Renal failure and hypercalcemia as initial manifestations of extrapulmonary sarcoidosis

Sarcoidosis is a granulomatous, multisystem disease. Rarely, sarcoidosis may present with both renal failure and hypercalcemia. A 27-year-old black man presented with severe abdominal pain and renal failure. A kidney biopsy demonstrated features of both interstitial nephritis and membranous glomerulopathy thought to be secondary to nonsteroidal anti-inflammatory drugs. His renal function and symptoms improved with short-term prednisone therapy. Discontinuation of steroids led to a recurrence of renal failure and severe hypercalcemia. On the basis of an elevated angiotensin-converting enzyme level of 160 U/L and anemia, a bone marrow biopsy was performed. Acid-fast bacillus-negative, noncaseating granulomas suggested the diagnosis of sarcoidosis. The patient recovered after restarting prednisone. Sarcoidosis may cause both interstitial and membranous nephritis from direct infiltration. Hypercalcemia results from increased calcium absorption secondary to 1,25-dihydroxyvitamin D production by sarcoid granulomas. Sarcoidosis must be considered in the differential diagnosis of renal failure in black patients. Serum calcium and angiotensin-converting enzyme levels may aid the diagnosis.     

The predictive value of serum angiotensin-converting enzyme activity in the differential diagnosis of hypercalcemia

Serum angiotensin-converting enzyme (SACE) activity is usually elevated in sarcoidosis, and this raises the possibility that SACE may be a useful diagnostic tool in distinguishing sarcoidosis from other hypercalcemic disorders. We therefore measured SACE in a large number of patients with various granulomatous, metabolic, and hypercalcemic disorders to determine its predictive value. We found elevated SACE activity in 4 of 35 surgically proven cases of primary hyperparathyroidism and in 3 of 13 patients with oncogenic hypercalcemia. In six patients with sarcoidosis and hypercalcemia, SACE activity was elevated; corticosteroid therapy lowered both the serum calcium and SACE levels to normal. We conclude that SACE activity is not a specific test for the differential diagnosis of hypercalcemia but that it remains useful as a chemical marker of successful treatment of sarcoidosis.     

Urinary cyclic AMP analyzed as a function of the serum calcium and parathyroid hormone in the idfferential diagnosis of hypercalcemia.

Urinary cyclic AMP (UcAMP) appropriate for the serum calcium concentration was determined in normal subjects during the base-line state and during alteration in their serum calcium concentrations by saline and calcium infusions. This was compared to the UcAMP in 76 patients with hypercalcemia and 5 patients with hypocalcemia. In 54 of 56 patients with primary hyperparathyroidism, the UcAMP was inappropriately high for their serum calcium concentration, the 2 exceptions having renal failure. In four patients with vitamin D intoxication, sarcoidosis, milkalkali syndrome, and thiazide-induced hypercalcemia and in five patients with hypocalcemia due to hypoparathyroidism, the UcAMP was appropriately low for their serum calcium concentration. In 16 patients with nonparathyroid neoplasms, 10 had UcAMP levels that were inappropriately high suggesting ectopic parathyroid hormone (PTH)-mediated hypercalcemia and 6 had UcAMP levels that were appropriately low suggesting that their hypercalcemia was due to osteolytic factors other than PTH. Correlations between UcAMP, serum calcium concentration, and carboxyl-terminal immunoreactive PTH suggest that random UcAMP is a sensitive accurate reflection of circulating biologically active PTH. If there is adequate renal function (serum creatinine concentration less than 2.0 mg/dl), a random UcAMP expressed as mumol/g creatinine and analyzed as a function of the serum calcium concentration completely separates patients with PTH and non-PTH-mediated hypercalcemia.     

Hypercalcemia and reversible renal failure in heavy-chain disease

We have reported a case of gamma heavy-chain disease associated with hypercalcemia and reversible renal failure. After combined chemotherapy the patient remains well after 21 months of follow-up, and serum calcium levels remain in the normal range. This case supports the notion of Kyle et al that heavy-chain disease may present a diverse picture, and documents the first use of aggressive combination chemotherapy in the management of associated moderately severe hypercalcemia and hypercalcemic renal failure.     

老年高钙血症3例并文献复习

目的 分析老年高钙血症患者的临床特点及原因。方法 回顾性分析陕西省人民医院收治的3例老年高钙血症患者的临床表现及诊治经过，并对相关文献进行复习。结果 3例老年高钙血症患者临床表现各异，其中以嗜睡为首发症状1例，全身肌无力症状1例，言语障碍1例。3例均行多项检查，最后查血清钙，确诊高钙血症，给予大量补液、利尿、鲑鱼降钙素肌肉注射、床旁血液滤过等治疗措施后，血清钙水平明显下降，临床症状改善。结论 当老年人突发意识改变、全身肌无力、言语障碍时，应警惕高钙血症的可能性，及时测定血清钙离子。由于老年患者高钙血症的发病常常较为隐匿，且临床症状无特异性，在排除了心脑血管疾病急性发作且疗效不理想时，要拓展诊疗思路，注意排除高钙血症的可能性。     

An unusual case of hyperthyroidism with recurrent vomiting and hypercalcemia as the main manifestations

Complicated vomiting and hypercalcemia are clinically rare in patients with hyperthyroidism. We describe a case of a woman whose main symptoms were palpitations, sweating, and vomiting. She was diagnosed with Graves’ disease by an analysis of thyroid function, thyroid-related antibodies, and color Doppler ultrasound. Biochemical tests showed that her serum calcium levels were greatly elevated. Her symptoms were relieved following the administration of antithyroid drugs, propranolol for heart rate control, fluid replacement, diuresis and calcium reduction, antiemesis, and liver protection. This case suggests that the thyroid function should be screened when hypercalcemia is seen in the clinic.     

Cinacalcet-associated cardiogenic shock in a patient with cardiomyopathy

INTRODUCTION: Cinacalcet is a calcimimtic agent used to treat secondary hyperparathyroidism in patients with end-stage renal disease on dialysis or hypercalcemia related to parathyroid carcinoma. This report describes recurring circulatory collapse in a patient treated with cinacalcet for unrelated refractory primary hyperparathyroidism. CASE SUMMARY: A white man, aged 54 years and weighing 68 kg, was admitted to the hospital with lethargy, dyspnea, and twitching in the extremities. He was diagnosed previously with primary hyperparathyroidism and nonischemic dilated cardiomyopathy. Surgical parathyroidectomy had been unsuccessful. His serum calcium concentration was 3.15 micromol/L and was refractory to bisphosphonate therapy. Therapy with cinacalcet 30 mg/d was reinitiated, resulting in a reduction in serum calcium concentration and greatly increased heart failure requiring inotropic drug therapy and hemofiltration. After 13 days of treatment, cinacalcet was withdrawn, and the patient's condition unproved. On reintroduction of cinacalcet 30 mg/d, the patient decompensated and required emergency circulatory support. Decompensation resolved 5 days after discontinuation of cinacalcet. DISCUSSION: Based on a score of 7 on the Naranjo adverse drug reaction probability scale, cinacalcet was the probable cause of cardiogenic shock in this patient. Calcium-channel antagonist poisoning is associated with hypotension and bradycardia, whereas the calcium sensitizer levosimendan has been reported to improve low-output heart failure, suggesting that calcium may have inotropic properties. CONCLUSIONS: It appears that cardiac function in this patient had adapted to hypercalcemia and became destabilized after introduction of cinacalcet. Caution should be exercised when considering treatment with cinacalcet in patients with heart failure.     

Pneumocystis carinii in a patient with hypercalcemia and renal failure secondary to sarcoidosis

A case of severe dyspnea, hypercalcemia and renal failure secondary to sarcoidosis is reported. The clinical diagnosis of sarcoidosis in a 48-year-old man was confirmed by histology and cytology. Transiently decreased numbers of CD4+ T cells (282/microliter) indicated impaired immunity in the absence of HIV-infection during the acute phase of the disease. Surprisingly, numerous "trophozoites" of Pneumocystis carinii were detected by immunofluorescence staining and PCR in the bronchoalveolar fluid indicating infection or colonization of the lungs. Corticosteroid therapy was administered together with trimethoprim-sulfamethoxazole and rapidly reduced elevated serum calcium and creatinine concentrations. Since airborne person-to-person transmission of P. carinii to susceptible individuals might be possible, patients with sarcoidosis could be a previously unrecognized reservoir for P. carinii distribution in hospitals and in the community at large.     

Gastric sarcoidosis: a case report and review of the literature

Sarcoidosis is a systemic granulomatous disease of unknown etiology that is characterized by the formation of noncaseating granulomas. Gastrointestinal (GI) tract involvement in sarcoidosis is rare. Gastric sarcoidosis, particularly involving the antrum, affects approximately 10% of patients with systemic disease. GI sarcoidosis commonly occurs subclinically, with clinical manifestations present in only 0.1 to 0.9% of patients with the disease. This is a rare case report of an individual with symptomatic gastric sarcoidosis. The patient presented with weight loss, nausea, and early satiety. An EGD and colonoscopy were performed and were grossly normal. However, biopsies of the gastric antrum revealed noncaseating granulomatous inflammation involving the gastric mucosa. Corticosteroid therapy was started and the symptoms abated almost immediately. We also offer a review of the literature.     

Investigation of hypercalcemia

Hypercalcemia is a relatively common clinical finding. Primary hyperparathyroidism, hypercalcemia associated with malignancy and chronic renal failure (with calcium and vitamin D metabolite treatment or tertiary hyperparathyroidism) are the most common causes. Less common causes of hypercalcemia include vitamin D-related (granulomatous diseases, lymphoma, vitamin D intoxication), other endocrine (thyrotoxicosis), medications (milk-alkali, thiazides, lithium) and other causes (immobilization, familial hypocalciuric hypercalcemia). The clinical laboratory is central to the diagnosis and differential diagnosis of hypercalcemia. Its role has expanded from measuring routine chemistry tests such as total calcium, phosphate, creatinine and alkaline phosphate to include quantification of ionized calcium, parathyroid hormone (PTH) and vitamin D metabolites. In spite of this progress, the diagnosis and differential diagnosis of hypercalcemia can be significantly improved by: 1) increasing the availability and utilization of ionized calcium since total and corrected calcium are often inaccurate; 2) establishing more accurate reference intervals for parathyroid hormone by excluding individuals who are vitamin D insufficient or deficient; and 3) harmonizing intact PTH immunoassays.     

Hypercalcemia and idiopathic hypoparathyroidism

Idiopathic primary hypoparathyroidism (prHP) is a rare disorder and clinical experience of its management is limited. Prolonged immobilization of such patients can cause hypercalcemia and hypercalciuria. We report on a boy with prHP who developed hypercalcemia and renal failure as a result of calcium and calcitriol substitution not being stopped while he was immobilized for 2 months. Any substitution in patients with prHP must be stopped during prolonged immobilization. Laboratory monitoring is mandatory during this period.     

An unrecognized cause of recurrent hypercalcemia: immobilization

We report a 66-year-old Chinese man with chronic renal insufficiency (creatinine 1.7 mg/dL) and gout suffering from slurred speech and right hemiplegia for 3 days. Acute cerebral infarction was confirmed by computed tomography. Conscious disturbance occurred on the tenth hospital day without significant changes on imaging study when compared with a previous scan. Hypercalcemia (total calcium 14.1 mg/dL) and acute exacerbation of chronic renal failure (serum creatinine 2.5 mg/dL) were noticed. Hypercalciuria (FECa 3.2%), and low serum levels of intact parathyroid hormone and 1,25(OH)2D3 suggested nonparathyroidal hypercalcemia. An extensive workup failed to identify any etiology of hypercalcemia. Hypercalcemia and renal failure were temporarily ameliorated after aggressive volume expansion and loop diuretic treatment but recurred 2 weeks later. Immobilization hypercalcemia was considered after the exclusion of other discernible causes and was successfully treated with rehabilitative exercises and bisphosphonates without further recurrence during a 2-year follow-up. Clinical alertness to immobilization as a possible cause of hypercalcemia may avoid unnecessary and invasive examinations, life-threatening complications and annoying recurrences.     

Acute amlodipine overdose treated by high dose intravenous calcium in a patient with severe renal insufficiency

Calcium salts are frequently used in the treatment of calcium antagonist poisoning. Different dosing regimens have been employed. The major risk of high dose calcium therapy is iatrogenic hypercalcemia, especially in patients with diminished renal function. Repeated doses of calcium are therefore often avoided; however, inadequate use of intravenous calcium may cause treatment failure in severe calcium antagonist overdose. We report our experience of using high dose intravenous calcium chloride effectively and safely to treat severe amlodipine overdose in a patient with severe renal insufficiency.     

Evidence that Increased Circulating 1α,25-Dihydroxyvitamin D is the Probable Cause for Abnormal Calcium Metabolism in Sarcoidosis

Mean plasma 1(alpha),25-dihydroxyvitamin D[1(alpha),25(OH)(2)D] was significantly increased and serum parathyroid hormone was suppressed in three patients with sarcoidosis and hypercalcemia. Prednisone lowered the mean plasma 1(alpha),25(OH)(2)D to normal range and corrected the hypercalcemia. To elucidate the mechanism for the increased sensitivity to vitamin D in this disorder, the effects of orally-administered vitamin D(2) were determined in seven normal subjects, four patients with sarcoidosis and normal calcium metabolism and three patients with sarcoidosis and a history of hypercalcemia who were normocalcemic when studied. Serum and urinary calcium, serum 25-hydroxyvitamin D (25-OHD), plasma 1(alpha),25(OH)(2)D and, in some studies, calcium balance were measured. Vitamin D(2), 250 mug a day for 12 d, produced little, if any, change in mean plasma 1(alpha),25(OH)(2)D and in urinary calcium in the normals and in the patients with normal calcium metabolism. In contrast, vitamin D(2) produced increases in plasma 1(alpha),25(OH)(2)D from concentrations which were within the normal range (20-55 pg/ml) to abnormal values and increased urinary calcium in two patients with abnormal calcium metabolism. In an abbreviated study in the third patient, vitamin D(2), 250 mug a day for 4 d, also increased plasma 1(alpha),25(OH)(2)D abnormally from a normal value. There was a highly significant correlation between plasma 1(alpha),25(OH)(2)D and urinary calcium. Serum 25-OHD and serum calcium remained within the normal range in all subjects and patients. These findings provide evidence that the defect in calcium metabolism in sarcoidosis probably results from impaired regulation of the production and(or) degradation of 1(alpha),25(OH)(2)D. Prednisone may act to correct the abnormal calcium metabolism by reducing circulating 1(alpha),25(OH)(2)D.     

Management of severe hypercalcemia

Severe hypercalcemia is a medical emergency requiring urgent treatment. It most commonly is caused by malignant tumors, as in the case study, but can also be caused by advanced hyperparathyroidism or high serum levels of vitamin D. The patient described in the case study shows clinical evidence of volume contraction due to hypercalcemia-related anorexia and vomiting. His elevated serum concentrations of urea nitrogen and creatinine reflect intravascular volume depletion and hypercalcemia-induced reduction of renal perfusion. He is also likely to have irreversible renal damage as a result of nephrocalcinosis. His central nervous system depression is most likely a result of hypercalcemia, but other central nervous system disorders such as cerebral metastases should be considered. Appropriate treatment would include intravenous fluids to correct volume depletion, dilute extracellular fluid calcium, and promote renal calcium excretion. Before waiting for the effects of volume expansion, the first dose of an inhibitor of bone resorption should be given. The agent of choice now (this may change when second-generation bisphosphonates become available) is plicamycin. Etidronate is a reasonable second choice. Because both drugs require at least 48 hours before their hypocalcemic action is manifest, calcitonin could be used to accelerate the rate of decline of the serum calcium. As the patient becomes more alert, weight-bearing and ambulation should be encouraged. With this combination of therapeutic modalities, this patient's serum calcium level should be corrected within 3 to 5 days. Intermittent injections of mithramycin or etidronate could be given on an outpatient basis approximately once a week in order to maintain the serum calcium within the normal range. One of the most important aspects of treatment in hypercalcemic patients is eradication of the underlying disease, which usually calls for specific antitumor therapy, including chemotherapy, radiation therapy, or surgery. Most of the agents currently available for the correction of hypercalcemia have cumulative toxicities or are only transiently effective and, therefore, their use should be considered a temporizing measure until specific treatment directed at the primary disease takes effect.     

Acute cardiac damage and acute kidney injury associated with hypercalcemia crisis in hyperparathyroidism: a case report

Hyperparathyroidism-induced hypercalcemic crisis is a rare presentation of primary hyperparathyroidism. Primary hyperparathyroidism is caused by uncontrolled and immoderate secretion of parathyroid hormone. The most common presentation in primary hyperparathyroidism is renal stones, soft tissue calcification, cystic bone disease, and even hypercalcemic crisis. We report a patient who presented with multiple organ dysfunction syndrome due to extreme hypercalcemia (serum calcium concentration, 4.79 mmol/L [2.15–2.25 mmol/L]) resulting from primary hyperparathyroidism (serum parathyroid hormone concentration, 2215 pg/mL). The complications in this patient were complete cardiac damage and acute kidney injury. On the basis of the hypercalcemic crisis, the patient subsequently underwent surgical resection of parathyroid adenoma. Two days after surgery, her serum calcium and parathyroid hormone concentrations were normal. The patient had a good recovery after a series of other relevant therapies. In conclusion, surgery should be taken into consideration for hyperparathyroidism.     

A hyperparathyroid case with pulmonary edema: can hypercalcemia trigger pulmonary edema?

Most cases of pulmonary edema presenting with hypercalcemia are associated with malignant hypercalcemia and related with metastatic calcification. Most patients have predisposing factors such as hematological and solid organ malignancies and chronic renal failure. Pulmonary edema, induced by moderate hypercalcemia, which is associated with primary hyperparathyroidism, has not been reported previously. A 72-year-old female patient was admitted to the emergency service with pulmonary edema and moderate hypercalcemia because of primary hyperparathyroidism. In this presented case, we have discussed the 72-year-old female patient admitted with acute pulmonary edema who had primary hyperparathyroidism.     

Hypercalcemia as an early sign of lymphoma in a patient with acquired immunodeficiency syndrome (AIDS).

Hypercalcemia is uncommon in patients infected with the human immunodeficiency virus (HIV). It has been described in association with cytomegalovirus infection, Pneumocystis carinii pneumonia, granulomatous diseases, and lymphoma. However, symptomatic hypercalcemia as an early sign of an underlying AIDS-related lymphoma is not well documented. We discuss the case of a patient with HIV and hypercalcemia, leading to the diagnosis of an underlying lymphoma. The hypercalcemia was associated with a suppressed serum level of intact parathyroid hormone and a normal serum phosphorus level. The possibility of a lymphoproliferative disorder should be considered in the differential diagnosis of HIV-associated hypercalcemia.     

Resectable bronchogenic carcinoma presenting with hypercalcemia: tumor-associated granulomatous reaction and probable production of 1,25-dihydroxyvitamin D

A patient with hypercalcemia, increased levels of 1,25-dihydroxyvitamin D, and a resectable squamous cell bronchogenic carcinoma surrounded by numerous non-caseating epithelioid granulomas, achieved normocalcemia, decreased levels of 1,25-dihydroxyvitamin D, and no evidence of tumor recurrence at 30 months following complete resection of his tumor. We suggest that an excess production of 1,25-dihydroxyvitamin D, through the granulomatous reaction around the tumor, was the mechanism of hypercalcemia. To our knowledge, no such mechanism of hypercalcemia has been previously reported with bronchogenic carcinoma. Furthermore, a review of the literature reveals that in cases of bronchogenic carcinoma, hypercalcemia is almost always associated with large and unresectable tumors, with a median survival after the discovery of hypercalcemia of only one month. This case, then, is unique because it describes an unusual mechanism of hypercalcemia with bronchogenic carcinoma and it emphasizes the rare occurrence of the potentially curable patient presenting with bronchogenic carcinoma complicated by hypercalcemia.