neoplasms (25 cases of PTC). The immunohistochemical reactions were performed on sections stained with anti-CD56 antibody. STATISTICAL ANALYSIS USED: We used the Chi-square test, values of P< 0.05 being considered statistically significant. Risk analysis was applied on these studied groups, by calculating the odds ratio (OR) value. RESULTS: Our results indicated that CD56 immunoexpression had differentiated PTC from benign nonneoplastic lesions (P = 0.002), as well as from follicular neoplasias (P = 0.046). There were no significant differences regarding CD56 expression between FV-PTC and classical PTC (P = 0.436). The immunoexpression of CD56 has differentiated PTC from other thyroid non-PTC lesions (P < 0.001), with 26.4 OR value. CONCLUSIONS: CD56 has been proved to be a useful marker in the diagnosis of PTC, including FV-PTC. Its absence can help differentiate FV-PTC from other thyroid nodules with follicular patterns.

Podocyturia parallels proximal tubule dysfunction in type 2 diabetes mellitus patients independently of albuminuria and renal function decline: A cross-sectional study.

AIMS: Detection of podocytes in the urine of patients with type 2 diabetes may indicate severe injury to the podocytes. In the course of type 2 diabetes the proximal tubule is involved in urinary albumin processing. We studied the significance of podocyturia in relation with proximal tubule dysfunction in type 2 diabetes. METHODS: A total of 86 patients with type 2 diabetes (34-normoalbuminuria; 30-microalbuminuria; 22-macroalbuminuria) and 28 healthy subjects were enrolled in the study and assessed concerning urinary podocytes, podocyte-associated molecules, and biomarkers of proximal tubule dysfunction. Urinary podocytes were examined in cell cultures by utilizing monoclonal antibodies against podocalyxin and synaptopodin. RESULTS: Podocytes were detected in the urine of 10% of the healthy controls, 24% of the normoalbuminuric, 40% of the microalbuminuric, and 82% of the macroalbuminuric patients. In multivariate logistic regression analysis, urinary podocytes correlated with urinary albumin:creatinine ratio (p=0.006), urinary nephrin/creat (p=0.001), urinary vascular endothelial growth factor/creat (p=0.001), urinary kidney injury molecule-1/creat (p=0.003), cystatin C (p=0.001), urinary advanced glycation end-products (p=0.002), eGFR (p=0.001). CONCLUSIONS: In patients with type 2 diabetes podocyturia parallels proximal tubule dysfunction independently of albuminuria and renal function decline. Advanced glycation end-products may impact the podocytes and the proximal tubule.

Therapy with atorvastatin versus rosuvastatin reduces urinary podocytes, podocyte-associated molecules, and proximal tubule dysfunction biomarkers in patients with type 2 diabetes mellitus: a pilot study.

BACKGROUND: Diabetic nephropathy is a severe complication of Type 2 diabetes. Tubular lesions may play an important role in its early stages. The aim of our study was to determine if atorvastatin protects the podocytes and the proximal tubule in patients with Type 2 diabetes. METHODS: A total of 63 patients with Type 2 diabetes completed this 6-months prospective pilot study. They were randomized to continue rosuvastatin therapy (control group) or to be administered an equipotent dose of atorvastatin (intervention group), and were assessed regarding urinary podocytes, podocyte-associated molecules, and biomarkers of proximal tubule dysfunction. RESULTS: The patients from the intervention group presented a significant reduction in podocyturia (from 7.0 to 4.0 cells/ml, p < .05), urinary nephrin (from 1.7 to 1.3 mg/g, p < .001), urinary vascular endothelial growth factor (from 262.8 to 256.9, p < .01), urinary alpha1-microglobulin (from 10.0 to 8.3 mg/g, p < .01), urinary kidney injury molecule-1 (from 139.5 to 136.3 ng/g, p < .001), and urinary advanced glycation end-products (from 112.6 to 101.3 pg/ml, p < .001). Podocyturia correlated directly with the podocyte damage biomarkers, proximal tubule dysfunction biomarkers, albumin to creatinine ratio, and advanced glycation end-products, and inversely with the glomerular filtration rate. CONCLUSIONS: In patients with Type 2 diabetes, atorvastatin exerts favorable effects on the kidney. There is a correlation between the evolution of the podocytes and of the proximal tubule biomarkers, supporting the hypothesis that the glomerular changes parallel proximal tubule dysfunction in the early stages of diabetic nephropathy.

Results of Surgical Therapy in Patients with Medullary Thyroid Carcinoma.

Medullary thyroid carcinoma (MTC) is a rare form of malignancy, having an intermediate prognosis. Controversies exist regarding the best surgical approach. The aim of the study was to analyze the outcome in a group of patients with MTC, diagnosed and followed up in a single care center. We performed a retrospective analysis of all the patients diagnosed with MTC in the Department of Endocrinology from the County Emergency Hospital Timisoara between 1992 and 2012. The study group included 19 patients, 6 men (31.6 %), mean age 41.2 ± 12.5 years (20-72 years). The preoperative diagnosis was based on the protocol for nodular thyroid disease. Total or near-total thyroidectomy was performed in 10 out of 16 patients who could be operated. Postoperative follow-up included repeated measurements of serum calcitonin and imaging investigations. Nine out of the total of 19 (47.3 %) patients had hereditary forms of MTC. Most of the cases (84.2 %) were submitted to surgery. The median duration of follow-up was 84 months. The pTNM staging indicated that the majority of the patients with hereditary MTC were diagnosed in an earlier stage. Disease remission was achieved in 7 cases (43.8 %). Four patients, all with sporadic forms, died. Survival rates at 1, 5 and 10 years were significantly higher (p = 0.048) in patients with hereditary MTC. An early diagnosis of MTC allows a better surgical approach and an improved survival rate. We support the general recommendation that modified radical neck dissection is not necessary for all the patients with MTC.

The usefulness of quantifying intraepidermal nerve fibers density in the diagnostic of diabetic peripheral neuropathy: a cross-sectional study.

BACKGROUND: Distal symmetric polyneuropathy (DSPN) is the most common complication of type 2 diabetes mellitus (T2DM) and the most common form of peripheral neuropathy. DSPN increases the risk of foot ulceration up to seven-fold, and is a significant risk factor in more than 60 % of the amputations of the lower limbs in patients with T2DM. The aims of our study were to evaluate the difference in the density of intraepidermal nerve fibers (IENF) in patients with respectively without DSPN, to evaluate the strength of the relationship between the symptomatology of the DSPN and IENF density and to define a cutoff value of the IENF density for the diagnosis of DSPN. METHODS: We enrolled, according to a consecutive, population-based method, 36 patients with T2DM admitted in our Clinic. For all patients, we measured HbA1c, lipid profile, body mass index and we assessed the presence and severity of DSPN using the evaluation of clinical symptoms, nerve conduction velocity and IENF density quantification. RESULTS: The presence of neuropathy was significantly associated with a decreased density of IENF for both the proximal (11.6 vs. 14.9 fibers/mm; p = 0.014) and the distal biopsies (7.2 vs. 8.6 fibers/mm; p = 0.020). The optimal threshold value of IENF density (the point with the maximum sum of specificity and sensitivity), according to our model, was 10.1 fibers/mm. CONCLUSIONS: Skin biopsy followed by IENF density quantification is a valid, reliable tool for the diagnosis of DSPN.

Real-time shear wave elastography may predict autoimmune thyroid disease.

OBJECTIVE: To evaluate and compare the values of the elasticity index as measured by shear wave elastography in healthy subjects and in patients with autoimmune thyroid disease, in order to establish if this investigation can predict the occurrence of autoimmune thyroid disease. METHODS: A total of 104 cases were included in the study group: 91 women (87.5%), out of which 52 (50%) with autoimmune thyroid disease diagnosed by specific tests and 52 (50%) healthy volunteers, matched for age and gender. For all the subjects, three measurements were performed on each thyroid lobe and a mean value was calculated. The data were expressed in kPa. The investigation was performed with an Aixplorer system (SuperSonic Imagine, France), using a linear high-resolution 15-4 MHz transducer. RESULTS: The mean value for the elasticity index was similar in the right and the left thyroid lobes, both in normal subjects and in patients with autoimmune thyroid disease: 19.6 ± 6.6 vs. 19.5 ± 6.8 kPa, p = 0.92, and 26.6 ± 10.0 vs. 25.8 ± 11.7 kPa, p = 0.71, respectively. This parameter was significantly higher in patients with autoimmune thyroid disease than in controls (p < 0.001). For a cut-off value of 22.3 kPa, which resulted in the highest sum of sensitivity and specificity, the elasticity index assessed by shear wave elastography had a sensitivity of 59.6% and a specificity of 76.9% (AUROC = 0.71; p < 0.001) for predicting the presence of autoimmune thyroid disease. CONCLUSION: Quantitative elasticity index measured by shear wave elastography was significantly higher in autoimmune thyroid disease than in normal thyroid parenchyma and may predict the presence of autoimmune thyroid disease.

Some clinical aspects in chronic autoimmune thyroiditis associated with thyroid differentiated cancer.

BACKGROUND: The coexistence of Hashimoto's thyroiditis (HT) with differentiated thyroid cancer (DTC) was reported with a heterogeneous incidence. The wide distribution of this association may be related to differences in the level of morphological examination, autoimmunity used criteria, patient selection, surgical indication, genetic background, geographical and environmental factors.Some consider the coexistence of these two entities a coincidental one, others suspecting a causative link between these conditions. METHODS: This retrospective paper included 216 patients with HT, issued from an iodine-replete area. 21 cases of nodular HT were investigated by means of: thyroid functional tests (TFT), immunological determinations, thyroid ultrasonography (US) and cytological analysis.ALL CASES WERE OPERATED BECAUSE OF DIFFERENT REASONS: compressive symptoms and signs, suspicious sonographic features and certain cytological smears (malignant, indeterminate and non-diagnostic). RESULTS: The morphologic investigation revealed 9 patients with DTC and 12 cases with benign thyroid disease (BTD).None of the US analyzed characteristics provided sufficient accuracy for the diagnosis of DTC in cases with HT. The preoperative cytological examination by means of fine-needle-aspiration biopsy (FNAB) showed a better sensitivity and specificity vs. US criteria. CONCLUSION: The coexistence of HT with DTC represents a clinical reality with yet unknown significance. The difficulty of diagnosis imposes the corroboration of different types of investigations. The best diagnostic accuracy seems to be offered by thyroid US and thyroid cytological investigation.

Evaluation of proliferation potential in thyroid normo-/hypofunctioning and hyperfunctioning nodules.

INTRODUCTION: Thyroid follicular adenomas (FA) and adenomatous thyroid nodules (AN) - lesions that are frequently found in areas with iodine deficiency, can be normo-/hypofunctioning (scintigraphically cold - SCN) or hyperfunctioning (scintigraphically hot - SHN) nodules. AIM: Evaluation of proliferation potential in thyroid nodules on tissue samples obtained at surgery from euthyroid patients clinically diagnosed with SCN and from patients with thyroid hyperfunction and SHN. MATERIALS AND METHODS: We investigated the proliferation activity estimated by assessing PCNA and Ki-67 proliferation markers in 20 SCN (eight FA and 12 AN) and 16 toxic nodules (six hyperfunctioning FA and 10 toxic multinodular goiters), on formalin-fixed and paraffin-embedded tissue samples, 4-5 µm thick; we used the immunohistochemical technique in LSAB system (DAB visualization) with anti-PCNA (PC10) and anti-Ki-67 (MIB-1) monoclonal antibodies. For each case, we calculated the proliferation index PI-PCNA and PI-Ki-67. The dates were statistically evaluated using the t-unpaired test. RESULTS: We observed a higher PI-PCNA in thyroid nodules than in the normal surrounding thyroid tissue, with statistically significant values for FA (14.3% vs. 3.8%; p<0.029) and also for AN (8.36% vs. 1.24%; p<0.001). The mean PI-Ki-67 in nodules vs. surrounding thyroid tissue was 1.64% vs. 1.10% in FA (p<0.35) and 1.07% vs. 0.51% in AN (p>0.05). We also noted: (1) significantly higher PI-PCNA values (p < 0.01) in FA (14.03%) than in AN (8.36%), as compared to statistically insignificant values for Ki-67 (1.64% vs. 1.07%; p>0.05); (2) increased proliferation rate (p<0.01) in thyroid nodules with aspects of lymphocytic thyroiditis (LT) (PI-Ki-67 was 1.21%) as compared to nodules without LT (PI-Ki-67 was 0.12%); (3) a mean PI-PCNA of 8.5% and PI-Ki-67 of 4.61% in toxic thyroid nodules (TTN) vs. 3.01% and 1.5% in normal surrounding thyroid, respectively. CONCLUSIONS: The clinical expression of SCN is the consequence of increased thyrocyte proliferation in the nodules; the increased proliferative potential of TTN thyrocytes is a common feature of nodules, independent of their histopathological characteristics.