Calciphylaxis in a hemodialysis patient: appearance after parathyroidectomy during a psoriatic flare.

Chronic renal failure patients are prone to soft tissue calcifications. A phenomenon of acute ischemic skin necrosis and dermohypodermic arteriolar medial calcification has been described recently in patients with chronic renal failure and secondary hyperparathyroidism (HPT). This phenomenon, termed calciphylaxis, occurs in response to certain factors, the most important of which appears to be an elevated blood calcium-phosphate product. Accordingly, parathyroidectomy in addition to normalization of calcium-phosphate product has been proposed as the only effective therapeutic approach for this condition. We describe a case of chronic renal failure with severe secondary HPT in which the patient developed calciphylaxis 4 days after the appearance of a psoriatic flare. Four months before, a subtotal parathyroidectomy was performed for severe HPT and at the time the ulcerations appeared, blood calcium-phosphate product was correct. Etiological and physiopathological aspects of calciphylaxis are discussed.     

Bilateral and simultaneous rupture of the triceps tendons in chronic renal failure and secondary hyperparathyroidism

Background We report a case of a 27-year-old (male) patient with bilateral and simultaneous rupture of the triceps tendons. He was suffering from chronic renal failure secondary to acute glomerulonephritis and for 4 years he underwent maintenance hemodialysis three times a week. This injury is extremely rare, and only one case has been reported in the international literature. Based on previous cases of tendon ruptures in patients with chronic renal failure, we believe that secondary hyperparathyroidism is the primary causative factor in his case.Case report A primary repair was performed using heavy, nonabsorbable sutures passed through holes drilled in the olecranon with the technique described by Levy. The suture line was then protected with a figure-of-eight tension band wire. Our patient obtained full range of motion bilaterally within 3 months.     

Mitral annular calcification and brown tumor of the rib in a child with chronic renal failure

Mitral annular calcification and liquefaction necrosis of this lesion mimicking intracardiac tumor because of secondary hyperparathyriodism have been described in adult patients with chronic renal failure, but have not been reported in children. Chronic renal failure is one of the predisposing factors of this condition. We report the case of a 13-year-old patient with continuous ambulatory peritoneal dialysis with severe hyperparathyroidism who was found to have intracardiac and rib lesions considered to be brown tumors.     

Prevention and treatment of renal osteodystrophy in children with chronic renal insufficiency and end-stage renal disease

Histologic features associated with secondary hyperparathyroidism remain the predominant skeletal lesion in adults and children with chronic renal failure. When instituted early, vitamin D therapy has been shown to ameliorate the development and progression of the biochemical, radiographic, and histologic evidence of secondary hyperparathyroidism in patients with chronic renal insufficiency. Aggressive parathyroid hormone suppression, however, has led to the increased prevalence of adynamic bone. Adynamic bone has been attributed partly to aggressive calcitriol therapy, administration of high amounts of exogenous calcium either as a phosphate binding agent or during dialysis therapy, presence of diabetes, older age, or previous parathyroidectomy. Several vitamin D analogues are currently being evaluated in patients with chronic renal failure to prevent complications associated with calcitriol therapy. In addition, calcium-free phosphate binding agents and the use of calcimimetic drugs may play a significant role in the effective management of secondary hyperparathyroidism in children with chronic renal failure.     

Facial leontiasis ossea: a rare presentation of hyperparathyroidism secondary to chronic renal insufficiency

The term renal osteodystrophy is often used in a generic sense to include skeletal disorders of patients with chronic renal failure due to secondary hyperparathyroidism. The prevalence of this condition among patients on hemodialysis is considerably high. However, extreme forms such as facial leontiasis ossea are very rare, only 2 well-characterized cases having been reported thus far in the literature. In the present article we report the case of a female patient who developed hyperparathyroidism secondary to end-stage renal disease which was manifested as facial leontiasis ossea and culminated in dysphagia and respiratory difficulties caused by excess bone tissue growth.     

Penile gangrene: a complication of secondary hyperparathyroidism from chronic renal failure

We present the third case and first reported survivor of penile gangrene due to secondary hyperparathyroidism from chronic renal failure. The patient was treated with distal penectomy and subtotal parathyroidectomy. This case stimulated us to review the metabolic and vascular changes associated with secondary hyperparathyroidism in chronic renal failure. Secondary hyperparathyroidism may cause diffuse vasculitis and vascular calcification, which can lead to widespread ischemic necrosis and gangrene. Early medical therapy, including oral phosphate binders, is crucial to maintain the serum calcium-phosphate product below precipitation level. Subtotal parathyroidectomy is indicated for patients in whom progressive arterial and soft tissue calcification develops despite medical therapy.     

Cell biology of renal osteodystrophy

Renal osteodystrophy, a well-recognized complication of chronic renal failure, encompasses a spectrum of skeletal disorders ranging from high-turnover lesions of secondary hyperparathyroidism, the most common histologic lesion in pediatric patients with end-stage renal disease, to low-turnover lesions of adynamic renal osteodystrophy, which has become a common skeletal lesion in adults with chronic renal failure. Several advances have been made in the understanding of the pathogenesis of secondary hyperparathyroidism, particularly the critical roles of calcium, phosphorus, and vitamin D in promoting excess parathyroid hormone (PTH) synthesis and secretion, and parathyroid gland hyperplasia in renal failure. These insights will guide the development of more effective strategies for the prevention and management of renal bone disease.     

Repeat parathyroid operation associated with renal disease

One hundred ten patients who had undergone operation for secondary and tertiary hyperparathyroidism have been described. Ninety patients had secondary disease and 20 patients had tertiary disease after renal transplantation. From these two groups, 18 patients had repeat operations for control of recurrent or persistent disease. The incidence of repeat operations was 14 percent. Causes were graft-dependent hyperparathyroidism, supernumerary glands in the neck or mediastinum, and incomplete identification of glands in the neck. The most important risk factor is continued long-term dialysis in functionally anephric patients. We recommend that patients with hyperparathyroidism associated with chronic renal failure undergo total parathyroidectomy with autotransplantation. If repeat operation is necessary, a reduction in glandular mass with autotransplantation is preferred. In selected patients, total parathyroidectomy can be considered because of the increased risk of aluminum bone disease.     

Distal Penile Gangrene in a Patient with Chronic Renal Failure

To date, only 10 cases of distal penile gangrene in patients with chronic renal failure have been reported. This rare condition is believed to result from progressive vascular calcification due to secondary hyperparathyroidism in patients with chronic renal failure. We report an additional case of distal penile gangrene in a 41-year-old man who presented with chronic renal disease and pulmonary tuberculosis. Since some authors have emphasized that aggressive surgical treatment in such cases has a significant mortality rate, we took a more conservative approach to treatment.     

Unresolved lytic lesions following parathyroidectomy in a patient with chronic renal failure

With advances in the treatment of patients with chronic renal failure, their life expectancy has increased. In turn, the prevalence of osteitis fibrosa cystica, a manifestation of secondary hyperparathyroidism, and beta2 microglobulin amyloidosis, a result of long-term haemodialysis, has risen. While both conditions share similar radiological features, their management is very different. We present the case of a patient with renal failure who had been receiving haemodialysis for over 20 years. Lytic lesions had been observed in the proximal part of both femurs for ten years. A presumptive diagnosis of osteitis fibrosa cystica was made. However, no regression of the lesions occurred after parathyroidectomy. The patient subsequently developed sequential pathological fractures through the lesions, for which bilateral total hip replacements were performed. Histology of the lesions revealed that the patient was in fact suffering from amyloidosis. In patients with chronic renal failure, osseous amyloidosis is a highly probable differential diagnosis, especially if no regression of a lytic lesion is observed after parathyroidectomy.     

Osteoporosis in end-state renal disease

Maintaining the intricate bone mineral homeostasis in patients with chronic renal failure and renal osteodystrophy is a complex and challenging process. In addition to the well described high-turnover bone disease caused by secondary hyperparathyroidism and low-turnover disease in the form of osteomalacia (either from aluminum or a dynamic bone disease) osteopenia also is present in end-stage renal disease patients. In contrast to abnormalities in the ability of bone to remodel, osteopenia is a deficiency in bone mass or volume. The prevalence of fractures in dialysis patients, regardless of histomorphometry appears to exceed that observed in elderly women. This osteopenia that occurs in chronic renal failure patients secondary to multiple factors that include hypogonadism, medications (such as corticosteroids), immobilization, and the typical osteopenia associated with aging. All of these factors amplify the risk of fracture in dialysis patients.     

Radiologic case study. Secondary hyperparathyroidism,osteomalacia with a pseudofracture,and amyloid deposition

The advancement of medical management of chronic renal failure has helped eliminate secondary hyperparathyroidism and osteomalacia. However, if a patient is recalcitrant, florid forms of both conditions can develop. Secondary amyloidosis is poorly understood but occurs in patients who are on long-term dialysis. As the survival rates for patients on long-term dialysis improve, it will be seen more frequently.     

Future role of calcimimetics in end-stage renal disease

Calcimimetic agents are small organic molecules that act as allosteric activators of the calcium-sensing receptor. In parathyroid cells, they lower the threshold for receptor activation by extracellular calcium ions and diminish parathyroid hormone (PTH) secretion. These compounds offer a novel way of controlling excess PTH secretion in clinical disorders associated with excess PTH secretion, including secondary hyperparathyroidism due to chronic renal failure. The first calcimimetic agent to be evaluated in clinical trials was R-568, but studies were discontinued because of its limited bioavailability and inconsistent pharmacokinetic profile. Extensive assessments are currently underway by using a second-generation calcimimetic compound, AMG 073, to treat secondary hyperparathyroidism. Work completed thus far has shown that AMG 073 effectively lowers plasma PTH, without increasing values for the calcium-phosphorus ion product in serum in patients with end-stage renal disease. Indeed, serum phosphorus levels often decline as plasma PTH levels fall during treatment. Recent experimental evidence also suggests that calcimimetic agents may impede the development of parathyroid gland hyperplasia, an integral component of secondary hyperparathyroidism due to chronic renal failure. Calcimimetics agents have considerable potential therefore as a new approach to the medical management secondary hyperparathyroidism.     

Serum phosphate, parathyroid hormone and vitamin D metabolites in patients with chronic renal failure: effect of aluminum hydroxide administration

Patients with chronic renal failure showed the existence of phosphate retention, secondary hyperparathyroidism, and reduced production of 1,25-(OH)2D. In order to determine the effect of correction of hyperphosphatemia on secondary hyperparathyroidism and vitamin D metabolism in those patients, 7 nondialyzed patients with chronic renal failure were treated with large doses of A1(OH)3 (15-18 g/day) to correct their high levels of serum phosphate. After treatment with A1(OH)3, serum phosphate fell significantly (p less than 0.005) from 6.3 +/- 1.3 (mean +/- SD) to 3.7 +/- 0.5 mg/dl. Serum parathyroid hormone decreased significantly (p less than 0.02) from 2.87 +/- 1.64 to 1.85 +/- 1.26 ngEq/ml. Serum 1,25-(OH)2D was low compared to the normal mean level before A1(OH)3 administration and decreased significantly (p greater than 0.02) from 19.4 +/- 6.1 to 11.4 +/- 4.3 pg/ml after the treatment. Aluminum levels increased significantly (p greater than 0.02) from 1.7 +/- 1.0 to 3.6 +/- 1.5 micrograms/dl. Serum calcium, calcitonin, and 25-(OH)D showed no significant change. Our data suggested that the suppression of secondary hyperparathyroidism by A1(OH)3 treatment results in a decrease of the 1,25-(OH)2D level in patients with chronic renal failure, even though their hyperphosphatemia has been corrected. We speculate that aluminum loading might play a role in diminishing the secretion of parathyroid hormone and the production of 1,25-(OH)2D in humans.     

Image diagnosis of parathyroid glands in chronic renal failure.

Twenty-two out of 31 patients with chronic renal failure and secondary hyperparathyroidism who underwent parathyroidectomy before operation underwent non-invasive image diagnosis of parathyroid glands by computed tomography (CT), scintigraphy with 201TlCl and 99mTcO4+, and/or ultrasonography. CT visualized 39 of 45 parathyroid glands (86.7%), weighing more than 500 mg. Scintigraphy with a subtraction method using a computer performed the diagnosis in 19 of 27 glands (70.4%). Ultrasonography detected 21 of 27 glands (77.8%). Image diagnosis was also useful in the postoperative follow-up study. The non-invasive image diagnosis of parathyroid glands in patients with chronic renal failure is thus valuable for 1) definite diagnosis of secondary hyperparathyroidism, 2) localization, and 3) diagnosis for effectiveness of conservative treatment.     

Sestamibi/iodine subtraction single photon emission computed tomography in reoperative secondary hyperparathyroidism

BACKGROUND: Sestamibi/iodine subtraction single photon emission computed tomography (SPECT) has been used successfully for the preoperative localization of adenomatous and hyperplastic parathyroid tissue in primary hyperparathyroidism, but the clinical usefulness of this technique in secondary hyperparathyroidism remains uncertain. The purpose of this study was to evaluate parathyroid localization that uses sestamibi/iodine subtraction SPECT in patients with secondary hyperparathyroidism before reoperative parathyroid surgery. METHODS: Fourteen consecutive patients with chronic renal failure and secondary hyperparathyroidism who had previously undergone total parathyroidectomy combined with parathyroid autotransplantation in a sternocleidomastoid muscle were studied. Before reoperation, each patient received 400 microCi of sodium iodide I 123 orally and 20 to 25 mCi of technetium Tc 99m ((99m)Tc)-sestamibi intravenously, followed by sestamibi/iodine subtraction SPECT of the neck and chest. At surgery, the location, weight, and histopathologic results of all identified parathyroid tissue were recorded. RESULTS: At surgery, 1 hyperplastic parathyroid gland was resected from each of 13 patients; including 1 undescended gland, 6 parathyroid autotransplants, and 5 mediastinal glands. The mean weight of the resected parathyroid glands was 1707 mg (range, 85-5300 mg). Sestamibi/iodine subtraction SPECT correctly identified and localized all 13 parathyroid glands (100% sensitivity) and was negative in the 1 patient whose surgery was unsuccessful. CONCLUSIONS: The (99m)Tc-sestamibi/(123)I subtraction SPECT is able to correctly localize hyperplastic parathyroid tissue in patients with secondary hyperparathyroidism who have previously undergone parathyroid surgery and is a clinically useful study before reoperation.     

Surgical management of secondary hyperparathyroidism

Most patients with renal failure maintained on chronic dialysis have elevated parathyroid hormone (PTH) levels and PTH-mediated bone disease (secondary hyperparathyroidism [sHPT]). Elevated PTH production in this setting represents a progressive, exaggerated physiologic response to hypocalcemia by the parathyroid glands, and generalized growth of the parathyroids is an adaptive response to chronic stimulation. Effective medical strategies to reduce PTH secretion and PTH-mediated bone turnover in sHPT (eg, controlling hyperphosphatemia, normalizing serum calcium, and administering vitamin D analogs) has decreased the need for parathyroidectomy in recent years. However, failure of medical therapy because of inadequate treatment, persistent hyperphosphatemia, or acquired parathyroid neoplasia still leads to recommendations for parathyroidectomy in select patients. Furthermore, increased awareness of potential long-term, irreversible cardiovascular effects of uncorrected hyperparathyroidism has led some to advocate parathyroidectomy earlier in the course of this disease. This monograph will review parathyroidectomy for secondary and tertiary hyperparathyroidism.     

Calcimimetics: a new tool for management of hyperparathyroidism and renal osteodystrophy in patients with chronic kidney disease

Calcimimetics: a new tool for management of hyperparathyroidism and renal osteodystrophy in patients with chronic kidney disease. Epidemiologic, clinical, and basic scientific studies led to an explosion in our understanding of disorders of mineral metabolism in the chronic kidney disease (CKD) patient. These advances are not always translated into improved care of renal osteodystrophy in CKD-5 patients. The introduction of a new class of drugs, calcimimetics, allows improved control of abnormal calcium/phosphorus metabolism. The calcimimetics compliment, rather than replace, current treatment options for secondary hyperparathyroidism in the chronic disease patient.     

Papillary microcarcinoma of the thyroid and secondary hyperparathyroidism in a patient on hemodialysis

Association between non-medullary thyroid carcinoma and secondary hyperparathyroidism have been rarely reported in patients with renal failure. A few cases of micropapillary thyroid carcinoma have been reported in patients before and after renal transplantation. We present a case of incidental detection of thyroid carcinoma at the time of parathyroidectomy in patient on dialysis after cadaver renal transplantation.     

Cinacalcet-induced hungry bone syndrome

Cinacalcet is a type II calcimimetic approved for treatment of secondary hyperparathyroidism in patients with end-stage renal disease. It is generally well tolerated with the most common side effects being nausea and vomiting. Symptomatic hypocalcemia is rare, and persistent hypocalcemia has not been reported to date. We present a case of a 66-year-old woman on chronic outpatient hemodialysis who was initiated on cinacalcet when her intact parathyroid hormone was 1091 pg/mL (normal 15-75 pg/dL). Two weeks later she developed diffuse muscle twitching. The patient required a 72-hour hospitalization and treatment with a continuous intravenous calcium infusion for symptomatic hypocalcemia. The intact parathyroid hormone level at this time was 176 pg/mL. This case is the first report of cinacalcet-induced prolonged and symptomatic hypocalcemia, closely resembling the hungry bone syndrome described in some patients with secondary hyperparathyroidism following surgical parathyroidectomy.