Dipika's Story: Innovative Treatment, Coordinated Care Combat Rare Condition

Rita Daryanani took her daughter to see Diane Krieger, MD, an endocrinologist near their Miami, FL, home. Krieger ordered testing for Cushing’s disease for Dipika. Coincidentally, Krieger had recently seen another young teenager with Cushing’s, a rare condition that causes increased levels of the hormone cortisol and typically affects adults ages 20-50.

Dipika’s tests showed elevated levels of cortisol and an MRI revealed a large tumor in her pituitary gland, a pea-sized organ in the base of the brain that produces many hormones. The tumor was responsible for increased production of a hormone called ACTH, which increases cortisol production by the adrenal glands. Dipika’s doctor recommended MassGeneral Hospital for Children (MGfC) as one of two centers with significant expertise in Cushing’s disease.

Rita Daryanani suspected there was something wrong with her 15-year-old daughter, Dipika, at the end of 2006. Dipika had begun to put on weight and was suffering from acne and stretch marks on her skin. Her menstrual cycles had also stopped, signaling a potential problem.

Multidisciplinary Care

The Daryananis flew to Boston in July 2007 to meet MGfC neurosurgeon Brooke Swearingen, MD, who would remove the part of the pituitary tumor that could be taken out surgically. Swearingen put the Daryananis in touch with the Program Director of Pediatric Endocrinology at MGfC, Madhusmita Misra, MD, MPH, and Chief of Radiation Oncology at Massachusetts General Hospital, Jay Loeffler, MD.

Dr. Swearingen successfully removed much of the pituitary tumor, and the family returned to Boston that October so Dipika could undergo proton therapy treatment at the Francis H. Burr Proton Therapy Center at Mass General Hospital in an attempt to shrink remaining tumor, which could not be removed surgically, in her nearby cavernous sinuses. During proton therapy, radiation targets a specific area of cells, reducing potential damage to nearby, healthy tissue.
 
While Dipika was undergoing proton therapy, she also received medical therapy to control her cortisol levels. Subsequently, her cortisol levels returned to normal.

Months later, upon return from a trip to India in late 2008, Dipika began experiencing new symptoms. She had double vision in her right eye and her mother noticed she was acting ‘spacey’ and unlike herself. Subsequently, while at a friend’s house, Dipika had a seizure. A repeat MRI showed that the tumor had grown back, this time larger than before and beyond the pituitary and the cavernous sinuses.  

“It’s a rare disease and she’s also a rare patient in having the tumor grow back as it did,” Rita Daryanani says. The Daryananis flew back to Boston and stayed for two months. They lived in an apartment close to the hospital that was arranged by MGfC staff. Rita Daryanani says they spent “every day trudging in the snow, but it was worth it.”

Dr. Swearingen again operated on Dipika’s pituitary gland to take out as much tumor as was surgically possible. Dipika began medical therapy (ketoconazole) to reduce cortisol production from the adrenal glands, and another medication, cabergoline, shown in recent studies to reduce cortisol levels and cause tumor shrinkage in some patients with Cushing’s disease.

Dipika also received additional proton beam therapy to target the residual tumor. Controlling cortisol levels is important even after radiation therapy, Dr. Misra says, as the effect of the latter can typically take more than a year to manifest. Unfortunately, Dipika developed some early side effects with ketoconazole.

Innovative Treatment

“The question is, what more can we do to treat this?” Misra says she asked herself at this point, “We then moved on to consider a rather experimental drug, with help from the Adult Neuroendocrine Unit.”

The new option was Pasireotide, a drug being studied in adults with Cushing’s disease that has been effective in reducing cortisol levels in some patients. Dipika’s doctors, particularly Dr. Misra in Boston and Dr. Kreiger in Miami, worked hard to gain permission from the drug’s maker to treat Dipika on compassionate grounds. The doctors also recommended continued use of cabergoline.  

Fortunately for Dipika, the team was able to procure Pasireotide for her, and the drug was effective in keeping Dipika’s cortisol levels in check. Subsequently, her cabergoline dose was reduced and her cortisol levels remained normal.

Dipika continues to inject herself twice a day with Pasireotide, but her doctors are working to wean her off it, particularly once proton beam therapy has fully taken effect. She continues to be monitored very closely by Dr. Krieger in Miami, who remains in close contact with Dr. Misra in Boston.

Of Dipika’s case, Misra says, “It does teach you that when there are unusual situations, you can be innovative both with therapy and the resources that we have at Mass General Hospital.”
 
Misra works closely with the adult neuroendocrine unit at Mass General Hospital and collaborates with colleagues from endocrinology, radiation oncology, neurosurgery, neurology, and occasionally psychiatry for input in weekly case conferences. Dipika’s case was one that Misra brought to those group meetings.

“The treatment at Mass General-- there are no words to say what they’ve done for me,” Rita Daryanani says. “All of them are amazing-- they always give the best treatment, if I need anything I call them,” she adds.

A Different Person

Since she left Boston in early 2008, Dipika has not had another seizure. A symptom of her disease is weight gain, and when she began treatment, she weighed 270 lbs. She has lost more than 100 lbs since beginning treatment. She no longer has double vision and her cortisol levels are controlled.

“When I had Cushing’s disease I looked like one person; and now if you look at me I’m a totally different person,” Dipika says.

Dipika missed a year of school due to her illness, but she has been back in high school since January and will be graduating next year from Palmer Trinity School in Miami, Florida. She wants to go to college for hospitality management.

The Daryananis keep in touch with Dr. Misra often and will visit her for a follow-up appointment this summer. Misra continues to share findings on Cushing’s disease with the family and she says, “Dipika’s always on my mind.”