For the 15th consecutive year, the CSRF exhibited at the annual meeting of The Endocrine Society. This year, the meeting was held in Washington, DC and was attended by over 8,000 endocrinologists, nurses and students. This year we used a new booth, which was very, very well received. Booth traffic this year was very good, as was our location on the exhibit floor. We had an opportunity to distribute information, talk with many US and international endocrinologists, and to meet with many members of our Medical Advisory Board. We are particularly thankful for the time we were able to spend with Dr. James Findling and Meg Keil, both of whom are on our Board of Directors and provided valuable insight.
As always, there were many very good presentations relating to Cushing’s and again, it is impossible to summarize them all. If you are interested, you can check the abstracts yourself at www.endo-society.org – select Abstracts to View under Endo 2009. What follows is a brief discussion of some of the presentations.
“Meet the Professor” (MTP) sessions are sessions where endocrinologists have an opportunity to hear from and ask questions of “experts” in a particular field. A MTP titled “Short and Long-Term Issues in Postoperative Pituitary Assessment” was presented by Dr. David Cook and discussed the use of post-surgical cortisol measurements to indicate cure. Dr. Cook also recommends an ACTH stimulation test every 6-8 weeks while on replacement to assess whether replacement is needed. Dr. Cook stressed the need for continued follow up of Cushing’s Disease patients for possible recurrence. In another MTP titled “Integration of Hormonal Replacement in Hypopituitarism” Dr. John Monson discussed the interaction between replacement of all the pituitary hormones, indicating that sometimes when additional replacement is started, dosages of other replacements might be affected. Dr. Susan Webb presented on the Quality of Life in Pituitary Patients (see Doctor’s Articles on this website) and Dr. Ed Laws presented on Radiosurgery. Dr. Franco Mantero presented on “Subclinical Hormone Excess and the Adrenal Incidentaloma (AI)”(accidently found adrenal tumor) which is an area of intense study at the present time. Numerous studies have found the prevalence of subclinical Cushing’s in AI patients to be between 5-20% and a 9.2% prevalence was found in a recent Italian study. While AI patients may show higher degrees hypertension, diabetes and osteoporosis, there is still not enough data to support surgical removal of the tumor in all cases and decisions need to be made on a case by case basis.
Case Management Forums provided input from 2 “experts” in the field. Dr. Lynnette Nieman and Dr. John Newell-Price presented on Cushing’s Syndrome: Medical, Surgical and Other Options” and Dr. Brew Atkinson and Dr. James Findling discussed “Optimum Strategy for Managing Cyclical Cushing’s Disease” (see Doctor’s Articles here on www.CSRF.net).
Testing for Cushing’s was discussed in many posters, and again, the fact remains that there is no one, single test; thus screening still requires several tests, usually a combination of the a night-time salivary cortisol, a 24-hr urine free cortisol and a 1mg over-night dexamethasone suppression test (See Testing and Doctors Articles—Endocrine Society Guideline at www.CSRF.net). One poster by Mepani, et al discussed the implications of discordant night-time salivary cortisol tests; meaning of 2 tests, one was high and the other normal. In this study of 34 patients with discordant results, 11 had Cushing’s, of which 5 were confirmed to be a recurrence of Cushing’s disease. Thus, discordant results should be further evaluated. Another interesting poster by Valassi, et al discussed the Dex-CRH test which is used to distinguish Cushing’s from Pseudo-Cushing’s. When this test was first utilized, it appeared to differentiate between the two 100% of the time. As the use of this test increased to include more patients, it was learned that this test is not 100%. This poster presented data that showed that some common medications that interfere with dex metabolism (antidepressants and calcium channel blockers) may to some degree explain the variability in testing. Thus, medications should be considered when utilizing this test.
It is well known that small pituitary tumors causing Cushing’s can be very difficult to see on an MRI. Two reports (Stobo, et al and Erickson, et al) compared the higher resolution 3T MRI to the lower resolution 1.5T scans and both found the higher resolution 3T scans could visualize more of the pituitary tumors than the 1.5T. Another report by Farhat, et al showed that MRI and PET scans may be complementary in detecting pituitary tumors.
Many drugs are still under study for Cushing’s. Phase II clinical trial data for pasireotide (SOM 230) was published in JCEM in January, ‘09 and Phase III clinical trials have finished enrolling. A clinical trial of mifepristone (Corlux) is still recruiting (see announcement on page 7). A study by Pivonello, et al used cabergoline in combination with low dose ketoconazole (50-200mg/day) in 6 patients and found that after 6 months, cortisol levels normalized in all patients. Another study by Feelders, et al involved the use of pasireotide (SOM 230) and if the Cushing’s was not controlled with pasireotide alone, cabergoline was added. If the combination of the these 2 were not sufficient, a low dose of ketoconazole was added. This 3 step process controlled cortisol levels in 13 out of 15 patients. Other potential drugs are under study at the cellular level including curcumin (Bangaru) and retinoic acid (Bush).
Osteoporosis during and after cure of Cushing’s was the subject of a study by van der Eerden. This study followed bone mineral density (BMD) of 156 Cushing’s patients for an average of 12.5 yrs. Complete recovery (>97%) was reported in most patients. Recovery takes time! Recovery of the lumbar spine BMD took between 9.5 and 12.5 years and recovery of the femoral neck BMD between 10-13.5 years. In pediatric patients of an average age of 12.8 years, Lodish, et al found that preoperatively, 38% of the children had osteopenia of the lumber spine and 23% of the femoral neck. At 13-18 months post operative, lumbar spine BMD increased significantly and more so than the femoral neck. This does indicate that osteopenia in children with Cushing’s is reversible and longer term studies are needed.
Jornayvaz, et al reported on 20 pregnancies in 11 women with pituitary Cushing’s who also had a bilateral adrenalectomy and found that pregnancy did not accelerate pituitary tumor growth. One patient developed gestational diabetes, one patient developed gestational hypertension, the median duration of pregnancy was 39 weeks and resulted in healthy children.
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