Colecalciferol

Abstract

Increased urinary calcium: case report A 29-year old woman exhibited increased urinary calcium during supplementation treatment with colecalciferol. The woman was initially evaluated for parathyroid hormone (PTH)-dependent hypercalcaemia in 2013 at the age of 22 years. Apart from chronic constipation and malaise, her clinical evaluation was non-contributory. Additionally, she had no history of nausea, vomiting, abdominal pain, polyuria or bone pain. Her past medical history was unremarkable and negative for fracture, pancreatitis, kidney stone and hypercalcaemia. Family history was also negative for hypercalcemia, kidney stones and neck surgery. Her past surgical history was notable for nasal septoplasty in 2010 and scoliosis corrective surgery in 2016 (posterior spinal fusion and instrumentation). Her physical examination was unremarkable. Her serum calcium level was always high-normal, but never >2.9 mmol/L. She received supplementation therapy with colecalciferol [cholecalciferol] 1000IU daily [route not stated] for low 25-hydroxy vitamin D level. 24-hour urine calcium level was initially low. However, urine calcium increased on one occasion following colecalciferol therapy. Fluorocholine-PET/CT (May 2019) revealed abnormal focal choline uptake inferior to the left thyroid lobe that corresponded to few millimeter soft tissue density in the same location. A fluorocholine-PET/CT was performed per standard protocol. Briefly, after a minimum of 4h fast, of IV fluorocholine-18f [18F-fluorocholine] injection was administered, and PET/CT examination was performed 60 minutes later. Whole-body PET/CT with a field of view from the mandible to the carina was obtained. Data were acquired in a cranio-caudal direction and in supine position with a headrest and arms along the body, using a standardised breathing protocol. Owing to persistently high serum calcium, an increase in 24-h urine calcium, and the fluorocholine-PET/CT finding, she underwent an uncomplicated left inferior parathyroidectomy in July 2019. Pathology revealed tan smooth glistening soft tissue weighing 0.12 grams and measuring 1.2×0.7×0.3cm with a histology consistent with parathyroid lipoadenoma or hyperplasia. Following surgery, serum calcium and PTH levels remained elevated, and 24-h urine calcium was low. A fluorocholine-PET/CT (Oct 2019) demonstrated persistent mild, focal, tracer-avid soft tissue thickening inferior to the left thyroid lobe, suspicious for a parathyroid adenoma, and thyroid US showed persistence of the previously noted hypoechoic nodules inferior to the left and right thyroid lobes. Whole exome sequencing revealed a previously reported heterozygous Arg15Cys (c.43C>T, p.R15C, chr19: 47,349,360) pathogenic variant in the AP2S1 gene, characteristic of familial hypocalciuric hypercalcemia (FHH) type-3. No other likely-pathogenic variants or variants of unknown clinical significance related to the clinical phenotype were detected. It was then revealed that in this was the case of underlying FHH type-3, which fluorocholine-PET/CT failed to localise to the hyperplastic parathyroid glands and localised instead to apparently a lymph node. This, together with increased urinary calcium after colecalciferol, led to unnecessary parathyroidectomy [time to reaction onset and outcome of ADR not stated].