Atypical parathyroid adenoma: clinical and anatomical pathologic features.

BACKGROUND: Primary hyperparathyroidism is an endocrine pathology that affects calcium metabolism. Patients with primary hyperparathyroidism have high concentrations of serum calcium or high concentrations of parathyroid hormone, or incorrect parathyroid hormone levels for serum calcium values. Primary hyperparathyroidism is due to the presence of an adenoma/single-gland disease in 80-85%. Multiple gland disease or hyperplasia accounts for 10-15% of cases of primary hyperparathyroidism. Atypical parathyroid adenoma and parathyroid carcinoma are both responsible for about 1.2-1.3% and 1% or less of primary hyperparathyroidism, respectively. METHODS: We performed a retrospective cohort study and enrolled 117 patients with primary hyperparathyroidism undergoing minimally invasive parathyroidectomy. Histological and immunohistochemical examination showed that 107 patients (91.5%) were diagnosed with typical adenoma (group A), while 10 patients (8.5%) were diagnosed with atypical parathyroid adenoma (group B). None of the patients were affected by parathyroid carcinoma. RESULTS: Significant statistical differences were found in histological and immunohistochemical parameters as pseudocapsular invasion (p <  0.001), bands of fibrosis (p <  0.001), pronounced trabecular growth (p <  0.001), mitotic rates of > 1/10 high-power fields (HPFs) (p <  0.001), nuclear pleomorphism (p = 0.036), thick capsule (p <  0.001), Ki-67+ > 4% (p <  0.001), galectin-3 + (p = 0.002), and protein gene product (PGP) 9.5 + (p = 0.038). CONCLUSIONS: Atypical parathyroid adenoma is a tumor that has characteristics both of typical adenoma and parathyroid carcinoma. The diagnosis is reached by excluding with strict methods the presence of malignancy criteria. Atypical parathyroid adenoma compared to typical adenoma showed significant clinical, hematochemical, histological, and immunohistochemical differences. We did not find any disease relapse in the 10 patients with atypical parathyroid adenoma during 60 months of follow-up time.

Cardio-Renal Syndrome Type 4: The Correlation Between Cardiorenal Ultrasound Parameters.

Bakground/Aims: Cardiovascular diseases represent the leading causes of morbidity and mortality in patients with cronich kidney disease (CKD). The pathogenesis includes a complex, bidirectional interaction between heart and kidney termed cardiorenal syndrome type 4. The aim of study was to evaluate the association between renal and cardiovascular ultrasonographic parameters and identify early markers of cardiovascular risk. METHODS: A total of 35 patients with CKD and 25 healthy controls, were enrolled and we have evaluated inflammatory indexes, mineral metabolism, renal function, renal and cardiovascular ultrasonographic parameters. RESULTS: Tricuspid anular plane systolic excursion (TAPSE) and estimated pulmonary artery systolic pressure (ePAPs) showed a statistically significant difference between CKD patients and healthy controls (p<0.001, p=0.05). Also 25 hydroxyvitaminD (25-OH-VitD), parathyroid hormone (iPTH), posphorus, serum uric acid, renal resistive index (RRI) and C-reactive protein (CRP) showed a significant difference between the two groups (p=0.002, p<0.001, p<0.001, p<0.001, p<0.001, p<0.001). Moreover the TAPSE correlated positively with estimated glomerula filtration rate (eGFR) and negatively with RRI (p=0.05, p=0.008), while ePAPs correlated negatively with eGFR and positively with RRI (p=0.029, p<0.001). CONCLUSION: CKD can contribute to the development and progression of right ventricle dysfunction with endothelial dysfunction, inflammation and mineral metabolism disorders. Accurate assessment of right ventricular function is recommended in patients with CKD. RRI and echocardiographic parameters can be an important instrument for the diagnosis, prognosis and therapeutic assessment of cardio-renal syndrome in these patients.

Early markers of cardiovascular risk in chronic kidney disease.

BACKGROUND: Patients with chronic kidney disease (CKD) present a markedly increased cardiovascular (CV) morbidity and mortality since the early stages and have a high prevalence of accelerated atherosclerosis, inflammation and endothelial dysfunction. Nontraditional cardiovascular risk factors and serum cardiac biomarkers would contribute to explain this increased morbidity. AIM: The aim is to investigate the relation among serum cardiac biomarkers (N-terminal pro-brain natriuretic peptide (NT-proBNP), cardiac troponin T (cTnT), nontraditional cardiovascular risk factors (serum uric acid, homocysteine), inflammatory indexes (C-reactive protein (CRP) serum ferritin, fibrinogen) and noninvasive predictors of atherosclerosis (carotid intima-media thickness (cIMT), brachial artery flow mediated dilation (baFMD), and left ventricular mass index (LVMI)) in CKD patients. MATERIALS AND METHODS: In 50 patients with CKD in stage 2/3 kidney disease outcomes quality initiative (KDOQI) and 18 age- and sex-matched healthy controls, the following parameters were measured: cardiac markers (cTnT and NT-proBNP), renal function, inflammatory markers (CRP, serum ferritin and fibrinogen), serum uric acid and homocysteine. We have also evaluated LVMIs, cIMT and baFMD. RESULTS: In our study, we showed an increase of NT-proBNP and the serum cTnT, of serum uric acid and homocysteine with a positive correlation with the increase of cIMT and LVMI and reduced baFMD compared with the controls. CONCLUSIONS: Serum cardiac biomarkers and nontraditional cardiovascular risk factors increase already in the stage 2/3 KDOQI contributing to explain the high cardiovascular morbidity and mortality of these patients. The NT-proBNP seems to have a rise earlier compared with serum cTnT; however, both seemed to be a useful clinical biomarker for evaluating noninvasive predictors of atherosclerosis in CKD patients.

Vitamin D deficiency, insulin resistance, and ventricular hypertrophy in the early stages of chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is associated with markedly increased cardiovascular (CV) risk. This increase is not fully explained by traditional CV risk factors but may in part be mediated by nontraditional risk factors, such as inadequate vitamin D (vit D) levels and insulin resistance (IR). Although IR is shown in nondiabetic CKD, its association with vit D deficiency and vascular disease in this population is unknown and what this study aims to investigate. MATERIALS AND METHODS: The study comprised 67 patients with CKD (eGFR ≥ 30 mL/min) and 15 healthy controls matched for age and sex. The phlogosis indexes, vit D levels, IR, carotid intima-media thickness (cIMT), and left ventricular mass index (LVMI) were measured. RESULTS: In our study, the mean value of LVMI and cIMT was significantly higher in patients with eGFR ≥ 30 mL/min compared with controls (p = 0.037 and p < 0.001). The IR and intact parathyroid hormone (iPTH) levels were increased in CKD patients, whereas the serum levels of vit D were significantly reduced (p = 0.044, p = 0.012, p = 0.038). A positive correlation was found between LVMI and IR (r = 0.704, p = 0.041) and a negative correlation was found between IR and vit D levels (r = -0.238, p = 0.031). CONCLUSIONS: In our study, IR and vit D deficiency were found to be independent predictors of left ventricular hypertrophy and atherosclerotic disease. Vitamin D deficiency and IR are thus associated with increased CV risk. More novel approaches to improving IR and vit D supplementation in the CKD population might lead to potential strategies for preventing excess CV mortality.

[The risk of bleeding associated with low molecular weight heparin in patients with renal failure]. / Rischio emorragico nell'utilizzo di eparina a basso peso molecolare nel paziente nefropatico?

Cardiovascular mortality and morbidity are higher in patients with chronic renal disease than in the general population. Patients with chronic renal disease are in the highest risk group for thromboembolic disease and many clinical trials have demonstrated the greater safety and efficacy of low-molecular-weight heparin (LMWH) versus unfractionated heparin (UFH). LMWH is cleared only by the kidneys while UFH is cleared by the renal and hepatic routes. Furthermore, LMWH has a significant accumulative effect in patients with impaired renal function (creatinine clearance <30 mL/min). The aim of this study was to evaluate the risk of bleeding when LMWH is used as an anticoagulant in hemodialysis or for treatment of acute thromboembolic disease in patients with renal failure. Twenty-one adult patients were enrolled, 13 with end-stage renal disease requiring chronic hemodialysis and 6 with acute thromboembolic disease and severe renal insufficiency (creatinine clearance <30 mL/min). Group A consisted of 13 patients receiving LMWH (enoxaparin 60 IU/kg/day) for preventing thrombosis of the extracorporeal dialysis circuit. Group B consisted of 8 patients with acute thromboembolic disease receiving LMWH (enoxaparin 60 IU/kg/day). In all patients anti-Xa activity was measured by a chromogenic assay (HEMONOX). In the first group 2 blood samples were taken during the dialysis session (2-4 hours) and a third sample after the end of the session up to 48 hours following enoxaparin injection; in the second group a blood sample was taken 4 days after the start of LMWH treatment, 2 hours after its daily administration. In group A, all dialysis sessions were performed with no minor or major bleeding. Anti-Xa activity was highest 2 hours after the start and remained above 100 seconds after the end of the session, while 44 hours after injection, at the start of the next dialysis session, it was low or absent (<100 seconds). In the second group there were 2 major bleeding episodes, 2 minor bleeding episodes, 1 prolonged time to hemostasis after needle removal, and 2 bleeding episodes at the vascular access site (central venous catheter). Anti-Xa activity was consistently higher than 200 seconds (therapeutic target range:100-200 seconds) and showed interindividual variability (in 2 patients the anti-Xa time was more than 900 seconds), indicating a high risk of bleeding. LMWH seems to be as effective and safe as UFH in terms of bleeding complications and in preventing extracorporeal circuit thrombosis in patients on hemodialysis. Our results indicate that it is preferable to avoid invasive procedures for 12 hours following a dialysis session performed with LMWH anticoagulation because the anticoagulant effect lasted at least 4 hours after its injection. These data suggest that in patients with acute thromboembolic events and severe renal insufficiency, standard anticoagulation with LMWH is not recommended because of an increased risk of major and minor bleeding.

Total Parathyroidectomy with Subcutaneous Parathyroid Forearm Autotransplantation in the Treatment of Secondary Hyperparathyroidism: A Single-Center Experience.

INTRODUCTION: Secondary hyperparathyroidism is common in chronic kidney disease. Parathyroidectomy is indicated in refractory hyperparathyroidism when medical treatments and so the parathyroid hormone levels cannot be lowered to acceptable values without causing significant hyperphosphatemia or hypercalcemia. The aim of this study is to compare the efficacy and safety of total parathyroidectomy with subcutaneous forearm autotransplantation with total parathyroidectomy with intramuscular forearm autotransplantation. MATERIALS AND METHODS: A single-center retrospective cohort study of total parathyroidectomy with forearm autotransplantation from January 2002 to February 2013 was performed. According to the surgical technique, patients were divided into an intramuscular group (Group 1) and a subcutaneous group (Group 2). 38 patients with secondary hyperparathyroidism were enrolled; 23 patients were subjected to total parathyroidectomy with parathyroid tissue replanting in the subcutaneous forearm of the upper nondominant limb, while 15 patients were subjected to replanting in the intramuscular seat. RESULTS: A total of 38 patients (56 ± 13 years) were enrolled. In both groups, the preoperative iPTH value was markedly high, 1750 ± 619 pg/ml in the intramuscular autotransplantation group and 1527 ± 451 pg/ml in the subcutaneous autotransplantation group (p = 0.079). Transient hypoparathyroidism was shown in 7 patients, and 1 patient showed persistent hypoparathyroidism (p = 0.387). 2 patients showed persistent hyperparathyroidism (p = 0.816), and in 2 others was found recurrent hyperparathyroidism (p = 0.816); 3 of them underwent autograftectomy. The anterior compartment of the forearm nondominant limb was sacrificed in 1 case of intramuscular autotransplantation with functional arm deficit. CONCLUSIONS: The efficacy and safety of parathyroid tissue autotransplantation in the subcutaneous forearm of the upper nondominant limb is confirmed with a good rate of tissue engraftment and with a comparable number of postsurgical transient and persistent hypoparathyroidism and hyperparathyroidism incidence in both techniques. Furthermore, this technique preserves arm functionality in the case of autograftectomy. Consequently, it is our opinion that total parathyroidectomy with subcutaneous forearm autotransplantation is currently the best choice.

Vascular Endothelial Growth Factor Inhibitor Therapy and Cardiovascular and Renal Damage in Renal Cell Carcinoma.

BACKGROUND: Sunitinib, a tyrosine kinase inhibitor of vascular endothelial growth factor (VEGF), is approved for first and second line treatment of advanced renal cell carcinoma (RCC). Knowledge on the effects of sunitinib on cardiovascular (CV) risk and renal damage is limited. AIM: To evaluate possible renal and CV damage in patients with RCC treated with sunitinib. MATERIALS AND METHODS: Patients with metastatic RCC treated with sunitinib were enrolled. This population was evaluated before starting treatment (T0) and after 3 months (T1). Laboratory and instrumental parameters, including interventricular septum (IVS) and left ventricular mass index (LVMI) were recorded before and after treatment. RESULTS: Thirty-two patients (13 female, 19 male, mean age 62.7±9.9 years) were enrolled. We observed overtime, a significant reduction in estimated glomerular filtration rate (eGFR) (p=0.01), hemoglobin (Hb) (p=0.04) and 25-hydroxyvitamin D (25-OH-VitD) (p=0.002), in association with a significant increase in serum phosphorus (p<0.001), systolic blood pressure (SBP) (p<0.001), diastolic blood pressure (DBP) (p<0.001), IVS (p=0.03) and proteinuria (p<0.001), while we showed no significant differences in glycosuria, phosphaturia, serum uric acid, intact parathormone, and LVMI. CONCLUSION: We observed the development of renal damage and worsening of CV indices in patients treated with sunitinib. We suggest to consider a careful assessment of renal function and CV risk factors, before initiation and during administration of this drug.

ASIA syndrome, calcinosis cutis and chronic kidney disease following silicone injections. A case-based review.

An immunologic adjuvant is a substance that enhances the antigen-specific immune response preferably without triggering one on its own. Silicone, a synthetic polymer used for reconstructive and cosmetic purposes, can cause, once injected, local and/or systemic reactions and trigger manifestations of autoimmunity, occasionally leading to an overt autoimmune disease. Siliconosis, calcinosis cutis with hypercalcemia and chronic kidney disease have all been reported in association with silicone injection. Here, we describe a case of autoimmune/auto-inflammatory syndrome induced by adjuvants, calcinosis cutis and chronic kidney disease after liquid silicone multiple injections in a young man who underwent a sex reassignment surgery, followed by a review of the literature. To our knowledge, this is the first report describing the concomitance of the three clinical conditions in the same patients. The link between silicone and the immune system is not completely understood yet and requires further reports and investigations with long-term data, in order to identify the main individual and genetical risk factors predisposing to the wide spectrum of the adjuvant-induced responses.