Microsatellite instability driven metastatic parathyroid carcinoma managed with the anti-PD1 immunotherapy, pembrolizumab.

The present case report describes a 65-year-old man with Lynch syndrome and hypercalcaemia associated with hyperparathyroidism. Parathyroid surgery confirmed the diagnosis of parathyroid carcinoma. Serum calcium and parathyroid hormone (PTH) concentrations serially increased after initial surgery. Imaging study and subsequent biopsy confirmed lung metastases with mismatch repair deficiency. Pembrolizumab was initiated achieving 60% reduction in tumour burden.

Secondary and Tertiary Hyperparathyroidism: A Narrative Review.

End-stage renal disease is often complicated by the occurrence of secondary and eventually tertiary hyperparathyroidism, characterized by increased parathormone, calcium, and phosphate concentrations. Related symptoms include pruritus and osteodynia, concentration difficulties, and feelings of depression may be present. In the long-term, end-stage renal disease patients with hyperparathyroidism have an increased risk of all-cause and cardiovascular mortality. Among treatment options are vitamin D supplements, phosphate binders, calcimimetics, and surgical parathyroidectomy. Determining the optimal treatment for the individual patient is challenging for nephrologists and endocrine surgeons. This review resumes the pathogenesis of hyperparathyroidism, clinical presentation, required diagnostic work-up, and discusses indications for the available treatment options for patients with secondary and tertiary hyperparathyroidism.

Effectiveness of cinacalcet treatment for secondary hyperparathyroidism on hospitalization: Results from the MBD-5D study.

OBJECTIVES: To elucidate the effect of cinacalcet use on all-cause and cause-specific hospitalization outcomes using a prospective cohort of maintenance hemodialysis patients. METHODS: We used data from a prospective cohort of Japanese hemodialysis patients with secondary hyperparathyroidism and examined baseline characteristics as well as longitudinal changes. All patients were cinacalcet-naïve at study enrollment. Further, we used a marginal structural model to account for time-varying confounders on cinacalcet initiation and hospitalization outcomes, and an Andersen-Gill-type recurrent event model to account for any recurring events of hospitalization in the outcome analysis using the weighted dataset. RESULTS: Among the 3,276 patients, cinacalcet treatment was initiated in 1,384 patients during the entire follow-up. Cinacalcet users were slightly younger, included more patients with chronic glomerulonephritis and fewer patients with diabetes, were more likely to have a history of parathyroidectomy, and were more often used receiving vitamin D receptor activator, phosphate binders, and iron supplements. The overall hospitalization analysis yielded a hazard ratio (HR) of 0.97 (95% confidence interval [CI]: 0.80, 1.18). A trend toward a mild protective association was observed for cardiovascular-related hospitalizations (HR: 0.85; 95% CI: 0.64, 1.14). In the subgroup analysis, a protective association was seen due to cinacalcet use for infection-related hospitalizations in the lowest intact parathyroid hormone group (HR: 0.36; 95% CI: 0.14, 0.95). CONCLUSIONS: Cinacalcet initiation in patients on maintenance hemodialysis had no effect on all-cause and cause-specific hospitalizations. Although the overall association was statistically not significant, cinacalcet may have a protective association on cardiovascular-related hospitalization in all patients and infection-related hospitalization in patient with low intact parathyroid hormone.

Parathyroid Diseases.

Although uncommon in pregnancy, parathyroid dysfunction may produce significant perinatal and maternal morbidity and mortality. The prevalence of hyperparathyroidism is 0.5%. The most common cause of primary hyperparathyroidism in pregnancy is a single parathyroid adenoma, which is present in nearly 80% of cases. Surgery is the only definitive treatment for primary hyperparathyroidism, with a cure rate that is excellent. The most common etiology of hypoparathyroidism is damage to the parathyroid glands after surgery, with an incidence of 0.2%. Treatment of hypoparathyroidism is usually a high-calcium diet with vitamin D supplementation. Vitamin D deficiency is common, associated with perinatal morbidity and easily corrected.

Effect of restricted protein diet supplemented with keto analogues in end-stage renal disease: a systematic review and meta-analysis.

AIM: To evaluate the efficacy and safety of the restricted protein diet supplemented with keto analogues when applied in end-stage renal disease (ESRD). METHODS: The Cochrane Library, PubMed, Embase, CBM and CENTRAL databases were searched and reviewed up to January 2017. Clinical trials were analyzed using RevMan 5.3 software. RESULTS: Five randomized controlled trials were selected and included in this study according to our inclusion and exclusion criteria. Changes in serum albumin, PTH, triglyceride, cholesterol, calcium, phosphorus, hemoglobin, Kt/v and CRP before and after treatment were analyzed. Meta-analysis results indicated that, compared with normal protein diet, low-protein diet (LPD) supplemented with keto analogues (sLPD) could improve serum albumin (P < 0.00001), hyperparathyroidism (P < 0.00001) and hyperphosphatemia (P = 0.008). No differences in triglyceride, cholesterol, hemoglobin, Kt/v and CRP were observed between different protein intake groups. CONCLUSION: Restricted protein diet supplemented with keto analogues (sLPD) may improve nutritional status and prevent hyperparathyroidism in ESRD patients. The current data were mainly obtained from short-term, single-center trails with small sample sizes and limited nutritional status indexes, indicating a need for further study.

Changes in Serum Concentrations of Fibroblast Growth Factor 23 and Soluble Klotho in Hemodialysis Patients after Total Parathyroidectomy.

Background. We examined the changes in circulating fibroblast growth factor 23 (FGF23) and Klotho concentrations in hemodialysis patients after parathyroidectomy (PTX). Methods. We enrolled a cohort of hemodialysis patients who received PTX. Postoperatively, patients received calcium supplements and/or vitamin D analogue (calcitriol) to maintain serum calcium within 7.0-8.0 mg/dL. Information on clinical parameters including bone-mineral metabolic variables was collected pre-PTX and on days 5 and 90 after PTX. Concomitantly, serum full-length FGF23 and α-Klotho levels were measured. The relationship between FGF23 and clinical parameters was analyzed by single linear regression. Results. Forty-six participants (33 women; 13 men) were enrolled in the study. Their mean age was 56.49 years. Serum FGF23 and α-Klotho concentrations were elevated on days 5 and 90 after PTX compared to baseline (p > 0.05). Serum FGF23 concentrations negatively correlated with serum calcium concentrations pre-PTX (Beta -0.31; R2 0.0949; p = 0.040), day 5 post-PTX (Beta -0.31; R2 0.0982; p = 0.036), and day 90 post-PTX (Beta -0.39; R2 0.1528; p = 0.008). Conclusions. There was no change in circulating FGF23 and Klotho concentrations after PTX in hemodialysis patients given postoperative calcium supplements and/or vitamin D analogue. Serum FGF23 concentrations pre-PTX and at days 5 and 90 after PTX were inversely related to serum calcium concentrations.

Bone disease in post-transplant patients.

PURPOSE OF REVIEW: Mineral and bone disorders are common problems in organ transplant recipients. Successful transplantation solves many aspects of abnormal mineral and bone metabolism, but the degree of improvement is frequently incomplete. Posttransplant bone disease can affect long-term outcomes as well as increase the likelihood of fracture. In this article, we reviewed the major posttransplant bone diseases and recent advances in treatment strategies. RECENT FINDINGS: Pretransplant bone disease and immunosuppressants are important risk factors for posttransplant bone disease. Corticosteroid withdrawal may result in minimal or no protection against fractures, with increased risk for acute rejection. Vitamin D analogue and bisphosphonate are frequently used to prevent and treat posttransplant osteoporosis. Posttransplant hyperparathyroidism increases the risk for all-cause mortality and graft loss, but not major cardiovascular events. Cinacalcet was well tolerated and effectively controlled hypercalcemic hyperparathyroidism; however, it did not improve bone mineral density and discontinuation led to parathyroid hormone rebound. Six-month paricalcitol supplementation reduced parathyroid hormone levels and attenuated bone remodeling and mineral loss in case of posttransplant hyperparathyroidism. SUMMARY: Posttransplant bone diseases present in various forms, including osteoporosis, hyperparathyroidism, adynamic bone disease, and osteonecrosis. Prophylactic and therapeutic approaches to both pretransplant and posttransplant periods should be considered.

Outcomes for dogs with primary hyperparathyroidism following treatment with percutaneous ultrasound-guided ethanol ablation of presumed functional parathyroid nodules: 27 cases (2008-2011).

OBJECTIVE: To describe outcomes for dogs with primary hyperparathyroidism following treatment with percutaneous ultrasound-guided ethanol ablation of presumed functional parathyroid nodules. DESIGN: Retrospective case series. ANIMALS: 24 dogs with primary hyperparathyroidism that underwent 27 ultrasound-guided ethanol ablation procedures of presumed functional parathyroid nodules identified by cervical ultrasonography. PROCEDURES: Dogs were anesthetized for each procedure. For each nodule, 95% ethanol was injected into the center with ultrasound guidance (volume injected calculated on the basis of ultrasonographic measurements). The interval from treatment to resolution of hypercalcemia, complications, and follow-up clinicopathologic data were recorded. RESULTS: 5 procedures involved simultaneous treatment of 2 nodules. Three dogs underwent a second treatment because of initial treatment failure or development of another nodule. Hypercalcemia resolved after 23 of 27 (85%) procedures. In those 23 treatments, 22 (96%) had resolution of hypercalcemia within 72 hours after treatment. Hypocalcemia was detected in 6 different dogs at 2 (1 dog), 7 (3 dogs), 14 (1 dog), and 21 (1 dog) days after treatment; 5 of these dogs had mild transient hypocalcemia and 1 developed clinical signs requiring calcium supplementation. Although there were no periprocedural adverse effects, 2 dogs had delayed adverse effects; the overall rate of complications (including delayed adverse events and clinical hypocalcemia) was 11.1%. Long-term follow-up data indicated sustained normocalcemia in 17 of 19 dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that percutaneous ultrasound-guided ethanol ablation of functional parathyroid nodules may be an effective treatment for primary hyperparathyroidism of dogs, with short duration of anesthesia, minimal complications, and low risk for hypocalcemia.

Therapeutic management of post-kidney transplant hyperparathyroidism.

Left uncontrolled, persistent post-kidney transplant hyperparathyroidism (HPT) may lead to or exacerbate pre-existing bone and cardiovascular disease. Parathyroidectomy has long been the primary treatment option for long-term uncontrolled HPT in post-kidney transplant patients. However, patients with contraindications for surgery and parathyroidectomy-associated complications, including graft loss, highlight the need for other approaches. Conventional medical therapies have limited impact on serum calcium (Ca) and parathyroid hormone (PTH) levels. Bisphosphonates and calcitonin, used to spare bone loss, and phosphorus supplementation, to correct hypophosphatemia, do not directly regulate PTH or Ca. Although vitamin D supplementation can reduce PTH, it is often contraindicated because of hypercalcemia. Studies of the calcimimetic cinacalcet in patients with post-kidney transplant HPT suggest that it can rapidly reduce serum PTH and Ca concentrations while increasing serum phosphorus concentrations toward the normal range. Although the clearest application for cinacalcet is the non-surgical treatment of hypercalcemic patients with persistent HPT, current indications for other transplant patients are as yet uncertain. Further studies are needed to determine the utility of cinacalcet in patients with spontaneous resolution of HPT or low bone turnover. This review discusses the pathophysiology of post-kidney transplant HPT, associated complications, and current options for clinical management.

Conjugated linoleic acid reduces parathyroid hormone in health and in polycystic kidney disease in rats.

BACKGROUND: Feeding conjugated linoleic acid (CLA) is reported to reduce prostaglandin E(2) synthesis, which is required for parathyroid hormone (PTH) release. OBJECTIVE: This study was undertaken to determine whether CLA would suppress hyperparathyroidism and the resulting high-turnover bone disease in a rat model of polycystic kidney disease (PKD). DESIGN: Outcome measurements were conducted after 8 wk of feeding diets supplemented with and without CLA (1% of dietary fat) to Han:SPRD-cy male rats (n = 52). PTH, bone formation, and resorption were assessed in addition to femur bone mass with use of dual-energy X-ray absorptiometry. RESULTS: CLA feeding resulted in attenuation of PTH concentrations in both PKD-affected and nonaffected rats (by 60%) but did not significantly alter bone formation and resorption. CONCLUSION: Reduction in PTH may open possibilities for CLA as an adjunctive therapy in secondary hyperparathyroidism.

Ultrasound-guided percutaneous ethanol ablation of parathyroid hyperplasia: preliminary experience in patients on chronic dialysis.

OBJECTIVE: We report on a 3-year experience using single-shot, ultrasonography-guided, percutaneous ethanol ablation (PEA) of hyperplastic parathyroid glands in chronic dialysis patients suffering from secondary or tertiary hyperparathyroidism. MATERIALS AND METHODS: Seventeen uraemic patients (mean age 52 +/- 14 years) with hypercalcaemia and elevated serum levels of parathyroid hormone were assessed for ethanol ablation. Ten patients did not fulfil the inclusion criteria and underwent surgical parathyroidectomy. Seven patients were treated using PEA. RESULTS: All patients treated with PEA tolerated the procedure well, and no major complications were observed. Three out of seven patients underwent further ethanol ablation due to recurrent symptomatic hyperparathyroidism. Following the procedures, serum values of total calcium and parathyroid hormone remained within target range with concomitant medical therapy in all patients. CONCLUSION: PEA performed as a single-shot therapy can be used as a minimally invasive and safe supplement to medical therapy in the treatment of secondary or tertiary hyperparathyroidism in selected patients. In case of recurrence, treatment can be repeated without any problems.

Cardiovascular disease determinants in chronic renal failure: clinical approach and treatment.

INTRODUCTION: Cardiovascular disease (CVD), as the leading cause of morbidity and mortality in patients on renal replacement therapy (RRT), has a central role in everyday nephrological practice. METHODS: Consensus was reached on key points relating to the clinical approach and treatment of the main cardiovascular risk factors in RRT patients (hypertension, anaemia, hyperparathyroidism, dyslipidaemia, new emerging risk factors). In addition, the role of convective treatments on cardiovascular outcomes was examined. RESULTS: Hypertension should be managed by aiming at blood pressure values of < or =140/90 mmHg (< or =160/90 mmHg in the elderly), firstly by ensuring target dry body weight is achieved. No single class of drug has proved superior to others in RRT patients, provided that the blood pressure target is achieved, although ACE inhibitors have shown specific organ protection in high-risk patients (HOPE study) and are well tolerated. Anaemia should be managed by using erythropoietin and iron supplements, aiming at haemoglobin levels of 12 g/dl and keeping serum ferritin levels < 500 ng/ml. The management of hyperparathyroidism is currently unsatisfactory, as calcium supplements have the potential to increase cardiovascular calcification. While awaiting new calcium- and aluminium-free phosphate binders, it is essential to ensure dialysis adequacy. Clinical studies are in progress to assess the real impact of lipid-lowering drugs in RRT. In the meantime, serum LDL-cholesterol < 160 mg/dl and triglycerides < 500 mg/dl may be desirable targets. The impact of new emerging risk factors (inflammation and chronic infection, hyperhomocysteinaemia, metabolic waste-product accumulation) and their proper management are still under research. Convective dialysis treatments may confer some degree of protection from dialysis-related amyloidosis and mortality, but clinical data on this important issue are still controversial and no definitive conclusions can be drawn at present. CONCLUSION: CVD prevention and treatment is a great challenge for the nephrologist. Achieving evidence-based consensus can help in encouraging the implementation of best clinical practice in line with the progress of current knowledge.

Hiperparatiroidismo en la insuficiencia renal aguda: estudio prospectivo / Hyperparathyroidism in acute renal failure: a prospective study

El rol del hiperparatiroidismo en la insuficiencia renal crónica (IRC) está bien estudiado, pero existe muy poca información en la insuficiencia renal aguda (IRA) en pediatría. Se realizó un estudio prospectivo en pacientes con IRA secundaria a Síndrome Urémico-Hemolítico (SUH) moderado o grave internados en el Hospital de Pediatría Juan P. Garrahan desde febrero de 1995 hasta abril de 1996. Los objetivos fueron: documentar las alteraciones del metabolismo fosfo-cálcico, determinar los niveles de PTH y evaluar los cambios en relación con el tratamiento de quelantes del fósforo (P). Se analizaron 19 pacientes con edad x de 21.5 meses, 9 niñas y 10 niños. El laboratorio solicitado en el comienzo de la IRA (T1), durante la situación de IRA prolongada (T2) al normalizar la función renal en el control ambulatorio (T3) fue el siguiente: PTH, calcio (Ca) (corregido pr albúmina sérica), P, creatinina y estado ácido-base. La población se dividió en 2 grupos al azar: Grupo A: tratados con hidróxido de aluminio y Grupo B: sin tratamiento quelante. Todos recibieron el tratamiento habitual para IRA. Se llevó a cabo el procesamiento de datos mediante el Test de U de Mann Whitney y el Test de Friedman. Los resultados fueron: la x de los niveles de Ca fue normal en los 3 tiempos de observación en ambos grupos, pero con diferencias significativas entre T1 y T3 en el grupo A. Los valores de P de T1 y T2 fueron altos en ambos grupos, con normalización en T3, pero al comparar ambos grupos, la x de P de T2 fue significativamente menor en el grupo tratado. Los dosajes de PTH fueron elevados en ambos grupos en T1 y T2 y todos volvieron a la normalidad en T3, pero en el grupo tratado los niveles alcanzados fueron menores. Conclusión: es necesaria la prevención del aumento exagerado en la PTH y el consiguiente disturbio del metabolismo Ca-P por lo que se aconseja la indicación precoz de quelantes de P en la IRA prolongada, con el objeto de evitar los síntomas y signos indeseables que provoca el hiperparatiroidismo secundario.

Hiperparatiroidismo en la insuficiencia renal aguda: estudio prospectivo / Hyperparathyroidism in acute renal failure: a prospective study

El rol del hiperparatiroidismo en la insuficiencia renal crónica (IRC) está bien estudiado, pero existe muy poca información en la insuficiencia renal aguda (IRA) en pediatría. Se realizó un estudio prospectivo en pacientes con IRA secundaria a Síndrome Urémico-Hemolítico (SUH) moderado o grave internados en el Hospital de Pediatría Juan P. Garrahan desde febrero de 1995 hasta abril de 1996. Los objetivos fueron: documentar las alteraciones del metabolismo fosfo-cálcico, determinar los niveles de PTH y evaluar los cambios en relación con el tratamiento de quelantes del fósforo (P). Se analizaron 19 pacientes con edad x de 21.5 meses, 9 niñas y 10 niños. El laboratorio solicitado en el comienzo de la IRA (T1), durante la situación de IRA prolongada (T2) al normalizar la función renal en el control ambulatorio (T3) fue el siguiente: PTH, calcio (Ca) (corregido pr albúmina sérica), P, creatinina y estado ácido-base. La población se dividió en 2 grupos al azar: Grupo A: tratados con hidróxido de aluminio y Grupo B: sin tratamiento quelante. Todos recibieron el tratamiento habitual para IRA. Se llevó a cabo el procesamiento de datos mediante el Test de U de Mann Whitney y el Test de Friedman. Los resultados fueron: la x de los niveles de Ca fue normal en los 3 tiempos de observación en ambos grupos, pero con diferencias significativas entre T1 y T3 en el grupo A. Los valores de P de T1 y T2 fueron altos en ambos grupos, con normalización en T3, pero al comparar ambos grupos, la x de P de T2 fue significativamente menor en el grupo tratado. Los dosajes de PTH fueron elevados en ambos grupos en T1 y T2 y todos volvieron a la normalidad en T3, pero en el grupo tratado los niveles alcanzados fueron menores. Conclusión: es necesaria la prevención del aumento exagerado en la PTH y el consiguiente disturbio del metabolismo Ca-P por lo que se aconseja la indicación precoz de quelantes de P en la IRA prolongada, con el objeto de evitar los síntomas y signos indeseables que provoca el hiperparatiroidismo secundario. (AU)

Consequences of long-term hyperparathyroidism.

We describe a young woman with long-term untreated hyperparathyroidism with a superimposed vitamin D deficiency and an extremely decreased bone mineral density that was complicated by a vertebral fracture. Despite pretreatment with intravenous pamidronate and short-term vitamin D supplementation, severe and long-standing hypocalcaemia ('hungry bone syndrome') developed after parathyroidectomy. We discuss the consequences of hyperparathyroidism, especially the effects on bone, the complications of parathyroidectomy and the possibilities of preoperative treatment with bisphosphonates.