Cinacalcet Reduces Serum Calcium Concentrations in Patients with Intractable Primary Hyperparathyroidism
ABSTRACT Patients with persistent primary hyperparathyroidism (PHPT) after parathyroidectomy or with contraindications to parathyroidectomy often require chronic treatment for hypercalcemia.
The objective of the study was to assess the ability of the calcimimetic, cinacalcet, to reduce serum calcium in patients with intractable PHPT.
This was an open-label, single-arm study comprising a titration phase of variable duration (2-16 wk) and a maintenance phase of up to 136 wk.
The study was conducted at 23 centers in Europe, the United States, and Canada.
The study included 17 patients with intractable PHPT and serum calcium greater than 12.5 mg/dl (3.1 mmol/liter).
During the titration phase, cinacalcet dosages were titrated every 2 wk (30 mg twice daily to 90 mg four times daily) for 16 wk until serum calcium was 10 mg/dl or less (2.5 mmol/liter). If serum calcium increased during the maintenance phase, additional increases in the cinacalcet dose were permitted.
The primary end point was the proportion of patients experiencing a reduction in serum calcium of 1 mg/dl or greater (0.25 mmol/liter) at the end of the titration phase.
Mean +/- sd baseline serum calcium was 12.7 +/- 0.8 mg/dl (3.2 +/- 0.2 mmol/liter). At the end of titration, a 1 mg/dl or greater reduction in serum calcium was achieved in 15 patients (88%). Fifteen patients (88%) experienced treatment-related adverse events, none of which were serious. The most common adverse events were nausea, vomiting, and paresthesias.
In patients with intractable PHPT, cinacalcet reduces serum calcium, is generally well tolerated, and has the potential to fulfill an unmet medical need.
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ABSTRACT: Objective: Asymptomatic primary hyperparathyroidism (PHPT) is a common clinical problem. The only available definitive therapy is parathyroidectomy, which is appropriate to consider in all patients. The purpose of this report is to provide an update on calcium and vitamin D supplementation and medical management for those patients with PHPT who cannot or do not want to undergo surgery. Methods: Questions were developed by the International Task Force on PHPT. A comprehensive literature search was undertaken, and relevant articles published between 2008 and 2013 were reviewed in detail. The questions were addressed by the panel of experts, and consensus was established at the time of the workshop. Conclusions: The recommended calcium intake in patients with PHPT should follow guidelines established for all individuals. It is not recommended to limit calcium intake in patients with PHPT who do not undergo surgery. Patients with low serum 25-hydroxyvitamin D should be repleted with doses of vitamin D aiming to bring serum 25-hydroxyvitamin D levels to ≥ 50 nmol/L (20 ng/mL) at a minimum, but a goal of ≥75 nmol/L (30 ng/mL) also is reasonable. Pharmacological approaches are available and should be reserved for those patients in whom it is desirable to lower the serum calcium, increase BMD, or both. For the control of hypercalcemia, cinacalcet is the treatment of choice. Cinacalcet reduces serum calcium concentrations to normal in many cases, but has only a modest effect on serum PTH levels. However, bone mineral density (BMD) does not change. To improve BMD, bisphosphonate therapy is recommended. The best evidence is for the use of alendronate, which improves BMD at the lumbar spine without altering the serum calcium concentration. To reduce the serum calcium and improve BMD, combination therapy with both agents is reasonable, but strong evidence for the efficacy of that approach is lacking.Journal of Clinical Endocrinology & Metabolism 08/2014; 99(10):jc20141417. DOI:10.1210/jc.2014-1417 · 6.31 Impact Factor
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ABSTRACT: Parathyrotoxic crisis in intractable and persistent primary hyperparathyroidism in the ICU: a case study of first and second line treatment failure Background: Primary hyperparathyroidism is a common disease, which may cause a spectrum of symptoms, from mild cognitive impairment to increased cardiovascular disease. Parathyroidectomy is curative in 95% of patients. A smaller number of patients progress to develop parathyrotoxic crises with severe hypercalcaemia requiring urgent hospital treatment. Aim: The aim of this case report is to describe the challenges of managing parathyrotoxic crisis in the Intensive Care Unit in a patient with parathyroidectomy failure and to describe the effectiveness of combination of treatments. Clinical Details: A woman in her late sixties with history of primary hyperparathyroidism with parathyroidectomy, extensive cardiovascular disease and other morbidities of “asymptomatic” hyperparathyroidism was admitted to the intensive care unit for parathyrotoxic crisis management with intractable, persistent primary hyperparathyroidism. Acute treatment included intravenous hydration, loop diuretic, haemodiafiltration, bisphosphonate, corticosteroids and calcitonin. Second line therapies used during the admission included crushed cinacalcet and cholecalciferol administered via a nasogastric tube with background use of first line therapies. Outcomes: Early treatment achieved normocalcaemia, with over 50% parathyroid hormone clearance by haemodiafiltration. However, over the prolonged and complicated admission, aetiology of primary hyperparathyroidism was elusive. Treatment resistance became apparent within three months of admission and delirium never resolved. After 6 months of admission the patient was palliated. Conclusions: Combination therapy of cinacalcet and cholecalciferol may achieve parathyroid hormone secretion suppression, with large clearance by haemodiafiltration. Nasogastric administration of treatments, including cinacalcet, should be used in the intensive care settings when no other alternatives are available.04/2014; Research(1):670. DOI:10.13070/rs.en.1.670