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Although the simultaneous occurrence of hyperparathyroidism and pancreatitis during pregnancy is rare, several points should be emphasized. Early recognition and treatment are essential. Pancreatitis should be kept in the differential diagnosis of unexplained nausea, vomiting, and abdominal pain during pregnancy. Hyperparathyroidism should always be included in the differential diagnosis of pancreatitis. Finally, the second trimester is the optimal period for surgical intervention.
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PMID:Hyperparathyroidism and pancreatitis during pregnancy. 865 Jun 14

Patients with end-stage renal disease commonly develop secondary hyperparathyroidism. Calcitriol may be administered to such patients to decrease the synthesis and secretion of parathyroid hormone (PTH) and to help maintain calcium and phosphorus homeostasis. However, the doses of calcitriol required to suppress serum PTH concentrations can lead to hypercalcemia or hyperphosphatemia in many patients undergoing hemodialysis. Paricalcitol is a new vitamin D analogue that is safe and effective in suppressing elevated concentrations of PTH in patients with established hyperparathyroidism who are maintained on chronic hemodialysis. As with vitamin D, the biologic action of paricalcitol is mediated through activation of the vitamin D receptor (VDR). The VDR functions as a ligand-induced transcription factor regulating the rate of expression of genes that are involved in controlling not only calcium homeostasis and bone remodeling but also hormone secretion, inhibition of cell growth, and induction of cell differentiation. In vitro studies have shown that paricalcitol inhibits PTH secretion from bovine parathyroid cells in a dose-dependent manner. Studies in renally insufficient rats demonstrated that paricalcitol caused approximately 10 times less elevation of serum calcium concentrations than calcitriol. In clinical studies, paricalcitol effectively decreased PTH by about 60% over a 12-week period. Mean serum concentrations of calcium were significantly increased but remained within the normal range. There were occasional (5/414 determinations) transient elevations in serum calcium above the upper limit of normal in some (5/401) patients. Serum phosphorus values did not change significantly compared with baseline, although they tended to be slightly higher in the paricalcitol-treated group than in the group receiving placebo. Elevations of the calcium-times-phosphorus product were relatively few but occurred more often in the paricalcitol than in the placebo group. The terminal half-life of paricalcitol was 5 to 7 hours in healthy subjects; in patients undergoing hemodialysis, it was 14 hours. Adverse events associated with paricalcitol use included, among others, chills, feeling unwell, fever, sepsis, palpitations, dry mouth, gastrointestinal bleeding, nausea, vomiting, edema, light-headedness, and pneumonia. Paricalcitol should be considered as an alternative to calcitriol in the treatment of patients who are undergoing maintenance hemodialysis for end-stage renal disease, as it has a decreased potential to induce hypercalcemia and hyperphosphatemia. Additional studies are required to determine the long-term effects of therapy.
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PMID:Paricalcitol, a new agent for the management of secondary hyperparathyroidism in patients undergoing chronic renal dialysis. 1032 13

Clinical symptoms of hyperparathyroidism are generally nausea, vomiting, fatigue, constipation, and hypotonicity of the muscles and ligaments; bone pain and tenderness are also seen but are more common in secondary hyperparathyroidism. We report a histologically confirmed case of a 28-year-old man whose sole symptom of primary hyperparathyroidism was lower extremity radicular pain due to a vertebral brown tumor. Magnetic resonance imaging demonstrated brown tumor to be hyperintense on T2-weighted and slightly hypointense on T1-weighted sequences; it showed intense contrast enhancement with gadolinium. Because brown tumors usually contain hemosiderin a short T2 should have been expected, but this was not seen in our case. Healing resulted in decreasing contrast enhancement on T1-weighted sequences and increasingly short T2. To our knowledge, this is the first report of a lumbar vertebral brown tumor associated with primary hyperparathyroidism.
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PMID:Radicular lower extremity pain as the first symptom of primary hyperparathyroidism. 1522 Dec 19

Hyperparathyroidism is a disease characterized by hypercalcemia with hypophosphoremia resulting from increased secretion of parathyroid hormone (PTH). The disease may be divided into 3 forms: a) primary, b) secondary, c) tertiary (secondary refractory form). Primary hyperparathyroidism is rare in children; hyperplasia is more frequent during the early years of life (neonates and infants) and is difficult to distinguish from adenoma in children. The disease may be asymptomatic; elevated calcemia levels (>12 <13.5 mg/dl) are accompanied by anorexia, asthenia and persistent stipsis; severely elevated concentrations (>13.5 mg/dl) are accompanied by nausea, vomiting, polyuria due to osmosis, with dehydration and progressive onset of lethargy, stupor and coma. Osteopenia or osteitis fibrosa cystica may be present due to augmented bone resorption. Height and weight increases are altered due to anorexia and dehydration. Differential diagnosis includes iatrogenic causes of hypercalcemia (excessive vitamin D intake, prolonged immobilization, etc.) and idiopathic familial hypercalcemia. Emergency treatment is required in cases of extremely elevated hypercalcemia (Ca >13.5-14 mg/dl), due to risk of injury to the heart, the central nervous system, the gastrointestinal tract and the kidneys. The 4 cardinal points of treatment are: hydration, calciuresis, inhibition of bone calcium resorption, treatment of the cause underlying hyperparathyroidism. Secondary hyperparathyroidism is found in cases where chronic hypocalcemia is present, particularly in chronic renal failure, untreated deficiency rickets, chronic intestinal malabsorption, hepatobiliary disease, types I and II vitamin D-dependent rickets, tubular acidosis or Fanconi's syndrome. The tertiary form is distinguished by the autonomous nature of the parathyroid glands which have become hypertrophic/hyperplastic due to uncontrollable, chronic severe renal failure. It can also be of iatrogenic origin due to excessive intake of inorganic phosphates in familial hypophosphatemic rickets or chronic vitamin D deficiency.
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PMID:Hyperparathyroidism. 1524 24

Hypercalcemia associated with malignancies is reported in up to 20 to 30% of patients with cancer during the course of the disease, and points to a poor prognosis. Symptoms related to the central nervous system, as progressive mental impairment, stupor and coma, predominate. Alterations in kidney function (water-concentrating defect leading to polyuria) and gastrointestinal tract (anorexia, nausea, vomiting) corroborate to dehydration and a further increase in serum calcium. Cancer-induced hypercalcemia may be classified as: 1) local osteolytic hypercalcemia (LOH), due to marked increase in osteoclastic bone resorption in areas surrounding the malignant cells within the marrow space; 2) humoral hypercalcemia of malignancy, caused by the secretion of parathyroid hormone-related protein (PTHrP) by the malignant tumor; 3) ectopic hyperparathyroidism; 4) 1,25(OH)2 D-secreting tumors. Adequate control of hypercalcemia is necessary to give the patient time to respond to anti-cancer therapy. Volume expansion with saline will correct dehydration, improve glomerular filtration and increase urinary calcium excretion, which may be further stimulated by loop diuretics. Intravenous bisphosphonates are the most effective agents to control hypercalcemia, as they block osteoclastic osteolysis and also have antitumoral effects, decreasing bone metastases. New approaches to control the skeletal manifestations of malignancies are anti-PTHrP and anti-RANKL antibodies, osteoprotegerin, and also proteasome inhibitors in the case of multiple myeloma.
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PMID:[Hypercalcemia of malignancy: clinical features, diagnosis and treatment]. 1644 66

(1) Patients who require dialysis for chronic renal failure develop phosphocalcium metabolic disorders that often lead to secondary hyperparathyroidism. Standard treatment consists of a phosphate chelator and vitamin D, along with the use of an appropriate calcium concentration in the dialysis bath, but is difficult to manage. (2) Parathyroid cancer is a rare malignancy frequently associated with hypercalcaemia. (3) Cinacalcet is a calcimimetic agent that reduces the parathormone level. Clinical evaluation includes more than a dozen dose-finding studies and clinical trials. The optimal dose seems to range from 30 to 180 mg/day and varies widely from one patient to another. (4) 3 double-blind placebo-controlled trials, lasting for a maximum of one year and involving a total of 1136 dialysis patients with chronic renal failure, showed no improvement in quality of life with cinacalcet. The target parathormone level was reached by 40% of patients on cinacalcet versus 5% of patients on placebo, while the effects of cinacalcet on calcium levels (-7%) and phosphate levels (-8%) were modest. No impact on bone complications is mentioned in available reports. (5) The assessment of treatment of parathyroid cancer is limited to one ongoing non comparative trial involving 21 patients. (6) During clinical trials, 11% of dialysis patients had low parathormone levels, creating a risk of adynamic bone disease and fractures, but available data are sparse. (7) Two-thirds of patients receiving cinacalcet have episodes of hypocalcaemia, which may in part account for reports of seizures (1.4% of patients), nausea (31%) and vomiting (27%). Many adverse effects seen in animal studies have not been adequately investigated in the clinical setting, such as an increase in the QT interval, thyroid disorders, and sexual dysfunction. Cinacalcet is a powerful CYP 2D6 inhibitor and is also metabolised by isoenzymes CYP 3A4 and CYP 1A2, creating an increased risk of drug interactions. (8) In practice, treatment with cinacalcet seems difficult to manage and to provide only limited benefits. Available assessment reports leave many questions unanswered, and this is a further reason not to use this product outside of clinical trials, either after failure of phosphate chelator and vitamin D therapy (especially as an alternative to surgery) or in parathyroid cancer.
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PMID:Cinacalcet: new drug. Secondary hyperparathyroidism: where are the clinical data? 1676 95

Cinacalcet HCl reduces iPTH, serum calcium, serum phosphorus, and the calcium-phosphorus product in patients with chronic kidney disease and secondary hyperparathyroidism who are receiving dialysis, and reduces elevated serum calcium associated with primary hyperparathyroidism and parathyroid carcinoma. Cinacalcet is administered orally, and thus concomitant administration with food may affect its bioavailability. The objective of this study was to examine the effect of fat and caloric intake on cinacalcet exposure. This phase 1, randomized, open-label, single-dose, 3-period, 3-treatment, 6-sequence crossover study enrolled 30 healthy subjects (19 men, 11 women) to receive a single oral dose of cinacalcet HCl (Sensipar/Mimpara; Amgen Inc. Thousand Oaks, CA) (90 mg) on 3 separate occasions: following a high-fat, high-caloric meal, a low-fat, low-caloric meal, and a 10-hour fast. Blood samples were obtained predose and up to 72 hours postdose for pharmacokinetic (AUCinfinity, Cmax) and safety evaluations. Twenty-nine subjects completed all the 3 treatment conditions. The mean (90% confidence intervals) AUCinfinity following high- and low-fat meals was increased by 68 (48 to 89)% and 50 (33 to 70)%, respectively, relative to fasting. The difference in mean AUCinfinity between high- and low-fat meals was small [12 (9.9-26)%]. The mean tmax of cinacalcet was prolonged in fasting subjects (6 h) in relation to high-fat (4 h) and low-fat (3.5 h) fed subjects. The mean t1/2beta was similar between treatment conditions. Adverse events (AE) were observed at a similar frequency across the treatment conditions [high fat (34%), low fat (23%), and fasting (31%)]; the type of AE did not differ among the treatment conditions. The most common treatment-related AEs were headache 6/30 (20%), nausea 5/30 (17%), and dyspepsia 4/30 (13%) subjects. Administration of cinacalcet with either high- or low-fat meals results in significant increases in exposure, relative to administration under fasting conditions. However, the small differences observed in exposure following the ingestion of the different types of meals suggest that although food has a significant effect, the type of food does not. The observed effect supports the labeling statement that cinacalcet be taken with food, or shortly after a meal.
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PMID:The pharmacokinetics of cinacalcet are unaffected following consumption of high- and low-fat meals. 1751 96

We describe a case of delayed union in a tibial fracture secondary to primary hyperparathyroidism. A closed intra-articular proximal tibia fracture was stabilized with a hybrid external fixator. At 5 months clinical and radiological evaluation failed to demonstrate evidence of fracture healing. Fixation was stable and inflammatory markers ruled out infection. Further questioning revealed symptoms of anorexia, nausea and constipation. Plasma biochemistry showed an elevated corrected calcium and parathyroid hormone concentration. Further investigation included a sestamibi scan which confirmed a diagnosis of hyperparathyroidism secondary to a parathyroid adenoma. Six weeks following partial parathyroidectomy the fracture site was pain free, non-tender and the fracture had united radiologically. In cases of delayed-union, once an infective cause has been excluded with a mechanically stable fracture, other causes of delayed union like primary hyperparathyroidism should be ruled out.
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PMID:Primary hyperparathyroidism presenting as delayed fracture union. 1925 42

Most common causes of hypercalcemia are hyperparathyroidism, malignancy, vitamin D-mediated conditions such as sarcoidosis, and vitamin D toxicity. Less commonly, hypercalcemia can be caused by drugs such as thiazide diuretics and lithium. Mild hypercalcemia is usually asymptomatic but severe hypercalcemia is associated with nausea, vomiting, abdominal pain, excessive thirst, muscle weakness, lethargy, confusion, and fatigue. We are reporting a case of abdominal pain and altered mental status caused by thiazide-induced severe hypercalcemia of 19.8 mg/dL. This is the most severe case of thiazide-induced hypercalcemia that we have seen reported. Patients on thiazide diuretics should have their electrolytes frequently checked, especially patients on calcium supplements. Management usually includes hydration and discontinuation of drugs causing hypercalcemia.
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PMID:Thiazide-induced severe hypercalcemia: a case report and review of literature. 2006 44

Background. Management of multiple-endocrine neoplasia type 1- (MEN1-) associated hyperparathyroidism is associated with high recurrence rates and high surgical morbidity due to multiple neck explorations. Cinacalcet, a calcimimetic agent licensed for the treatment of secondary hyperparathyroidism and parathyroid carcinoma, may provide a medical alternative for the management of these complex patients. Methods. A prospective audit was performed of eight patients; three males and five females, aged 20-38 at diagnosis. Two patients commenced cinacalcet as primary treatment and six had previous surgery. Six patients had complications of hyperparathyroidism: renal calculi, renal dysfunction, and reduced bone mineral density. All were commenced on cinacalcet 30 mg bd for MEN1 associated hyperparathyroidism; doses were subsequently reduced to 30 mg od in four patients. Results. Significant reductions were observed in serum calcium and PTH measurements. Serum calcium reduced by a median of 0.35 mmol/L (P = .012 Wilcoxon Signed Rank). Serum PTH levels decreased by a median of 5.05 pmol/L (P = .012). There was no change in urine calcium. Duration ranged from 10-35 months with maintenance of control. Cinacalcet was well tolerated by six patients; one experienced nausea and one experienced diarrhoea. Conclusion. Cinacalcet is an effective and well-tolerated medical treatment for the management of complex primary hyperparathyroidism.
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PMID:Clinical Use of Cinacalcet in MEN1 Hyperparathyroidism. 2058 52


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