Recurrent Renal Hyperparathyroidism Caused by Parathyromatosis

Background Parathyromatosis is defined as multiple foci of benign hyperfunctioning parathyroid tissue in the neck or mediastinum. Parathyromatosis is a problematic cause of recurrent hyperparathyroidism (HPT). In renal HPT, the stimuli of the parathyroid cells persist after parathyroidectomy (PTx), and for this reason, parathyromatosis might be important in renal HPT. Methods Between July 1973 and December 2005, 1,932 patients underwent PTx for advanced renal HPT in our department. We evaluated the frequency, clinical findings and the prognosis of this kind of parathyroid disorder. Results After total PTx with forearm autograft for renal HPT, which was performed initially in our department, the risk for developing parathyromatosis was 0.11% (2/1837); after sub-total PTx, it was 5% (1/20). The risk for developing parathyromatosis was lower after total PTx with forearm autograft than after sub-total PTx (P < 0.05). In patients who developed persistent or recurrent HPT and were referred to our department for neck re-operation, parathyromatosis occurred in 12.1% (7/58); in those originally operated on at our hospital, the corresponding figure was 7.1% (3/42). This difference was not significant (P = 0.42). Only in 4 of 10 patients was parathyromatosis suggested before re-operation. However, in spite of several re-operations, high parathyroid hormone (PTH) levels persisted in 6 of 10 patients with parathyromatosis. Conclusion Parathyromatosis is a non-negligible cause of recurrent renal HPT in patients who require neck re-exploration. Parathyromatosis is difficult to diagnose pre-operatively and completely controlled by re-operation. Parathyromatosis should be kept in mind when performing neck re-exploration for recurrent renal HPT.     

Calciphylaxis in pediatric end-stage renal disease

Calciphylaxis is a rare, but life-threatening complication of end-stage renal disease (ESRD) that has been reported mostly in adult patients. The exact etiology is unknown, but the disease is commonly associated with a high calcium-phosphorus product and elevated levels of parathyroid hormone (PTH). We herein review the published reports on calciphylaxis in ESRD patients less than 18 years old and report the case of a patient with severe calciphylaxis who presented with lower extremity pain, muscle tenderness and difficulty in walking. The serum PTH was low, and the calcium-phosphorus product was normal. The diagnosis of calciphylaxis was confirmed by a muscle biopsy. Treatment with low calcium peritoneal dialysate and substitution of calcium-based phosphorus binders with sevelamer (Renagel) was unsuccessful. The patients clinical condition progressed to extensive soft tissue calcification and ulcerating skin lesions. Nine months after the onset of symptoms, the patient died of cardiopulmonary arrest.     

Two cases of calciphylaxis treated by parathyroidectomy: importance of increased bone formation

Calciphylaxis (calcific uremic arteriolopathy) is a poorly understood and highly morbid syndrome of both vascular calcification and skin necrosis. The main histopathological finding is calcium deposits within arteriolar and small vessel walls, showing endovascular fibrosis associated with fat necrosis. The therapeutic strategy is to normalize the high calcium-phosphate products (Ca x P). When calciphylaxis is complicated with advanced renal hyperparathyroidism (HPT), parathyroidectomy (PTX) should be performed promptly. However, for patients with low PTH level, calciphylaxis is unresponsive to PTX, and such an approach may worsen hyperphosphatemia and hypercalcemia. We report two patients with calciphylaxis confirmed by skin biopsy. PTX was performed in both patients based on high PTH levels. PTH and Ca x P level decreased in both patients post PTX. In Case 1, the skin ulcers gradually improved and almost disappeared after PTX. However, in Case 2, new ulcers appeared after PTX. In Case 1, alkaline phosphatase (ALP) after PTX was approximately twice its level before surgery and PTX resulted in normalization of uptake on bone scintigraphy. However, no rise in ALP was noted in Case 2, probably due to long-term use of aluminum, which prevented bone formation. These findings suggest that differences in the extent of bone formation explain the different response in post-PTX ulcer healing.     

Calciphylaxis in moderate renal insufficiency: changing disease concepts

Calciphylaxis is a rare but frequently fatal complication in patients with end-stage renal disease. Original concepts regarding groups at risk for the disease, predisposing factors, and associated morbidity have changed significantly in the past few years as more cases are reported. We present a patient who developed fatal calciphylaxis in the setting of moderate renal insufficiency to illustrate some of the evolving concepts in this disease process.     

Proximal calciphylaxis treated with calcimimetic 'Cinacalcet'.

Calciphylaxis is a rare condition affecting patients suffering from end-stage renal failure, characterised by cutaneous ischaemia and necrosis. The management of calciphylaxis is challenging owing to the lack of optimal medical therapy, although parathyroidectomy has shown some benefit. We present a case of severe proximal calciphylaxis treated with a small dose of the calcimimetic 'Cinacalcet'.     

Effects of a parathyroidectomy on the immune system and nutritional condition in chronic dialysis patients with secondary hyperparathyroidism

BACKGROUND: Parathyroid hormone (PTH) has an adverse effect on the immune system and may cause immunologic disorders in patients with chronic renal failure. The in vivo effects of a parathyroidectomy on the immunologic parameters was examined. METHODS: Thirty-four patients under dialysis therapy received a parathyroidectomy (PTx) for secondary hyperparathyroidism (HPT). They were prospectively studied regarding serum immunoglobulins, complements, CD markers, and serum soluble IL-2 receptor (sIL-2R) until 12 months after PTx. RESULTS: The serum levels of IgG, IgA and IgM showed significant increase until 12 months after PTx (P<0.001, respectively). C3, C4, and CH50 also indicated significant increase at 12 months after PTx. In cellular immunity, only serum sIL-2R showed significant increase 2 weeks after PTx (P = 0.028). The hematocrit and serum albumin also improved significantly at 12 months. CONCLUSIONS: PTx showed beneficial effects on humoral immunological markers. The effects are probably due to the remarkable PTH reduction and partly improved nutritional state after PTx.     

Aortic valve involvement in calciphylaxis: uremic small artery disease with medial calcification and intimal hyperplasia

Calciphylaxis is a rare manifestation of abnormal calcium metabolism seen in some patients with renal disease. We describe the transesophageal echocardiographic (TEE) findings in a patient with calciphylaxis. These findings included calcification of ascending aorta and aortic valve. TEE was normal before the development of calciphylaxis.     

Cases with Fewer than Four Parathyroid Glands in Patients withRenal Hyperparathyroidism at Initial Parathyroidectomy

In the surgical treatment of secondaryhyperparathyroidism (2HPT) due to uremia, it is considered necessary toremove all parathyroid glands from the neck to prevent persistent andrecurrent parathyroid hyperfunction. However, in some cases fewer thanfour parathyroid glands can be recognized at initial operation; in thepresent study, we evaluated the long-term prognosis and estimatedsurgical strategy in such cases. Between March 1981 and January 1999,822 patients underwent total parathyroidectomy (PTx) with forearmautograft for advanced 2HPT at the Department of Transplant Surgery of Nagoya Second Red Cross Hospital. In 21 cases (2.6%) fewer than fourparathyroid glands were macroscopically found at the initial operation.These cases were followed up and their parathyroid function wasevaluated by measurement of intact parathyroid hormone (PTH). In 20 ofthe 21 cases three glands were found, in 1 patient only two glands. In5 of these cases the fourth gland was identified first afterpostoperative histopathologic evaluation. In all these cases the intactPTH level was normalized. In 8 of the remaining 16 cases high PTHlevels persisted after the initial operation, including 3 patients who underwent neck reexploration. However, in the other 7 patients PTHlevels dropped within normal range immediately after PTx and a fourthgland has never been recognized. One patient was lost to follow-up. Thus, using our operative strategy, 12 of 822 cases (0.85%) did notdevelop persistent or recurrent HPT even though only three glands wereidentified at the operation. To avoid postoperative hypoparathyroidism,autotransplantation should be performed when fewer than four parathyroid glands are found at the initial operation.     

We Do Too Many Parathyroidectomies for Calciphylaxis

Calciphylaxis, a disorder of dermal arteriolar calcification with a distinct predilection for patients with advanced kidney disease, remains an enigmatic condition that challenges clinicians. Observations regarding positive associations between levels of circulating parathyroid hormone (PTH) and the risk of calciphylaxis, combined with experimental data suggesting a pathogenic role of secondary hyperparathyroidism in vascular calcification, have led to the assumption that reducing PTH levels will improve the outcomes in patients with calciphylaxis. This editorial communicates the contemporary data regarding surgical parathyroidectomy as a treatment option for these patients. We raise concerns regarding the quality of available data and discuss the direction of future comparative effectiveness research in this field.     

Surgical and Medical Treatment of Secondary Hyperparathyroidism in Patients on Continuous Dialysis

Background  

Secondary hyperparathyroidsm (2HPT) is a common complication in hemodialysis patients associated with morbidity and sometimes mortality. The majority of patients with 2HPT can be managed by medical treatment. However, medical treatment does not always provied control of parathyroid disorder. Some patients require surgical treatment, parathyroidetomy (PTx). Successful surgical treatment often results in dramatic drop of the parathyroid hormone (PTH) levels, relieves the patients from clinical symptoms, and reduces mortality. However, at present we do not have reliable evidences showing that PTx.     

Reoperation for renal hyperparathyroidism

Reoperation for secondary hyperparathyroidism (HPT) due to uremia (2HPT) may be required among patients with persistent renal failure if not all parathyroid glands are removed at the initial operation. Between March 1981 and July 2001, altogether 1110 patients underwent total parathyroidectomy with forearm autograft for advanced 2HPT in our department. In this study, we evaluated the clinical features of patients who required reoperation and classified them into persistent HPT [the lowest intact parathyroid (PTH) level after initial operation remained higher than 60 pg/ml] and recurrent HPT (the lowest intact PTH level was normalized after surgery but reelevated became high enough to require reoperation). Removal of residual glands was indicated in 30 (2.7%) cases for persistent or recurrent HPT. All remaining glands were detected by preoperative imaging diagnoses. In 44 (4.0%) patients persistent HPT was recognized and in 15 of them (1.4% of all cases) reoperation was required. In 11 cases, the responsible glands were supernumerary ones removed from the mediastinum. In 4 cases, the glands were resected from the neck. In 15 cases (1.4%), reoperation was performed for recurrent HPT when residual glands were left either in the neck or in the thymic tongue. In all but one case, the missed glands were supernumerary. This study reveals that it is often difficult to avoid persistent HPT induced by mediastinal supernumerary glands and recurrent HPT caused by small glands left in the neck. Our findings indicate that patients with uremia should be closely followed considering the possibility that persistent or recurrent HPT may occur after parathyroidectomy.     

Cardiovascular complications caused by advanced secondary hyperparathyroidism in chronic dialysis patients; special focus on dilated cardiomyopathy

Background The frequency and prognosis of dilated cardiomyopathy (DCM) caused by secondary hyperparathyroidism (2°HPT) is not known. The purpose of this study was to determine the morbidity of DCM caused by 2°HPT and the efficacy of parathyroidectomy (PTx) in chronic dialysis patients with advanced 2°HPT was analyzed prospectively.Methods Between November 2000 and January 2003, 237 dialysis patients who underwent total PTx with forearm autograft at our department were enrolled in this study. Cardiac complications that existed before PTx were examined. Ten patients (4%) had DCM without valvular disease (VD) or ischemic heart disease (IHD). In these 10 patients with DCM before operation, we estimated left ventricular (LV) function at 6 months after PTx, according to echocardiography findings and clinical symptoms.Results Six months after PTx, left ventricular ejection fraction (LVEF) in these 10 patients was significantly improved, from 31.0 ± 9.8% before PTx, to 56.8 ± 13.5% (P = 0.0003), and left ventricular end-diastolic dimension (LVDd) was reduced, from 59.8 ± 9.7 mm to 46.3 ± 7.0 mm (P = 0.0014). The symptoms due to DCM and the fall of blood pressure that had occurred during dialysis were clearly improved after PTx.Conclusions Advanced 2°HPT can influence LV function, and in patients who suffered from DCM, LV function was dramatically improved by PTx. PTx should be performed immediately in patients with DCM caused by 2°HPT.This study was presented at the American Society of Nephrology Annual Meeting, held at San Diego, CA, USA, on November 12–17, 2003.     

Calciphylaxis precipitated by ultraviolet light in a patient with end-stage renal disease secondary to systemic lupus erythematosus.

Calciphylaxis is a rare and severe calcification syndrome described mainly in patients with end-stage renal disease (ESRD) undergoing dialysis or with a renal transplant. This life-threatening condition is characterized by the abrupt onset of painful ischemic skin ulcers and necrosis. Secondary local and systemic infection may supervene and, without timely and appropriate interventions, calciphylaxis may be fatal. A precipitant or challenging agent is believed to be necessary to initiate the process. We describe a case of a woman with ESRD receiving continuous ambulatory peritoneal dialysis who developed calciphylaxis in the setting of severe hyperparathyroidism after receiving UV photoradiation therapy. We suggest that the UV light served as the challenging agent in the precipitation of this devastating condition.     

Calciphylaxis of the Breast: A Case Report and Literature Review

Calciphylaxis, or calcific uremic arteriolopathy, is a rare but particularly morbid condition involving systemic medial calcification of arterioles causing ischemia and subsequent tissue necrosis. Although most commonly occurring over the abdomen and proximal extremities, calciphylaxis can present on nearly any skin surface with a tendency toward areas of increased adiposity. We report a case of a 53‐year‐old female with end‐stage renal disease who presented with bilateral palpable breast masses and overlying skin changes. Diagnostic mammography and percutaneous biopsy of the lesion facilitated the diagnosis of calciphylaxis and she was treated with medical therapy, local wound care, and eventual tissue extirpation. Due to the morbidity attributed to calciphylaxis and associated wound complications, surgical extirpation is at times unavoidable. Once malignancy has been excluded, we recommend nonoperative management with prompt referral to Nephrology for medical optimization, reserving surgical debridement for nonhealing wounds and superinfection.     

Tenth Argentine Congress of Nephrology

Calciphylaxis is usually a fatal condition that develops in a few chronic renal failure patients, and it is characterized by calcifications in subcutaneous arteries, infarcts in skin, and the neighboring subcutis. Calciphylaxis, once considered as a rare condition, has been reported to have an annual incidence of 1% and a prevalence of 4% in dialysis patients. We describe our clinical experience in six end-stage renal disease patients on dialysis that presented with calciphylaxis and died due to sepsis, and review the pathogenesis, epidemiology, clinical and histopathologic features, and treatment of calciphylaxis. Physicians should initially consider the possibility of calciphylaxis in case of development of skin lesions in chronic renal failure patients with impaired calcium, phosphorus, and parathyroid hormone levels. The most important cause of mortality in this condition is infection. Therefore, differential diagnosis of these lesions from systemic vasculitis in their early stages and withdrawal of immunosuppressive therapy that increases the tendency to infections are essential.     

Wet gangrene in hemodialysis patients with calciphylaxisis is associated with a poor prognosis

Calciphylaxis is a rare syndrome characterized by progressive vascular calcification and ischemic tissue loss in patients with chronic renal failure. We report our five-year experience with five patients who developed foot gangrene due to calciphylaxis. All five patients had characteristic clinical, laboratory, and radiologic findings of the disorder, but no diagnostic variable was uniformly present. All five had progressed to advanced gangrene at the time of surgical consultation. Despite aggressive local attempts to control infection, all five patients died of septic complications. Parathyroidectomy was performed in three patients but did not alter the course in any case. This small experience suggests that the outcome of foot gangrene associated with calciphylaxis is predicated on the degree of tissue loss. Aggressive local wound care does not appear to be adequate to control infection in patients who have already developed gangrene. Although parathyroidectomy may have important long-term advantages in patients with calciphylaxis, it does not appear to affect outcome in these advanced cases.     

Manifestation of Nonuremic Calciphylaxis in the Extremities: Case Report and Review

Nonuremic calciphylaxis is a rare condition presenting with peripheral ischemic ulcerations. Calciphylaxis is the deposition of calcium and phosphate into arteriolar walls caused by exceeding their solubility range in the blood. It is most commonly seen in patients with end-stage renal disease; however, nonuremic calciphylaxis occurs in patients with normal or mildly impaired renal function. Risk factors for nonuremic calciphylaxis include Coumadin therapy, obesity, and diabetes mellitus. Histopathologic examination of deep skin biopsy containing subcutaneous adipose tissue reveals medial calcification of dermal and subcutaneous arterioles. This diagnosis must be managed locally with wound care and systemically by control of blood calcium solubility. Avoidance of infection is critical to survival. Here we report a case of calciphylaxis in a patient with normal renal function and serum levels of calcium and phosphorus who presented with gangrene of the extremities. Increased awareness of this debilitating disease will lead to earlier diagnosis, proper treatment and improved patient outcomes.     

Leg revascularization in patients with calciphylaxis

Calciphylaxis is a rare complication in patients undergoing hemodialysis. The pathogenesis and risk factors for this disease are poorly understood, although an association with secondary hyperparathyroidism has been suggested. Only two cases of lower-extremity revascularization of patients with calciphylaxis appear in the literature; this report adds two more.     

Severe necrotizing mastopathy caused by calciphylaxis alleviated by total parathyroidectomy

Calciphylaxis is a complication caused by secondary hyperparathyroidism in patients with chronic renal failure. These patients may present with clinical findings of ischemic necrosis involving the skin and muscle resulting in subsequent gangrene and vascular calcifications. We report a rare case of necrotizing mastopathy caused by calciphylaxis in a 70-year-old female with end-stage renal disease whose symptoms resolved with a total parathyroidectomy.