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      The use of cinacalcet in pregnancy to treat a complex case of parathyroid carcinoma

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          Summary

          We present the case of a patient with metastatic parathyroid carcinoma whose hypercalcaemia was medically managed through two pregnancies. The diagnosis was made when the patient presented with chronic knee pain and radiological findings consistent with a brown tumour, at the age of 30. Her corrected calcium and parathyroid hormone (PTH) levels were significantly elevated. Following localisation studies, a right parathyroidectomy was performed with histology revealing parathyroid carcinoma, adherent to thyroid tissue. Aged 33, following biochemical recurrence of disease, the patient underwent a second operation. A subsequent CT and FDG–PET revealed bibasal pulmonary metastases. Aged 35, the patient was referred to our unit for treatment of persistent hypercalcaemia. The focus of treatment at this time was debulking metastatic disease using radiofrequency ablation. Despite advice to the contrary, the patient conceived twice while taking cinacalcet. Even though there are limited available data regarding the use of cinacalcet in pregnancy, both pregnancies continued to term with the delivery of healthy infants, using intensive medical management for persistent hypercalcaemia.

          Learning points

          • Parathyroid carcinoma is a rare cause of primary hyperparathyroidism.

          • Hypercalcaemia during pregnancy can result in significant complications for both the mother and the foetus.

          • The use of high-dose cinacalcet in pregnancy has been shown, in this case, to aid in the management of resistant hypercalcaemia without teratogenicity.

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          Most cited references9

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          Hyperparathyroidism during pregnancy and the effect of rising calcium on pregnancy loss: a call for earlier intervention.

          Hyperparathyroidism (HPT) during pregnancy is rare but poses a significant danger to mother and baby yet the incidence of pregnancy loss and its relationship to the degree of calcium elevation is not known. A retrospective patient series from a single practice examined the past and current obstetrical histories of pregnant patients with primary HPT. Over a period of 6-years, 32 women age ranging from 19 to 40 years had a total of 77 pregnancies while having elevated serum calcium levels because of primary HPT (incidence 0.7% of all women with primary HPT). Fifteen patients underwent parathyroidectomy during the second trimester resulting in an uneventful delivery of a healthy infant between 36 and 40 weeks gestation. There were no maternal or infant complications at surgery or during the subsequent delivery. Thirty of the remaining 62 pregnancies (48%) were lost, a rate that is 3.5-fold higher than expected (P < 0.05). In those who did not have the HPT addressed after the first miscarriage, one-third lost one or more additional pregnancies. Pregnancy loss occurred typically in the late first or early second trimester, with second trimester losses (30%) being sixfold higher than expected (P < 0.01) and over 4 weeks later than typical (P < 0.05). Foetal loss was seen at all levels of elevated maternal calcium but most were above 11.4 mg/dl (2.85 mmol/l). The rate of foetal loss increased directly with increasing maternal serum calcium levels (R = 0.972). HPT during pregnancy is under recognized and is associated with a 3.5-fold increase in miscarriage rates. Pregnancy loss often occurs in the second trimester and is associated with multiple miscarriages when not addressed. Pregnancy loss is more common as calcium levels exceed 11.4 mg/dl (2.85 mmol/l), but can be seen at all elevated calcium levels. Emphasis is placed on earlier recognition and surgical cure before becoming pregnant, however, once pregnant, surgery should be offered early in the second trimester for those with calcium levels above 11.4 mg/dl.
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            Parathyroid carcinoma.

            Parathyroid carcinoma is a rare endocrine malignancy. The reported incidence is from 0.5 to 5% of primary hyperparathyroidism cases in various series. The cause is unknown, but clinical correlations with different genetic syndromes exist. Mutations in the HPRT2 gene seem to play a significant role in the pathogenesis of this disease. Men and women are equally affected, usually in the fourth or fifth decade of life. Most patients will present with signs and symptoms of hypercalcaemia. Cases of non-functioning carcinoma are exceedingly rare. Surgical resection is the most effective method of treatment and palliation. A significant proportion of patients will experience recurrence, and will need further surgical and, eventually, medical management of hypercalcaemia. The disease is progressive but slow growing. Most patients will require multiple operations to resect recurrent disease. The main cause of morbidity and mortality is the sequela of uncontrolled chronic hypercalcaemia rather than tumour burden. The current paper will review the epidemiology, pathogenesis, clinical presentation and diagnostic work-up of this disease. Surgical management in different scenarios is reviewed in detail, followed by other types of treatment and management of incurable disease. Copyright (c) 2010 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
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              Cinacalcet hydrochloride reduces the serum calcium concentration in inoperable parathyroid carcinoma.

              Management of inoperable parathyroid carcinoma presents a challenge because until recently, effective medical therapy was not available. Morbidity and mortality result primarily from severe hypercalcemia. We assessed the ability of the calcimimetic cinacalcet HCl to reduce serum calcium in patients with parathyroid carcinoma as well as its effect on PTH concentrations, bone turnover markers, safety, and health-related quality of life variables. Twenty-nine patients with parathyroid carcinoma were enrolled in this open-label, single-arm study consisting of titration and maintenance phases. Cinacalcet doses were titrated (30 mg twice daily to 90 mg four times daily) for 16 wk or until serum calcium was no more than 10.0 mg/dl. The study endpoint was the proportion of patients with at least a 1 mg/dl reduction in serum calcium at the end of the titration phase (responders). Mean (+/- se) serum calcium (14.1 +/- 0.4 mg/dl) and PTH (697 +/- 94 pg/ml) were markedly elevated at baseline. At the end of the titration period, serum calcium was reduced by at least 1 mg/dl in 62% of patients (mean decline to 12.4 +/- 0.5 mg/dl). In the 18 responders, serum calcium fell from 15.0 +/- 0.5 to 11.2 +/- 0.3 mg/dl (P < 0.001). The greatest reductions in serum calcium were observed in patients with highest baseline calcium levels. PTH levels decreased, but not significantly, to 635 +/- 73 pg/ml (-4.6%). Adverse events included nausea, vomiting, headache, and fracture. Cinacalcet effectively reduces hypercalcemia in approximately two thirds of patients with inoperable parathyroid carcinoma and may represent an important new treatment option for these patients.
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                Author and article information

                Journal
                Endocrinol Diabetes Metab Case Rep
                Endocrinol Diabetes Metab Case Rep
                edm
                EDM Case Reports
                Endocrinology, Diabetes & Metabolism Case Reports
                Bioscientifica Ltd (Bristol )
                2052-0573
                1 September 2014
                2014
                : 2014
                : 140056
                Affiliations
                [1]Department of Endocrinology, St Bartholomew's Hospital , London, UK
                [1 ]Imperial Centre for Endocrinology, Imperial College Healthcare NHS Trust , London, UK
                [2 ]Department of Neonatology, King's College Hospital , London, UK
                [3 ]Department of Diabetes, King's College Hospital , London, United Kingdom
                Author notes
                Correspondence should be addressed to K Nadarasa Email: k.nadarasa@ 123456hotmail.com
                Article
                EDM140056
                10.1530/EDM-14-0056
                4174590
                25298882
                3b2af673-f623-40e3-b70e-bf6a17df3ebf
                © 2014 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License.

                History
                : 12 August 2014
                : 19 August 2014
                Categories
                Novel Treatment

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