Hyperparathyroidism complicating CYP 24A1 mutations

Camille Loyer; Clara Leroy; Arnaud Molin; Marie-Françoise Odou; Damien Huglo; Georges Lion; Olivier Ernst; Maxime Hoffmann; Nicole Porchet; Bruno Carnaille; François Pattou; Marie-Laure Kottler; Marie-Christine Vantyghem

doi:10.1016/j.ando.2016.03.002

Hyperparathyroidism complicating CYP 24A1 mutations

Ann Endocrinol (Paris). 2016 Oct;77(5):615-619. doi: 10.1016/j.ando.2016.03.002. Epub 2016 Jul 1.

Authors

Affiliations

¹ Endocrinology and Metabolism Department, C. Huriez Hospital, Lille University Hospital, 1, rue Polonovski, 59037 Lille cedex, France. Electronic address: [email protected].
² Endocrinology and Metabolism Department, C. Huriez Hospital, Lille University Hospital, 1, rue Polonovski, 59037 Lille cedex, France. Electronic address: [email protected].
³ Department of Genetics, University Hospital, 14000 Caen, France. Electronic address: [email protected].
⁴ Department of Biology, Lille University Hospital, 59037 Lille cedex, France. Electronic address: [email protected].
⁵ Department of Nuclear Medicine, Lille University Hospital, 59037 Lille cedex, France. Electronic address: [email protected].
⁶ Department of Nuclear Medicine, Lille University Hospital, 59037 Lille cedex, France. Electronic address: [email protected].
⁷ Department of Radiology, Lille University Hospital, 59037 Lille cedex, France. Electronic address: [email protected].
⁸ Department of Nephrology, Lille University Hospital, 59037 Lille cedex, France. Electronic address: [email protected].
⁹ Department of Biology, Lille University Hospital, 59037 Lille cedex, France. Electronic address: [email protected].
¹⁰ Department of Endocrine Surgery, Lille University Hospital, 59037 Lille cedex, France. Electronic address: [email protected].
¹¹ Department of Endocrine Surgery, Lille University Hospital, 59037 Lille cedex, France. Electronic address: [email protected].
¹² Department of Genetics, University Hospital, 14000 Caen, France. Electronic address: [email protected].
¹³ Endocrinology and Metabolism Department, C. Huriez Hospital, Lille University Hospital, 1, rue Polonovski, 59037 Lille cedex, France. Electronic address: [email protected].

PMID: 27378451
DOI: 10.1016/j.ando.2016.03.002

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.

Publication types

Case Reports
Letter

MeSH terms

Adult
Cinacalcet / therapeutic use
Female
Humans
Hypercalcemia / complications*
Hypercalcemia / drug therapy
Hypercalcemia / genetics
Hyperparathyroidism / complications*
Hyperparathyroidism / drug therapy
Hyperparathyroidism / genetics
Male
Middle Aged
Mutation
Vitamin D3 24-Hydroxylase / genetics*

Substances

Vitamin D3 24-Hydroxylase
Cinacalcet

Supplementary concepts

Hypercalcemia, Infantile