Kelly DuBois doesn’t remember her 30s much at all. That decade of her life was essentially “stolen” from her thanks to a series of misdiagnoses, a botched brain surgery, and a host of medications that caused more side effects than benefits. After 12 years of failing health, had she not come to Mayo Clinic — where pharmacogenomic testing revealed polymorphisms (genetic mutations) that were causing her body to metabolize her meds in harmful ways — she believes she “would have died by now.”
It began in 2003. Kelly was 31 at the time, a new mother of two infant daughters. She was healthy, back to her normal weight, and on no medications.
“I started having heartburn a lot. This happens to people in my family when we hit our early 30s,” says Kelly, now 51, a tech writer who resides in Rochester, New York, with her husband, Chuck. She was prescribed esomeprazole for the heartburn as a maintenance drug.
Soon after, Kelly started putting on weight, fast. “My doctors checked my thyroid, and they're like, ‘Well, your thyroid is fine. At 32, your metabolism just slows down.’ And I'm thinking ‘but it shouldn't come to a screeching halt.’ Because I was gaining like 10 pounds a month.”
Over the next few years, her weight gain continued, and Kelly began to experience all sorts of unexplained symptoms, like profuse sweating, achiness, fatigue, headaches, swelling, abdominal pain, an excessively high pulse rate when at rest, and high blood pressure. “I was feeling horrible all the time, and I felt like this wasn’t normal,” she says.
In 2007, Kelly’s then-primary care physician strongly suspected an endocrine problem and sent her for an MRI, which revealed an extraordinarily small pituitary tumor (4 millimeters). She then saw two endocrinologists. One told her there was “no way a tumor that small could cause this.” The other thought the same but agreed to monitor Kelly.
By early 2009, Kelly’s symptoms worsened, and her growth hormone levels (GH and IGF-1) were substantially above normal ranges. “My doctors thought I had a medical condition called acromegaly, where you have too much growth hormone,” says Kelly, who was referred to a neurosurgeon specializing in pituitary tumors.
“DESPITE ADDITIONAL TESTING THAT CAME BACK NORMAL, AND ZERO ACROMEGALY SYMPTOMS, HE EXPLAINED THAT, UNLESS I HAD BRAIN SURGERY, NOT ONLY WOULD I FEEL LIKE CRAP CONSTANTLY, BUT THE GROWTH HORMONE WOULD MAKE MANY OF MY INTERNAL ORGANS GROW, CAUSING AN ENLARGED HEART, HEART FAILURE, KIDNEY FAILURE, ETCETERA.”
So, in the spring of 2009, Kelly underwent a transsphenoidal resection of her pituitary tumor. “They go up through your nostril and slice open your pituitary, the membrane over it, and remove the tumor,” she says.
Kelly was supposed to go home the next day but ended up in the ICU for almost a week with a spinal fluid leak. “Every time I sat up, spinal fluid rushed out of my nose and my brain would sink to the base of my skull,” she recalls. “The pain was excruciating, worse than childbirth and kidney stones.”
After returning to work eight weeks later, she noticed something disturbing. “My memory was garbage,” Kelly says. She had trouble remembering faces of newer acquaintances and forgot how to spell simple words; she had challenges with decoding her thoughts before speaking them. She also had heightened irritability and crying spells.
Once she reported this to her doctor, another MRI was ordered. Images revealed a large spot, due to spinal fluid that had collected over her right frontal lobe. “My doctors admitted this was not supposed to happen but told me I was fine, that they’d consulted with other doctors, and that this wouldn’t affect me much at all,” Kelly says.
Kelly did feel better, and her hormone levels stabilized, for about a year. Then her symptoms came back, and her growth hormone levels climbed again — 12 times higher than normal at one point. More tests were run but none of them revealed why her symptoms persisted. More meds were prescribed.
By 2015, Kelly’s weight ballooned from 130 to 200 pounds. Between researching her strange symptoms and knowing her own body, Kelly now doubted her diagnosis of acromegaly.
One day, after yet another doctor’s visit, she came home “and cried again for the millionth time,” she says.
“BY THEN I HAD ABOUT 20 DOCTORS, AND I KEPT TELLING THEM ‘I DON’T FEEL RIGHT, THERE’S SOMETHING ELSE WRONG WITH ME,’” SHE SAYS. “AND THEY WERE ALWAYS LIKE ‘ALL YOUR TESTS ARE FINE.’ AFTER I GOT DONE CRYING, I GOT REALLY MAD. I FELT LIKE ALL THESE DOCTORS THOUGHT I WAS CRAZY, OR THEY WEREN’T ‘GETTING IT.’ THEY OBVIOUSLY WEREN’T HELPING ME, AND I KNEW I WAS DYING.”
Kelly’s anger made her do something she’d never done before. She called Mayo Clinic. That one phone call in 2015 changed her life. Once she was accepted as a patient, she flew to Mayo four times within a six-month period, overseen by a series of specialists. One of them was Eric Matey, Pharm.D., R.Ph., a pharmacist in Mayo Clinic’s Department of Pharmacy.
“She presented us with a list of medications that, back then, had some pharmacogenomic implications,” Dr. Matey says. “So I reviewed her medications and recommended pharmacogenomic testing.”
Kelly was given a pharmacogenomic test panel that looked for variants in nine different genes. Prior to this test, only single-gene testing had been available. The nine-gene panel marked the first multigene pharmacogenomic test of its kind, launched by Mayo Clinic Laboratories in 2014. This explained why none of Kelly’s multitude of doctors knew this kind of testing existed. It was too new on the market at that time.
“Mayo led the way in pharmacogenomic testing, period. Especially in the psychiatric field but also in the rest of medicine,” says John Black, M.D., a hereditary practice physician in Mayo Clinic’s Division of Laboratory Genetics and Genomics. “We marketed it first. And we still lead the way. We really have thorough testing, and we do large-scale research in this area.”
Unlike most labs, Mayo Clinic Laboratories offers “inclusive testing,” meaning test panels include rarer gene alleles from populations that are typically non-European. Thus, these panels are expanded to detect non-European variants. “We add these alleles because we are the laboratory to the world,” Dr. Black says. “We want to provide testing for the alleles of patients from wherever they come from. So if we’ve got somebody from Asia, we know that their gene alleles are going to be different. They’ll be common in that population, so we had better test for them or we’re not serving that patient.”
When her test results came back from Mayo Clinic Laboratories, Kelly met with Dr. Matey, who told her she had six polymorphisms. “It all depends on different populations, but in my clinical work, I would say to find more than, let’s say four or five variants, is usually very rare for the number of genes that we were testing at that time,” he says. “Now, we’ve gone all the way up to a 27-gene panel. And so the probability of finding a variant that is not normal increases, because you’re looking at more genes.”
Mayo Clinic Laboratories still offers smaller gene panels because some people only want to know what’s going on with one particular gene, or a couple of genes. “We’ve got one panel that’s for azathioprine, which has two genes on it, and one for warfarin, which has four genes on it, for example,” Dr. Black says. “So we mix and match these gene panels according to what the patient’s physician wants, and what the patient needs.”
While many polymorphisms are innocuous to one’s health, some can, as in Kelly’s case, wreak havoc. Her panel detected she has multiple polymorphisms in the cytochrome P450 genes, which encode enzymes involved in how the body metabolizes medications, primarily in the liver. The mutations explained why Kelly was having so many adverse side effects from her medications. Her body was metabolizing them either too quickly, too slowly, or not at all.
“WHEN DR. MATEY EXPLAINED MY RESULTS, THAT WAS THE BIG EUREKA MOMENT FOR ME,” KELLY SAYS. “MY MAYO CARE TEAM FINALLY FIGURED OUT WHAT WAS MAKING ME SICK FOR 12 YEARS. TWO OTHER MEDICAL CENTERS I WENT TO COULDN’T FIGURE IT OUT IN ALL THAT TIME. MAYO CLINIC FIGURED IT OUT IN SIX MONTHS. WHAT’S AWESOME ABOUT MAYO IS THE DOCTORS ARE COLLABORATIVE. THEY LISTEN TO EACH OTHER, AND THEY LISTEN TO THE PATIENT.”
Kelly also met with an endocrinologist at Mayo Clinic who specializes in acromegaly. “The endocrinologist, after researching my prior medical reports, believes I never had acromegaly,” Kelly says. “She told me, ‘Do not take an acromegaly medication ever again unless an endocrinologist from Mayo Clinic tells you to.’ And she said I never needed my brain surgery — that I was misdiagnosed. My Mayo cognitive testing also shows that I have executive function brain damage that they could only attribute to that surgery.”
Much of Kelly’s suffering could have been avoided had she had preventive pharmacogenomic testing early on instead of “reactive testing” after her problems began. Regardless, today, she finally has her life back. She’s now only on medications that are compatible with her genetics and is back to her normal weight. And she’s been working with a neuropsychologist who specializes in people with brain damage.
“It's amazing how the brain can recover,” Kelly says. “I'm slowly able to regain things. My linear thinking started coming back about two years ago. It's slow, but my emotional Teflon is also slowly coming back. I still have some unexplainable health issues, but since ceasing meds that aren’t appropriate for me because of my genetics, my GH and IGF-1 levels are normal.”
This story originally posted to the Mayo Clinic Laboratories blog.