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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Rally for Medical Research Hill Day

Posted on May 26, 2016 by MaryO

Held every September, this Capitol Hill Day event continues the momentum established in 2013, and includes nearly 300 national organizations coming together in support of the Rally for Medical Research.

The purpose of the Rally is to call on our nation’s policymakers to make funding for National Institutes of Health (NIH) a national priority and raise awareness about the importance of continued investment in medical research that leads to MORE PROGRESS, MORE HOPE and MORE LIVES SAVED.

The next Rally for Medical Research Hill Day is Sept. 22, 2016.

Sign up to receive updates, including a link to register once it becomes available.

Filed under: Clinical trials, General Health, Health Care, Meetings and Conferences, Rare Diseases | Tagged: , , , | Leave a comment »

Nominations Now Open for RareVoice Awards

Posted on May 24, 2016 by MaryO

rare-voice

Rare Disease Legislative Advocates is pleased to open nominations for the 5th Annual RareVoice Awards, a celebration to honor advocates who give rare disease patients a voice on Capitol Hill and in state government.

Wednesday, November 16, 2016
Arena Stage in Washington, DC

If you know of someone who has been a “Voice” for the rare disease community and should be honored for their work, please click here to submit your nomination.

RareVoice Award nominations are open to the public.  We encourage the community to nominate individuals and organizations who have gone above and beyond to become rare disease policy leaders and political advocates in their state and our nation. We have nominations open for the following categories: Congressional Staff, Patient Advocate or Patient Organization (at the state or federal level), and Government Agency Staff.

Deadline to submit nominations is July 31, 2016.

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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

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

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