Familial isolated hyperparathyroidism (FIHP) is an inherited form of primary hyperparathyroidism that is not associated with other features. The age of diagnosis varies from childhood to adulthood. In FIHP, tumors involving the parathyroid glands cause the production and release of excess parathyroid hormone, which in turn causes increased calcium in the blood (hypercalcemia). The tumors are usually benign, but a cancerous tumor can develop in rare cases. Abnormal levels of calcium cause many of the symptoms of FIHP, including kidney stones, nausea, vomiting, high blood pressure (hypertension), weakness, and fatigue. Osteoporosis often also develops. FIHP may be caused by mutations in the MEN1, CDC73 (also known as the HRPT2 gene), or CASR genes and is typically inherited in an autosomal dominant manner. In some cases, the cause is unknown. Mutations in the MEN1 and CDC73 genes cause other conditions in which hyperparathyroidism is one of many features, but some people with mutations in these genes have only isolated hyperparathyroidism. FIHP can also represent an early stage of other syndromes. Treatment for FIHP often includes surgical removal of the affected gland(s).

The diagnosis of familial isolated hyperparathyroidism (FIHP) is primarily a diagnosis of exclusion. This means that it is diagnosed when no symptoms or genetic features of other forms of familial hyperparathyroidism are present. FIHP may be the only feature of another condition that is not manifesting completely, or it may be a distinct condition due to mutations in genes that have not yet been identified. Clinical exams, laboratory tests, and histological (microscopic) findings are needed before making a diagnosis of FIHP.

A diagnosis of FIHP may include the findings of:

• hypercalcemia (defined as a serum calcium level greater than 10.5 mg/dL)
• inappropriately high parathyroid hormone (PTH) concentrations
• parathyroid adenomas
• exclusion of multiple endocrine neoplasia type 1 (MEN 1) and hyperparathyroidism-jaw tumor syndrome (HPT-JT)

In the majority of people with FIHP, genetic mutations are not found. However, in some people, mutations in
the MEN1, CASR, and CDC73 (HRPT2) genes have been reported. At this time, no gene has been associated exclusively with FIHP.

Familial isolated hyperparathyroidism (FIHP) is typically inherited in an autosomal dominant manner. This means that having only one changed (mutated) copy of the responsible gene in each cell is enough to cause signs or symptoms of the condition. When a person with an autosomal dominant condition has children, each child has a 50% (1 in 2) chance to inherit the mutated copy of the gene from the affected parent.