Familial isolated hyperparathyroidism

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.^[1]

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.^[1]

We cannot estimate the chance that primary hyperparathyroidism (PHP) in an affected person is due to a hereditary form of the condition, or the chance that a relative may be affected. Whether PHP is familial may depend on a number of factors, including the presence of associated features or abnormalities; if other family members are diagnosed with PHP; and results of genetic testing. People with specific questions about whether they have PHP, or whether a familial form of PHP is present in their family, should speak with their healthcare provider or a genetics professional.

Most cases of PHP are sporadic, which means it usually occurs in people with no family history of the condition. Hereditary forms of hyperparathyroidism are rare; about 10% of people with PHP have a hereditary condition. Hereditary conditions associated with PHP may include complex tumor syndromes such as MEN1, MEN2 or hyperparathyroidism-jaw tumor syndrome (HPT-JT); or familial isolated hyperparathyroidism (FIHP).^[2] Currently, the underlying cause of PHP can be identified in only a small number of affected people. Genetic testing may help to diagnose familial hyperparathyroid conditions, but in some cases, the gene responsible for the condition in an individual or family remains unknown.^[3]

Even when a family is known to be affected by a hereditary hyperparathyroid disorder, distinguishing between FIHP and the other hereditary conditions can be hard. One reason is that some people who were first diagnosed with FIHP have later developed features of MEN1. The diagnosis of FIHP is largely made by excluding the presence of the other known genetic causes, because finding a mutation in a specific gene would change the diagnosis.

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.