Stress Wasn't The Problem
Accurate Diagnosis Came After Two Years
Tuesday, August 19, 2008; Page HE01
Karima Hijane could not believe what she was hearing: The obstetrician who for two years had insisted that her mystifying constellation of symptoms was the result of stress had discovered the real cause, imparting devastating news that would alter Hijane's plans for her future.
Now this trusted doctor, who had delivered her only child several years earlier, was telling the IT consultant to make an appointment to discuss the results -- in two weeks.
"I think perhaps she was shocked and didn't know what to say," Hijane, 34, speculated. She remembers feeling numb during that March 2007 phone call, then weeping in the privacy of her Northern Virginia office before heading off to client meetings during which, she said, she acted "like a robot."
For more than two years, Hijane had made the rounds of various specialists: an endocrinologist, a rheumatologist, an orthopedic surgeon and several internists. Yet none ordered the blood test that would have revealed the reason for her night sweats, insomnia, light periods and, possibly, her persistent bone pain.
"She's representative of what happens to the patients we see," said research gynecologist Lawrence M. Nelson of the National Institute of Child Health and Human Development (NICHD). Six weeks after receiving the life-altering news, Hijane checked into the clinical center at the National Institutes of Health to participate in a long-running study of the disorder, which affects about 1 percent of women younger than 40.
"A lot of the patients we see think they're going crazy," said Nelson, who sees about two new patients per week with the same diagnosis as Hijane's. "It's appropriate for doctors to ask about stress. The mistake is to assume that's what it is."
In Hijane's case, he added, her first symptom, bone pain, was something of a red herring that initially may have led doctors in the wrong direction.
Hijane said her problem began several months after the birth of her son in December 2004. During the pregnancy she developed a complication involving a separation of the pubic bones; the baby was delivered by Caesarean section. Stressing that a second pregnancy would be dangerous before the pubic separation healed, her obstetrician prescribed birth control pills, which Hijane began taking.
Several months later she was bothered by pain in her right hand. Doctors told her it was probably caused by computer use. When it continued, her OB-GYN referred her to an orthopedic surgeon, who found nothing amiss. Soon the pain began spreading to other parts of her body and was sometimes accompanied by muscle twinges. She began experiencing new problems: intermittent migraines, painful intercourse and light periods. Some nights she would awaken bathed in sweat. Blood tests, X-rays and an MRI revealed nothing.
"They told me it was stress," Hijane recalled. She was young and healthy, the doctors assured her. She just needed to relax.
"After a while," she said, "their reactions made me feel like a whiner, like I was making up all of these bizarre symptoms."
In 2006, after the bone pain continued, the obstetrician sent her to a rheumatologist, who performed a work-up for arthritis. She, too, found nothing.
"She suggested I should work out," Hijane said.
A visit to an ear, nose and throat specialist for the migraines did nothing to relieve the headaches. He did find two nodules on her thyroid and sent her to an endocrinologist, who ordered a standard blood chemistry panel -- but not the blood test that would have immediately revealed the reason for her other symptoms. A few months later Hijane was back in the gynecologist's office, complaining of vaginal dryness and painful intercourse; the doctor treated her for a possible yeast infection.
At one point, Hijane said, her frustrated OB-GYN told her there was nothing more she could do and suggested Hijane gather her records and take them to the Cleveland Clinic or another major medical center. "She said, 'I do believe there's something wrong with you, but we don't know what it is,' " Hijane recalled.
By November 2006, more than a year after her symptoms began, Hijane noticed that at times during the day she felt overwhelmingly hot. Her insomnia and night sweats had gotten worse, and her periods had dwindled to occasional spotting. Hijane's husband, who searched the Internet for possible causes, decided the problem might be the birth control pills. Hijane stopped taking them and began to feel slightly better.
But in February 2007, when she hadn't gotten her period for three months, Hijane returned to the obstetrician.
Thinking she might be pregnant, the doctor ordered a pregnancy test. When that was negative, she ordered another blood test: for FSH, or follicle-stimulating hormone, which is essential to reproduction; levels rise when the ovaries fail to produce enough estrogen.
Hijane's level showed she was squarely in the post-menopausal range. She was 33 years old, 18 years younger than the average age of menopause.
Hijane's elevated FSH level explained many of her symptoms: insomnia, night sweats, painful intercourse, hot flashes, light and dwindling periods. It did not account for bone pain (a possible cause would emerge later at NIH) or her migraines.
Hijane's doctor told her she had premature ovarian failure, or POF, and was in menopause for reasons that were unclear. Hijane was crushed: She and her husband had wanted more children.
The condition, also known as POI, for premature ovarian insufficiency, affects 1 in 200 women by age 35, said Nelson of NICHD. The condition was first described in the 1940s by a Harvard physician who is regarded as the father of modern endocrinology, and it is diagnosed on the basis of two blood tests, FSH and estradiol.
The disorder has several causes, among them chemotherapy and a genetic disorder called fragile X syndrome; in many cases, Hijane's included, the cause is unknown. There is no cure, though doctors typically place patients on replacement hormones until about age 50 to ease symptoms and protect their bones from osteoporosis. POI patients face an elevated risk of heart disease, dry eye and other problems.
Days after her diagnosis, Hijane found Nelson, head of NICHD's Integrative Reproductive Medicine Unit, during an online search. She was accepted as a patient and in early May underwent a three-day inpatient evaluation at NIH.
Doctors discovered she was severely deficient in Vitamin A and Vitamin D, as are many POI patients, said Nelson, who has seen about 1,000, the youngest of whom was 13. Although it is not clear that her bone pain was related to Vitamin D deficiency, Hijane said the pain vanished after she took the huge doses of Vitamin D prescribed by NIH specialists. She also began wearing an estrogen patch.
Her husband, she said, has been supportive. "He said, 'I didn't marry your ovaries; I married you.' He has been there for me. And all the doctors at NIH have been great."
Her greatest regret, she said, is the toll two years of undiagnosed medical problems took on her young son. "I was not able to enjoy him," she said. "I was in pain, I had bad depression, I was irritable. I lost my mom when I was 3, and I worried that history was repeating itself."
Hijane quit her job shortly after she was diagnosed and has since founded Rachel's Well, a nonprofit group that lobbies on behalf of women's health.
Nelson, a member of the group's board, said he think Hijane's diagnostic ordeal could have been prevented. Although POI is uncommon, the average gynecologist probably sees a case every five years or so.
"Over half the women we've seen had seen over three different doctors before an FSH test was ordered," he said. "It takes some out-of-the-box thinking in that 15-minute window" that many doctors allot for each patient visit. "The health-care community needs to be more aware of this."