85% of sporadic hyperparathyroidism cases have a solitary adenoma. The remainder of cases have multiple tumors. About 95% of all cases achieve a long remission at initial operation. Adverse outcomes are increased in cases with multiple tumors. The cause of solitary parathyroid adenoma is believed to be mutation of some gene, with overgrowth of a tumor clone. Mutation of the cyclin D1 (PRAD1) gene accounts for about 3-4%. Sporadic (nonhereditary) mutation of the MEN1 gene is the most common known mutation, causing 25-30% of solitary and common variety adenomas. Of the 15% of cases with multigland disease, 5% (1/3 of 15%) have a familial form. Most have familial MEN1 or familial hypocalciuric hypercalcemia. About 1% have familial isolated hyperparathyroidism (FIH). When we tested 40 nonsyndromal kindreds with FIH for occult syndromal mutations, there were no MEN1 mutations but about 10% had CASR mutation or HRPT2 mutation. The underlying gene(s)for the remaining majority of FIH are not known, but mutation of a gene on chromosome 2 seems likely, from linkage analysis. And among all MEN1-like cases without identified mutation, 3.5% have mutation in a cyclin dependent kinase inhibitor gene, specifically p15, p18, p21, or p27.

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