GH therapy increases fracture risk in patients previously treated for acromegaly

Posted on July 16, 2016 by MaryO

van Varsseveld NC, et al. Pituitary. 2016;doi:10.1007/s11102-016-0716-3.

Adult patients with severe growth hormone deficiency previously treated for acromegaly saw an increased fracture risk after 6 years of growth hormone replacement therapy, whereas those previously treated for Cushing’s disease did not experience the same risk, according to a recent observational study.

Nadege C. van Varsseveld, MD, of the department of internal medicine at VU University Medical Center in Amsterdam, and colleagues analyzed data from 1,028 patients with previous nonfunctioning pituitary adenoma (NFPA; n = 783), acromegaly (n = 65) and Cushing’s disease (n = 180), identified through the Dutch National Registry of Growth Hormone Treatment in Adults, a nationwide, long-term surveillance study in patients with severe GH deficiency. Data were collected biannually from medical records through 2009. Baseline DXA measurements were available for 414 patients; 71 (17.1%) had osteoporosis at one or more of the measured sites; 147 (35.5%) had osteopenia.

During a mean follow-up of 5.2 years, researchers found that 166 of patients with previous NFPA were prescribed osteoporosis medications (21.3%), as were 69 patients with previous Cushing’s disease (38.5%) and 22 patients with previous acromegaly (33.4%). During follow-up, 39 patients experienced fractures (3.8%; 32 experiencing one fracture), including 26 patients in the previous NFPA group, eight patients in the previous Cushing’s disease group and five patients in the previous acromegaly group. The median time between baseline and first fracture was 2.4 years (mean age, 59 years).

Researchers found that fracture risk did not differ between groups before 6 years’ follow-up. Fracture risk increased in patients with previous acromegaly after 6 years’ follow-up, but not for those with previous Cushing’s disease vs. patients with NFPA. Results persisted after adjustment for multiple factors, including sex, age, fracture history and the extent of pituitary insufficiency.

The researchers noted that patients with previous Cushing’s disease were younger and more often women and had a greater history of osteopenia or osteoporosis, whereas patients with acromegaly had a longer duration between tumor treatment and the start of GH therapy and were treated more often with radiotherapy.

“During active acromegaly, increased bone turnover has been observed, but reported effects on [bone mineral density] are heterogeneous,” the researchers wrote. “It is postulated that cortical BMD increases, whereas trabecular BMD decreases or remains unaffected.

“The increased fracture risk in the present study may be a long-term effect of impaired skeletal health due to previous GH excess, even though this was not reflected by an increased occurrence of osteopenia or osteoporosis in the medical history,” the researchers wrote. – by Regina Schaffer

Disclosure: One researcher reports receiving consultancy fees from Novartis and Pfizer.

From http://www.healio.com/endocrinology/hormone-therapy/news/online/%7B92a67ad7-3bd5-46f0-b999-0a8e3486edab%7D/gh-therapy-increases-fracture-risk-in-patients-previously-treated-for-acromegaly

Filed under: Cushing's, pituitary, Rare Diseases, Treatments | Tagged: , , , , , , , , , | Leave a comment »

Elevated late-night salivary cortisol may indicate recurrent Cushing’s disease

Posted on July 15, 2016 by MaryO

Carroll TB, et al. Endocr Pract. 2016;doi:10.4158/EP161380.OR.

 

Elevated late-night salivary cortisol may serve as an early biochemical marker of recurrent Cushing’s disease, and prompt intervention may result in clinical benefits for people with Cushing’s disease, according to recent study findings.

According to the researchers, late-night salivary cortisol level is more sensitive for detecting Cushing’s disease recurrence compared with urinary free cortisol or a dexamethasone suppression test.

Ty B. Carroll, MD, assistant professor at the Medical College of Wisconsin Endocrinology Center and Clinics in Menomonee Falls, and colleagues evaluated 15 patients (14 women; mean age, 49.1 years) with postsurgical recurrent Cushing’s disease (mean time to recurrence, 3.3 years) after initial remission to determine the performance of urinary free cortisol and late-night salivary cortisol measurements for detecting recurrent Cushing’s disease.

Participants were identified as having Cushing’s disease between 2008 and 2013; there was no standard for follow-up, but after remission confirmation participants were followed at least every 6 months after surgery for 2 years and then annually thereafter. Late-night salivary cortisol was the primary biochemical test to screen for recurrence, and follow-up tests with a dexamethasone suppression test, urinary free cortisol or other tests were performed if late-night salivary results were abnormal or if suspicion of recurrence was high.

Of the cohort, 80% had normal urinary free cortisol (< 45 µg/24 hours) at recurrence. Primary transphenoidal adenoma resection was performed in all participants. Evidence of pituitary adenoma on MRI at the time of recurrence was present in seven of 12 participants with normal urinary free cortisol and two of three participants with abnormal urinary free cortisol. Normal renal function was present in all participants, and 14 underwent testing with late-night salivary cortisol, dexamethasone suppression test and urinary free cortisol.

Of participants with normal urinary free cortisol at recurrence, nine had an abnormal dexamethasone suppression test (cortisol 1.8 µg/dL), and all had at least one elevated late-night salivary cortisol measurement (> 4.3 nmol/L). Mean late-night salivary cortisol was 10.2 nmol/L, and mean urinary free cortisol was 19.9 µg/24 hours.

Therapy for recurrent Cushing’s disease was administered in 11 of the 12 participants with abnormal urinary free cortisol. Adrenocorticotropic hormone (ACTH)-staining pituitary adenoma was confirmed in three participants who underwent repeat transphenoidal adenoma resection. Pharmacotherapy was administered to seven participants with normal urinary free cortisol, and two additional participants underwent bilateral adrenalectomy.

Abnormal dexamethasone suppression test was found in two participants with elevated urinary free cortisol at the time of recurrence, and two participants had confirmed abnormal late-night salivary cortisol. All three participants with elevated urinary free cortisol at the time of recurrence underwent therapy.

“This study has shown potential clinical benefit of either surgical or medical therapy in recurrent [Cushing’s disease] patients with elevations of [late-night salivary cortisol] and normal [urinary free cortisol],” the researchers wrote. “We believe that the outcomes observed in this retrospective case series suggest that the risk/benefit ratio of early treatment needs to undergo a more rigorous prospective evaluation utilizing [late-night salivary cortisol] elevation as an early biochemical marker of recurrent [Cushing’s disease].” – by Amber Cox

Disclosure: Carroll reports being a consultant for Corcept Therapeutics. Please see the full study for a list of all other authors’ relevant financial disclosures.

From http://www.healio.com/endocrinology/adrenal/news/online/%7B9ea4e4ed-6428-49b8-9b2a-11462cb21349%7D/elevated-late-night-salivary-cortisol-may-indicate-recurrent-cushings-disease

Filed under: Cushing's, Diagnostic Testing, pituitary, Treatments | Tagged: , , , , , , , , , , | Leave a comment »

Surgery Preferred Option in Cushing’s Disease for Best Survival

Posted on June 21, 2016 by MaryO

Patients with Cushing’s disease who have been in remission for more than 10 years still have an increased mortality risk compared with the general population, says an international team of researchers, who found the risk of early death was particularly increased in those with Cushing’s and accompanying circulatory disease.

Richard N Clayton, MD, department of medicine, Keele University, Stoke-on-Trent, United Kingdom, showed that Cushing’s disease, which is characterized by increased secretion of adrenocorticotropic hormone by the anterior pituitary gland, is associated with an increased mortality risk of more than 60% and a median survival of around 40 years.

In patients who also had circulatory disease, the mortality risk was even higher, say Dr Clayton and colleagues.

However, patients who had undergone curative pituitary surgery had a long-term risk of death no different from that of the general population. US Endocrine Society guidelines published last August recommend that optimal treatment of Cushing’s syndrome involves direct surgical removal of the causal tumor.

But Dr Clayton and colleagues point out that even patients who undergo pituitary surgery will nevertheless “require lifelong follow-up at a center experienced in dealing with this condition, having regular checks for diabetes, hypertension, and other cardiovascular risk factors.”

The study was published online June 2 in Lancet Diabetes & Endocrinology.

In an accompanying editorial, Rosario Pivonello, MD, PhD, department of clinical medicine and surgery, section of endocrinology, University of Naples Federico II, Italy, and colleagues write that, although surgery is not suitable for all patients, “Prompt pituitary surgery might be the preferred treatment for Cushing’s disease to guarantee the best mortality outcome.”

Calling for further research to better understand why one treatment “has a better effect on mortality than another,” they state: “The results from this study might also motivate rapid interventions, cure, and long-term follow-up in patients with Cushing’s disease — even for a long time after hypercortisolism resolution.”

Studying Those Who Have Survived More Than 10 Years

Dr Clayton and colleagues explain that previous studies have explored mortality in patients with Cushing’s disease during either active disease or remission. But the outcome of patients in remission, especially long-term remission, is still a matter of debate, and assessing long-term survival has been limited by various methodological differences. To overcome some of these issues, they performed a retrospective analysis of case records from specialist referral centers in the United Kingdom, Denmark, the Netherlands, and New Zealand.

They identified 320 patients diagnosed with Cushing’s disease and cured for a minimum of 10 years at enrollment and had no relapses during the study period. The ratio of women to men was 3:1.

Median patient follow-up was 11.8 years, yielding a total of 3790 person-years of follow-up 10 years after cure. There was no difference in follow-up between countries. And as there were no significant demographic and clinical differences between men and women, the data were pooled.

During the study 16% of patients died. Median survival was 31 years for women and 28 years for men, at approximately 40 years following remission. The overall standardized mortality ratio (SMR) for all-cause mortality compared with the general population was 1.61 (P = .0001).

Patients with Cushing’s and circulatory disease had an SMR vs the general population of 2.72 (P < .0001), but deaths from cancer among those who had survived Cushing’s disease were not higher than the general population, at an SMR of 0.79 (P = .41).

Patients with Cushing’s and diabetes also had an increased mortality risk, at a hazard ratio (HR) of 2.82 (P < .0096) compared with the general population, while hypertension was not significantly associated with increased mortality, at an HR of 1.59 (P = .08).

There was also an association between mortality and number of treatments, at an HR of 1.77 for two vs one treatment (P = .08) and an HR of 2.6 for three vs one treatment (P = .02).

Pituitary Surgery Alone Associated With No Increased Risk of Death

Pituitary surgery performed as the first and only treatment was associated with an SMR vs the general population of 0.94 compared with an SMR of 2.58 for other patients (P < .0005).

Patients who had pituitary surgery only had a median survival of 31 years compared with 24 years if surgery had been required at any time (P = 0.03).

The research team states: “For patients who have been cured of Cushing’s disease for 10 years or more, treatment complexity and an increased number of treatments, reflecting disease that is more difficult to control, appears to negatively affect survival.”

“Pituitary surgery alone achieves a mortality outcome that is not different from the normal population and should be performed in a center of excellence,” they conclude.

However, in the editorial, Dr Pivonello and colleagues point out that the surgical approach “is not a treatment option for some patients, either because of contraindications (eg, severe clinical complications) or because of an absence of clear indication for surgery (eg, tumor is not completely removable by surgery).”

The authors and editorialist have reported no relevant financial relationships.

Lancet Diabetes Endocrinol. Published online June 2, 2016. Abstract, Editorial

From http://www.medscape.com/viewarticle/865073#vp_2

Filed under: Cushing's, Treatments | Tagged: , , , , , , , , | Leave a comment »

Webinar: Endoscopic Endonasal Surgery for the Treatment of Cushing’s Disease

Posted on June 6, 2016 by MaryO

Mon, Jun 13, 2016 11:00 AM – 12:00 PM EDT

Show in My Time Zone
Presented by:
Dr. Maria Koutourousiou
Webinar DescriptionAn update on the diagnosis and treatment options of Cushing’s disease. Description of the endoscopic endonasal approach for the management of CD. Surgical videos demonstration and comparison with the microscopic transsphenoidal approach. Surgical outcomes and adjuvant treatment.

Presenter Bio

Dr. Mary Koutourousiou is an attending Neurosurgeon and Assistant Professor at the University of Louisville. She is the Director of the Pituitary and Skull Base Program. Dr. Koutourousiou received her M.D. from the Aristotle University of Thessaloniki, Greece and completed her neurosurgical residency at the General Hospital of Athens “G. Gennimatas”, in Greece. She underwent subspecialty fellowship training in Endoscopic Pituitary Surgery and Minimally Invasive Neurosurgery at the UMC St. Radboud, Nijmegen, in the Netherlands. She moved to the United States in 2010 and completed four years of research and a clinical fellowship in Endoscopic and Open Skull Base Surgery at UPMC Presbyterian in Pittsburgh, Pennsylvania.

Dr. Koutourousiou has published extensively in the field of endoscopic skull base surgery. Her studies have been presented in national and international neurosurgical meetings. Dr. Koutourousiou’s work in skull base surgery has been recognized by the European Skull Base Society and the World Federation of Skull Base Societies.

Register here: https://attendee.gotowebinar.com/register/4982773766837282305?utm_source=newsletter_199&utm_medium=email&utm_campaign=webinar-announcement-endoscopic-endonasal-surgery-for-the-treatment-of-cushing-s-disease

Filed under: Cushing's, Meetings and Conferences, pituitary, Treatments, Webinar | Tagged: , , , , , | Leave a comment »

Cushing’s disease recurrence predictive factors: Outcome analysis of patients in VANCOUVER over 30 years

Posted on May 27, 2016 by MaryO

Screenshot 2016-05-27 13.12.55

 

Pituitary Disorders/Neuroendocrinology

R Chen, J Levi, M Almalki, S Yi, M Johnson, E Ur

Summary: The objective of this study was to describe the management and outcomes of patients with Cushing’s disease (CD) in the Vancouver region over a 30-year period and to investigate the predictive factors of CD recurrence. Researchers found CD recurrence in 45.8% of patients who received initial transsphenoidal surgery (TSS), and that a post-operative serum cortisol level > 140nmol/L may be a positive predictor of recurrence in these patients.

Methods:

  • Researchers retrospectively reviewed the clinical charts from endocrinologists in Vancouver who provided consent to participate in this study.
  • Included in this study were 48 patients diagnosed with CD since 1985.

Results:

  • All 48 patients received initial TSS; the mean follow-up time was 11.73 (±6.98) years.
  • More than half of the patients (n=26, 54.2%) remained in remission, and 22 patients (45.8%) received subsequent interventions due to CD recurrence.
  • Second-line therapies included repeat TSS (40.9%), stereotactic radiotherapy (18.2%), and bilateral adrenalectomy (36.4%).
  • Among patients with disease recurrence, the average post-operative serum cortisol level was significantly higher (489.0 nmol/L vs 114.7nmol/L; P=0.003).
  • The positive predictive value for recurrence with post-operative serum cortisol > 140nmol/L was 76.5% (P=0.049), while serum cortisol < 140nmol/L had an 80% predictive value for non-recurrence (P=0.035).

From http://www.mdlinx.com/endocrinology/conference-abstract.cfm/ZZ37C4C5D3BF1A4FAE9C479A696660535B/57894/?utm_source=confcoveragenl&utm_medium=newsletter&utm_content=abstract-list&utm_campaign=abstract-AACE2016&nonus=0

Filed under: Cushing's, Meetings and Conferences, Treatments | Tagged: , , , , , , , , , , | Leave a comment »

« Previous Page — Next Page »