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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Bilateral testicular tumors resulting in recurrent Cushing’s syndrome after bilateral adrenalectomy

Posted on December 21, 2016 by MaryO
Troy Puar1,2, Manon Engels3,4, Antonius E. van Herwaarden4, Fred C. G. J. Sweep4, Christina Hulsbergen-van de Kaa5, Karin Kamphuis-van Ulzen6, Vasileios Chortis7,8, Wiebke Arlt7,8, Nike Stikkelbroeck1, Hedi L Claahsen–van der Grinten3, Ad R.M.M. Hermus1
Corresponding author: Troy Puar, MRCP (UK), Department of Medicine, Div. of Endocrinology, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands. Phone: +31 243614599, Fax: +31 243618809, e-mail: Troy_puar@cgh.com.sg
DOI: http://dx.doi.org/10.1210/jc.2016-2702
Received: July 14, 2016
Accepted: November 29, 2016
First Published Online: November 30, 2016
Abstract
Context:

Recurrence of hypercortisolism in patients after bilateral adrenalectomy for Cushing’s disease is extremely rare.

Patient:

We present a rare case of a 27-year-old man who previously underwent bilateral adrenalectomy for Cushing’s disease with complete clinical resolution. Cushingoid features recurred 12 years later, along with bilateral testicular enlargement. Hormonal tests confirmed ACTH-dependent Cushing’s. Surgical resection of the testicular tumors led to clinical and biochemical remission.

Design and Results:
Gene expression analysis of the tumor tissue by qPCR showed high expression of all key steroidogenic enzymes. Adrenocortical-specific genes were 5.1 x 105 (CYP11B1), 1.8 x 102 (CYP11B2) and 6.3 x 104 (MC2R) times higher than non-steroidogenic fibroblast control. This correlated with urine steroid metabolome profiling showing 2-5 fold increases in the excretion of the metabolites of 11-deoxycortisol, 21-deoxycortisol and total glucocorticoids. Leydig-specific genes were 4.3 x 101 (LHCGR) and 9.3 x 100(HSD17B3) times higher than control and urinary steroid profiling showed 2-fold increased excretion of the major androgen metabolites androsterone and etiocholanolone. These distinctly increased steroid metabolites were suppressed by dexamethasone, but unresponsive to hCG stimulation, supporting the role of ACTH, but not LH, in regulating tumor-specific steroid excess.
Conclusion:

We report bilateral testicular tumors occurring in a patient with recurrent Cushing’s disease 12 years after bilateral adrenalectomy. Using mRNA expression analysis and steroid metabolome profiling, the tumors demonstrated both adrenocortical and gonadal steroidogenic properties, similar to testicular adrenal rest tumors found in patients with congenital adrenal hyperplasia. This suggests the presence of pluripotent cells even in patients without CAH.

Affiliations
  • 1Department of Medicine, Division of Endocrinology, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands.
  • 2Department of Endocrinology, Changi General Hospital, Singapore 529889, Singapore.
  • 3Department of Paediatrics, Division of Endocrinology, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands.
  • 4Department of Laboratory Medicine, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands.
  • 5Department of Pathology, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands.
  • 6Department of Radiology, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands.
  • 7Institute of Metabolism and Systems Research, University of Birmingham, Birmingham N15 2TT, United Kingdom.
  • 8Centre for Endocrinology, Diabetes, and Metabolism, Birmingham Health Partners, Birmingham B15 2TH, United Kingdom.

– See more at: http://press.endocrine.org/doi/abs/10.1210/jc.2016-2702#sthash.F4lfWg9j.dpuf

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“How can you leave her like this?”

Posted on September 8, 2016 by MaryO

A mother has revealed the anguish her family suffered after her daughter (16), who is in need of brain surgery, was turned away from Beaumont Hospital.

The National Centre for Neurosurgery had no beds or theatre access for nine patients with malignant brain tumours last Friday.
One of the people who was turned away was 16-year-old Chloe Holian from Donegal.

Her mother Caitriona explained to the Anton Savage Show on TodayFM that the road to treatment has been fraught with setbacks.

“I can’t stress how happy I am with the neurosurgeon and his team are there but it seems our consultant’s hands are tied, what am I supposed to do?” she said.

Chloe was diagnosed in July with a recurrence of Cushing’s syndrome, a metabolic disorder which is caused by abnormally high levels of the hormone cortisol in the blood stream.

After being promised treatment in July and then August, the Letterkenny girl was finally admitted on Thursday and was fasting for a procedure on Friday morning when she was told it was cancelled.

“When we got down they told us that they decided to put off the surgery for a couple of days,” said Caitriona.

She was told that the doctors wanted to perform a dexamethasone suppression test first to confirm that Chloe was, in fact, suffering from Cushing’s – despite previous diagnosis revealing that she was.

However, she soon found out that the test couldn’t be performed.

“At 11am someone in scrubs came around to say it wasn’t fair but he had to tell us she won’t be doing the surgery… and she wouldn’t be getting the major test either,” said Caitriona.

She said he was very empathetic of their situation.

“I felt sorry for him having to tell us that news… I asked him ‘how can you leave her like this?’

“He promised that he was going to organise this test himself. It was quite difficult as you need four people in the surgery to do this test, you need the radiographer, neurosurgeon, endocrinologist and anesthetist.”

Unfortunately, an anesthetist was not available for the test.

Caitriona said that Chloe was quite upset at the news. One of the side-effects of her condition is excessive weight gain and the student has gained six stone since last September.

“She had psyched herself up for the surgery,” explained her mother.

“Everybody was around her encouraging her, they threw a party for her before she went because it was a big thing. Chloe has no confidence because she’s put on an extra six stone. She was looking forward to getting her old self back, she just wanted to go and do this operation and get it over and done with.

“For anybody to have a little bit of a weight gain they can be conscious of it but if you’re 16-years-old and you’ve gained six stone and you can’t explain it…”

Caitriona said the family were forced to pack their bags and return to Donegal but, as of today, they have still not received a rescheduled appointment.

The mother-of-three is struggling to juggle home life with trips to Dublin but she said the family’s life is on hold until the tumour is removed.

This is the second time that Chloe has developed Cushing’s, in 2009 she was sent to London for surgery as treatment was not yet available in Ireland.

Patients lives are being threatened by delays, according to the head of the country’s national brain surgery centre. Clinical Director Mohsen Javadpour says people are at risk of dying while they’re waiting for treatment.

From http://www.independent.ie/life/how-can-you-leave-her-like-this-mothers-anguish-as-daughter-16-in-need-of-brain-surgery-is-turned-away-from-beaumont-35029557.html

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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

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Role of radiosurgery in management of pituitary adenoma-The BNI experience

Posted on May 30, 2016 by MaryO

Screenshot 2016-05-27 13.12.55

 

S Meah, E Youssef, W White

Summary: Researchers conducted this study to determine the efficacy of stereotactic radiosurgery with CyberKnife for the treatment of recurrent pituitary adenoma. They concluded that stereotactic radiosurgery for recurrent/residual pituitary adenomas using CyberKnife appears to be relatively safe and effective when compared to conventional radiotherapy.

Methods:

  • Included in this retrospective study were patients who underwent cyberKnife radiosurgery for recurrent or residual pituitary adenoma at Barrow Neurological Institute (n=48).
  • Patients were followed for an average of 44 months.
  • Thirty-three patients had non-functioning adenomas, 10 had acromegaly, and 5 had Cushing’s disease.
  • Researchers analyzed the change in tumor size, hormonal function, and complication of therapy for each patient.

Results:

  • Tumor resection operation was performed through either the transsphenoidal or transcranial approach before CyberkKnife treatment.
  • All patients had either recurrence or residual mass in the cavernous sinus before CyberKnife treatment.
  • The total irradiation dose ranged from 2100-4000 cGy in an average of 3-5 fractions.
  • Slightly more than half of the patients (n=26, 54.2%) had smaller tumors at follow-up, while 22 (45.8%) had stable tumors.
  • Visual acuity remained unchanged post-treatment.
  • One patient developed radiation-induced temporal lobe necrosis.
  • Four patients (8.3%) required hormonal replacement due to panhypopituitarism.
  • Of the 15 patients with functioning adenoma, hormonal function improved in 12.
  • Treatment failed in 1 patient with acromegaly, 2 patients with Cushing’s disease, and 1 patient with non-functioning adenoma.

From http://www.mdlinx.com/endocrinology/conference-abstract.cfm/ZZFEBE5A85394340E188330278A399E6CF/57978/?utm_source=confcoveragenl&utm_medium=newsletter&utm_content=abstract-list&utm_campaign=abstract-AACE2016&nonus=0

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