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Therapy-Resistant Hypercalcemia in a Patient with Inactivating CYP24A1 Mutation and Recurrent Nephrolithiasis: Beware of Concomitant Hyperparathyroidism

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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.

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References

  1. Schlingmann KP, Kaufmann M, Weber S, Irwin A, Goos C, John U et al (2011) Mutations in CYP24A1 and idiopathic infantile hypercalcemia. N Engl J Med 365(5):410–421

    Article  CAS  Google Scholar 

  2. Cools M, Goemaere S, Baetens D, Raes A, Desloovere A, Kaufman JM et al (2015) Calcium and bone homeostasis in heterozygous carriers of CYP24A1 mutations: a cross-sectional study. Bone 81:89–96

    Article  CAS  Google Scholar 

  3. Nesterova G, Malicdan MC, Yasuda K, Sakaki T, Vilboux T, Ciccone C et al (2013) 1,25(OH)2D–24 hydroxylase (CYP24A1) deficiency as a cause of nephrolithiasis. Clin J Am Soc Nephrol 8(4):649–657

    Article  CAS  Google Scholar 

  4. Jacobs TP, Kaufman M, Jones G, Kumar R, Schlingmann KP, Shapses S et al (2014) A lifetime of hypercalcemia and hypercalciuria finally explained. J Clin Endocrinol Metab 99(3):708–712

    Article  CAS  Google Scholar 

  5. Keeffe DT, Tebben PJ, Kumar R, Singh RJ, Wu Y, Wermers RA (2016) Clinical and biochemical phenotypes of adults with monoallelic and biallelic CYP24A1 mutations: evidence of gene dose effect. Osteoporos Int 27(3):3121–3125

    Google Scholar 

  6. Vanderschueren D, Pye SR, O’Neill TW, Lee DM, Jans I, Billen J et al (2013) Active vitamin D (1,25-Dihydroxyvitamin D) and Bone health in middle-aged and elderly men: the european male aging study (EMAS). J Clin Endocrinol Metab 98(3):995–1005

    Article  CAS  Google Scholar 

  7. Ketha H, Kumar R, Singh RJ (2016) LC-MS/MS for Identifying patients with CYP24A1 mutations. Clin Chem 62(1):236–242

    Article  CAS  Google Scholar 

  8. Cavalier E, Huyghebaert L, Rousselle O, Bekaert AC, Kovacs S, Vranken L et al (2020) Simultaneous measurement of 25(OH)-vitamin D and 24,25(OH)2-vitamin D to define cut-offs for CYP24A1 mutation and vitamin D deficiency in a population of 1200 young subjects. Clin Chem Lab Med 58(2):197–201

    Article  CAS  Google Scholar 

  9. Helmuth A, Konrad M, Schlingmann KP, Pasch A (2014) Hypercalcemia in a 60-year-old male. Kidney Int 85(1):219–221

    Article  Google Scholar 

  10. Figueres ML, Linglart A, Bienaime F, Allain-Launay E, Roussey-Kessler G, Ryckewaert A et al (2015) Kidney function and influence of sunlight exposure in patients with impaired 24-hydroxylation of vitamin D due to CYP24A1 mutations. Am J Kidney Dis 65(1):122–126

    Article  CAS  Google Scholar 

  11. Colussi G, Ganon L, Penco S, De Ferrari ME, Ravera F, Querques M et al (2014) Chronic hypercalcaemia from inactivating mutations of vitamin D 24-hydroxylase (CYP24A1): implications for mineral metabolism changes in chronic renal failure. Nephrol Dial Transplant 29(3):636–643

    Article  CAS  Google Scholar 

  12. Evenepoel P, Daenen K, Bammens B, Claes K, Meijers B, Naesens M et al (2015) Microscopic nephrocalcinosis in chronic kidney disease patients. Nephrol Dial Transplant 30(5):843–848

    Article  CAS  Google Scholar 

  13. Tebben PJ, Singh RJ, Kumar R (2016) Vitamin D-mediated hypercalcemia: mechanisms, diagnosis, and treatment. Endocr Rev 37(5):521–547

    Article  CAS  Google Scholar 

  14. Tebben PJ, Milliner DS, Horst RL, Harris PC, Singh RJ, Wu Y, Foreman JW, Chelminski PR, Kumar R (2012) Hypercalcemia, hypercalciuria, and elevated calcitriol concentrations with autosomal dominant transmission due to CYP24A1 mutations: effects of ketoconazole therapy. J Clin Endocrinol Metab 97(3):E423–E427

    Article  CAS  Google Scholar 

  15. Bouillon R, Bikle D (2019) Vitamin D metabolism revised: fall of dogmas. J Bone Miner Res 34(11):1985–1992

    Article  Google Scholar 

  16. Hawkes C, Dong L, Hakonarson H, Meyers KE, Thummel KE, Levine MA (2017) CYP3A4 Induction by rifampin: an alternative pathway for vitamin D inactivation in patients with CYP24A1 mutations. J Clin Endocrinol Metab 102(5):1440–1446

    Article  Google Scholar 

  17. Loyer C, Leroy C, Molin A, Odou MF, Huglo D, Lion G et al (2016) Hyperparathyroidism complicating CYP24A1 mutations. Ann Endocrinol (Paris) 77(5):615–619

    Article  Google Scholar 

  18. Walker MD, Silverberg SJ (2018) Primary hyperparathyroidism. Nat Rev Endocrinol 14(2):115–125

    Article  CAS  Google Scholar 

  19. Guilmette J, Sadow PM (2019) Parathyroid pathology. Surg Pathol Clin 12(4):1007–1019

    Article  Google Scholar 

  20. Mizamtsidi M, Nastos C, Mastorakos G, Dina R, Viassiliou I, Gazouli M et al (2018) Diagnosis, management, histology and genetics of sporadic primary hyperparathyroidism: old knowledge with new tricks. Endocr Connect 7(2):R56–68

    Article  CAS  Google Scholar 

  21. Brewer K, Costa-Guda J, Arnold A (2019) Molecular genetic insights into sporadic primary hyperparathyroidism. Endocr Relat Cancer 26(2):R53–72

    Article  CAS  Google Scholar 

  22. Tassone F, Guarnieri A, Castellano E, Baffoni C, Attanasio R, Borretta G (2015) Parathyroidectomy halts the deterioration of renal function in primary hyperparathyroidism. J Clin Endocrinol Metab 100(8):3069–3073

    Article  CAS  Google Scholar 

  23. Caliskan M, Kizilgül M, Beysel S, Ucan B, Akcan F, Takir M et al (2019) Factors associated with glomerular filtration rate variation in primary hyperparathyroidism after parathyroidectomy. Turk J Med Sci 49(1):295–300

    Article  CAS  Google Scholar 

  24. Minisola S, Gianotti L, Bhadada S, Silverberg SJ (2018) Classical complications of primary hyperparathyroidism. Best Pract Res Clin Endocrinol Metab 32(6):791–803

    Article  Google Scholar 

  25. Rejnmark L, Ejlsmark-Svensson H (2020) Effects of PTH and PTH hypersecretion on bone: a clinical perspective. Curr Osteopors Rep 18(3):103–114

    Article  Google Scholar 

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Funding

KD receives grant from Flemish Fund for Scientific Research (FWO; 1196520N) not related to this work.

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Authors and Affiliations

  1. Department of Chronic Diseases and Metabolism, Laboratory of Clinical and Experimental Endocrinology, KU Leuven, Herestraat 49, ON1 box 902, 3000, Leuven, Belgium

    K. David, R. Khalil & B. Decallonne

  2. Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium

    K. David, R. Khalil & B. Decallonne

  3. Department of Nephrology, Maria Middelares Hospital Ghent, Ghent, Belgium

    H. Hannon

  4. Department of Immunology and Microbiology, Laboratory of Nephrology, KU Leuven, Leuven, Belgium

    P. Evenepoel

  5. Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium

    P. Evenepoel

Authors
  1. K. David
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  2. R. Khalil
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  3. H. Hannon
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  4. P. Evenepoel
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  5. B. Decallonne
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Correspondence to K. David.

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This case report has been approved by the ethical committee of the University Hospitals Leuven.

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David, K., Khalil, R., Hannon, H. et al. Therapy-Resistant Hypercalcemia in a Patient with Inactivating CYP24A1 Mutation and Recurrent Nephrolithiasis: Beware of Concomitant Hyperparathyroidism. Calcif Tissue Int 107, 524–528 (2020). https://doi.org/10.1007/s00223-020-00738-8

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  • DOI: https://doi.org/10.1007/s00223-020-00738-8

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