title: Hyperparathyroidism complicating CYP 24A1 mutations.
abstract: CYP24A1 gene mutations induce infantile hypercalcemia, with high 1,25(OH)2D contrasting with low PTH levels. The adult phenotype is not well known. Two unrelated adult patients were referred for nephrolithiasis, hypertension, hypercalcemia, hypercalciuria, normal 25-OHD levels, and inappropriate PTH levels (22 to 92pg/mL;N: 15-68) suggesting primary hyperparathyroidism, leading to surgery. Hypercalciuria improved despite persistent hypercalcemia, treated with cinacalcet. The ratio 25-OHD3/24-25-(OH)2D3>100 (N<25) suggested the diagnosis of CYP24A1 mutations which were confirmed through Sanger sequencing. In conclusion, the adult phenotype associated with CYP24A1 mutations can evolve over time from hypercalcemia with suppressed PTH towards hyperparathyroidism with moderately increased PTH level, adenoma and/or slightly increased parathyroid glands. Surgery decreased calciuria and improved kidney function. Cinacalcet was partially effective on hypercalcemia since PTH was inappropriate. This novel phenotype, a phenocopy of hyperparathyroidism, might evolve in few cases towards hyperparathyroidism despite random association of the 2 diseases cannot be excluded.
authors.affiliation: Endocrinology and Metabolism Department, C. Huriez Hospital, Lille University Hospital, 1, rue Polonovski, 59037 Lille cedex, France. Electronic address: cloyer88@gmail.com.
authors.forename: Camille
authors.initials: C
authors.lastname: Loyer
authors.affiliation: Endocrinology and Metabolism Department, C. Huriez Hospital, Lille University Hospital, 1, rue Polonovski, 59037 Lille cedex, France. Electronic address: Clara.LEROY@chru-lille.fr.
authors.forename: Clara
authors.initials: C
authors.lastname: Leroy
authors.affiliation: Department of Genetics, University Hospital, 14000 Caen, France. Electronic address: molin-a@chu-caen.fr.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Molin
authors.affiliation: Department of Biology, Lille University Hospital, 59037 Lille cedex, France. Electronic address: Marie-Francoise.ODOU@chru-lille.fr.
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: Odou
authors.affiliation: Department of Nuclear Medicine, Lille University Hospital, 59037 Lille cedex, France. Electronic address: Damien.HUGLO@chru-lille.fr.
authors.forename: Damien
authors.initials: D
authors.lastname: Huglo
authors.affiliation: Department of Nuclear Medicine, Lille University Hospital, 59037 Lille cedex, France. Electronic address: georges.lion@chru-lille.fr.
authors.forename: Georges
authors.initials: G
authors.lastname: Lion
authors.affiliation: Department of Radiology, Lille University Hospital, 59037 Lille cedex, France. Electronic address: Olivier.ERNST@chru-lille.fr.
authors.forename: Olivier
authors.initials: O
authors.lastname: Ernst
authors.affiliation: Department of Nephrology, Lille University Hospital, 59037 Lille cedex, France. Electronic address: maxime.hoffman@chru-lille.fr.
authors.forename: Maxime
authors.initials: M
authors.lastname: Hoffmann
authors.affiliation: Department of Biology, Lille University Hospital, 59037 Lille cedex, France. Electronic address: Nicole.BOULANGER@chru-lille.fr.
authors.forename: Nicole
authors.initials: N
authors.lastname: Porchet
authors.affiliation: Department of Endocrine Surgery, Lille University Hospital, 59037 Lille cedex, France. Electronic address: Bruno.CARNAILLE@chru-lille.fr.
authors.forename: Bruno
authors.initials: B
authors.lastname: Carnaille
authors.affiliation: Department of Endocrine Surgery, Lille University Hospital, 59037 Lille cedex, France. Electronic address: fpattou@univ-lille2.fr.
authors.forename: François
authors.initials: F
authors.lastname: Pattou
authors.affiliation: Department of Genetics, University Hospital, 14000 Caen, France. Electronic address: kottler-ml@chu-caen.fr.
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Kottler
authors.affiliation: Endocrinology and Metabolism Department, C. Huriez Hospital, Lille University Hospital, 1, rue Polonovski, 59037 Lille cedex, France. Electronic address: mc-vantyghem@chru-lille.fr.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Vantyghem
mesh_terms: D000328:Adult; D000069449:Cinacalcet / Q000627:therapeutic use; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000150:complications* / Q000188:drug therapy / Q000235:genetics; D006961:Hyperparathyroidism / Q000150:complications* / Q000188:drug therapy / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D065668:Vitamin D3 24-Hydroxylase / Q000235:genetics*
chemical_list: D065668:Vitamin D3 24-Hydroxylase; D000069449:Cinacalcet