Early-onset, severe, and recurrent primary hyperparathyroidism associated with a novel CDC73 mutation

Hyperparathyroidism-jaw tumor syndrome (HPT-JT) is a rare autosomal dominant hereditary tumor syndrome characterized by synchronous or metachronous occurrence of primary hyperparathyroidism (PHPT), ossifying fibroma of the maxilla and/or mandible, renal tumor and uterine tumors. Early diagnosis of t...

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Bibliographic Details
Published in:Endocrine Journal 2015, Vol.62(7), pp.627-632
Main Authors: Shibata, Yusuke, Yamazaki, Masanori, Takei, Masahiro, Uchino, Shinya, Sakurai, Akihiro, Komatsu, Mitsuhisa
Format: Article
Language:English
Subjects:
Adenoma - genetics
Adenoma - pathology
Adult
CDC73
DNA Mutational Analysis
Fibroma - genetics
Fibroma - pathology
Humans
Hyperparathyroidism - genetics
Hyperparathyroidism - pathology
Hyperparathyroidism-jaw tumor syndrome
Jaw Neoplasms - genetics
Jaw Neoplasms - pathology
Male
Mutation
Pedigree
Primary hyperparathyroidism
Recurrence
Severity of Illness Index
Tumor Suppressor Proteins - genetics
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Summary:Hyperparathyroidism-jaw tumor syndrome (HPT-JT) is a rare autosomal dominant hereditary tumor syndrome characterized by synchronous or metachronous occurrence of primary hyperparathyroidism (PHPT), ossifying fibroma of the maxilla and/or mandible, renal tumor and uterine tumors. Early diagnosis of this syndrome is essential because it is associated with increased risk of parathyroid cancer. A 30-year-old man with urolithiasis had severe hypercalcemia (15.0 mg/dL after correction) induced by inappropriate parathyroid hormone (PTH) secretion (intact PTH 1390 pg/mL), indicating severe PHPT. An underlying parathyroid tumor was surgically removed and was histologically confirmed to be an adenoma. However, PHPT due to another parathyroid tumor reoccurred two years after the surgery. Although no HPT-JT-associated manifestations other than PHPT were detected, HPT-JT was strongly suspected based on the exclusion of multiple endocrine neoplasia (MEN) and the young age of disease occurrence. Genetic analysis revealed a novel nonsense mutation (p.Arg91X; c.271C>T) in exon 3 of the causative gene, CDC73, which encodes the tumor suppressor protein parafibromin. The residual parathyroid glands were all removed without autotransplantation of parathyroid gland taking into consideration prospective parathyroid carcinogenesis. The resected parathyroid tumor was also an adenoma. The present case highlights that HPT-JT should be considered and CDC73 mutation analysis should be performed, especially in cases of early-onset PHPT, recurrent PHPT, PHPT with polyglandular parathyroid involvement, and PHPT presenting with severe hypercalcemia even if there is no positive family history.
ISSN:0918-8959
1348-4540
DOI:10.1507/endocrj.EJ15-0057