Contact endoscopy for identifying the parathyroid glands during thyroidectomy

Aim of this study was to analyse contact endoscopy as an auxiliary method for identifying parathyroid glands during thyroid surgery and to identify other variables that may interfere with this correlation. overall, 125 patients underwent thyroid surgery between January 2004 and February 2006. The variables analysed were: the total duration of surgery; time taken to locate and identify parathyroid glands; improvement in identifying these; numbers of parathyroid glands located by the surgeon and confirmed by contact endoscopy; histopathological diagnosis; presence of thyroiditis; thyroid weight; number of parathyroid glands left in thyroid specimens; and number of parathyroid gland autotransplantations. A total of 331 parathyroid glands were observed by the surgeon. however, 282 glands were identified by contact endoscopy. nine parathyroid glands (7.2%) were observed together with thyroid specimens (Kappa = 0.534). The longer the total duration of surgery (p = 0.03) and time taken to locate and identify (p = 0.00) the parathyroid glands by contact endoscopy, the lower the observed agreement. The second year of performing contact endoscopy led to better agreement between the results (p = 0.02). in conclusion, contact endoscopy is an efficient auxiliary method for identifying parathyroid glands during thyroid surgery. During the period studied, association between total duration of surgery and time taken to locate and identify parathyroid glands was statistically significant.

Accentuated osteoclastic response to parathyroid hormone undermines bone mass acquisition in osteonectin-null mice

Matricellular proteins play a unique role in the skeleton as regulators of bone remodeling, and the matricellular protein osteonectin (SPARC, BM-40) is the most abundant non-collagenous protein in bone In. the absence of osteonectin, mice develop progressive low turnover osteopenia, particularly affecting trabecular bone. Polymorphisms in a regulatory region of the osteonectin gene are associated with bone mass in a subset of idiopathic osteoporosis patients, and these polymorphisms likely regulate osteonectin expression. Thus it is important to determine how osteonectin gene dosage affects skeletal function. Moreover, intermittent administration of parathyroid hormone (PTH) (1-34) is the only anabolic therapy approved for the treatment of osteoporosis, and it is critical to understand how modulators of bone remodeling, such as osteonectin, affect skeletal response to anabolic agents. In this study, 10 week old female wild type, osteonectin-haploinsufficient, and osteonectin-null mice (C57Bl/6 genetic background) were given 80 mu g/kg body weight/day PTH(1-34) for 4 weeks. Osteonectin gene dosage had a profound effect on bone microarchitecture. The connectivity density of trabecular bone in osteonectin-haploinsufficient mice was substantially decreased compared with that of wild type mice, suggesting compromised mechanical properties. Whereas mice of each genotype had a similar osteoblastic response to PTH treatment, the osteoclastic response was accentuated in osteonectin-haploinsufficient and osteonectin-null mice. Eroded surface and osteoclast number were significantly higher in PTH-treated osteonectin-null mice, as was endosteal area. In vitro studies confirmed that PTH induced the formation of more osteoclast-like cells in marrow from osteonectin-null mice compared with wild type. PTH treated osteonectin-null bone marrow cells expressed more RANKL mRNA compared with wild type. However, the ratio of RANKL:OPG mRNA was somewhat lower in PTH treated osteonectin-null cultures. Increased expression of RANKL in response to PTH could contribute to the accentuated osteoclastic response in osteonectin(-/-) mice, but other mechanisms are also likely to be involved. The molecular mechanisms by which PTH elicits bone anabolic vs. bone catabolic effects remain poorly understood. Our results imply that osteonectin levels may play a role in modulating the balance of bone formation and resorption in response to PTH. (c) 2008 Elsevier Inc. All rights reserved.

Effects of Time on Ultrastructural Integrity of Parathyroid Tissue Before Cryopreservation

Cryopreservation of parathyroid tissue is used in the surgical treatment of secondary hyperparathyroidism. After surgical resection, the tissue is temporarily maintained in a cell culture solution until it arrives at the specialized laboratory where the cryopreservation process will take place. The present study evaluates the time that the human hyperplastic parathyroid gland tissue can wait before cryopreservation, based on parathyroid cell ultrastructural integrity. This prospective study included 11 patients who underwent total parathyroidectomy with heterotopic autotransplantation and cryopreservation of parathyroid tissue fragments. Part of the tissue was kept in cell culture solution at 4A degrees C. Five time periods between 2 and 24 h were defined, and parathyroid fragments were kept in the solution for that length of time. At the end of each period, the fragments were removed from the transport solution, fixed, and prepared for ultrathin sections. Of the 11 cases studied, 10 showed ultrastructural findings consistent with cellular viability in tissue fragments that remained in the transport solution up to 12 h. Electron microscopy revealed that cell adhesion and the integrity of plasma membranes, nuclei, and mitochondria were preserved in one case for up to 24 h. Changes in mitochondrial structure represented the most constant ultrastructural damage seen in the cases studied, in addition to the presence of edema and cell vacuoles. Analysis of the ultrastructure of hyperplastic parathyroid gland tissue showed that ultrastructural integrity was in most cases properly maintained in fragments stored up to 12 h in a cell culture solution at 4A degrees C.

The Bone Histology Spectrum in Experimental Renal Failure: Adverse Effects of Phosphate and Parathyroid Hormone Disturbances

Bone disease is a common disorder of bone remodeling and mineral metabolism, which affects patients with chronic kidney disease. Minor changes in the serum level of a given mineral can trigger compensatory mechanisms, making it difficult to evaluate the role of mineral disturbances in isolation. The objective of this study was to determine the isolated effects that phosphate and parathyroid hormone (PTH) have on bone tissue in rats. Male Wistar rats were subjected to parathyroidectomy and 5/6 nephrectomy or were sham-operated. Rats were fed diets in which the phosphate content was low, normal, or high. Some rats received infusion of PTH at a physiological rate, some received infusion of PTH at a supraphysiological rate, and some received infusion of vehicle only. All nephrectomized rats developed moderate renal failure. High phosphate intake decreased bone volume, and this effect was more pronounced in animals with dietary phosphate overload that received PTH infusion at a physiological rate. Phosphate overload induced hyperphosphatemia, hypocalcemia, and changes in bone microarchitecture. PTH at a supraphysiological rate minimized the phosphate-induced osteopenia. These data indicate that the management of uremia requires proper control of dietary phosphate, together with PTH adjustment, in order to ensure adequate bone remodeling.

Expression of neurotensin and its receptors in pituitary adenomas

The neurotensin (NT) produced in the hypothalamus and in pituitary gonadotrophs and thyrotrophs participates in neuroendocrine regulation. Recently, the involvement of this peptide in normal and neoplastic cell proliferation has been postulated. In the present study, we evaluated the expression of NT and its receptors (NTR1, 2 and 3) in a series of 50 pituitary adenomas [11 growth hormone (GH)-, eight prolactin (PRL)-, four adrenocorticotrophic hormone (ACTH)- and 27 nonfunctioning adenomas]. NT mRNA expression was significantly higher in functioning compared to nonfunctioning adenomas and with normal pituitary. Nonfunctioning pituitary adenomas showed lower expression of NT mRNA than normal pituitary. In the immunohistochemical study of functioning adenomas, NT was colocalised with GH, PRL and ACTH secreting cells. In nonfunctioning adenomas, the NT immunoreactivity intensity was variable among the samples. NTR3 mRNA expression was observed in all examined samples and was higher in the adenomas, both functioning and nonfunctioning, compared to normal pituitary. By contrast, NTR1 and NTR2 mRNA were not detected in either pituitary adenomas or normal tissue. The higher expression of NTR3, as well as the expression of NT by tumoural corticotrophs, lactotrophs and somatotrophs, which are cells types that do not express this peptide in the normal pituitary, suggests that NT autocrine and/or paracrine stimulation mediated by NTR3 may be a mechanism associated with the tumourigenesis of functioning adenomas.

Dynamics of Parathyroid Hormone Secretion After Total Parathyroidectomy and Autotransplantation

Secondary hyperparathyroidism is a common complication in uremic patients. Total parathyroidectomy combined with partial autotransplantation into brachioradialis muscle has been the preference among the options for surgical treatment. This study was designed to evaluate the reserve and ability of suppression of autotransplanted parathyroid tissue using dynamics tests. We studied, prospectively, 12 patients in recent (RP) and late (LP) postoperative of total parathyroidectomy with autotransplantation. For analysis of the secretory reserve capacity, we induced hypocalcemia by ethylenediaminetetraacetic acid (EDTA) infusion. Furthermore, for analysis of the ability for parathyroid hormone (PTH) suppression, the hypercalcemia test was used, by intravenous administration of calcium in LP. In RP, there was a decrease in the average serum levels of PTH, phosphorus, and alkaline phosphatase, which ranged from 13 to 231 (87 +/- A 65) pg/ml, 2.3 to 6.2 (3.3 +/- A 1.1) mg/dl, and 77 to 504 (250 +/- A 135) U/L, respectively, similar to that observed in LP. The analysis of the average curve of variations in PTH during testing of the stimulus with EDTA showed lack of secretion in RP and partial response in LP. Impaired suppression ability of the graft in LP was observed in the test with intravenous calcium. Total parathyroidectomy followed by partial autotransplantation was effective in reducing PTH serum levels in patients with terminal kidney disease. The elevation of serum calcium during the suppression test was not able to inhibit the autograft gland secretion of PTH. The assessment of parathyroid graft function demonstrated an inability to respond to the stimulus of hypocalcemia induced by EDTA, although there was a partial recovery, in late postoperative period.

Parathyroid hormone secretion in women in late menopause submitted to EDTA-induced hypocalcemia

Objective: The physiological role of parathormone (PTH) in the maintenance of bone mass in humans has not been fully defined. The main objective of the present study was to evaluate basal and EDTA-stimulated PTH levels in Young women (Group Y = 30.9 years, N = 7) and in women in late menopause (Group M = 64.7 years, N = 7) and their relationship to bone mineral density. Methods: The PTH secretion test was performed by induction of hypocalcemia through intravenous administration of EDTA for 2 h. Blood samples were collected every 10 min and used for ionic calcium and PTH measurements. During the basal period, an additional sample was collected for the determination of osteocalcin, FSH, and estradiol. A sample of early morning second voided urine was collected for analysis of deoxypiridinoline and creatinine Lis well as bone mass density (BMD) was determined by dual X-ray energy absorptiometry (DEXA). Results: The aged patients presented lower femoral BMD (Y = 0.860 g/cm(2) vs. M = 0.690 g/cm(2), P < 0.01), With four of them having a T score lower than - 2.5 S.D. Basal, and during the EDTA infusion, PTH values were similar in both groups. However, among aged volunteers, the rise in PTH levels was higher for subjects with normal bone mass (NM: peak = 236 pg/ml) than for subjects with osteoporosis (OM: peak = 134.4 pg/ml). Conclusions: The present results suggest that PTH can have a modulating effect on the rate of bone loss during late menopause. (c) 2007 Elsevier Ireland Ltd. All rights reserved.

Mechanisms underlying the long-term regulation of NHE3 by parathyroid hormone

The activity of the Na(+)/H(+) exchanger NHE3 is regulated by a number of factors including parathyroid hormone (PTH). In the current study, we used a renal epithelial cell line, the opossum kidney (OKP) cell, to elucidate the mechanisms underlying the long-term effects of PTH on NHE3 transport activity and expression. We observed that NHE3 activity was reduced 6 h after addition of PTH, and this reduction persisted almost unaltered after 24 h. The decrease in activity was associated with diminished NHE3 cell surface expression at 6, 16, and 24 h after PTH addition, total cellular NHE3 protein at 16 and 24 h, and NHE3 mRNA abundance at 24 h. The lower levels of NHE3 mRNA were associated to a small, but significant, decrease in mRNA stability. Additionally, by analyzing the rat NHE3 gene promoter activity in OKP cells, we verified that the regulatory region spanning the segment -152 to +55 was mildly reduced under the influence of PTH. This effect was completely abolished by the presence of the PKA inhibitor KT 5720. In conclusion, long-term exposure to PTH results in reduction of NHE3 mRNA levels due to a PKA-dependent inhibitory effect on the NHE3 promoter and a small reduction of mRNA half-life, and decrease in the total amount of protein which is preceded by endocytosis of the apical surface NHE3. The decreased NHE3 expression is likely to be responsible for the reduction of sodium, bicarbonate, and fluid reabsorption in the proximal tubule consistently perceived in experimental models of PTH disorders.

Association between osteoporosis and rheumatoid arthritis in women: a cross-sectional study

CONTEXT AND OBJECTIVES: Osteoporosis has frequently been observed in patients with rheumatoid arthritis. The present study was undertaken in order to evaluate factors associated with osteoporosis among women with rheumatoid arthritis. DESIGN AND SETTING: Cross-sectional study, carried out in a public hospital in São Paulo. METHODS: The participants were 83 women with rheumatoid arthritis (53.7 ± 10.0 years old). Bone mineral density (BMD) and body composition were measured by dual energy X-ray absorptiometry. The patients were divided into three groups according to BMD: group 1, normal BMD (n = 24); group 2, osteopenia (n = 38); and group 3, osteoporosis (n = 21). Tests were performed to compare differences in means and correlations, with adjustments for age, duration of disease and cumulative corticosteroid. The relationships between clinical factors, physical activity score, dietary intake, body composition and biochemical parameters were analyzed using linear regression models. RESULTS: Mean calcium, vitamin D and omega-6 intakes were lower than the recommendations. Associations were found between BMD and age, disease duration, parathyroid hormone concentration and fat intake. The linear regression model showed that being older, with more years of disease and lower weight were negatively correlated with BMD [Total femur = 0.552 + 0.06 (weight) + 0.019 (total physical activity) - 0.05 (age) - 0.003 (disease duration); R² = 48.1; P < 0.001]. CONCLUSION: The present study indicates that nutritional factors and body composition are associated with bone mass in women with rheumatoid arthritis.

Half-Pringle Maneuver: A Useful Tool in Laparoscopic Liver Resection

Introduction: Laparoscopic liver resections are becoming a common procedure, and bleeding remains the major concern during parenchymal transection. Total vascular inflow occlusion can be performed, but ischemic reperfusion injuries can lead to postoperative morbidity. On the other hand, hemihepatic inflow occlusion, leading to hemiliver ischemia, decreases the amount of liver parenchyma submitted to reperfusion damage and offers the advantage of reduced blood loss. Objective: The aim of this work was to describe our experience with laparoscopic the half-Pringle maneuver for segmentar or nonanatomic liver resctions. Patients and Methods: Eight patients submitted to laparoscopic liver resection in a single tertiary center. Results: There were 5 women and 3 men with a mean age of 40.2 years (range, 26-54). Mean tumor size was 4.1 cm (range, 2.6-6.0), and mean hospital stay was 3.1 days (1-5). There were 3 liver adenomas, 2 hepatocellular carcinomas, 1 metastatic melanoma, 1 metastatic colorectal carcinoma, and 1 peripheral colangiocarcinoma. No postoperative complications or mortalities were observed. Conclusions: Results demonstrate that laparoscopic liver resection with the half-Pringle maneuver is feasible and safe and may be included in the technical armamentarium of laparoscopic liver resections for a selected group of patients.

Primary Hyperparathyroidism as the First Clinical Manifestation of Multiple Endocrine Neoplasia Type 2A in a 5-Year-Old Child

Background: Primary hyperparathyroidism occurs in only 10%-30% of patients with multiple endocrine neoplasia type 2A (MEN2A), rarely as the sole clinical manifestation, and is usually diagnosed after the third decade of life. Summary: A5-year-old girl was referred for prophylactic thyroidectomy as she carried the p.C634R RET mutation. She was clinically asymptomatic, with a normally palpable thyroid and with the cervical region free of lymphadenopathy or other nodules. Preoperative tests revealed hypercalcemia associated with elevation of parathyroid hormone (PTH) (calcium = 11.2mg/dL, calcium ion = 1.48mmol/L, phosphorus = 4.0 mg/dL, alkaline phosphatase = 625U/L, parathyroid hormone (PTH) PTH = 998 pg/mL). A thyroid ultrasound was normal and parathyroid scintigraphy with (99m)Tc-Sestamibi revealed an area of radioconcentration in the upper half of the left thyroid lobe suggesting hyperfunctioning parathyroid tissue. She underwent total thyroidectomy and parathyroidectomy and developed hypocalcemia. The anatomopathological examination showed no histopathological changes in the thyroid tissue and an adenoma of the parathyroid gland, confirming the diagnosis of hyperparathyroidism. Conclusions: Primary hyperparathyroidism can be a precocious manifestation of MEN2A. This case report highlights that asymptomatic hypercalcemia should be scrutinized in children related to patients with MEN2A who carry a mutation in the RET proto-oncogene, especially mutations in the codon 634, before the currently recommended age of 8 years.

Mate attenuates DNA damage and carcinogenesis induced by diethylnitrosamine and thermal injury in rat esophagus

Drinking hot mate has been associated with risk for esophageal cancer in South America. Thus. the aims of this study were to evaluate the modifying effects of mate intake on DNA damage and esophageal carcinogenesis induced by diethylnitrosamine (DEN) and thermal injury (TI) in male Wistar rats. At the initiation phase of carcinogenesis, rats were treated with DEN (8 x 80 mg/kg) and submitted to TI (water at 65 degrees C, 1 ml/rat, instilled into the esophagus). Concomitantly, the animals received mate (2.0% w/v) for 8 weeks. Samples of peripheral blood were collected 4 h after the last DEN application for DNA damage analysis. At weeks 8 and 20, samples from esophagus and liver were also collected for histological and immunohistochemical analysis. Mate significantly decreased DNA damage in leukocytes, cell proliferation rates in both esophagus and liver and the number of preneoplastic liver lesions from DEN/TI-treated animals at week 8. A significant lower incidence of esophageal papillomas and liver adenomas and tumor multiplicity was observed in the animals previously treated with mate at week 20. Thus, mate presented protective effects against DNA damage and esophageal and liver carcinogenesis induced by DEN. (C) 2009 Elsevier Ltd. All rights reserved.

Electronegative LDL and lipid abnormalities in patients undergoing hemodialysis and peritoneal dialysis

Background: Oxidative modification of low-density lipoprotein (LDL) has been demonstrated in patients with end-stage renal disease, where it is associated with oxidative stress and plays a key role in the pathogenesis of atherosclerosis. In this context, the generation of minimally oxidized LDL, also called electronegative LDL [ LDL(-)], has been associated with active disease, and is a detectable sign of atherogenic tendencies. The purpose of this study was to evaluate serum LDL(-) levels and anti-LDL(-)IgG autoantibodies in end-stage renal disease patients on dialysis, comparing patients on hemodialysis (HD), peritoneal dialysis (PD) and a control group. In addition, the serum lipid profile, nutritional status, biochemical data and parameters of mineral metabolism were also evaluated. Methods: The serum levels of LDL(-) and anti-LDL(-) IgG autoantibodies were measured in 25 patients undergoing HD and 11 patients undergoing PD at the Centro Integradode Nefrologia, Rio de Janeiro, Brazil. Ten healthy subjects served as a control group. Serum levels of albumin, total cholesterol, triglycerides and lipoproteins were measured. Calculations of subjects` body mass index and measurements of waist circumference, triceps skin fold and arm muscle area were performed. Measurements of hematocrit, serum blood urea nitrogen, creatinine, parathyroid hormone, phosphorus and calcium were taken. Results: Levels of LDL(-) were higher in HD patients (575.6 +/- 233.1 mu g/ml) as compared to PD patients (223.4 +/- 117.5 mu g/ml, p < 0.05), which in turn were higher than in the control group (54.9 +/- 33.3 mu g/ml, p < 0.01). The anti-LDL(-) IgG autoantibodies were increased in controls (0.36 +/- 0.09 mu g/ ml) as compared to PD (0.28 +/- 0.12 mu g/ml, p < 0.001) and HD patients (0.2 +/- 0.1 mu g/ml, p < 0.001). The mean values of total cholesterol and LDL were considered high in the PD group, whereas the mean triceps skin fold was significantly lower in the HD group. Conclusion: Levels of LDL(-) are higher in renal patients on dialysis than in normal individuals, and are reciprocally related to IgG autoantibodies. LDL(-) may be a useful marker of oxidative stress, and this study suggests that HD patients are more susceptible to cardiovascular risk due to this condition. Moreover, autoantibodies reactive to LDL(-) may have protective effects in chronic kidney disease. Copyright (C) 2008 S. Karger AG, Basel.

Coronary Calcification Is Associated With Lower Bone Formation Rate in CKD Patients Not Yet in Dialysis Treatment

Vascular calcification is a strong prognostic marker of mortality in hemodialysis patients and has been associated with bone metabolism disorders in this population. In earlier stages of chronic kidney disease (CKD), vascular calcification also has been documented. This study evaluated the association between coronary artery calcification (CAC) and bone histomorphometric parameters in CKD predialysis patients assessed by multislice coronary tomography and by undecalcified bone biopsy. CAC was detected in 33 (66%) patients, and their median calcium score was 89.7 (0.4-2299.3 AU). The most frequent bone histologic alterations observed included low trabecular bone volume, increased eroded and osteoclast surfaces, and low bone-formation rate (BFR/BS). Multiple logistic regression analysis, adjusted for age, sex, and diabetes, showed that BFR/BS was independently associated with the presence of coronary calcification [p=.009; odd ratio (OR) = 0.15; 95% confidence interval (Cl) 0.036-0.619] This study showed a high prevalence of CAC in asymptomatic predialysis CKD patients. Also, there was an independent association of low bone formation and CAC in this population. In conclusion, our results provide evidence that low bone-formation rate constitutes another nontraditional risk factor for cardiovascular disease in CKD patients. 2010 American Society for Bone and Mineral Research.

Early Control of PTH and FGF23 in Normophosphatemic CKD Patients: A New Target in CKD-MBD Therapy?

Background and objectives: Levels of parathyroid hormone (PTH) and the phosphaturic hormone FGF23, a fibroblast growth factor (FGF) family member, increase early in chronic kidney disease (CKD) before the occurrence of hyperphosphatemia. This short-term 6-wk dose titration study evaluated the effect of two phosphate binders on PTH and FGF23 levels in patients with CKD stages 3 to 4. Design, setting, participants, and measurements: Patients were randomized to receive over a 6-wk period either calcium acetate (n = 19) or sevelamer hydrochloride (n = 21). Results: At baseline, patients presented with elevated fractional excretion of phosphate, serum PTH, and FGF23. During treatment with both phosphate binders there was a progressive decline in serum PTH and urinary phosphate, but no change in serum calcium or serum phosphate. Significant changes were observed for FGF23 only in sevelamer-treated patients. Conclusions: This study confirms the positive effects of early prescription of phosphate binders on PTH control. Prospective and long-term studies are necessary to confirm the effects of sevelamer on serum FGF23 and the benefits of this decrease on outcomes. Clin J Am Soc Nephrol 5: 286-291, 2010. doi: 10.2215/CJN.05420709