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      Hypercalcemia in pregnancy – a multifaceted challenge: case reports and literature review

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          Key Clinical Message

          Hypercalcemia in pregnancy is an uncommon event that can cause major maternal morbidity and/or fetal or neonatal morbidity and mortality. Management is a challenge for the clinicians, especially as regards to investigations in pregnancy, surgery, and the use of cinacalcet and bisphosphonates. We present three case reports and discuss management.

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          Parathyroid hormone-related peptide (PTHrP) regulates fetal-placental calcium transport through a receptor distinct from the PTH/PTHrP receptor.

          J Hunzelman, C Kovacs, H Kronenberg … (1996)
          To determine the role of PTHrP in fetal calcium metabolism, blood calcium was measured in mice homozygous (HOM) for deletion of the PTHrP gene. On day 18.5 of gestation, ionized calcium and the maternal-fetal calcium gradient were significantly reduced in HOM PTHrP-ablated fetuses compared with that of their littermates. To assess the placental contribution to the effect of PTHrP, 45Ca and 51Cr-EDTA (as a blood diffusional marker) were administered by intracardiac injection to pregnant, heterozygous dams on day 17.5 of gestation. Five minutes after the injection, whole fetal 45Ca accumulation was significantly decreased in HOM PTHrP-ablated fetuses compared with that of their littermates. Next, two fetuses from each litter were injected in utero with fragments of PTHrP, PTH, or diluent 1 h before administering 45Ca and 51Cr to the dam. PTHrP-(1-86) and PTHrP-(67-86) significantly increased relative 45Ca accumulation in HOM PTHrP-ablated fetuses, but PTHrP-(1-34), PTH-(1-84), and the diluent had no effect. Finally, similar studies were performed on fetal mice that lacked the PTH/PTHrP receptor gene. Ionized calcium was significantly reduced in HOM PTH/PTHrP receptor-ablated fetuses. However, 5 min after maternal injection of 45Ca and 51Cr, relative accumulation of 45Ca was significantly increased in these fetuses. It was concluded that PTHrP is an important regulator of fetal blood calcium and placental calcium transport. In addition, the bioactivity of PTHrP for placental calcium transport is specified by a mid-molecular region that does not use the PTH/PTHrP receptor.
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            Pregnancy outcomes in women with primary hyperparathyroidism.

            DANIA HIRSCH, Vered Kopel, Varda Nadler … (2015)
            Primary hyperparathyroidism (PHPT) during pregnancy may pose considerable risks to mother and fetus. This study examined pregnancy outcomes in women with gestational PHPT in relation to clinical and laboratory parameters.
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              Primary hyperparathyroidism in pregnancy.

              Peter Kamenicky, Agnès Linglart, Gonzalo Díaz-Soto … (2013)
              Primary hyperparathyroidism (PHPT) is rarely diagnosed during pregnancy but is associated with significant maternal and fetal morbidity and mortality. Information on appropriate management is limited. We reviewed the medical literature through December 2012 for key articles on PHPT during pregnancy, focusing on large series. Clinical knowledge in this area is restricted to isolated case reports and a few retrospective studies. Diagnosis can be difficult, owing to the non-specific nature of signs and symptoms of hypercalcemia during pregnancy. Pregnant women with a calcium level over 2.85 mmol/L (11.4 mg/dL) and prior pregnancy loss are at a particularly high risk of maternal complications (hypercalcemic crisis, nephrolithiasis, pancreatitis, etc.) and fetal loss. Around one-half of neonates born to mothers with untreated PHPT have hypocalcemia and tetany. Algorithms proposed for the management of the pregnant woman with PHPT are not evidence based, reflecting the paucity of data. Treatment should thus be individually tailored. Gestational age and the severity of hypercalcemia should be taken into account when assessing the risk-benefit balance of a conservative approach (hyperhydration and vitamin D supplementation) versus parathyroid surgery. Current evidence supports parathyroidectomy as the main treatment, performed preferably during the second trimester, when the serum calcium is above 2.75 mmol/L (11 mg/dL). In the patients with mild forms of PHPT, which are nowadays the most frequent, a conservative management is generally preferred.
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                Author and article information

                Contributors
                Evelyne Rey: evelyne_rey@ssss.gou.qc.ca
                Journal
                Journal ID (nlm-ta): Clin Case Rep
                Journal ID (iso-abbrev): Clin Case Rep
                Journal ID (doi): 10.1002/(ISSN)2050-0904
                Journal ID (publisher-id): CCR3
                Title: Clinical Case Reports
                Publisher: John Wiley and Sons Inc. (Hoboken )
                ISSN (Electronic): 2050-0904
                Publication date (Electronic): 17 September 2016
                Publication date Collection: October 2016
                Volume: 4
                Issue: 10 ( doiID: 10.1002/ccr3.2016.4.issue-10 )
                Pages: 1001-1008
                Affiliations
                [ 1 ]CHU Sainte‐Justine Research Center Montreal QuebecCanada
                [ 2 ] Division of Obstetric Medicine Department of Obstetrics and GynaecologyCHU Sainte‐Justine Montreal QuebecCanada
                [ 3 ] Department of MedicineUniversity of Montreal Montreal QuebecCanada
                [ 4 ] Division of Maternal‐Fetal Medicine Department of Obstetrics and GynaecologyCentre Hospitalier de l'Université de Montréal Montreal QuebecCanada
                [ 5 ] Department of MedicineMcGill University Health Centre Montreal QuebecCanada
                Author notes
                [*] [* ] Correspondence

                Evelyne Rey, Division of Obstetric Medicine, Department of Obstetrics and Gynaecology, Centre Hospitalier Universitaire Sainte‐Justine, 3175 Côte Sainte‐Catherine, H3T 1C5 Montreal, QC, Canada. Tel: 514 345 4706; Fax: 514 345 4648; E‐mail: evelyne_rey@ 123456ssss.gou.qc.ca

                Article
                Publisher ID: CCR3646
                DOI: 10.1002/ccr3.646
                PMC ID: 5054480
                SO-VID: 4ad857ab-6fb2-450e-bf80-5f536030d959
                Copyright © © 2016 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.
                License:

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                Date received : 05 March 2016
                Date revision received : 21 June 2016
                Date accepted : 09 July 2016
                Page count
                Figures: 0, Tables: 4, Pages: 8, Words: 5236
                Categories
                Subject: Case Report
                Subject: Case Reports
                Custom metadata
                source-schema-version-number 2.0
                component-id ccr3646
                cover-date October 2016
                details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_NLMPMC version:4.9.4 mode:remove_FC converted:07.10.2016

                Keywords: bisphosphonates,cinacalcet,fibroma,hypercalcemia,hyperparathyroidism,pregnancy
                Data availability:
                Keywords: bisphosphonates, cinacalcet, fibroma, hypercalcemia, hyperparathyroidism, pregnancy

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