{
  "abstract": "Hypercalcemia is mostly caused by primary hyperparathyroidism (PHPT) or malignancy. Less commonly, hypercalcemia results from vitamin D-dependent mechanisms. Pathogenic variants in CYP24A1, which encodes the 24-hydroxylase responsible for inactivating 1,25(OH)₂D₃, can lead to hypercalciuria, nephrolithiasis/nephrocalcinosis, and hypercalcemia, typically with suppressed PTH. When CYP24A1-related disease coexists with PHPT, their biochemical features may overlap, potentially masking a vitamin D catabolic defect and complicating postoperative interpretation of hypercalcemia. We report 2 unrelated patients with moderate-to-severe hypercalcemia in whom PHPT and CYP24A1 variants coexisted. The first patient was a 26-yr-old man with longstanding nephrolithiasis who initially had hypercalcemia with an inappropriately normal PTH level and imaging consistent with a hyperfunctioning parathyroid lesion, treated with parathyroidectomy (PTx). Several years later, PTH-suppressed hypercalcemia and elevated 25(OH)D₃ and 1,25(OH)₂D₃ concentrations was detected despite the absence of vitamin D supplementation. Genetic testing revealed a heterozygous pathogenic CYP24A1 variant (p.Leu409Ser), consistent with partial 24-hydroxylase deficiency. The second patient was a 59-yr-old woman with severe PHPT requiring surgery and later experienced life-threatening hypercalcemia (19.8 mg/dL) requiring hemodialysis, marked calcium fluctuations, particularly after calcium and calcitriol exposure following a second surgery, nephrocalcinosis, and progressive renal impairment. Genetic testing identified compound heterozygous CYP24A1 variants (p.Glu143del and p.Gln82Arg). These cases broaden the clinical spectrum of combined PHPT and CYP24A1-related disease and highlight that persistent or recurrent hypercalcemia after PTx, particularly when PTH is suppressed, may prompt evaluation for CYP24A1 defects, with potential implications for vitamin D avoidance and long-term renal surveillance.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Clinical and Experimental Medicine, University of Pisa, Pisa, 56126, Italy.",
    "Endocrine Unit 2, University Hospital of Pisa, Pisa, 56124, Italy.",
    "Laboratory of Molecular Genetics, University Hospital of Pisa, Pisa, 56126, Italy.",
    "Department of Surgical, Medical and Molecular Pathology and Critical Care Area, University of Pisa, Pisa, 56126, Italy."
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Simone Della Valentina"
    },
    {
      "affs": [
        0
      ],
      "name": "Laura Pierotti"
    },
    {
      "affs": [
        1
      ],
      "name": "Chiara Sardella"
    },
    {
      "affs": [
        0
      ],
      "name": "Anna Dal Lago"
    },
    {
      "affs": [
        2
      ],
      "name": "Maria Adelaide Caligo"
    },
    {
      "affs": [
        3
      ],
      "name": "Agnese Giamborino"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Filomena Cetani",
      "orcid": "0000-0003-2558-9547"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9d542x0t9134z.bib",
  "cited_by": 0,
  "doi": "10.1093/jbmrpl/ziag164",
  "fulltext_url": "https://europepmc.org/articles/PMC13695950",
  "id": "9d542x0t9134z",
  "issns": [
    "2473-4039"
  ],
  "landing_url": "https://europepmc.org/article/MED/42928911",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2727|Parathyroid Disorders and Treatments"
    ]
  ],
  "openalex": "W7221168787",
  "pdf_url": "https://europepmc.org/articles/PMC13695950?pdf=render",
  "pmcid": "PMC13695950",
  "pmid": "42928911",
  "published": "2026-10-09",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/9d542x0t9134z.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:21:18Z",
      "native_id": "MED:42928911",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42928911"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2727|Parathyroid Disorders and Treatments",
      "subfield": "general"
    }
  ],
  "title": "Co-occurrence of pathogenic CYP24A1 gene variants and primary hyperparathyroidism: a diagnostic challenge.",
  "title_text": "Co-occurrence of pathogenic CYP24A1 gene variants and primary hyperparathyroidism: a diagnostic challenge.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:18Z",
  "url": "https://research.draconitic.com/paper/9d542x0t9134z",
  "venue": "JBMR plus",
  "versions": []
}