Brielle Painter scheduled an appointment with an endocrinologist near her Boyertown, Pennsylvania home about a year after she gave birth to her son. She hadn’t lost any of the 75 pounds she gained during pregnancy, and she was starting to lose her hair.
After conducting a physical exam and running some tests, the specialist informed Painter she was insulin-resistant, a condition that could lead to type 2 diabetes, and that she had an underactive thyroid (hypothyroidism). She was told insulin resistance and her weight gain, if left unchecked, could increase the risk for high cholesterol and heart problems in the future.
She was sent home with a prescription for Metformin, a medication commonly used to treat type 2 diabetes. The endocrinologist also encouraged her to adopt a vegan diet, which she did.
After eight months, Painter had lost barely any weight, and her blood work was unchanged.
In search of a diagnosis
Frustrated by her lack of progress, she saw another endocrinologist, and then another. And then a fourth. Painter was gaining about nine pounds every two weeks, regardless of her diet or activity level. She had also developed multiple bald spots on her head, stopped having her period, and was becoming increasingly crippled by anxiety and depression.
“My son loved being outside. He was playing so many sports,” Painter said. “But I wouldn’t even leave my house sometimes. I didn’t want to be seen. I was so depressed and felt like I was making my son’s life terrible. I felt like a really bad mom.”
The latest endocrinologist confirmed her hypothyroidism, and believed it stemmed from Hashimoto’s disease, an autoimmune disorder where immune-system cells damage the thyroid gland. However, he also suspected Cushing’s syndrome, a condition where an excess of cortisol in the blood results in a wide variety of symptoms, and tested her accordingly.
While Painter’s lab results were not normal, they didn’t quite meet the standards for diagnosing Cushing’s syndrome. So, for the next two years, Painter’s doctor treated her hypothyroidism and retested for Cushing’s syndrome every six months.
Even though the results remained largely unchanged, Painter’s physical and mental decline was generating more and more momentum. By February 2023, she couldn’t take it anymore and broke down in the specialist’s office.
He arranged for her to have an MRI, which revealed a mass on her pituitary gland. It was relatively small, but its presence was clear enough. Painter finally had reason to hope she might get better.
A multidisciplinary approach to care at Penn Pituitary Center
Painter was referred to the Penn Pituitary Center, where she was promptly seen by pituitary endocrinologist Caitlin A. White, MD, and neurosurgeon and pituitary surgery specialist Daniel Yoshor, MD.
“When patients come to the Penn Pituitary Center, they benefit from the expertise of multiple pituitary specialists who work together very closely,” Yoshor said. “It is common for patients with pituitary tumors to obtain consultations from three or more pituitary specialists in just one visit, typically including an endocrinologist, a neurosurgeon, and an ear, nose, and throat [ENT] surgeon. This is a level of teamwork that is quite special. It’s an impressive, multidisciplinary approach that makes things easier for our patients and results in better care.”
Even though doctors saw a small pituitary tumor on Painter’s MRI, her initial lab results were not clearly diagnostic of Cushing’s syndrome, and it was far from clear her pituitary tumor caused her symptoms.
Painter’s blood test results were consistently “borderline,” as White described them: higher than normal parameters, but lower than what you’d expect in someone with classic Cushing’s syndrome. This kind of diagnostic quandary is not uncommon, as Cushing’s syndrome can be especially challenging to pin down.
“Cortisol is one of the stress response hormones our body produces, and cortisol production in the body is naturally dynamic, it’s ever-changing,” White said.
There is a typical pattern. Cortisol is highest when we wake, it gradually declines during the course of the day, and its generally low overnight while we sleep. However, there are countless variables that can disrupt this pattern, including staying up late to work, illness, and psychological stress. It can be difficult to pinpoint what qualifies as an abnormal cortisol level, especially in a case like Painter’s.
Understanding Cushing’s disease
“That’s why it requires the perspective of an expert, or, better yet, a team of experts,” White said.
Her diagnosis was ultimately based on the totality of her data, including her tests, most of which were abnormal, and observed “significant and substantial” symptoms that were clearly affecting her quality of life.
More specifically, White diagnosed Painter with Cushing’s disease, a specific type of Cushing’s syndrome caused by a pituitary tumor that produces an excessive level of ACTH, one of several hormones normally secreted by the pituitary gland.
The production of ACTH stimulates the adrenal glands to make cortisol. Normally the pituitary gland stops making ACTH when it detects the presence of cortisol. But in Painter’s case, the tumor on her pituitary gland was unresponsive to the presence of cortisol and made too much ACTH. This led her adrenal glands to intermittently flood her body with an unhealthy level of cortisol.
There could be other reasons Painter was overproducing ACTH. But after much discussion, her team of specialists at the pituitary center determined her age (32 at the time) and other factors made it likely the pituitary tumor was the cause of her disabling symptoms.
Yoshor, one of the nation’s most experienced pituitary surgeons, was confident he could safely remove Painter’s pituitary tumor in its entirety using minimally invasive surgery.
They scheduled Painter’s surgery. She was ecstatic.
Pituitary surgery: the first step on the road to recovery
Arriving at the Hospital of the University of Pennsylvania early in the morning of July 17, 2023, Yoshor immediately put Painter at ease, making sure she was comfortable and in good spirits. She had grown to appreciate his down-to-earth demeanor, especially helpful that morning.
Painter was slated to undergo an endoscopic endonasal transsphenoidal selective adenomectomy, a surgical procedure Yoshor estimated he had done more than 2,000 times during his career.
In the past, pituitary surgery required incisions in the scalp, under the lip, or in the nose. Modern endoscopic surgical techniques and instruments, along with collaborations between neurosurgeons and ENT surgeons, have revolutionized the way pituitary tumors are removed.
To access the tumor, the ENT surgeon enters the nostrils without making an incision, and then opens the sphenoid sinus–the hollow space in the skull behind the nasal passages. An endoscope, a thin fiberoptic tube with a tiny video camera at the tip, is used to see the tumor and nearby structures. The tumor is then removed with specially designed surgical instruments through the nose.
“We use angled endoscopes that enable us to see around corners,” Yoshor said. “And that’s key, because the best way to completely remove a pituitary tumor is by going around the tumor.”
Painter, like most patients who undergo a TSA at the Hospital of the University of Pennsylvania, went home the day after her surgery. She was closely monitored from the comfort of her home for the next two weeks, and her care was updated daily.
This is important because fluid balance can be an issue for some patients right after surgery. Based on its extensive experience with pituitary surgery patients, the Penn Pituitary Center has developed and validated a protocol where patients are contacted by a provider regularly for the first 10 days following surgery and asked a series of questions. Their responses, combined with lab test results, determine their course of care for the day.
“Before we implemented this protocol, about 10 percent of our pituitary surgery patients experienced some temporary issues with fluid balance and sodium levels after surgery,” Yoshor said. “But with our post-operative protocol, the incidence has dropped to less than one percent. We’re now close to eliminating an uncomfortable and potentially dangerous problem, without keeping the patient in the hospital. In doing so, we’re helping patients get home and get back to their normal lives, and, often, helping them enjoy an even better life with the tumor removed.”
Working with his ENT partner, Nithin Adappa, MD, another key member of the Penn Pituitary Center, Yoshor was able to remove all of Painter’s tumor. But that was only the first part of her recovery, albeit a significant one.
Treatment after surgery
Once a pituitary tumor like Painter’s is removed, it can take months for the pituitary gland to rebound and produce normal amounts of ACTH. During this period, the patient transitions from a state of producing too much cortisol to suddenly producing too little. This can be jarring and lead to a whole new set of symptoms that include extreme fatigue, headaches, body aches, and nausea.
To counter this effect, Painter was given cortisol replacement pills after her surgery. A week after her surgery, her ACTH and cortisol blood levels were checked to confirm they were no longer being overproduced. White said Painter’s levels for both hormones were “very low.” This result confirmed White’s diagnosis of Cushing’s disease was correct, and that Yoshor’s removal of the tumor was a success.
White began lowering Painter’s cortisol dosage. She was finally taken off cortisol replacement pills completely in January, six months after her surgery.
“I saw Brielle in May, and it looks like her body’s production of cortisol is now completely normal,” White said. “She has successfully made it through the cortisol withdrawal period and not surprisingly, she is feeling much better.”
A completely different person
Ten months after surgery, her outlook on life has continued to improve. In the past, she dreaded summer. It meant her family and friends would want to be outside, hiking, kayaking, and enjoying the outdoors. Painter wanted to avoid all of that. Inside her home was the only place where she could try and cope with her worsening physical and mental health.
But by spring Painter was looking forward to joining in. She and her son had been exercising together, which helped her shed more than 50 pounds. It was impossible for her to achieve this kind of weight loss before the surgery cured her of Cushing’s disease, no matter how hard she tried.
All of her other symptoms have also subsided. Exactly four weeks after surgery, she got her period for the first time in more than a year. Her hair grew back, and her bald spots disappeared, as did her dorsocervical fat pad, the buildup of fat on the back of her neck. This inspired her to start wearing her hair up again, something she hadn’t done for years.
She marveled at just how much her life has improved in the last year. Her arrival at the Penn Pituitary Center, she said, was the catalyst for all of it.
“That referral saved me.”