TY - JOUR
T1 - Diagnosis of parathyroid tumors in familial isolated hyperparathyroidism with HRPT2 mutation
T2 - Implications for cancer surveillance
AU - Guarnieri, Vito
AU - Scillitani, Alfredo
AU - Muscarella, Lucia Anna
AU - Battista, Claudia
AU - Bonfitto, Nazzareno
AU - Bisceglia, Michele
AU - Minisola, Salvatore
AU - Mascia, Maria Lucia
AU - D'Agruma, Leonardo
AU - Cole, David E C
PY - 2006
Y1 - 2006
N2 - Context: Mutations of the HRPT2 gene have recently been implicated in the development of parathyroid carcinoma. Objective: The objective of this study was early diagnosis of parathyroid tumor in a family with germline HRPT2 mutation. Patients, Methods, and Results: In a 40-yr-old male previously treated for parathyroid atypical adenoma, we screened the 17 translated HRPT2 exons and their exon-intron boundaries and found a germline frameshift mutation in exon 7 (685delAGAG) predicting a premature stop codon at nucleotides 767-769. Nine family members (age, 33.9 ± 19.8 yr, mean ± SD) also carry the mutation, but eight have had normal serum calcium. Biochemical and ultrasonographic evaluation uncovered a 27-yr-old hypercalcemic carrier niece with an atypical parathyroid adenoma, and a 43-yr-old normocalcemic carrier sister was found by ultrasonography to have an extrathyroidal nodule, which proved to be parathyroid carcinoma. The index case, 12 yr after surgery, was normocalcemic, but ultrasonography revealed an extrathyroidal nodule in the contralateral hemithyroid tissue that proved to be atypical adenoma. Conclusions: Our report confirms that germline mutations of HRPT2 gene may be associated with multiple parathyroid neoplasms. Our experience suggests that longitudinal surveillance by serum biochemistry alone may not be 100% sensitive, and addition of routine neck ultrasonography is a readily accepted adjunct that may facilitate earlier disease detection in some families.
AB - Context: Mutations of the HRPT2 gene have recently been implicated in the development of parathyroid carcinoma. Objective: The objective of this study was early diagnosis of parathyroid tumor in a family with germline HRPT2 mutation. Patients, Methods, and Results: In a 40-yr-old male previously treated for parathyroid atypical adenoma, we screened the 17 translated HRPT2 exons and their exon-intron boundaries and found a germline frameshift mutation in exon 7 (685delAGAG) predicting a premature stop codon at nucleotides 767-769. Nine family members (age, 33.9 ± 19.8 yr, mean ± SD) also carry the mutation, but eight have had normal serum calcium. Biochemical and ultrasonographic evaluation uncovered a 27-yr-old hypercalcemic carrier niece with an atypical parathyroid adenoma, and a 43-yr-old normocalcemic carrier sister was found by ultrasonography to have an extrathyroidal nodule, which proved to be parathyroid carcinoma. The index case, 12 yr after surgery, was normocalcemic, but ultrasonography revealed an extrathyroidal nodule in the contralateral hemithyroid tissue that proved to be atypical adenoma. Conclusions: Our report confirms that germline mutations of HRPT2 gene may be associated with multiple parathyroid neoplasms. Our experience suggests that longitudinal surveillance by serum biochemistry alone may not be 100% sensitive, and addition of routine neck ultrasonography is a readily accepted adjunct that may facilitate earlier disease detection in some families.
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U2 - 10.1210/jc.2005-1239
DO - 10.1210/jc.2005-1239
M3 - Article
C2 - 16720667
AN - SCOPUS:33747668789
VL - 91
SP - 2827
EP - 2832
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 8
ER -