Abstract
BackgroundFamilial hypocalciuric hypercalcemia (FHH) is a heterogeneous autosomal-dominant disorder of calcium hemostasis that may be difficult to distinguish clinically from mild primary hyperparathyroidism. Loss-of-function mutations mainly involving Arg15 residue of the adaptor-related protein complex 2, sigma subunit 1 (AP2S1) cause a rarer, more recently recognized form of FHH, FFH type-3. Recently, 18F-fluorocholine positron emission tomography/computed tomography (FCH-PET/CT) showed superior sensitivity to conventional imaging in localizing parathyroid adenomas. We report a new FFH type-3 patient who underwent unnecessary parathyroidectomy in association with misleading FCH-PET/CT imaging.Case presentationA 29-year old woman was initially evaluated for parathyroid hormone (PTH)-dependent hypercalcemia in 2013. Medical history was positive only for chronic constipation and malaise with no personal or family history of hypercalcemia, kidney stones, or neck surgery. Over seven years, serum calcium level was 2.51–2.89 mmol/L with concomitant PTH level of 58.7–94.8 mmol/L. Serum phosphate levels were in the low/low normal range. Serum creatinine and magnesium levels were normal. 25-hydroxy vitamin D level was 13 nmol/L. 24-hour urine calcium level was 1.92 mmol/day but increased to 6.99 mmol/day after treatment with cholecalciferol 1000 IU daily. Bone mineral density and renal ultrasound were normal. Parathyroid ultrasound showed two hypoechoic nodules inferior to the left and right thyroid lobes; however, 99mtechnitium-sestamibi scans (2013, 2016, 2018) were negative. FCH-PET/CT (2019) showed focal uptake co-localizing with the nodule inferior to the left thyroid lobe. The patient underwent left inferior parathyroidectomy and pathology was consistent with parathyroid hyperplasia. However, postoperatively, serum calcium and PTH levels remained elevated and FCH-PET/CT and ultrasound showed persistence of the uptake/nodule. Whole exome sequencing showed Arg15Cys mutation in the AP2S1 gene characteristic of FHH type-3.ConclusionsIn this new case of FHH type-3, FCH-PET/CT failed to localize to the hyperplastic parathyroid glands and localized instead to apparently a lymph node. This, together with increased urinary calcium after vitamin D supplementation, led to unnecessary parathyroidectomy. Given the increasingly lower cost of genetic testing and the cost of follow up and unnecessary surgery, it may prudent to include genetic testing for FHH early on in patients with mild PTH-dependent hypercalcemia.
Highlights
Familial hypocalciuric hypercalcemia (FHH) is a heterogeneous autosomal-dominant disorder of calcium hemostasis that may be difficult to distinguish clinically from mild primary hyperparathyroidism
Mukhtar et al BMC Endocrine Disorders (2021) 21:20 (Continued from previous page). In this new case of FHH type-3, FCH-PET/Computed tomography (CT) failed to localize to the hyperplastic parathyroid glands and localized instead to apparently a lymph node
The three genes are involved in circulating calcium signaling to the parathyroid glands and renal tubules, Guanine nucleotide-binding protein subunit alpha 11 (GNA11) mediated the action of calcium-sensing receptor (CaSR) and AP2S1 is important for clathrin-coated vesicle-mediated endocytosis of the CaSR [3]
Summary
FCH-PET/CT failed to localize hyperplastic parathyroid glands and localized instead to apparently a lymph node. Given the increasingly reduced cost of genetic testing and the cost of follow up and unnecessary surgery, it may prudent to include genetic testing for FHH early on in patients with mild non-progressive PTH-dependent hypercalcemia despite negative family history and even positive localization. Abbreviations AP2S1: Adaptor-related protein complex 2 sigma subunit 1; BMI: Body mass index; CaSR: Calcium-sensing receptor gene; CCCR: Calcium to creatinine clearance ratio; CT: Computed tomography; FCH-PET/CT: 18Ffluorocholinepositron emission tomography/computed tomography; FHH: Familial hypocalcuric hypercalemia; GNA11: Guanine nucleotide-binding protein subunit alpha 11; PHPT: Primary hyoerparathyroidism; PTH: Parathyroid hormone; MIBI scan: 99mTechnetium-sestamibi dual phase scan; US: Ultrasound; 4D-CT: Four-dimensional computed tomography
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.