Search

Traditional dietary recommendations for patients with chronic kidney disease (CKD) focus on the quantity of nutrients consumed. Without appropriate dietary counselling, these restrictions can result in a low intake of fruits and vegetables and a lack of diversity in the diet. Plant nutrients and plant-based diets could have beneficial effects in patients with CKD: increased fibre intake shifts the gut microbiota towards reduced production of uraemic toxins; plant fats, particularly olive oil, have anti-atherogenic effects; plant anions might mitigate metabolic acidosis and slow CKD progression; and as plant phosphorus has a lower bioavailability than animal phosphorus, plant-based diets might enable better control of hyperphosphataemia. Current evidence suggests that promoting the adoption of plant-based diets has few risks but potential benefits for the primary prevention of CKD, as well as for delaying progression in patients with CKD G3-5. These diets might also help to manage and prevent some of the symptoms and metabolic complications of CKD. We suggest that restriction of plant foods as a strategy to prevent hyperkalaemia or undernutrition should be individualized to avoid depriving patients with CKD of these potential beneficial effects of plant-based diets. However, research is needed to address knowledge gaps, particularly regarding the relevance and extent of diet-induced hyperkalaemia in patients undergoing dialysis. Emerging evidence suggests that plant-based diets could help to prevent chronic kidney disease (CKD), manage its symptoms and metabolic complications and delay disease progression. Here, the authors discuss the potential risks and benefits of these diets in patients with CKD, as well as implementation strategies and knowledge gaps.

Background Logbooks are being increasingly widely used as a means of improving medical education and further training. They will in all probability continue to be mandatory in the Practical Year (PJ) in Germany even after the upcoming amendment of the Medical Licensing Regulations (ÄAppO). However, there are different approaches to their design and use, and these are also currently undergoing considerable change. This study for the first time examines and discusses the influence of logbooks on students’ evaluation of a gynecology internship. Methods The study was based on a well-established two-part 1-week internship course, with initially unstructured morning classes on wards and duty areas, along with precisely planned afternoon classes with skills training by peer teachers and seminars supervised by duty-exempted physicians. The postgraduate lecturers were prepared for the introduction of the logbook in a special course, and the aim was to optimize morning classes by introducing learning objectives adapted to the respective locations. The effects over 38 weeks of practical training were examined in evaluations by 235 prospectively group-randomized students with and without logbooks (n = 166 and n = 66, respectively; three datasets were not evaluable). Results In the cohort comparison, the logbook group responded significantly more positively toward the internship at the start of the course (P = 0.046). In the final evaluation, however, medical supervision during the entire internship was rated significantly more poorly (P = 0.007). The logbook cohort also considered that guidance based on learning objectives was significantly worse, as was the extent to which wards and duty areas were prepared for the students (P = 0.001 and P = 0.029). Conclusions Introducing a logbook to optimize clinical teaching in internships may raise expectations that cannot always be met. In addition to adapting the learning objectives to a general framework that is less favorable in comparison with the Practical Year, the least that is required appears to be simultaneous and continuous mentoring of the lecturers, as well as an increase in staffing resources.

Background: Medullary thyroid carcinoma (MTC) accounts for ∼5% of all thyroid malignancies. To date, surgery is the first-line therapy with curative intention. However, for advanced MTC, conventional chemotherapeutic agents do not provide convincing results. Therefore, the identification of biomarkers that can be antagonised by small-molecule therapeutics may lead to novel encouraging treatment options. Methods: Seventy-nine patients with surgically resected and histologically confirmed MTC were included in this study. Tissue microarrays were constructed to assess the relationship between inhibitor of apoptosis proteins (IAPs) survivin or XIAP expression levels and clinicopathological variables as well as overall survival. Results: High survivin or XIAP expression was associated with an advanced T-stage and metastatic disease. Whereas tissue expression levels of survivin correlated with serum calcitonin levels, XIAP was overexpressed in the subgroup of patients with sporadic MTC. Both IAPs were negatively associated with patient survival in the multivariate Cox regressions analysis (survivin: hazard ratio (HR) 1.62; 95% confidence interval (CI): 1.21–2.16; P=0.001; XIAP: HR 1.78; 95% CI: 1.16–2.72; P=0.008). Conclusions: Survivin and XIAP demonstrate distinct expression patterns in MTCs, which are associated with advanced disease and poor prognosis. We thus provide first evidence that both IAPs might serve as viable targets in patients with MTC.

In the general population, moderate exercise is associated with several health benefits including a decreased risk of obesity, coronary heart disease, stroke, certain types of cancer and all-cause mortality. In chronic kidney disease (CKD), physical inability is an independent risk of death. Health benefits of regular exercise in CKD patients include improvements in functional and psychological measures such as aerobic and walking capacity and health-related quality of life. Nonetheless, in CKD patients exercise rehabilitation is not routinely prescribed. Renal patients are heterogeneous across the different stages of CKD so that the assessment of physical capability is mandatory for a correct exercise program prescription. To plan appropriate exercise programs in the CKD setting, targeted professional figures should be actively involved as many psychological or logistic barriers may hamper exercise implementation in these subjects. Different approaches, such as home exercise rehabilitation programs, supervised exercise training or in-hospital gym may theoretically be proposed. However, physical exercise should always be tailored to the individual capacity and comorbidities and each patient should ideally be involved in the decision-making process.

Background Nutritional treatment has always represented a major feature of CKD management. Over the decades, the use of nutritional treatment in CKD patients has been marked by several goals. The first of these include the attainment of metabolic and fluid control together with the prevention and correction of signs, symptoms and complications of advanced CKD. The aim of this first stage is the prevention of malnutrition and a delay in the commencement of dialysis. Subsequently, nutritional manipulations have also been applied in association with other therapeutic interventions in an attempt to control several cardiovascular risk factors associated with CKD and to improve the patient's overall outcome. Over time and in reference to multiple aims, the modalities of nutritional treatment have been focused not only on protein intake but also on other nutrients. Discussion This paper describes the pathophysiological basis and rationale of nutritional treatment in CKD and also provides a report on extensive experience in the field of renal diets in Italy, with special attention given to approaches in clinical practice and management. Summary Italian nephrologists have a longstanding tradition in implementing low protein diets in the treatment of CKD patients, with the principle objective of alleviating uremic symptoms, improving nutritional status and also a possibility of slowing down the progression of CKD or delaying the start of dialysis. A renewed interest in this field is based on the aim of implementing a wider nutritional therapy other than only reducing the protein intake, paying careful attention to factors such as energy intake, the quality of proteins and phosphate and sodium intakes, making today’s low-protein diet program much more ambitious than previous. The motivation was the reduction in progression of renal insufficiency through reduction of proteinuria, a better control of blood pressure values and also through correction of metabolic acidosis. One major goal of the flexible and innovative Italian approach to the low-protein diet in CKD patients is the improvement of patient adherence, a crucial factor in the successful implementation of a low-protein diet program.

Phosphate metabolism is crucial in the pathophysiology of secondary hyperparathyroidism and vascular calcification. High phosphate levels have been consistently associated with unfavorable outcomes in dialysis patients, but several limitations are still hampering a resolutive definition of the optimal targets of phosphate serum levels to be achieved in this cohort. Nonetheless, hyperphosphatemia is a late marker of phosphate overload in humans. Clinical nephrologists routinely counteract the positive phosphate balance in dialysis patients through nutritional counseling, stronger phosphate removal by dialysis and prescription of phosphate binders. However, the superiority against placebo of phosphate control by diet, dialysis or binders in terms of survival has never been tested in dedicated randomized controlled trials. The present review discusses this conundrum with particular emphasis on the rationale supporting the value of a simultaneous intervention against phosphate overload in dialysis patients via the improvement of dietary intakes, dialysis efficiency and an individualized choice of phosphate binders.

The odor of amniotic fluid is repeatedly discussed with regard to its potential to provide olfactory cues to the unborn. However, the chemical basis for such assumptions is still unclear and the odorous composition of amniotic fluid, as well as inter-individual variances, has not yet been fully investigated. However, thorough examination of the odor and flavor profiles of the intra-uterine environment might support our understanding of early sensory triggers and potential sensory conditioning processes. Therefore, the aim of the present study was to characterize specific odorants in individual samples of amniotic fluid and to identify the most potent odor-active substances in this physiological fluid by means of gas chromatography olfactometry and aroma extract dilution analysis. The identification led to six new substances, which were not reported, to the best of our knowledge, for amniotic fluid before—among them the two steroids 5α-androst-16-en-3-one and 4, 16-androstadien-3-one.

Background Double adenomas (DAs) occur in 2–15 % of primary hyperparathyroidism (pHPT) patients. To date, the existence of this distinct entity remains controversial. The aim of this study was to evaluate the clinical characteristics and anatomic distribution of DAs to identify anatomic patterns and implications for surgical management.

Liver metastases of GEP-NETs are a known major prognostic factor with a strong effect on patients’ survival. To date, various treatment options are available, whereas surgery remains the only curative option. Because large liver resections often cannot be performed due to insufficient remnant liver volume, a special operative technique, “cherry picking” (multiple nonanatomic liver resections), can be used as a tissue-preserving procedure. Of 91 patients with various GEP-NETs, 16 patients were identified with synchronous or metachronous multifocal, bilobular liver metastases (>10). All were treated with “cherry picking.” Patient records were reviewed retrospectively and clinical data and pathology results were analyzed. Mean survival after primary tumour resection was 82.8 versus 41.2 months after liver surgery. All 16 patients are still alive. Mean recurrence-free survival after primary tumour operation was 49.8 versus 24.6 months after liver surgery. Complications of cherry picking included two postoperative biliary leakages and three small hepatic abscesses (conservative/interventional approach 25 % (n = 4), surgical approach 6.25 % (n = 1). There was no postoperative mortality. Initial hormonal symptoms (5/16 patients) completely disappeared postoperatively in 2 patients and were significantly decreased in 3 patients. The tissue-preserving surgical technique “cherry picking” has developed due to improved imaging techniques and increased knowledge in liver anatomy, which has helped to make this approach safer and easier. Highly selected patients with multiple bilobular liver metastases of GEP-NET can benefit from this special surgical approach, also applicable for recurrent metastases.

The incidence of neuroendocrine neoplasias (NENs), especially of the gastro-entero-pancreatic (GEP), system relatively increased over the past decades, as a result of advanced diagnostic tools, a better clinical awareness, and distinguished pathological diagnostic recognition. Previous reports hypothesized an increased risk for secondary malignancies in patients with NEN especially in GEP-NENs. The present study was designed to investigate the coincidence of NENs and secondary malignancies in a large patient collective. A retrospective analysis was performed on 161 patients (85 female and 76 male) with NEN of various origins. Clinical data of these patients, different classification systems (TNM/WHO), proliferations-based grading, and clinical follow-up were collected and analyzed. Out of 143 patients with a sporadic NEN, 15 (10.49 %) patients were identified with secondary malignant tumors. Median age at the time of the primary operation for NEN was 65 years, whereas the median age of initial diagnosis of associated tumors was 59 years. Mean follow-up time was 61 months. The risk of developing a secondary malignancy was most elevated for patients with an NEN of the lung, the stomach, and the ileum (60, 50 and 20 %, respectively). The spectrum of secondary malignancies included various types of cancer. Kaplan-Meier survival analysis shows a difference suggesting that patients with a secondary malignancy demonstrate a worse survival compared to patients without a secondary tumor; no significance was detected (p = 0.349). Our data suggest that secondary malignancies in patients with NEN's especially in GEP-NENs are found more frequently than in general population. Therefore, patients with NEN need a continuous and detailed follow-up. The reason for the increased incidence of secondary malignancies in patients with NENs remains to be elucidated.

To date, very little is known about the development of benign organic hyperinsulinism and its metastatic potential. Typical morphologic, biochemical, or genetic differentiations for benign or malign tumor course of insulinomas do not exist. As signaling pathways may affect pancreatic cancer development and the maintenance of the neoplastic phenotype, the purpose of this study was to examine the role of Notch1 expression in organic hyperinsulinism. We examined 32 well-differentiated pancreatic endocrine tumors (wd PET); 11 wd PET of unknown behavior (wd PET ub); and 15 wd pancreatic endocrine cancer (wd PEC) for Notch1 expression by immunohistochemistry. Demographic data, clinical data, and follow-up of all patients were analyzed. Islets of the Langerhans show the strongest Notch1 staining in nearly 90 %. Positive Notch1 staining was absent in the acinar of the pancreas. In patients with a wd PET more than every second tumor (56.3 %/n = 18/32) demonstrated a negative Notch1 staining. The other 14 patients were positive for Notch1. Tumors of unknown behavior (wd PET ub) and malignant insulinomas had no signs of Notch expression in contrast to benign insulinomas. Considering the clinical and histomorphological tumor behavior, no correlation between Notch1 expression and clinical data was found. The missing Notch expression in the malignant tumor course might be used as a potential predictive marker, but further studies are needed to investigate the underlying molecular mechanism.

Evidence exists that nutritional therapy induces favorable metabolic changes, prevents signs and symptoms of renal insufficiency, and is able to delay the need of dialysis. Currently, the main concern of the renal diets has turned from the efficacy to the feasibility in the daily clinical practice. Herewith we describe some different dietary approaches, developed in Italy in the last decades and applied in the actual clinical practice for the nutritional management of CKD patients. A step-wise approach or simplified dietary regimens are usually prescribed while taking into account not only the residual renal function and progression rate but also socio-economic, psychological and functional aspects. The application of the principles of the Mediterranean diet that covers the recommended daily allowances for nutrients and protein (0.8 g/Kg/day) exert a favorable effect at least in the early stages of CKD. Low protein (0.6 g/kg/day) regimens that include vegan diet and very low-protein (0.3-0.4 g/Kg/day) diet supplemented with essential amino acids and ketoacids, represent more opportunities that should be tailored on the single patient’s needs. Rather than a structured dietary plan, a list of basic recommendations to improve compliance with a low-sodium diet in CKD may allow patients to reach the desired salt target in the daily eating. Another approach consists of low protein diets as part of an integrated menu, in which patients can choose the “diet” that best suits their preferences and clinical needs. Lastly, in order to allow efficacy and safety, the importance of monitoring and follow up of a proper nutritional treatment in CKD patients is emphasized.

Primary aldosteronism (PA) is the most common cause of secondary hypertension with a prevalence of 5–10% in unreferred hypertensive patients. Aldosterone producing adenomas (APAs) constitute a large proportion of PA cases and represent a surgically correctable form of the disease. The WNT signaling pathway is activated in APAs. In other tumors, a frequent cause of aberrant WNT signaling is mutation in the CTNNB1 gene coding for β-catenin. Our objective was to screen for CTNNB1 mutations in a well-characterized cohort of 198 APAs. Somatic CTNNB1 mutations were detected in 5.1% of the tumors, occurring mutually exclusive from mutations in KCNJ5, ATP1A1, ATP2B3 and CACNA1D. All of the observed mutations altered serine/threonine residues in the GSK3β binding domain in exon 3. The mutations were associated with stabilized β-catenin and increased AXIN2 expression, suggesting activation of WNT signaling. By CYP11B2 mRNA expression, CYP11B2 protein expression and direct measurement of aldosterone in tumor tissue, we confirmed the ability for aldosterone production. This report provides compelling evidence that aberrant WNT signaling caused by mutations in CTNNB1 occur in APAs. This also suggests that other mechanisms that constitutively activate the WNT pathway may be important in APA formation.

The increasing detection of adrenal tumors and the availability of a more sophisticated biochemical work-up leading to rising numbers of sub-clinical Conn's and Cushing's syndromes coincide with a rising number of adrenalectomies worldwide. The aim of our study was to report a single institution's experience with adrenal surgery.We report data of 528 adrenalectomies, operated at our institution before and after the onset of minimally invasive endoscopic surgery (1986-1994, 1995-2008). Gender, age, indication, imaging, surgical approach, operating time, histology, tumor size, hospital stay, and complications were analyzed retrospectively.A total of 478 patients underwent adrenal surgery during the time observed. The average number of yearly adrenalectomies increased from 14 to 21 (p = 0.001) after the onset of laparoscopic surgery. Imaging techniques showed a significant shift towards magnetic resonance imaging (p 0.001) and preoperative assessment of tumor size was significantly correlated to malignancy: 10.8 % (11/102) and 42 % (21/50) of tumors measuring 4-6 cm and ≥6 cm, respectively, were malignant in the final histology report (p 0.001). Patients operated by minimally invasive endoscopy were significantly younger (mean 49.4 years, p = 0.046), had significantly shorter operating times (mean 118 min, p 0.001), had shorter hospital stays (mean 7.1 days, p 0.001), and had less complications (6.9 %, p = 0.004) compared to patients resected through open procedures.Although adrenalectomy rates increased and minimally invasive endoscopic surgery reduced hospital stay and complications at our institution, the yearly number of procedures was still low with often high surgical complexity. We therefore believe that adrenal surgery remains a highly specialized procedure that should preferably be performed at endocrine surgery centers.

In mouse retinal explants, octreotide, a somatostatin [somatotropin release-inhibiting factor (SRIF)] receptor 2 (sst(2)) agonist, prevents the hypoxia-induced vascular endothelial growth factor upregulation. In mice with oxygen-induced retinopathy (OIR), a model of retinopathy of prematurity, either sst(2) overexpression or octreotide have been found to limit hypoxia-induced angiogenic processes. Here, we investigated whether sst(2) influences retinal degeneration in response to hypoxia in wild-type (WT), sst(1)- and sst(2)-knockout (KO) mice. In retinal explants, we determined the role of sst(2) on apoptotic signals. In control condition, caspase-3 activity and the Bax/Bcl-2 ratio were lower in sst(1)-KO than in WT, but higher in sst(2)-KO than in WT retinas. In all strains, a comparable increase in caspase-3 activity and the Bax/Bcl-2 ratio was observed after hypoxia. The hypoxia-induced increase in apoptotic signals was recovered by octreotide in both WT and sst(1)-KO retinas. To investigate the role of sst(2) on retinal function, we recorded electroretinogram (ERG) in response to light flashes in OIR mice. ERG responses did not differ between WT and KO mice with the exception of oscillatory potentials (OPs) which, in sst(1)-KO mice, displayed much larger amplitude. In all strains, hypoxia drastically reduced a-, b-waves and OPs. In both WT and sst(1)-KO mice, octreotide recovered a- and b-waves, but did not recover OPs in sst(1)-KO mice. Neither apoptotic signals nor ERG was affected by octreotide in sst(2)-KO mice. These results show that sst(2) may protect retinal cells from hypoxia, thus implementing the background to establish potential pharmacological targets based on sst(2) pharmacology.

The present investigation aimed to point out some epidemiological and clinical features of renal colic in our region. All emergency department (ED) visits performed from 1 January to 31 December 2005 were reviewed to select those with diagnosis of renal colic or kidney stones. There were 70,621 visits to the University of Pisa ED. Renal colic or stone were diagnosed in 696 cases (1%); 21.6% of them were recurrent stone formers; the males to female ratio was 1.4-1. The age distribution showed a higher rate from 25 to 44 years of age, whereas seasonal distribution showed a higher risk during summer months, particularly in July. Ultrasonography (US) was the only examination in 70.2% cases, it was coupled with plain abdomen X-ray (KUB) in 10% of the cases. NSAIDs were always used (100%), sometimes in association with opiate (15.8%) or with anti-cholinergic (26.5%) medications. The data of our investigation are in a substantial agreement with the reported literature as far as concerns the main epidemiological features of renal colic and its treatment. On the contrary, the diagnostic approach is mainly based on US whereas KUB is rarely performed. Until the 31st of December 2005, CT-scan was not used as the first and only imaging study in cases of renal colic. This different diagnostic approach may be linked to financial and cultural reasons, and structural and functional organization of the National Health Service facilities.

The object of this study was to assess the extent of surgery required for small sporadic medullary thyroid cancers (sMTCs). We retrospectively studied 261 patients with MTCs treated in our institution between 1986 and 2002 and identified 15 patients with small pT1 or pT2 sMTCs. The tumors were diagnosed incidentally, so surgical therapy was less than total thyroidectomy. Total thyroidectomy with or without neck dissection was applied to all other patients as standard surgical treatment of care. Patients were systematically followed up by postoperative ultrasonography, calcitonin, carcinoembryonic antigen levels, and pentagastrin stimulation tests. On long-term follow-up over a period of 4.6 years, the rate of biochemical cure in these patients who underwent less than total thyroidectomy for a sporadic incidentally diagnosed tumor was 100%. We concluded that completion thyroidectomy and neck dissection are not mandatory in patients in whom a solitary small sMTC is incidentally discovered by histologic diagnosis following operation so long as a genetic background is excluded. Nevertheless, such patients require systematic careful long-term follow-up.

Background and aims: Ectopic mediastinal parathyroid adenoma as a cause of primary hyperparathyroidism (pHPT) can normally be resected from conventional collar incision. In rare cases with adenomas deeper in the chest, a transthoracic approach is necessary. Patients/methods: We report our experience of 19 patients with suspected mediastinal parathyroid adenomas from a total of 1035 patients with pHPT who were operated on between 1986 and 2000 using an open approach (sternotomy or thoracotomy) or video-assisted mediastinal or thoracoscopic surgery (VAMS/VATS). Results: Fourteen patients underwent an open approach with a success rate of 71% (10 of 14). Four patients remained hypercalcaemic. There were four complications in three patients: three permanent recurrent nerve palsies and one chylus fistula, requiring further surgery. VATS was successful in three of four patients with conversion to sternal splitting because of a false-negative frozen section in one patient. Another patient had parathyroid adenoma retrosternally which could not be resected by means of VAMS and had to be excised using a transsternal approach. There were no complications of minimal invasive procedures. All five patients were normocalcaemic after the operation. Conclusion: Ectopic parathyroid adenomas not resectable by means of a collar incision are rare causes of pHPT and comprise 1.25% of all patients with pHPT in our series. For these patients, VATS revealed an alternative to conventional open procedures. In questionable cases, however, the collar incision should precede the VATS procedure.

Background: The purpose of this investigation was to analyze the individual diagnostic and operative strategy in the treatment of medullary thyroid carcinoma (MTC) in international specialized centers and to assess whether standard procedures are carried out in practice everywhere. Methods: A questionnaire concerning diagnosis and treatment of patients with primary, persistent, or recurrent sporadic or familial MTC was sent to 263 members of the International Association of Endocrine Surgeons. Results: Primary treatment of MTC does not show significant differences for patients with sporadic or familial disease (Chi-square, n.s.), and standard procedures are performed in only 25–40% of patients. Computed tomography scan is the most common localization procedure in persistent or recurrent disease (52–72%), followed by scintigraphy (43–71%), ultrasonography (41–56%), and magnetic resonance imaging (31–49%). In case of negative localization studies, 68–86% of colleagues do not recommend reoperation. In symptomatic patients with stage-IV tumors, however, 84% of colleagues advocate reoperation to provide relief from the tumor burden. Conclusions: Even with experienced endocrine surgeons, a consensus to uni- and/or bilateral neck dissection in primary MTC is lacking. The majority of authors supports at least total thyroidectomy with central lymph-node dissection. In recurrent disease, there is a general tendency to reoperate in case of positive localization studies and in case of symptomatic disease.

Background and aims: The surgical strategy in small sporadic C-cell carcinomas of the thyroid that are incidentally diagnosed after goiter resection for benign disease is controversial. It remains unclear whether a completion thyroidectomy should be performed in every case. Patients and methods: We present nine patients who were operated on between October 1992 and October 1997 in whom an unexpected, small sporadic C-cell carcinoma (seven with pT1, two with pT2) was found in the postoperative histology. Results: All patients were calcitonin negative and there were no signs of the disease being inherited (no familial history, negative RET proto-oncogene). No patient underwent a completion thyroidectomy. All patients had a follow-up with pentagastrin-stimulated calcitonin and carcinoembryonic antigen (CEA) 3 months, 6 months and annually after the operation. No patient became calcitonin positive or showed any other signs of tumor recurrence after a follow-up period of 2–7 years. Conclusion: A completion thyroidectomy is not necessary in small sporadic C-cell carcinoma that is incidentally diagnosed after resection for benign disease if there is no sign of familial cancer and if calcitonin is negative. A close follow-up is necessary.

In kidney stone patients, high protein intake and calcitriol overproduction are factors leading to hypercalciuria, but there are conflicting reports on the effects of dietary protein on calcitriol production. To investigate the relationships between serum calcitriol, dietary protein intake, and urinary calcium excretion, 33 male idiopathic calcium stone formers (aged 20-60 years), with normal renal function and on unrestricted diet, have been studied. Dietary protein intake was estimated by the protein catabolic rate determination. Abnormally elevated calcitriol levels were found in 16 patients (48.5%) who had similar levels of serum intact parathyroid hormone and phosphate, creatinine clearance, and calcium and phosphate urinary excretion, but lower protein catabolic rate (82+/-16 vs. 97+/-20 g/day, P0.05) than the patients with normal calcitriol levels. The calcitriol to intact parathyroid hormone ratio was higher in hypercalciuric than in normocalciuric patients (2.4+/-1.1 vs. 1.6+/-0.8, P0.05). Calcitriol was positively correlated with plasma calcium (r=0.41, P0.01) and inversely with protein catabolic rate (r=-0.42, P0.01). Protein catabolic rate was positively correlated with creatinine clearance (r=0.69, P0.001) and urinary phosphate excretion (r=0.72, P0.001). No relationship was observed between calcitriol and creatinine clearance. These results confirm the calcitriol overproduction in calcium stone disease and that the high calcitriol to intact parathyroid hormone ratio is the main feature associated with hypercalciuria. Calcitriol serum levels appear to be unrelated to creatinine clearance, whereas there is an inverse relationship with protein catabolic rate. This suggests that low rather than high dietary protein intake may favor the increase of calcitriol synthesis in male calcium stone formers with normal renal function.

The development of biochemical and genetic screening tests for inherited endocrine diseases has dramatically changed our approach to surgical patients with endocrine tumors. Among more than 1800 patients with endocrine tumors and a possible inherited disease operated on between 1986 and 1997, there were 6.1% to 7.3% who were found to have a familial disease associated with familial medullary thyroid cancer, (MTC), multiple endocrine neoplasia type IIa (MEN-IIa), MEN-IIb, or MEN-I. Genetic testing for the RET proto-oncogene is therefore recommended for all patients with MTC, and testing for the MEN-I gene is recommended in patients with suspected MEN-I and in specific clinical subgroups with an increased probability of endocrine tumor heredity. Early treatment based on early diagnosis by genetic testing appears to improve survival and to decrease morbidity in these patients.