Aspectos Nutricionais na Doença Renal Crônica em Cães

It is understood by Chronic Renal Failure (CRF) or Stage IV Chronic Kidney Disease (CKD) the morbid state in which there is a substantial and irreversible loss of functional capacity, metabolic and endocrine function in both kidneys, leading to a framework of dehydration, azotemia, electrolyte imbalance, anemia, uremic syndrome, secondary hyperparathyroidism, among other conditions that make the patient's life without treatment unfeasible. An adequate nutritional support to patients with CKD at any stage aims to maintain a good clinical condition and an attempt to delay the progression of the disease. The basis of a diet for patients with CKD is the restriction in this protein being of high biological value, low-phosphorus, high energy density, fiber and antioxidants combined with a good dietary practices that allow the patient a good quality of life

Multiple endocrine neoplasia type 1 presenting as refractory epilepsy and polyneuropathy - A case report

Hypoglycemia is a well recognized cause of acute symptomatic seizures. The fact that hypoglycemia can cause peripheral neuropathy is less appreciated. We describe a case of insulinoma associated peripheral neuropathy. A 17 year-old previously healthy man was referred for investigation of refractory epilepsy. A history of recurrent seizures, slowly progressive weakness of his feet and hands, and weight gain was obtained. Physical examination showed signs of a chronic sensory-motor polyneuropathy. He was diagnosed with insulinoma and primary hyperparathyroidism, characterizing multiple endocrine neoplasia, type 1 syndrome. Cases of insulinoma associated peripheral neuropathy are very rare. The more characteristic clinical picture appears to be distal weakness, worse in the intrinsic hand and feet muscles, and no or mild sensory signs. Peripheral nervous system symptoms may not completely resolve, despite removal of the cause of hyperinsulinism/hypoglycemia and full reversion of central nervous system symptoms. Mechanisms underlying hypoglycemic neuropathy are still poorly understood. (C) 2011 Elsevier B.V. All rights reserved.

Potential Effects of Alendronate on Fibroblast Growth Factor 23 Levels and Effective Control of Hypercalciuria in an Adult with Jansen's Metaphyseal Chondrodysplasia

Context: Jansen's metaphyseal chondrodysplasia (JMC) is a rare autosomal dominant disorder caused by activating mutations in the PTH 1 receptor (PTH1R; PTH/PTHrP receptor), leading to chronic hypercalcemia and hypercalciuria. Hypophosphatemia is also a hallmark of JMC, and recently, increased fibroblast growth factor 23 (FGF23) levels have been reported in this syndrome. Hypercalcemia has been associated with increased cardiovascular risk; however, cardiovascular disease has not been extensively investigated in JMC patients. Objective: The aim of the study was to describe the long-term follow-up of a JMC patient with regard to the management of hypercalciuria, the evaluation of FGF23 levels under bisphosphonate treatment, and the investigation of cardiovascular repercussion of chronic hypercalcemia. Results: The diagnosis of JCM was confirmed by molecular analysis (p.H223R mutation in PTH1R). The patient was followed from 5 to 27 yr of age. Asymptomatic nephrolithiasis was diagnosed at 18 yr of age, prompting pharmacological management of hypercalciuria. Treatment with alendronate reduced hypercalciuria; however, normocalciuria was only obtained with the association of thiazide diuretic. Serum FGF23 levels, measured under alendronate treatment, were repeatedly within the normal range. Subclinical cardiovascular disease was investigated when the patient was 26 yr old, after 19 yr of sustained mild hypercalcemia; carotid and vertebral artery ultrasonography was normal, as well as coronary computed tomography angiography (calcium score = 0). Conclusion: The long-term follow-up of our JMC patient has provided insight on therapeutic strategies to control hypercalciuria, on the potential effects of alendronate on FGF23 levels, and on the lack of detectable cardiovascular disease at young adulthood after prolonged exposure to hypercalcemia. (J Clin Endocrinol Metab 97: 1098-1103, 2012)

Giant cell bone lesions in the craniofacial region: a diagnostic and therapeutic challenge

Background: Giant cell tumors of bone (GCTs) are common in the long bones, but rare in the craniofacial region, with only 1% of cases occurring in the latter. Clinical, radiological, and anatomical diagnosis of this locally aggressive disease, which occurs in response to trauma or neoplastic transformation, poses a major challenge in clinical practice. Methods: The present study describes a series of 4 cases and highlights the main features of the differential diagnosis and treatment of these lesions: GCT, giant cell reparative granuloma (GCRG), and the brown tumor of hyperparathyroidism. Results: GCT presents as a benign neoplasm, most typically affecting the knees, and rarely in the temporal and sphenoid bones. It is radiologically indistinguishable from GCRG due to its lytic, poorly defined appearance. The distinction can only be made microscopically, as the presence of multinucleated giant cells scattered throughout the stroma and the absence of a history of trauma favor a diagnosis of GCT. The brown tumor of hyperparathyroidism occurs with rapid, localized osteoclast activity secondary to the effects of increased parathyroid hormone (PTH) levels; parathyroid examination is indispensable. Conclusion: The diagnosis and treatment of these lesions poses a major challenge due to their similar clinical presentation and radiological appearance. Accurate diagnosis is essential for definition of appropriate management, as complete resection is the goal in GCT and GCRG to avoid recurrence, whereas the brown tumor often yields to treatment of the underlying hyperparathyroidism.

Alterações de parâmetros relacionados ao metabolismo ósseo em mulheres submetidas à derivação gástrica em Y de Roux

OBJETIVO: Avaliar o metabolismo ósseo e a densidade mineral óssea (DMO) em mulheres adultas pós-derivação gástrica em Y de Roux (DGYR). SUJEITOS E MÉTODOS: Estudo transversal com 48 mulheres submetidas a DGYR há três anos e 41 saudáveis. Dados obtidos: índice de massa corporal (IMC), atividade física, consumo alimentar e DMO da coluna lombar, colo e fêmur total. Dosagem de cálcio, fósforo, magnésio, albumina, fosfatase alcalina, telopeptídeo-C (CTX), paratormônio (PTH), 25-hidroxivitamina D (25OHD), osteocalcina e cálcio urinário. RESULTADOS: Maiores alterações no grupo DGYR observadas nos níveis de osteocalcina (p < 0,001), CTX (p < 0,001) e PTH (p < 0,001). Deficiência de 25OHD foi a mais frequente no grupo DGYR (p = 0,010). Deficiência/insuficiência de 25OHD associou-se com hiperparatiroidismo secundário (p = 0,025). Não houve diferença entre os grupos em relação à DMO. A ingestão de energia (p = 0,036) e proteína (p = 0,004) foi maior no grupo controle. CONCLUSÃO: Em mulheres pós-DGYR, encontraram-se alta frequência de deficiência de vitamina D, hiperparatireoidismo secundário e elevação nos marcadores de remodelação óssea, sem alteração na DMO quando comparado com o grupo controle não obeso.

Surgical treatment of pancreatic endocrine tumors in multiple endocrine neoplasia type 1

Surgical approaches to pancreatic endocrine tumors associated with multiple endocrine neoplasia type 1 may differ greatly from those applied to sporadic pancreatic endocrine tumors. Presurgical diagnosis of multiple endocrine neoplasia type 1 is therefore crucial to plan a proper intervention. Of note, hyperparathyroidism/multiple endocrine neoplasia type 1 should be surgically treated before pancreatic endocrine tumors/multiple endocrine neoplasia type 1 resection, apart from insulinoma. Non-functioning pancreatic endocrine tumors/multiple endocrine neoplasia type 1 >1 cm have a high risk of malignancy and should be treated by a pancreatic resection associated with lymphadenectomy. The vast majority of patients with gastrinoma/multiple endocrine neoplasia type 1 present with tumor lesions at the duodenum, so the surgery of choice is subtotal or total pancreatoduodenectomy followed by regional lymphadenectomy. The usual surgical treatment for insulinoma/multiple endocrine neoplasia type 1 is distal pancreatectomy up to the mesenteric vein with or without spleen preservation, associated with enucleation of tumor lesions in the pancreatic head. Surgical procedures for glucagonomas, somatostatinomas, and vipomas/ multiple endocrine neoplasia type 1 are similar to those applied to sporadic pancreatic endocrine tumors. Some of these surgical strategies for pancreatic endocrine tumors/multiple endocrine neoplasia type 1 still remain controversial as to their proper extension and timing. Furthermore, surgical resection of single hepatic metastasis secondary to pancreatic endocrine tumors/multiple endocrine neoplasia type 1 may be curative and even in multiple liver metastases surgical resection is possible. Hepatic trans-arterial chemo-embolization is usually associated with surgical resection. Liver transplantation may be needed for select cases. Finally, pre-surgical clinical and genetic diagnosis of multiple endocrine neoplasia type 1 syndrome and localization of multiple endocrine neoplasia type 1related tumors are crucial for determining the best surgical strategies in each individual case with pancreatic endocrine tumors.

Facial lesions caused by renal osteodystrophy in a patient with chronic renal insufficiency: a case report

PURPOSE: Chronic renal insufficiency (CRI) is the last stage of a chronic renal condition in which the kidney loses its filtration and endocrine functions. Chronic endocrine hypofunction causes generalized damage to the body known as Uremic Syndrome, which affects the central nervous system as well as the cardiovascular, hematologic, dermatologic, ophthalmic, endocrine, respiratory, gastrointestinal and skeletal systems. The present study reports the case of a female patient with CRI who presented facial osteodystrophy of the osteitis fibrosa type, and highlights the main features of this condition. CASE DESCRIPTION: A 24-year old, female, Caucasian patient presented chronic glomerulonephritis recurrence and lost the transplanted kidney five years before, undergoing arteriovenous fistula hemodialysis three times a week. She presented swelling of the left masseter area with a hard consistency on palpation, covered by intact skin, swelling at the bottom of the left atrium, with a hard consistency on palpation, a mucosa-like color and absence of inflammation signs, suggesting expansive bone lesions on the face. These features were compatible with hyperparathyroidism brown tumor and/or osteodystrophy. The CT scan showed expansive bone lesions of heterogeneous appearance on the left jaw, maxilla/nasal floor, and right frontotemporal suture areas. The clinical and histopathological characteristics of the lesion, in association with PHT hormone high serum levels led to renal osteodystrophy diagnosis. The patient was referred to the nephrology services. CONCLUSION: Osteodystrophic bone alterations have a high prevalence in renal disease patients, and the dentist must take these alterations into consideration in bone lesion diagnosis for this specific group of patients.

Alterazioni del metabolismo osseo e fratture vertebrali dopo trapianto di rene

Introduction:Persistent Hyperparathyroidism after transplantation (HPT),bone disease and vertebral fractures are an important clinical problem in renal transplant patients. Several factors such as renal osteodystrophy, immunosuppressive therapy, deficit/insufficiency Vitamin D may contribute to that.In literature are described different percentages of HPT, vertebral fractures and Osteoporosis/Osteopenia that may be due to the different therapy and to the different employ of steroid. We analyzed 90 patients who received a renal graft between 2005 e 2010. Patients and Methods: 44 male and 46 female. Average age 52,2± 10,1 years, follow-up 31,3±16,6 months, time on dialysis 37±29,6 months. Patients who had creatinine level greater than 2,5 mg/dl were excluded. Immunosuppressive therapy was based on basiliximab, steroids (1.6 to 2 mg/kg/day progressively reduced to 5 mg/day after 45 days from the transplantation) in all patients + calcineurin inhibitor+ mycophenolate mophetil/mycophenolic acid in 88,8% of patients or Everolimus± calcineurin inhibitor in the others. Patients were studied with X-ray of the spine, dual-energy-X-ray, PTH, 25(OH)VitD. Results: 41,1% had HPT; 41,1% had osteopenia at femoral neck and 36,7% at vertebral column; 16,7% had osteoporosis at femoral neck and 15,6% at vertebral column. 10 patients (11%) had vertebral fractures. Patients with normal bone mineral density, compared to those with osteoporosis/osteopenia, are more younger (average age 46,4±11,7 years vs 54.3±8,6); they have spent less time on dialysis (26,5±14,8 months vs 40,7±32,6) and they have values of 25(OH)VitD higher (22,1±7,6 ng/ml vs 17,8±8,5). Patients with vertebral fractures have values of 25(OH)VitD lowest (14,1±6,4 ng/ml vs 19,7±8,5) and they had transplant since more time (29,1±16,2 vs 48,1±8,7 months). There is a significant correlation between HPT and PTH pre transplantation; HPT and levels of VitD (p<0,05) Conclusion: Prevention of Bone disease and vertebral fractures after renal transplant includes: a)treatment before transplantation b)supplementation of vitamin D with cholecalciferol or calcidiol c)shorten the dialysis time.

Risk profiles and penetrance estimations in multiple endocrine neoplasia type 2A caused by germline RET mutations located in exon 10

Multiple endocrine neoplasia type 2 is characterized by germline mutations in RET. For exon 10, comprehensive molecular and corresponding phenotypic data are scarce. The International RET Exon 10 Consortium, comprising 27 centers from 15 countries, analyzed patients with RET exon 10 mutations for clinical-risk profiles. Presentation, age-dependent penetrance, and stage at presentation of medullary thyroid carcinoma (MTC), pheochromocytoma, and hyperparathyroidism were studied. A total of 340 subjects from 103 families, age 4-86, were registered. There were 21 distinct single nucleotide germline mutations located in codons 609 (45 subjects), 611 (50), 618 (94), and 620 (151). MTC was present in 263 registrants, pheochromocytoma in 54, and hyperparathyroidism in 8 subjects. Of the patients with MTC, 53% were detected when asymptomatic, and among those with pheochromocytoma, 54%. Penetrance for MTC was 4% by age 10, 25% by 25, and 80% by 50. Codon-associated penetrance by age 50 ranged from 60% (codon 611) to 86% (620). More advanced stage and increasing risk of metastases correlated with mutation in codon position (609?620) near the juxtamembrane domain. Our data provide rigorous bases for timing of premorbid diagnosis and personalized treatment/prophylactic procedure decisions depending on specific RET exon 10 codons affected.

PA21, a New Iron-Based Noncalcium Phosphate Binder, Prevents Vascular Calcification in Chronic Renal Failure Rats

Chronic renal failure (CRF) is associated with the development of secondary hyperparathyroidism and vascular calcifications. We evaluated the efficacy of PA21, a new iron-based noncalcium phosphate binder, in controlling phosphocalcic disorders and preventing vascular calcifications in uremic rats. Rats with adenine-diet-induced CRF were randomized to receive either PA21 0.5, 1.5, or 5% or CaCO3 3% in the diet for 4 weeks, and were compared with uremic and nonuremic control groups. After 4 weeks of phosphate binder treatment, serum calcium, creatinine, and body weight were similar between all CRF groups. Serum phosphorus was reduced with CaCO3 3% (2.06 mM; P ≤ 0.001), PA21 1.5% (2.29 mM; P < 0.05), and PA21 5% (2.21 mM; P ≤ 0.001) versus CRF controls (2.91 mM). Intact parathyroid hormone was strongly reduced in the PA21 5% and CaCO3 3% CRF groups to a similar extent (1138 and 1299 pg/ml, respectively) versus CRF controls (3261 pg/ml; both P ≤ 0.001). A lower serum fibroblast growth factor 23 concentration was observed in the PA21 5%, compared with CaCO3 3% and CRF, control groups. PA21 5% CRF rats had a lower vascular calcification score compared with CaCO3 3% CRF rats and CRF controls. In conclusion, PA21 was as effective as CaCO3 at controlling phosphocalcic disorders but superior in preventing the development of vascular calcifications in uremic rats. Thus, PA21 represents a possible alternative to calcium-based phosphate binders in CRF patients.

[Calcium and blood pressure]

The regulation of blood pressure is complex with several organs being involved. Intracellular calcium plays a crucial role in the regulation of cardiovascular functions: An increased influx of calcium into the vascular smooth muscle cells leads to an augmental muscular tone and therefore to an increased vascular resistance and rise in blood pressure. Parathormone plays a permissive role since it regulates the calcium-influx into the cells and thus increases the vasoconstrictive effect. There is a positive correlation between parathormone and blood pressure, present in primary as well as secondary hyperparathyroidism. Moreover, patients with essential hypertension have high parathormone levels already before hypertension is diagnosed. A calcium-rich diet (> 1000 mg calcium daily) slightly decreases blood pressure. This positive effect is due to parathormone suppression with a subsequently decreased calcium content in the vascular smooth muscle cells. A calcium-rich diet inhibits lipogenesis in the fat tissue; thus additionally improving the cardiovascular risk profile.

Mechanisms and regulation of epithelial Ca2+ absorption in health and disease

Ca2+ is essential for numerous physiological functions in our bodies. Therefore, its homeostasis is finely maintained through the coordination of intestinal absorption, renal reabsorption, and bone resorption. The Ca2+-selective epithelial channels TRPV5 and TRPV6 have been identified, and their physiological roles have been revealed: TRPV5 is important in final renal Ca2+ reabsorption, and TRPV6 has a key role in intestinal Ca2+ absorption. The TRPV5 knockout mice exhibit renal leak hypercalciuria and accordingly upregulate their intestinal TRPV6 expression to compensate for their negative Ca2+ balance. In contrast, despite their severe negative Ca2+ balance, TRPV6-null mice do not display any compensatory mechanism, thus resulting in secondary hyperparathyroidism. These results indicate that the genes for TRPV5 and TRPV6 are differentially regulated in human diseases associated with disturbed Ca2+ balance such as hypercalciuria, osteoporosis, and vitamin D-resistant rickets.

Changes in bone mineral density over 18 months following kidney transplantation: the respective roles of prednisone and parathyroid hormone

Prednisone is a major factor of bone loss after kidney transplantation. The role of hyperparathyroidism and immunosuppressors is less clear.

Diagnostic approach to hypercalcemia: relevance of parathyroid hormone and parathyroid hormone-related protein measurements

Background: Parathyroid hormone (PTH) and parathyroid hormone-related protein (PTH-rP) are two potent hypercalcemic hormones that act on the same targets. Autonomous secretion of the former is involved in primary hyperparathyroidism (PHPT), whereas the latter is responsible for humoral hypercalcemia of malignancy (HHM). Methods: From 250 consecutive, hypercalcemic serum samples sent to our laboratory for assessment of intact PTH, we were able to obtain clinical information, as well as an additional plasma sample for PTH-rP measurement, in 134 patients. At the time of sampling, patients could be classified into seven groups: cancer without known bone metastases (CaNoMeta, n=36), cancer with bone metastases (CaMeta, n=9), no evidence of cancer (noEvCa, n=71), sarcoidosis (Sarc, n=3), end-stage renal disease (ESRD, n=12), vitamin D overdose (VIT-D, n=2), and hyperthyroidism (Thyr, n=1). Results: In the CaNoMeta group, 29/36 patients had elevated PTH-rP levels, 9/36 patients had inappropriately elevated PTH levels, and 5/36 had elevated levels of both hormones. In the CaMeta group, three of the nine patients had inappropriately elevated PTH levels, two of them with concomitantly elevated PTH-rP levels. In the NoEvCa group, 63/71 patients had an inappropriate elevation of PTH levels and were diagnosed as having PHPT. Four of the 71 patients had elevated levels of both PTH and PTH-rP; three of them were in poor health and died within a short period of time. All of the ESRD patients had very high PTH and normal PTH-rP levels, except for one woman with high PTH-rP and undetectable PTH levels; she died from what later turned out to be a recurrent bladder carcinoma. In the Sarc, Vit-D, and Thyr groups, both PTH and PTH-rP levels were normal. Conclusions: (1) Elevated PTH-rP levels are a common finding in cancer patients without bone metastases. Intact PTH, however, should always be measured in hypercalcemic patients with malignancy because concurrent primary hyperparathyroidism is not rare. (2) Primary hyperparathyroidism accounts for hypercalcemia in 90% of patients without evidence of cancer whose PTH-rP levels may also be found to be elevated in a few cases, even some with surgically demonstrated parathyroid adenoma.

Effect of calcium-channel blockers on calcium-phosphate metabolism in patients with end-stage renal disease

After EDTA-induced hypocalcaemia, healthy volunteers treated with diltiazem display more severe hyperparathyroidism than subjects on felodipine studied under identical conditions. Therefore patients with end-stage renal disease (ESRD) and severe secondary hyperparathyroidism might be particularly sensitive to this side-effect.