Familial isolated primary hyperparathyroidism with parathyroid carcinomas: clinical and molecular features

• Published in: Clinical endocrinology (Oxford) Vol. 48; no. 1; pp. 67 - 72
• Main Authors: Yoshimoto, Katsuhiko, Endo, Hideko, Tsuyuguchi, Masaru, Tanaka, Chisato, Kimura, Takehiko, Iwahana, Hiroyuki, Kato, Genichi, Sano, Toshiaki, Itakura, Mitsuo
• Format: Journal Article
• Language: English
• Published: Oxford BSL Blackwell Science Ltd 01.01.1998; Blackwell
• Subjects: Adenoma - complications; Adenoma - genetics; Adult; Biological and medical sciences; Carcinoma - complications; Carcinoma - genetics; Chromosomes, Human, Pair 13; Chromosomes, Human, Pair 9; Endocrinopathies; Female; Genetic Markers; Humans; Hyperparathyroidism - etiology; Hyperparathyroidism - genetics; Loss of Heterozygosity; Male; Malignant tumors; Medical sciences; Parathyroid Neoplasms - complications; Parathyroid Neoplasms - genetics; Parathyroids. Parafollicular cells. Cholecalciferol. Phosphocalcic homeostasis (diseases); Pedigree; Asia; Japan; Endocrinopathy; Human; Carcinoma; Retinoblastoma gene; Family study; Malignant tumor; Adenoma; Genetic determinism; Genetic disease; Pathology; Multiple endocrine neoplasia type I; Histopathology; Parathyroid diseases; Loss of heterozygosity; Adult; Benign neoplasm; Hyperparathyroidism; Tumor suppressor gene
• ISSN: 0300-0664; 1365-2265
• DOI: 10.1046/j.1365-2265.1998.00354.x

OBJECTIVE Familial isolated primary hyperparathyroidism (FIHP) is a rare hereditary disorder. We present four patients from a single family with FIHP, and genetic analysis of their parathyroid adenomas and parathyroid carcinoma. DESIGN DNA was extracted from tumours resected at surgery. Tumours were examined for loss of heterozygosity (LOH) with microsatellite polymorhpic markers. PATIENTS The 27‐year‐old proband (Patient 1) died of parathyroid carcinoma with metastases to the lungs and chest wall. Sixteen years later, his 34‐year‐old sister (Patient 2) presented with a neck tumour and primary hyperparathyroidism. Family screening revealed parathyroid tumours in his 36‐year‐old sister (Patient 3) and 29‐year‐old cousin (Patient 4). Histological examination of resected tumours showed parathyroid carcinoma and adenoma in Patient 2, a parathyroid adenoma in Patient 3, and an atypical parathyroid adenoma in Patient 4. Autopsy of the proband ruled out multiple endocrine neoplasia (MEN) type 1, and the three patients who underwent parathyroidectomy did not exhibit any abnormalities in the pancreas or the pituitary gland. RESULTS Analysis of tumour DNA from one parathyroid carcinoma (Patient 2), the atypical parathyroid adenoma (Patient 4), and two parathyroid adenomas (Patients 2 and 3) showed limited LOH on chromosomes 13q12.3–q32 in an adenoma of Patient 2 and 9p21–p22 and 13q12.3–q32 in an adenoma of Patient 3. CONCLUSION These results suggest the possible contribution of tumour suppressor genes including the retinoblastoma gene and the hereditary breast cancer susceptibility gene (BRCA2) on 13q to parathyroid tumours in this family.