SYMPTOMS
A fiercely independent and active 76-year-old woman spent the past decade caring for her aged mother, who died at 99. Weeks after her mother's death, the woman collapsed at home. She was found to have bleeding from a collection of abnormal blood vessels (known as AVMs, or arteriovenous malformations) in her colon. In the months after, the patient's red-blood-cell count returned to normal, but she never regained her old energy and strength. She told her daughters that she was weaker and more tired than she had ever been in her life.
THE EXAM
Dr. Susan Wiskowski, a family physician in Hartford, was the woman's doctor. Until recently, the patient was in good health for her age, with only a few medical problems: high blood pressure, which was controlled with one medication; hypothyroidism, treated with Synthroid; and cataracts, which had been surgically repaired. Now, out of the blue, she was experiencing rapid weight gain, swelling and weakness in her legs, which made it hard to walk.
Possible Diagnoses: Heart disease can manifest as weakness and fatigue, particularly in the elderly. The patient was referred to a cardiologist. An elevated white-blood-cell count was detected during the bleeding episode. She was sent to a hematologist.
RESULTS
The hematologist's report was unrevealing. The cardiologist found no coronary-artery disease but noted a partly obstructed heart valve, which, though longstanding, might be contributing to the patient's fatigue.
ANOTHER SYMPTOM
A couple of weeks after the cardiac work-up, the patient's behavior became erratic and strange. Despite her complaints of weakness, she veered between bursts of activity — endlessly cleaning her house, giving large dinner parties — and days of isolation and fatigue. She was sometimes elated, telling her four daughters that she'd found where heaven was located. She began to talk about giving away her possessions. One afternoon she seemed completely out of control. A neighbor called 911, and the patient was rushed by ambulance to St. Francis Hospital in Hartford.
IN THE HOSPITAL
In the emergency room, doctors discovered an extensive hematoma on the patient's right groin and leg, which developed after a cardiac catheterization she had as part of her work-up. She was admitted to the hospital.
A psychiatrist diagnosed hypomania and started the patient on several medications to stabilize her mood.
The patient complained of severe weakness, which made minor chores difficult. A neurologist performed nerve-conduction tests, which revealed damage in the region where the nerves meet the muscle. He suggested that the injury might be a postviral neuropathy, an unusual reaction to a recent infection. He told her it should improve with time. The specialist sent her to physical therapy, but the weakness persisted.
ADDITIONAL SYMPTOMS
Walking became extremely painful, and within weeks she needed a wheelchair to get around. Dark purple lesions appeared on the back of the patient's hand and arms. A daughter took pictures of the lesions and showed them to the patient's doctor. After seeing the images, Wiskowski recommended that she take her mother to the emergency room right away.
READERS' RESPONSES
After the case was posted on The New York Times Well Blog on April 20, more than 500 readers weighed in.
Many readers thought there could be something wrong with her diet.
Katherine of Cambridge, Mass., suggested that she might have a niacin (vitamin B3) deficiency, which could cause what doctors refer to as the four D's: diarrhea, dermatitis (rash), dementia and death: "Could it be pellagra?"
Patrick H. worried about the lack of a different B vitamin: "I will take a stab and go with B12 deficiency."
Iron and vitamin C were also among the suspects. Amy of Ohio read up on the patient's symptoms: "I just learned that high iron deposits can decrease insulin secretion, and that, in turn, would elevate her glucose levels. . . . My diagnosis: iron poisoning."
Others focused on the timing of this illness. Diana of Long Island, N.Y., offered: "I'm going to go out on a limb here and say it may be due to chronic stress. It was mentioned that the patient just lost her mother, and she was her primary caregiver. Having helped my mother with my grandmother (who has Alzheimer's), I know that stress can cause very odd symptoms and do major damage to the body."
Josie of St. Louis suggested: "[Her] mother's death triggered depression, also eliminated need for treatment with high-blood-pressure medicine. Unneeded blood-pressure medicine aggravated psychosis and caused bleeding and skin spots."
The first correct answer came 54 minutes after the case was posted online. Elizabeth Neary, a pediatrician from Madison, Wisc., wrote, "Sounds like Cushing's syndrome. . . . Rash looks like ecchymoses [bruises] — personality changes are common, as is weakness and edema."
By the time the answer was posted the next morning, 18 readers had nailed the diagnosis and five others were on the verge. The most commonly cited wrong diagnosis was porphyria — a group of inherited diseases that usually present with a combination of abdominal pain, psychiatric symptoms and skin findings. It was a thoughtful suggestion, although porphyrias usually show themselves by early adulthood.
FINAL DIAGNOSIS
When the patient's daughters were told to take their mother to the emergency room, they took her to Waterbury Hospital in Waterbury, Conn., to see a friend of theirs, Dr. Rachel Lovins. Lovins, who met their mother some years earlier, didn't recognize the woman who sat before her in a wheelchair.
As she watched the E.R. doctor examine the patient, Lovins noted reddish purple stretch marks on the patient's abdomen. Suddenly, the whole case made sense. These stretch marks, known as striae, are a result of the thinning of the skin caused by excess cortisol. It's a classic finding in Cushing's syndrome.
THE DISEASE
Cushing's syndrome was first described by Dr. Harvey Cushing, a neurosurgeon, in 1932. In this disease, the adrenal glands churn out too much cortisol, a hormone involved in our body's response to stress. Cortisol helps maintain blood pressure, reduces the immune system's inflammatory response and increases blood-sugar levels. Long-term exposure to an excess of this hormone, however, can cause weight gain, osteoporosis, diabetes, high blood pressure, muscle weakness, memory loss and psychiatric disease. It causes the skin to weaken, making it susceptible to injury and bleeding, which occurred in her colon, or bruising, which occurred on her hands.
After Lovins saw the striae, the patient was tested for Cushing's, and her cortisol level was very high — eight times the normal level. Usually this disease is caused by a tumor in the pituitary gland in the brain, which in turn causes the adrenal gland to overproduce cortisol. Surgical removal of the tumor is the cure. But in this patient's case, doctors couldn't find the tumor; it was too small. Since the tumor couldn't be removed, the patient was started on a medication to prevent the overproduction of cortisol.
WHY IT WAS A DIFFICULT CASE
When making a diagnosis, doctors frequently cite the principle of Occam's razor: the simplest answer is most likely to be the right answer, and a single diagnosis is more likely than a collection of diagnoses. This principle, however, doesn't necessarily hold with older patients. High blood pressure is seen in 80 percent of those over age 70. Nearly half over 60 are overweight. A quarter are depressed. One in six Americans over age 40 will have cataracts in one or both eyes. Given these numbers, having a 76-year-old patient with all of these distinct diseases — as was the case with this patient — is common, and a doctor might not feel the need to look for a single, unifying disease process.
As one of her daughters wrote in an e-mail to friends: "We were told that her psychological state, her neurological problem, her circulation issues and her excessive bleeding were an unrelated bunch of unfortunate circumstances conspiring to make this woman ill. It happens when you are old, we were told more than once." This thinking was familiar to many readers. Jonquil of Utopia wrote: " 'It happens when you are old' is such a dangerous diagnosis, yet it's given every day. . . . G.P.'s need to be better trained in geriatrics."
Readers know that this column often reads like a detective story in which a single criminal (one disease) is responsible for a variety of crimes (symptoms). As a result, the reader has an advantage over a doctor, who has to figure out which patient, out of all those she has seen that day, has many individual problems without a unifying cause, and which will need Occam's razor. While that distinction may not be sufficient, it is the necessary start of diagnosis.
