Clinical Advisory: Women with Rare Lung Disease Found to Also Have High Prevalence of Meningiomas, First Study to Document Tumor Connection; Possible Hormonal Cause
National Heart, Lung, and Blood Institute (NHLBI)
18 October 2001
Scientists at the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) report that women with a rare lung disease known as LAM (lymphangioleiomyomatosis) have a high prevalence of meningiomas, a type of brain tumor.
The study, published in the October 17 issue of the Journal of the American Medical Association, is the first to document the extent of the association between LAM and meningiomas.
"These findings provide important new information on the nature of this disease and have implications for both the diagnosis and treatment of patients with LAM," said NHLBI Director Dr. Claude Lenfant.
The meningiomas were detected in an ongoing study of the natural history of LAM. LAM is associated with a rare genetic neurological disorder called tuberous sclerosis (TS). In an effort to determine whether patients with LAM also showed signs of tuberous sclerosis, NHLBI scientists performed magnetic resonance imaging (MRI) and computed tomography (CT) brain scans on 250 women with the lung disease. They were looking for brain abnormalities called "tubers," one of the criteria for diagnosing TS. Unexpectedly, MRI scans revealed that 8 patients had meningiomas — a rate that far exceeds the 1 in 20,000 expected in the general population.
According to the investigators, it is not clear whether the meningiomas are caused by LAM itself, hormonal treatments for the disease — or a combination of the two. They note that the abnormal smooth muscle cells found in the lungs and other tissues of LAM patients produce certain growth factors that are believed to foster meningiomas. However, the possibility that the meningiomas have a hormonal cause has implications for the overall treatment of LAM.
Because LAM occurs primarily in women of childbearing age, it has been thought to be affected by hormonal factors. As a result, it has been commonly treated with the hormone progesterone.
However, studies have found that progesterone can stimulate growth of meningiomas. Anti-progestins (drugs that interfere with this hormone's action) have even been used to treat meningiomas.
"We cannot rule out the possibility that the high prevalence of meningiomas may be a result of both LAM and progesterone therapy," said Joel Moss, M.D., chief of NHLBI's Pulmonary-Critical Care Medicine Branch and lead investigator of the study, which was conducted at the NIH Clinical Center in Bethesda, MD. Moss noted that although some of the women in the study had never been exposed to progesterone, low doses in contraceptives or hormone replacement therapy could have played a role in initiating the tumor or fueling its growth.
Moss and colleagues recommend using MRI to screen for meningiomas in LAM patients and if the tumors are found, they advise against the use of progesterone. The scientists also suggest that patients with meningiomas have yearly MRI scans to evaluate tumor growth. Surgery is the preferred treatment for these tumors which are slow-growing and rarely spread to other parts of the body.
An estimated 8,000 U.S. women have LAM, which is characterized by an unusual type of muscle cell that invades and obstructs the tissue of the lungs, including the airways, and blood and lymph vessels. Over time, these muscle cells interfere with the lung's ability to supply oxygen to the rest of the body. The progression of the disease varies among patients — as does survival, which may extend more than 20 years after diagnosis.
According to Moss, patients with LAM are often misdiagnosed, partly because many of the early symptoms are similar to other lung diseases. "A common symptom of LAM is shortness of breath, which is seen in other lung diseases such as asthma and emphysema. Other symptoms of LAM include chest pain and coughing up blood-stained sputum or blood," he said.
Moss noted that both spontaneous and inherited forms of LAM have been reported. LAM's connection to tuberous sclerosis has been documented and there is evidence that both diseases can have a common genetic basis.
To increase understanding about the clinical course of LAM, including its connection to tuberous sclerosis, Moss and colleagues at NHLBI are conducting research as part of an Institute-funded study of patients with LAM. Moss is actively seeking patients with LAM, including those who may have been diagnosed with TS.
To interview Dr. Joel Moss, contact the NHLBI Communications Office at (301) 496-4236.