Cushing's Awareness: Heritable Cushing's

There are several forms of known heritable Cushing's.    The most well-known is MEN1. Carney Complex is also fairly well understood.  The least studied, and newest researched is FIPA.

MEN1:   (Multiple endocrine neoplasia, Type 1)  According to Medscape, "the combination of parathyroid tumors, pancreatic islet cell tumors, and anterior pituitary tumors is characteristic of MEN1. Although usually inherited as an autosomal dominant disorder, MEN1 can also occur sporadically (without a family history) as a result of new mutations. It is also important to keep in mind that family members of an MEN1-affected individual may have been undiagnosed at the time of death. Patients with untreated MEN1 have a decreased life expectancy, with a 50% probability of death by age 50 years."

Carcinoid tumors can occur in patients with MEN1 and are located in the bronchi, gastrointestinal tract, pancreas, and thymus. In men, especially smokers, the thymus is most often affected. Thymic carcinoids[8] associated with MEN1 are often nonfunctional and aggressive. In women, bronchial carcinoids are most common. Carcinoids can actively secrete hormones such as serotonin, somatostatin, corticotropin, and growth hormone.

Carney Complex:  Two genes have been associated with Carney complex. They are called PRKAR1A and CNC2. It is believed that about 60% of people with Carney complex have a mutation in the PRKAR1A gene and up to 6% may have deletions in this gene.There may be other genes associated with Carney complex, and studies are ongoing to learn more about it.  It is an autosomeal dominant disease.

Fewer than 500 cases of Carney Complex have been reported. It is estimated that between 50% and 70% of cases of Carney complex run in families. The other percentage occurs by chance and may be due to a new gene mutation.

FIPA:  (Familial isolated pituitary adenoma) This is an inherited condition characterized by development of a pituitary adenoma. FIPA can be caused by mutations in the AIP gene which is thought to act as a tumor suppressor.  According to this FIPA site, "about 1 in 20 pituitary tumours do seem to run in families. If the condition only seems to affect the pituitary gland in the family, then the disease is known as Familial Isolated Pituitary Adenoma (FIPA). "  It is an autosomal dominant disease with incomplete penetrance (not all patients who carry the abnormal gene will develop the disease).

There are also several mutations which occur to cause Cushing's, some very recently discovered. I'll talk about those next time.