Patients with ARMC5 mutations: The NIH clinical experience

Posted on May 27, 2016 by MaryO

Screenshot 2016-05-27 13.12.55

 

Adrenal Disorders

R Correa, M Zilbermint, A Demidowich, F Faucz, A Berthon, J Bertherat, M Lodish, C Stratakis

Summary: Researchers conducted this study to describe the different phenotypical characteristics of patients with armadillo repeat containing 5 (ARMC5) mutations, located in 16p11.2 and a likely tumor-suppressor gene. They determined that patients with bilateral adrenal enlargement, found on imaging tests, should be screened for ARMC5 mutations, which are associated with subclinical Cushing’s syndrome (CS) and primary hyperaldosteronism (PA).

Methods:

  • Researchers identified 20 patients with ARMC5 mutations (germline and/or somatic) who were enrolled in a National Institutes of Health (NIH) protocol.
  • They obtained sociodemographic, clinical, laboratory, and radiological data for all participants.

Results:

  • Three families (with a total of 8 patients) were identified with ARMC5 germline mutations; the rest of the patients (13/20) had sporadic mutations.
  • The male to female ratio was 1.2:1; mean age was 48 years and 60% of patients were African American.
  • Forty percent of patients were diagnosed with CS, 20% with subclinical CS, 30% with hyperaldosteronism, and 10% had no diagnosis.
  • The mean serum cortisol (8 am) and Urinary Free Cortisol were 13.1 mcg/dl and 77 mcg/24 hours, respectively.
  • Nearly all patients (95%) had bilateral adrenal enlargement found on CT or MRI.
  • Patients underwent the following treatments: Bilateral adrenalectomy (45%), unilateral adrenalectomy (25%), medical treatment (20%), and no treatment (10%).
  • ARMC5 mutations are associated with primary macronodular adrenal hyperplasia (PMAH) and are also seen in patients with PA, especially among African Americans.

From http://www.mdlinx.com/endocrinology/conference-abstract.cfm/ZZ37C4C5D3BF1A4FAE9C479A696660535B/57884/?utm_source=confcoveragenl&utm_medium=newsletter&utm_content=abstract-list&utm_campaign=abstract-AACE2016&nonus=0

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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

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Primary versus revision transsphenoidal resection for nonfunctioning pituitary macroadenomas: matched cohort study

Posted on May 22, 2016 by MaryO

 

Departments of 1Neurosurgery and 2Otolaryngology-Head and Neck Surgery, University of Virginia Health System, Charlottesville, Virginia; and 3Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts

ABBREVIATIONS DI = diabetes insipidus; GTR = gross-total resection; NFPMA = nonfunctioning pituitary macroadenoma; PFS = progression-free survival;SIADH = syndrome of inappropriate antidiuretic hormone; SRS = stereotactic radiosurgery; STR = subtotal resection; TSR = transsphenoidal resection.

INCLUDE WHEN CITING Published online May 20, 2016; DOI: 10.3171/2016.3.JNS152735.

Correspondence John A. Jane Jr., Department of Neurological Surgery, University of Virginia, Box 800212, Charlottesville, VA 22908. email:.

Abstract

OBJECTIVE

The object of this study was to compare the outcomes of primary and revision transsphenoidal resection (TSR) of nonfunctioning pituitary macroadenomas (NFPMAs) using endoscopic methods.

METHODS

The authors retrospectively reviewed the records of 287 consecutive patients who had undergone endoscopic endonasal TSR for NFPMAs at their institution in the period from 2005 to 2011. Fifty patients who had undergone revision TSR were retrospectively matched for age, sex, and duration of follow-up to 46 patients who had undergone primary TSR. Medical and surgical complications were documented, and Kaplan-Meier analysis was performed to assess rates of radiological progression-free survival (PFS).

RESULTS

The median follow-up periods were 45 and 46 months for the primary and revision TSR groups, respectively. There were no significant differences between the primary and revision groups in rates of new neurological deficit (0 in each), vascular injury (2% vs 0), postoperative CSF leak (6% vs 2%), transient diabetes insipidus (DI; 15% vs 12%), chronic DI (2% vs 2%), chronic sinusitis (4% vs 6%), meningitis (2% vs 2%), epistaxis (7% vs 0), or suprasellar hematoma formation (0 vs 2%). However, patients who underwent primary TSR had significantly higher rates of syndrome of inappropriate antidiuretic hormone (SIADH; 17% vs 4%, p = 0.04). Patients who underwent primary operations also had significantly higher rates of gross-total resection (GTR; 63% vs 28%, p < 0.01) and significantly lower rates of adjuvant radiotherapy (13% vs 42%, p < 0.01). Radiological PFS rates were similar at 2 years (98% vs 96%) and 5 years (87% vs 80%, p = 0.668, log-rank test).

CONCLUSIONS

Patients who underwent primary TSR of NFPMAs experienced higher rates of SIADH than those who underwent revision TSR. Patients who underwent revision TSR were less likely to have GTR of their tumor, although they still had a PFS rate similar to that in patients who underwent primary TSR. This finding may be attributable to an increased rate of adjuvant radiation treatment to subtotally resected tumors in the revision TSR group.

From http://thejns.org/doi/abs/10.3171/2016.3.JNS152735?journalCode=jns

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A Team Effort to Treat a Pea-Sized Gland

Posted on May 12, 2016 by MaryO

HYANNIS – Endoscopic surgery for pituitary tumors involves the use of small instruments, but neurosurgeon Nicholas Coppa, MD, FAANS, is quick to say it takes a big team to make the surgeries a success.

“It’s very much a collaborative effort among endocrinology, neurosurgery and otolaryngology specialties,” he said.

Dr. Coppa frequently works with endocrinologist Catalina Norman, MD, PhD, and ear, nose and throat surgeon Ross Johnston, MD.

The pituitary gland sits at the base of the brain. It makes important hormones that control several different systems in the body and help maintain normal body function.

“The overwhelming majority of patients with big tumors present with visual problems,” said Dr. Coppa. “They get tunnel vision from a tumor putting pressure on the vision nerves.

Many patients’ pituitary problems are detected incidentally while the physician is trying to diagnose a set of symptoms, most commonly headaches, he added. A variety of asymptomatic tumors are detected this way.

A subset of pituitary tumors secrete excess hormones, which create syndromes characterized by whatever hormone is being secreted in excess, Dr. Coppa added. Oftentimes these problems are diagnosed by an endocrinologist.

Before coming to Neurosurgeons of Cape Cod – now known as Cape Cod Healthcare Neurosurgery – in 2013, Dr. Coppa was professor of skull base surgery at Oregon Health and Science University’s Northwest Pituitary Center. He has performed more than 200 endoscopic surgeries for pituitary tumors, sinonasal malignancies and anterior skull base encephaloceles. The procedure is fairly new on Cape Cod, he said.

The pituitary gland is about the size of a pea, so operating on it is a tricky and delicate procedure.

The surgeon commonly works with an endoscope inserted through one nostril, and microsurgical instruments through the other nostril. This allows him to maneuver to the surgical area.

According to the Northwest Pituitary Center’s web site, “The tube is connected to a TV monitor that helps your doctor see the surgical area even more clearly than with a microscope. Your doctor can also use intraoperative neuro-navigation to perform image-guided surgery, based on a pre-operative CT scan or MRI. This helps the doctor see exactly where the tumor is and avoid damaging healthy brain tissue that is nearby.”

Nasal endoscopy for the neurosurgeon has really taken off in the last 10 years, according to Dr. Coppa. The main reason for the increase is because the technique allows better visualization of the anatomy, he said.

“We find that it allows, at least in my experience, more maneuverability of your micro-surgical instruments. That’s been very satisfying for patients. The nasal morbidity [adverse effects] is lower compared to historic ways of doing it.”

Ear, nose and throat doctors use trans-nasal surgery to treat many sinus conditions, said Dr. Coppa. But the procedure is predominantly used by neurosurgeons for pituitary tumors, other tumors of the skull base and malignancies of the sinus cavity that often invade the brain.

After endoscopic pituitary surgery, patients are typically in the hospital for several days and resume day-to-day activities within that first week.

By BILL O’NEILL, OneCape Health News

 

From http://www.capecod.com/newscenter/a-team-effort-to-treat-a-pea-sized-gland/

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Delayed diagnosis, barriers to care increase morbidity in children with Cushing’s syndrome

Posted on May 6, 2016 by MaryO

Hispanic and black children diagnosed with Cushing’s syndrome are more likely to present with higher cortisol measurements and larger tumor size vs. white children, according to study findings presented at the annual Pediatric Academic Societies Meeting in Baltimore.

“Racial and socioeconomic disparities may contribute to the severity of disease presentation for children with Cushing’s [syndrome],” Alexandra Gkourogianni, MD, of the section on endocrinology and genetics at the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and colleagues wrote. “Minority children from disadvantaged backgrounds present more frequently with comorbidities associated with longstanding [Cushing’s syndrome].”

Gkourogianni and colleagues analyzed data from 135 children treated for Cushing’s syndrome (transsphenoidal surgery) at the NIH between 1997 and 2015 (mean age, 13 years; 51% girls; 33% Hispanic or black). Researchers used a 10-point index for rating severity in pediatric Cushing’s syndrome based on predefined cutoffs; degree of hypercortisolemia, impaired glucose tolerance, and hypertension were graded on a 3-point scale (0-2); height, BMI z scores, duration of disease, and tumor invasion were graded on a 2-point scale (0-1).

Researchers found that midnight cortisol measurements were higher among Hispanic and black children vs. white children (23.3 µg/dL vs. 16 µg/dL; P = .019), as were tumor sizes (mean 6.3 mm vs. 3.3 mm; P = .016). Height standard deviation score was more severely affected in black and Hispanic children (–1.6 vs. –1.1; P = .038), and mean Cushing’s syndrome score for Hispanic and black children was higher vs. white children (4.5 vs. 3.8; P = .033).

Researchers found that median income had an independent correlation with Cushing’s syndrome score in univariate regression analysis for covariates of socioeconomic status and demographics (P = .025). Multivariable regression analysis using race, prevalence of obesity, estimated income, access to pediatric endocrinologist, age and sex confirmed that race, along with lower socioeconomic status and older age, were predictors of a higher Cushing’s syndrome score (P = .002).

“We speculate that delayed diagnosis, barriers to access to care and poorer quality health care for these underserved patients may contribute to presentation at a later age and increased morbidity,” the researchers wrote. “Additional research is needed to identify potential modifiable factors that may improve care for these patients.” – by Regina Schaffer

Reference:

Gkourogianni A, et al. Poster #445. Presented at: Pediatric Academic Societies Meeting; April 30- May 3, 2016; Baltimore.

Disclosure: Endocrine Today was unable to determine relevant financial disclosures.

From http://www.healio.com/endocrinology/adrenal/news/online/%7Be79d7c84-d539-4a04-a548-882b9f4caadd%7D/delayed-diagnosis-barriers-to-care-increase-morbidity-in-children-with-cushings-syndrome

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