Women with Premature Menopause at Increased Risk for Potentially Fatal Adrenal Condition Early Diagnosis Can Lead to Effective Treatment

Women with spontaneous premature ovarian failure (POF) are three hundred times more likely than members of the general population to develop a serious condition in which the body attacks the adrenal glands, according to a study by researchers at the National Institute of Child Health and Human Development (NICHD). The study also reports that a test measuring immune system proteins known as antibodies is an effective way to diagnose the adrenal condition in women with spontaneous POF. The researchers published their findings in the August issue of Human Reproduction.

Premature ovarian failure occurs when the ovaries stop producing eggs and reproductive hormones well in advance of natural menopause. An estimated one percent of American women develop the condition by age 40.

Primary auto-immune adrenal insufficiency, also known as Addison's disease, occurs when the body's own immune system makes antibodies that attack and destroy the adrenal glands. Antibodies ordinarily bind to disease-causing organisms, tagging them for later destruction by the immune system. The adrenal glands produce hormones (cortisol and aldosterone) that regulate salt metabolism and the body's response to stress. Addison's disease is easily treated with medication that replaces the hormones that the adrenal glands are not making. However, if a person with untreated adrenal insufficiency experiences a stressful event, like a severe illness, injury, or surgery, he or she can die from the condition. Despite the fact that adrenal insufficiency can be life threatening, there has been ongoing debate in the medical community as how to best detect this condition in the early stages.

"This study shows that an adrenal antibody test is an effective way to determine if women with POF are at risk for primary auto-immune adrenal insufficiency," said Duane Alexander, M.D., Director of the NICHD.

The researchers, led by V.K. Bakalov, M.D., a member of the Developmental Endocrinology Branch at the NICHD, screened 123 women with POF for primary adrenal insufficiency. They used three different testing mechanisms to screen for the disease: 1) the adrenocorticotrophic hormone (ACTH) stimulation test (the standard test for diagnosing adrenal insufficiency); 2) the adrenal antibody test; and 3) the morning cortisol test.

In all, the researchers found that four (3.2 percent) of the 123 women with POF had previously undetected adrenal insufficiency. These women had abnormal adrenal function despite having none of the common symptoms of adrenal insufficiency, such as unusual tiredness and weakness, dizziness when standing, loss of appetite, darkened skin, and craving for salt. The rate of adrenal insufficiency among women with POF in this study is 300 times higher than the 1 in 10,000 rate seen in the general population.

The researchers found that one of the three tests-the adrenal antibody test-was most effective in detecting adrenal insufficiency in women with POF. In fact, all four of the women with demonstrated adrenal insufficiency had a positive adrenal antibody test. In contrast, the morning cortisol test was positive in only one of the four women who was subsequently found to have adrenal insufficiency. In addition, the morning cortisol test had a high rate of false positives, finding ten women positive who were later found to have normal adrenal function. Finally, the standard ACTH test was positive in two women found to have normal adrenal function. The authors do not advise using the ACTH test, which is a diagnostic test, as a screening tool because it may result in the unnecessary treatment of individuals with normal adrenal function. Instead, they recommend reserving it for use as a diagnostic test.

"It is probably a good idea to screen all women with POF for the presence of asymptomatic adrenal insufficiency by measuring adrenal antibodies," said Lawrence Nelson, M.D., one of the study's authors and a member of NICHD's Unit on Gynecologic Endocrinology. "This screening is especially important before any surgery or other physical stress."


The NICHD is part of the National Institutes of Health, the biomedical research arm of the federal government. The Institute sponsors research on development, before and after birth; maternal, child, and family health; reproductive biology and population issues; and medical rehabilitation. NICHD publications, as well as information about the Institute, are available from the NICHD Web site, http://www.nichd.nih.gov, or from the NICHD Information Resource Center, 1-800-370-2943; E-mail NICHDInformationResourceCenter@mail.nih.gov.

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