An unusual case of Gitelman's syndrome with hypercalcemia

We reported a case of a 41-year-old woman who had been diagnosed with Gitelman's syndrome since the age of 31 years. The diagnosis was established by the typical biochemical pictures including renal wasting hypokalemia, hypomagnesemia, hypocalciuria, metabolic alkalosis, and hyperreninemic hyperaldosteronism. She had normal blood pressure and had never used diuretics. She had a sibling with similar syndrome. The patient was treated with oral potassium and magnesium supplementation. She began to have hypercalcemia at the age of 39 years. The diagnostic approach to hypercalcemia became more complicated because of normal parathyroid hormone levels and underlying hypocalciuria due to Gitelman's syndrome. Thorough evaluation eventually identified primary hyperparathyroidism as the cause of hypercalcemia. To our best knowledge, this is the first report of combined occurrence of Gitelman's syndrome and primary hyperparathyroidism in the literature.     

Acute pancreatitis associated with primary hyperparathyroidism

Coexistence of primary hyperparathyroidism and acute pancreatitis has widely been reported in literature, but a causal relationship remains controversial. A case of acute pancreatitis as a first symptom of primary hyperparathyroidism with severe hypercalcemia is reported. In this patient a reduction of serum calcium level was obtained with medical therapy and resulted in the resolution of acute pancreatitis symptoms within 10 days. At the same time a parathyroid adenoma was clinically identified and elective parathyroidectomy was performed with complete normalization of intact parathyroid hormone and serum calcium level. At three-year follow-up, no recurrence or complications of pancreatitis were documented. The presented case suggests a cause and effect relationship between acute pancreatitis and severe hypercalcemia which should be kept in mind in the differential diagnosis of non-biliary, non-alcoholic acute pancreatitis. Reduction of hypercalcemia with medical treatment can represent a good chance for elective surgical neck exploration.     

Genetic hypercalcemia

A genetic disorder should be suspected in patients with hypercalcemia, notably those who are young; have family members with hypercalcemia; or have had a tumor of the endocrine pancreas, thyroid, pituitary, adrenal gland, or jaw bone. All forms of hypercalcemia should be interpreted according to the serum level of parathyroid hormone (PTH). Genetic forms are thus classified as related or unrelated to a parathyroid gland disorder. When the PTH level is elevated or is not depressed despite the hypercalcemia, findings that suggest family history of hypercalcemia due to a genetic cause include syndromic manifestations in the patient or family members, parathyroid cancer (either suspected before surgery or confirmed during parathyroidectomy), multiple or recurrent parathyroid tumors, a family history of primary hyperparathyroidism, and the onset of primary hyperthyroidism before 50 years of age. In patients with moderate hypercalcemia, a normal PTH level, and relative hypocalciuria, the first hypothesis is a mutation in the calcium-sensing receptor gene, which is often difficult to distinguish from primary hyperparathyroidism, particularly when there is no known family history of hyperparathyroidism, as is often the case. A low PTH level suggests non-parathyroid hypercalcemia due to a genetic defect in patients with no evidence of other conditions associated with hypercalcemia and low PTH levels and in those whose calcitriol levels are elevated or normal (instead of depressed as expected when PTH is elevated). Patients with hypercalciuria but no evidence of conditions such as granulomatous diseases should be evaluated for increased vitamin D sensitivity due to a CYP 4A1 mutation. Other very rare causes include hypophosphatasia due to ALPL mutations, which is characterized by a low alkaline phosphatase level; and renal phosphate wasting due to an NPT2A mutation, in which serum phosphate levels are low. A thorough analysis of the clinical and laboratory data can point toward a genetic disorder in patients with hypercalcemia. The diagnosis is then confirmed by obtaining genetic tests tailored to the clinical and laboratory test abnormalities. The current development of diagnostic genetic testing is shedding new light on the phenotypes, thereby improving their management.     

Secondary hyperparathyroidism as a palpable intrathyroid parathyroid gland in a patient with hypophosphatemic osteomalacia

Secondary hyperparathyroidism is sometimes seen in patients with hypophosphatemic osteomalacia after long-term oral phosphate therapy. Parathyroidectomy is sometimes needed for the correction of hypercalcemia in these patients, and is rarely performed in patients without hypercalcemia. A 46-year-old female patient had hypophosphatemic osteomalacia with unknown cause and secondary hyperparathyroidism. A palpable neck mass developed after long-term oral phosphate therapy. An intrathyroid parathyroid gland was confirmed through partial thyroidectomy and parathyroidectomy. Renal phosphate wasting decreased strongly, and serum parathyroid hormone was in the normal range after the operation. A correction of secondary hyperparathyroidism may partially overcome hyperphosphaturia in some patients with hypophosphatemic rickets.     

Hypercalcemia and elevated serum 1.25-dihydroxyvitamin D in an end-stage renal disease patient with pulmonary cryptococcosis

Hypercalcemia occurs relatively often in dialysis patients. The most common cause of hypercalcemia in dialysis patients is the conventional therapy with calcium and calcitriol. Besides, secondary hyperparathyroidism, low turnover bone diseases, and immobilization are also common causes of hypercalcemia in dialysis patients. Fungal infection associated with hypercalcemia has been infrequently reported. We describe a 71-year-old female woman with end-stage renal disease and diabetes mellitus, who developed severe hypercalcemia. Pulmonary cryptococcosis, with increased concentration of serum 1,25-dihydroxyvitamin D (1,25(OH)2D), was diagnosed. Her serum concentration of calcium and 1,25(OH)2D returned to normal after antifungal treatment. Thus, hypercalcemia was mediated by extrarenal overproduction of 1,25(OH)2D in this patient.     

Disodium pamidronate in the preoperative treatment of hypercalcemia in patients with primary hyperparathyroidism.

Nine patients (median age, 81 years) with primary hyperparathyroidism were treated with intravenous infusions of disodium pamidronate (APD), which is a bisphosphonate drug. Six patients had severe hypercalcemia (serum calcium concentration, greater than 3 mmol/L) persisting after rehydration with saline and treatment with furosemide; three patients had moderate hypercalcemia with pronounced symptoms (serum calcium concentration 2.8 to 2.9 mmol/L). Three of the patients were considered to have hypercalcemic crises. In all patients, the raised serum calcium levels were lowered by the disodium pamidronate infusions. One week after a single infusion of 15 to 60 mg disodium pamidronate, six of the nine patients had serum calcium concentrations within the normal reference interval and two patients had slightly raised values. Transient asymptomatic hypocalcemia was noted in one patient. All patients tolerated the infusions well, and no side effects were noted. In the patients with verified parathyroid adenomas, a temporary increase in parathyroid hormone levels were observed concomitant with the drop in serum calcium level. The patient with parathyroid cancer displayed no such effect indicating an autonomous parathyroid hormone secretion from the parathyroid carcinoma tumor. The good effect of treatment with the osteoclast inhibitor disodium pamidronate on hypercalcemia caused by primary hyperparathyroidism suggests that this hypercalcemia is mainly due to an increased osteoclast activity. The number of patients in this series is yet too small to allow general conclusions. But the case histories in this series show that disodium pamidronate promises to be of value in different clinical situations for the treatment of severe hypercalcemia in patients with hyperparathyroidism. It can be used (1) preoperatively to investigate whether the patient's symptoms are related to the hypercalcemia, (2) in the treatment of hypercalcemic crises when "forced diuresis" has failed to normalize the serum calcium, (3) after unsuccessful parathyroid surgery when it can be used as a long-term treatment before reoperation, giving time for localization studies and healing of the scar reaction, and (4) in aged and fragile patients where it can be tried as an alternative to surgery.     

A case of renal pelvic squamous cell carcinoma accompanied with humoral hypercalcemia of malignancy

A 74-year-old male was urgently admitted to our hospital because of consciousness disturbance. Laboratory data showed remarkable hypercalcemia (7.8 mEq/L), hypophosphatemia, low % TRP, low intact PTH level, normal nephrogenic cyclic AMP and normal 1,25 (OH)2D level. Serum bone Gla protein, which was thought to express osteoblastic activity, was low. Serum tartarate resistant acid phosphatase and urinary excretion of hydroxyproline, which were thought to express osteoclastic activity, were high. CT scan showed an enlarged mass in the left renal pelvis, which was found to be a squamous cell carcinoma (SCC) by biopsy through percutaneous nephroscopy. Bone scintigram appeared normal. Therefore, we diagnosed it as renal pelvic SCC with humoral hypercalcemia of malignancy (HHM) and performed left nephrectomy. After nephrectomy, serum calcium returned to normal. But after a few weeks, lung metastasis appeared and serum calcium was reelevated. As to PTH related protein (PTHrP) which was thought to induce HHM, PTHrP content of the resected tumor measured by RIA assay was 13 pmol/g wet weight of tissue, which suggested that this tumor might have been producing PTHrP.     

Hypercalcemia and primary hepatic tumors

We treated a case of hypercalcemia and primary liver tumor and reviewed a series of such cases treated at the Mayo Clinic (Rochester, Minn). Primary tumor of the liver was diagnosed in 192 patients (152 had hepatocellular carcinomas; 40, cholangiocarcinomas) between 1969 and 1980. Hypercalcemia of unknown cause was found in eight patients with hepatocellular carcinoma (5.3%) and seven with cholangiocarcinoma (17.5%). Five hypercalcemic patients had serum immunoreactive parathyroid hormone values consistent with ectopic hyperparathyroidism. An additional five patients had high serum calcium, low phosphate, and low chloride concentrations that met Lafferty's criteria for pseudohyperparathyroidism. Our results suggest that hypercalcemia associated with primary hepatic tumors is relatively common, and incidences vary according to the type of primary tumor. Hypercalcemia may be controlled when surgical excision of the primary tumor is possible.     

Postpartum hypercalcemia in a patient with medullary sponge kidneys

Previous associations of primary hyperparathyroidism-induced hypercalcemia and medullary sponge kidney (MSK) have been reported. In this report, we describe a lactating woman MSK noted to be hypercalcemic throughout lactation, without evidence of hyperparathyroidism. After the baby was weaned, the serum calcium returned to normal. A bone biopsy performed while the patient was hypercalcemic was consistent with hyperparathyroidism, suggesting the presence of a parathyroid-like protein produced during lactation.     

Experience with the radioimmunoassay for parathyroid hormone in the diagnosis of primary hyperparathyroidism

Our results with radioimmunoassay studies for parathyroid hormone performed during the last 6 years are compared retrospectively to results of the laboratory tests customarily secured when hyperparathyroidism is suspected. The results obtained in patients with known primary hyperparathyroidism and in patients with unconfirmed but presumptive hyperparathyroidism are compared to the results obtained from a group of normal controls. Despite the fact that certain discrepant results were noted in the earlier assay techniques the over-all results and, in particular, those of more recent years have been highly sensitive and reproducible corroboratives of the existence of primary hyperparathyroidism. About two-thirds of the patients with primary hyperparathyroidism will present to the urologist. All patients with calcium-containing stones should have at least 3 determinations of the serum calcium in screening for primary hyperparathyroidism. The radioimmunoassay for parathyroid hormone provides the most reliable confirmation. The patient with calculous disease, elevation of the immunoreactive parathyroid hormone level and hypercalcemia is virtually certain to have primary hyperparathyroidism.     

Water-clear cell adenoma associated with primary hyperparathyroidism: report of a case

We report a case of water-clear cell adenoma associated with primary hyperparathyroidism. A 59-year-old woman with a history of renal stones and bone fracture was referred for investigation of hypercalcemia and an elevated serum parathyroid hormone level. Skeletal X-rays showed osteopenia and ultrasound showed enlarged tumors in both sides of the inferior thyroid region. Computed tomography demonstrated a tumor in the posterior aspect of the left thyroid lobe but no lesion in the right aspect of the neck. Grossly, we found a 500 mg left lower parathyroid gland (PTG) and a 100 mg right lower PTG. Histologically, the left lower PTG comprised mainly water-clear cells (WCCs) containing numerous vacuoles. Chief cells were dispersed among the WCCs, but the right lower PTG showed normal parathyroid tissue. Several investigators have speculated that WCCs are derived from chief cells, and we diagnosed WCC adenoma. Following this case report, we review the relevant literature.     

Mechanisms of hypercalcemia in patients with head and neck cancer

Hypercalcemia associated with head and neck malignancy is not an uncommon occurrence; its causes are multiple. Eight hypercalcemic patients with head and neck malignancy were studied. Serum calcium, serum phosphorus, tubular phosphorus threshold, fasting calcium excretion, plasma 1,25-dihydroxyvitamin D, nephrogenous cyclic adenosine monophosphate (AMP), and immunoreactive parathyroid hormone were measured. Excessive dietary calcium administration in the form of an oral hyperalimentation preparation appeared to be the cause of hypercalcemia in 2 patients. Six patients demonstrated humorally mediated hypercalcemia. These patients resembled patients with primary hyperparathyroidism in having elevated nephrogenous cyclic AMP excretion and reduced proximal tubular phosphorus reabsorption, but they differed from patients with primary hyperparathyroidism by having normal levels of immunoreactive parathyroid hormone, MA rkedly increased fasting calcium excretion, and strikingly reduced mean plasma levels of 1,25-dihydroxyvitamin D. These data strongly suggest that the humoral factor responsible for hypercalcemia in patients with head and neck cancer is not parathyroid hormone, and that patients with hyperparathyroidism can now be distinguished with confidence from those with malignancy-associated hypercalcemia.     

Parathyroid lipoadenoma: The particularities of a rare entity a case report and review of the literature

Parathyroid lipoadenoma is a rare and anusual cause of primary hyperparathyroidism. The clinical presentation usually resembles other causes of primary hyperparathyroidism and the imaging is not always contributory considering its location. However, the histologic criteria are specific.We present a case that supplements and supports the rare literature data concerning the clinical and therapeutic aspects of parathyroid lipoadenoma.The case is about a 73 years old female with a right inferior parathyroid lipoadenoma that caused biological primary hyperparathyroidism. Initially followed and treated in Rheumatology department for hypercalcemia and osteoporosis, she was sent to our structure to diagnose and possibly treat the causal etiology. After non-contributory clinical examination and ultrasound imaging, the tumor was diagnosed in the cervical CT scan. The patient underwent successful surgical removal of the lipoadenoma, confirmed postoperatively on histological analysis. The follow up showed rapid normalization of the parathormon level.Even if it’s a rare condition, the diagnosis of lipoadenoma should always be considered in front of primary hyperparathyroidism with a parathyroid lesion.     

Parathyroid hormone: before and after parathyroidectomy

The clinical value of measuring serum immunoreactive parathyroid hormone (iPTH) for the diagnosis of primary hyperparathyroidism is sometimes debated, and the clinical significance of an elevated postoperative serum iPTH level is unknown. Therefore we studied 141 consecutive patients with primary hyperparathyroidism before and after parathyroidectomy to determine the clinical value of measuring serum iPTH by a mid-region-specific radioimmunoassay. Eighty-eight percent of the patients with primary hyperparathyroidism had an absolute increase in the level of serum iPTH (greater than 40 microliter Eq/ml) before surgery, and the remaining patients had an inappropriately increased level of serum iPTH for the simultaneous serum calcium level. Preoperative serum iPTH level correlated positively with serum calcium level and parathyroid tumor size. Postoperative elevation of serum iPTH level was common (as high as 40%) and was associated with higher preoperative levels of blood urea nitrogen, serum creatinine, and alkaline phosphatase and larger tumors. An elevated postoperative serum iPTH level without hypercalcemia did not indicate a failed parathyroidectomy, whereas negative parathyroid exploration and postoperative hypercalcemia were the best predictors of persistent hyperparathyroidism. We conclude that preoperative serum iPTH measurement is a very sensitive diagnostic test for primary hyperparathyroidism, but postoperative serum iPTH measurement is not a good predictor for persistent or recurrent hyperparathyroidism.     

Parathyroid exploration for primary hyperparathyroidism

Parathyroidectomy was studied retrospectively in 107 patients with primary hyperparathyroidism. This condition was diagnosed by measuring both the total serum calcium and ultrafilterable calcium (non-protein-bound) levels. The identification of ultrafilterable calcium is an important adjunct to parathyroid surgery as it allows the diagnosis of hyperparathyroidism when the total serum calcium level is normal. The surgical technique for selective parathyroidectomy and multiple biopsies was uniform. Parathyroid adenoma was discovered in 73 patients, diffuse hyperplasia in 26 and combined disease in 8. Postoperatively, two patients suffered from permanent hypocalcemia and three had hypercalcemia.     

Hypercalcemia and Elevated Serum 1.25‐Dihydroxyvitamin D in an End‐stage Renal Disease Patient with Pulmonary Cryptococcosis

Hypercalcemia occurs relatively often in dialysis patients. The most common cause of hypercalcemia in dialysis patients is the conventional therapy with calcium and calcitriol. Besides, secondary hyperparathyroidism, low turnover bone diseases, and immobilization are also common causes of hypercalcemia in dialysis patients. Fungal infection associated with hypercalcemia has been infrequently reported. We describe a 71‐year‐old female woman with end‐stage renal disease and diabetes mellitus, who developed severe hypercalcemia. Pulmonary cryptococcosis, with increased concentration of serum 1,25‐dihydroxyvitamin D (1,25(OH)₂D), was diagnosed. Her serum concentration of calcium and 1,25(OH)₂D returned to normal after antifungal treatment. Thus, hypercalcemia was mediated by extrarenal overproduction of 1,25(OH)₂D in this patient.     

Milk alkali syndrome. Does it exist and can it be differentiated from primary hyperparathyroidism?

Four patients with milk-alkali syndrome (MAS) presented with many of the characteristics of primary hyperparathyroidism including hypercalcemia, low or normal serum phosphorus levels, normal or increased urinary calcium levels, and inappropriately high or elevated serum parathyroid hormone levels. These laboratory findings differ from those classically described in MAS, i.e., hypercalcemia without hypercalciuria and a normal or high plasma phosphate level. Because the serum calcium level failed to return to normal after two weeks of hydration and a low calcium diet, and because of the inability to distinguish this syndrome from primary hyperparathyroidism, two of the four patients underwent neck exploration. Four normal parathyroid glands were histologically proven in each, and at autopsy in a third patient, there was no evidence of parathyroid hyperplasia or adenoma. Hypercalcemia eventually resolved in all patients with a low-calcium diet for as long as six months. Of the several features of MAS, hypercalcemia, alkalosis in the presence of azotemia, a history of increased calcium and alkali intake, and a response to dietary calcium restriction are helpful in differentiating this syndrome from primary hyperparathyroidism. Laboratory tests in patients with MAS may be confusing and the return to normocalcemia in response to a calcium deficient diet may be delayed.     

Intracranial metastatic parathyroid carcinoma: case report

OBJECTIVE AND IMPORTANCE: Parathyroid carcinoma is a rare entity, and fewer than 200 cases have been described. It is a slowly progressive disease characterized by frequent recurrences and local metastases. Most patients with parathyroid carcinoma die from metabolic complications of hyperparathyroidism. Five-year survival rates range from 25 to 50%. Functional parathyroid carcinoma is a rare cause of hyperparathyroidism that affects only 0.32 to 5% of all patients who undergo surgery for hypercalcemia. A review of the literature revealed only one other reported case of metastatic intracranial parathyroid carcinoma, in a patient who experienced local recurrence and metastatic disease when she was diagnosed with an intracranial lesion. CLINICAL PRESENTATION: We report the case of a 44-year-old African-American man with recent-onset, right lower-extremity weakness and hypercalcemia 4 years after he underwent a parathyroidectomy for parathyroid carcinoma. At presentation, his parathyroid level was 467 pg/ml, and his serum calcium level was 15.2 mg/dl. Imaging studies revealed an isolated enhancing left mesial frontoparietal mass. A systemic Cardiolite study demonstrated a single focus of radiotracer uptake in this region. No abnormal uptake was demonstrated in the neck or elsewhere. INTERVENTION: The patient underwent a frameless stereotactic interventional magnetic resonance imaging-guided resection via a parasagittal interhemispheric approach. Pathological findings were consistent with parathyroid carcinoma. After resection, his right lower-extremity weakness and secondary hyperparathyroidism resolved. CONCLUSION: The typical natural history of parathyroid carcinoma concludes with death from complications of hyperparathyroidism. This case report supports aggressive surgical management to eliminate all parathyroid hormone-secreting malignant tissue and prevent metabolic complications. In this patient, intraoperative magnetic resonance imaging was helpful to ensure complete resection.     

无症状原发性甲状旁腺功能亢进症的治疗

目的 探讨无症状原发性甲状旁腺功能亢进症(PHPT)的诊断和治疗方法 .方法 回顾性分析1990年1月至2006年12月间收治的46例PHPT患者的临床资料,其中5例为无症状PHPT,均为女性,年龄54～71岁.5例患者中3例为体检发现,1例因疲乏无力就诊而发现,1例误诊为甲状腺肿物,后经手术及病理学检查证实为甲状旁腺病变.4例血钙及血甲状旁腺素(PTH)高于正常范围,1例血钙及血PTH正常.5例患者均接受手术治疗,均为单侧探查术.结果 本组无手术死亡,无切口感染及喉返神经损伤等并发症.围手术期1例患者血钙低于正常范围,发生手足搐搦,静脉注射钙剂3 d后症状缓解.3例患者仅出现轻微的口唇及手足麻木感,但血钙在正常范围,口服补钙后缓解.术后平均住院时间6.5 d.4例获得随访,随访时间2个月～2年,血钙及血PTH均在正常范围.结论 无症状PHPT患者早期手术效果好,对于定位诊断明确的PHPT患者应该行手术治疗,定位不明确的或不适合手术的患者可行保守疗法.     

Tertiary hyperparathyroidism after renal transplantation: operative indications

A retrospective analysis of our renal transplant population between 1981 and 1987 was undertaken to study the natural history of posttransplant hypercalcemia and to review indications and recommendations regarding the timing of parathyroidectomy. During this period, 1158 renal transplant procedures were performed in 1025 patients, with 819 allografts (71%) functioning currently. Posttransplant hypercalcemia greater than 10.5 mg/dl was associated with a longer duration of dialysis and developed in 227 patients, with onset of hypercalcemia occurring in 90% of these patients by 1 year. In 69% of these patients, spontaneous resolution of the hypercalcemia occurred between 6 months and 7 years after transplantation. A total of 42 patients with asymptomatic hypercalcemia are currently being followed up, with a mean serum calcium level of 11.0 +/- 0.41 mg/dl and a mean follow-up interval of 3.3 +/- 1.6 years since transplantation. Nine symptom-free patients with moderate hypercalcemia (12.0 to 12.4 mg/dl) more than 1 year after transplantation were identified. Five of these patients had spontaneous resolution of the hypercalcemia between 2 and 7 years. Fifteen patients with posttransplant hyperparathyroidism (6.6%) required parathyroidectomy--11 for symptomatic and four for asymptomatic hyperparathyroidism. One patient had symptomatic hyperparathyroidism despite the presence of normocalcemia. One symptom-free patient with significant hypercalcemia (serum calcium level, 14.7 mg/dl) underwent parathyroidectomy 3 months after transplantation. The remaining three symptom-free patients had serum calcium determinations of greater than or equal to 12.5 mg/dl more than 1 year after renal transplantation. Patients with pretransplant and posttransplant hypercalcemia required parathyroidectomy more frequently than did patients with only posttransplant hypercalcemia (18% versus 3.0%; p less than 0.001). An unusual finding was the occurrence of a single adenoma in two patients, which represents sporadic primary hyperparathyroidism in the patient undergoing renal transplantation rather than tertiary hyperparathyroidism. We recommend a conservative approach to posttransplant hypercalcemia, with surgery reserved for patients with symptomatic disease and patients with asymptomatic persistent hypercalcemia greater than or equal to 12.5 mg/dl more than 1 year after transplantation.