Postsurgical treatment often necessary in persistent, recurrent Cushing’s disease

Posted on March 30, 2017 by MaryO

Nearly half of adults with Cushing’s disease that persists or recurs after surgical treatment require second and sometimes third therapeutic interventions, including pituitary surgical reintervention, radiotherapy, pharmacotherapy or bilateral adrenalectomy, study data from Mexico show.

Moisés Mercado, MD, FRCPC, of the ABC Hospital Neurological and Cancer Centers in Mexico City, and colleagues evaluated 84 adults (median age, 34 years; 77 women) with Cushing’s disease to determine the long-term efficacy of secondary interventions for persistent and recurrent Cushing’s disease. Median follow-up was 6.3 years.

Overall, 81 participants were primarily treated with transsphenoidal surgery. More than half experienced long-lasting remission (61.7%); disease remained active in 16%, who were diagnosed with persistent Cushing’s disease; and 22% experienced relapse after remission and were diagnosed with recurrent Cushing’s disease.

After the initial procedure, 18 participants required pituitary surgical reintervention, including 10 with recurrent and eight with persistent disease. Radiation therapy was administered to 14 participants, including two as primary therapy and 12 after failed pituitary surgery. Pharmacologic treatment with ketoconazole was prescribed for 15 participants at one point during the course of disease. Bilateral adrenalectomy was performed in 12 participants.

Pituitary surgical reintervention was the most commonly used secondary treatment (22.2%), followed by pharmacologic therapy with ketoconazole (16%), radiotherapy (14.8%) and bilateral adrenalectomy (14.8%). More than half of participants experienced early remissions after a second operation (66.6%) and radiotherapy (58.3%), whereas long-lasting remission was reached in only 33.3% of participants who underwent a second surgery and 41.6% of participants who underwent radiotherapy. Half of participants who underwent bilateral adrenalectomy were diagnosed with Nelson’s syndrome.

Overall, 88% of participants achieved remission, and disease was biochemically controlled with pharmacologic treatment in 9.5% of participants after their initial, secondary and third-line treatments.

“The efficacy of treatment alternatives for recurrent or persistent [Cushing’s disease] vary among patients, and often, more than one of these interventions is required in order to achieve a long-lasting remission,” the researchers wrote. – by Amber Cox

Disclosure: The researchers report no relevant financial disclosures.

From http://www.healio.com/endocrinology/adrenal/news/in-the-journals/%7B5519b312-5912-4c65-b2ed-2ece3f68e83f%7D/postsurgical-treatment-often-necessary-in-persistent-recurrent-cushings-disease

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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

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Webinar on Management Options for Pituitary Tumors March 22

Posted on March 19, 2016 by MaryO

Dr. Andaluz will cover the full breadth of treatment options from managing endocrine function, surgical procedures (transsphenoidal, endoscopic, and keyhole approaches), radiotherapy / radiosurgery, and the importance of getting care at a multidisciplinary center.

Dr. Norberto Andaluz is a neurosurgeon with the Mayfield Clinic and University of Cincinnati Brain Tumor Center. He is also Associate Professor of Neurosurgery at the University of Cincinnati, Surgical Director of the Neuroscience Intensive Care Unit, and Director of Neurotrauma at the University of Cincinnati Neuroscience Institute. He specializes in the treatment of all disorders and diseases of the brain and spine, but in particular, traumatic brain injury, aneurysms, arteriovenous malformations (AVMs), intracerebral hemorrhage, stroke, carotid artery disease, moyamoya disease and brain tumors (with special training in skull base tumors like pituitary adenoma). Dr. Andaluz received his medical degree from Unversidad Nacional de Rosario in Argentina. He completed his residency in neurosurgery at Instituto de Neurología y Neurocirugía at Sanatorio Parque in Rosario, Argentina and earned a fellowship in cerebrovascular surgery from the University of Cincinnati. Professional memberships include the American Heart Association, Congress of Neurological Surgeons, National Neurotrauma Society, Neurocritical Care Society and North American Skull Base Society.

Register at http://pituitary.org/events/webinar-management-options-for-pituitary-tumors

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The New Molecular Landscape of Cushing’s Disease

Posted on September 27, 2015 by MaryO
Silviu Sbiera#, Timo Deutschbein#, Isabel Weigand, Martin Reincke, Martin Fassnachtcorrespondence, Bruno Allolio†
#These authors contributed equally to this work.
†A few days after acceptance of this manuscript, Bruno Allolio passed away.
DOI: http://dx.doi.org/10.1016/j.tem.2015.08.003

Cushing’s disease (CD) is caused by corticotropin-secreting pituitary adenomas and results in substantial morbidity and mortality. Its molecular basis has remained poorly understood until the past few years, when several proteins and genes [such as testicular orphan nuclear receptor 4 (TR4) and heat shock protein 90 (HSP90)] were found to play key roles in the disease. Most recently, mutations in the gene of ubiquitin-specific peptidase 8 (USP8) increasing its deubiquination activity were discovered in a high percentage of corticotroph adenomas. Here, we will discuss emerging insights in the molecular alterations that finally result in CD. The therapeutic potential of these findings needs to be carefully evaluated in the near future, hopefully resulting in new treatment options for this devastating disorder.

Trends

Transsphenoidal surgery and radiotherapy are the treatment of choice in CD. However, despite high initial remission rates, a significant percentage of patients relapse.

Owing to the poor understanding of the pathophysiology of CD, drug therapy is still limited and often only ameliorates the clinical manifestations through blocking of ACTH release or adrenal cortisol synthesis.

Recent research has identified several important proteins (e.g., EGFR, HSP90, TR4, and AVPR1b) whose deregulation is associated with CD and may therefore represent potential therapeutic targets.

Frequent, novel mutations in the USP8 gene that are associated with corticotroph pituitary adenomas were recently discovered that result in reduced EGFR degradation and increased POMC activation in vitro.

Keywords:

Cushing’s disease, pituitary, gene expression, epidermal growth factor receptor, ubiquitin-specific peptidase 8, 14-3-3 proteins

The entire article is available by subscription only.  More information here.

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Call for Papers: Cushing’s Syndrome: New Evidence and Future Challenges

Posted on November 13, 2014 by MaryO

Call for Papers

Cushing’s syndrome is a rare and potentially lethal disease which still represents a challenge for the endocrinologists, being characterized by elevated morbidity even long-term after the remission of hypercortisolism. Several diagnostic issues prevent an early recognition of the disease and rate of recurrence is significantly high after surgical, medical, or radiotherapy management.

Recent advances of biology and medicine are improving our knowledge on genetics and pathophysiology of this disease, both at the pituitary and adrenal level. New therapeutic agents are currently under investigation and an impelling need for efficacy and safety studies is rising in the endocrinology community. At the same time, the role of the “old” agents in the clinical practice is under debate and deserves a thorough analysis on larger series than those currently available. Likewise, the need for specific treatment of comorbidities is a clinical question which still remains unsolved.

We invite authors to submit original research and review articles that will stimulate the continuing efforts to understand the molecular pathology underlying Cushing’s syndrome, the development of strategies to diagnose and treat this condition in adults and children, and the evaluation of outcomes.

Potential topics include, but are not limited to:

  • Advances in genetics of Cushing’s syndrome
  • Diagnostic issues in Cushing’s syndrome
  • Novel paradigms for treatment of Cushing’s syndrome
  • Role of the “old” pharmacological agents in the treatment of Cushing’s syndrome
  • Persistent increased mortality and morbidity after “cure” of Cushing’s syndrome
  • Role of inflammation in the pathogenesis of Cushing’s syndrome
  • Cushing’s syndrome as model of metabolic derangements
  • Challenges in the diagnosis and treatment of paediatric Cushing’s syndrome
Manuscript Due Friday, 8 May 2015
First Round of Reviews Friday, 31 July 2015
Publication Date Friday, 25 September 2015

Lead Guest Editor

  • Elena Valassi, Autonomous University of Barcelona, Barcelona, Spain

Guest Editors

From http://www.hindawi.com/journals/ije/si/156126/cfp/

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