Therapy-Resistant Hypercalcemia in a Patient with Inactivating CYP24A1 Mutation and Recurrent Nephrolithiasis: Beware of
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CASE REPORTS
Therapy‑Resistant Hypercalcemia in a Patient with Inactivating CYP24A1 Mutation and Recurrent Nephrolithiasis: Beware of Concomitant Hyperparathyroidism K. David1,2 · R. Khalil1,2 · H. Hannon3 · P. Evenepoel4,5 · B. Decallonne1,2 Received: 19 May 2020 / Accepted: 23 July 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract We describe a case harboring a homozygous CYP24A1 mutation with mild loss of function, first presenting with recurrent nephrolithiasis from the age of 22 onward, initially associated with hypercalcemia and low PTH concentrations. Over the years, hyperparathyroidism developed, resulting in more severe hypercalcemia. Also, kidney function deteriorated, most probably as a consequence of biopsy-proven nephrocalcinosis. Conventional treatment options for CYP24A1 mutation were not effective and/or tolerated (avoidance of sun exposure, diet, pamidronate, itraconazole). A total parathyroidectomy was performed resulting in a normocalcemic hypoparathyroidism without need for treatment with vitamin D analogs, a positive bone mineral balance and an improved kidney function. Keywords CYP24A1 mutation · Nephrolithiasis · Primary hyperparathyroidism · Parathyroidectomy
Introduction Mutations in CYP24A1 (24-hydroxylase), the enzyme responsible for the inactivation of 25-OH-vitaminD (25OHD) and 1,25(OH)2vitaminD (1,25(OH)2D) are inherited in an autosomal recessive manner. A loss of function in CYP24A1 can result in inappropriate concentrations of 1,25(OH)2D, causing hypercalcemia and hypercalciuria while suppressing parathyroid hormone (PTH). Infantile hypercalcemia represents the most overt clinical phenotype [1]. However, the manifestations of CYP24A1 mutations can * K. David [email protected] 1
Department of Chronic Diseases and Metabolism, Laboratory of Clinical and Experimental Endocrinology, KU Leuven, Herestraat 49, ON1 box 902, 3000 Leuven, Belgium
2
Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium
3
Department of Nephrology, Maria Middelares Hospital Ghent, Ghent, Belgium
4
Department of Immunology and Microbiology, Laboratory of Nephrology, KU Leuven, Leuven, Belgium
5
Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium
sometimes remain occult until adult age and are typically unmasked by the occurrence of nephrolithiasis at young age [2–5]. Treatment is challenging and long-term outcomes are uncertain.
Case Presentation A 44-year-old male was referred to the outpatient endocrinology clinic because of recurrent nephrolithiasis, with a first episode occurring at the age of 22, and chronic hypercalcemia. Eleven years earlier biochemical analysis already showed hypercalcemia with normophosphatemia and appropriate suppression of PTH (Table 1). Kidney function was at the lower limit of normal. Thyroid function was normal and there was no evidence of cortisol deficiency. Granulomatous and malignant diseases were excluded by negative imaging (FDG-PET, bone scin
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