Beyond pituitary surgery: Radiosurgery vs.

Adrenalectomy vs. Medical Treatment when

Cushing’s Disease persists or recurs

Theodore C. Friedman, M.D., Ph.D.

Ian McCutcheon, M.D.
Magic Foundation
Symposium on Cushing’s Syndrome
February 22, 2009
Las Vegas, NV
What to do if the patient is
not cured by initial surgery
• Confirm diagnosis
• Medical management (Dr. F)
• Re-operate (Dr. M)
• Radiation therapy-conventional or
high-dose (Dr. M)
• Bilateral adrenalectomy (Dr. F)
 Medical treatment for
Cushing’s syndrome
• Ketoconazole * -The best
• Metyrapone- available on a compassion use basis from
company
• Aminoglutethimide- not sure if available
• RU486-easy to get adrenal insufficiency and hard to
monitor or correct adrenal insufficiency
• Mitotane-permanent adrenal insufficiency, hard to
swallow
• Trilostane- can be given IV
• Carbergoline-sporadic
• Avandia- diabetes medicine-works in a percentage of
Cushing’s patients
*SOM230-somatostatin analog
 Ketoconazole
• Works by blocking several steps in cortisol
biosynthesis.
• May also inhibit pituitary cell growth
• Has a pretty short half-life-usually given 3X/day
• Side effect-elevation of liver tests, which is
reversible on stopping drug.
• Liver test abnormalities are more pronounced at
higher doses.
• Check liver tests at baseline and every 3 months
 Ketoconazole
• Cushing’s syndrome is a disease of high night
time cortisol, some patients have low daytime
cortisol.
• Several options
– Give 200 mg 1 hr before bedtime to decrease
night time cortisol
– Give 200 mg 3X/day-often lunch, dinner and
bedtime
– Give 800-1200 mg throughout day plus 20 mg
of hydrocortisone in the morning
– Can go up on the dose for severe
hypercortisolism
 Ketoconazole
• Works in almost all patients
• Educate patients about adrenal insufficiency
• Can be used to determine how much of patients
symptoms are due to high cortisol.
• Can be used to get patients healthier prior to surgery.
• May decrease the drop from high cortisol to normal
cortisol
• I use it often before adrenalectomy (may decrease
hyperplasia seen on pathology)
• Monitor symptoms, UFC (not 17OHS) and serum cortisol
• Can be used for years with monitoring of liver tests
(LFTs) and pituitary tumor
• Should be gold-standard to compare new drugs
 SOM230 (Pasireotide)
• Somatostatin analogue-investigational drug-may shrink
tumor and decrease ACTH secretion
• Boscaro et al. JCEM 2009, 94:115-122 (Dr. Ludlam 2nd
author)
• 15 day open label study-39 patients, 29 completed
study and were included in analysis
• 22/29 (76%) had a reduction in UFC
• 5/29 had normalization of UFC
• Decrease in cortsiol and ACTH levels.
• 92% had side effects
• Nausea, diarrhea and high blood sugar (36%)!.
• Does not seem as good as ketoconazole to me.
 Repeat Surgery/RT
• Dr. McCutcheon
 Adrenalectomy
• Cures Cushing’s 99% of the time -adrenal rest tissue is
very rare
• Can be done laproscopically
• Much less mortality than before
• Can be done one adrenal (larger one) at a time (with
radiation after first adrenal)
• Need lifelong hydrocortisone, fludrocortisone and probably
DHEA
• Higher risk of adrenal insufficiency than if hypopituitarism
• Bracelet and solucortef, emergency letter, nausea meds.
• Most of my patients have done well with adrenalectomy
• Still I recommend pituitary surgery over adrenalectomy as
most pituitary patients are off most medicines in one year.
 Adrenalectomy:
Nelson’s syndrome
• Absence of glucocorticoid feedback can in theory
cause pituitary tumors to grow unchecked
• Leads to pituitary tumor growth, high ACTH levels
(< 1500 pg/mL is probably normal) and
hyperpigmentation.
• Happens more frequently in aggressive, rapidly
growing tumors, most of my patients have slow
growing tumors
• Need to monitor pituitary tumor by MRI yearly-if
tumor grows, need surgery
• Pituitary radiation probably decreases likelihood
of Nelson’s syndrome
 Adrenalectomy vs RT
• I usually recommend adrenalectomy as most of my patients want
an immediate cure and can’t wait the time for RT to kick in
• Exception, someone well controlled on ketoconazole
• Aggressively growing pituitary tumors may also lead me to RT
• How hypopit they are affects the decision, if already hypopit, I’m
less worried about RT.
• Some patients get both RT and adrenalectomy
 Cushing’s Syndrome
• It’s not so rare
• Lets get better
• “A topic not addressed is that many patients
who are obese, depressed, hypertensive, or
diabetic have “researched” the Internet and are
convinced they have CS.”-Another Prominent
Endocrinologist.
• I like patients to research the Internet and
become informed.
• Lets educate everyone
Thanks to:
Dianne Andrews
Magic foundation
All my patients
Surgeons:Ian McCutcheon, M.D., Hrayr Shahinian,
M.D., Hae Dong Jho, M.D., Ph.D. , Sandeep
Kunwar, M.D., Ed Phillips, M.D., Manfred
Chiang, M.D.
Assistants: Lynne Drabkowski and Erik
Zuckerbraun, M.D.