Use late-night salivary cortisol to catch recurrent Cushing’s

Posted on July 4, 2014 by MaryO

By: M. ALEXANDER OTTO, Clinical Endocrinology News Digital Network

JULY 3, 2014

AT ICE/ENDO 2014

CHICAGO – Late-night salivary cortisol exceeded normal limits in 10 women with recurrent Cushing’s disease a mean of 3.5 years after transsphenoidal surgery, but their urinary free cortisol remained in normal limits, according to a retrospective review from the Medical College of Wisconsin, Milwaukee.

That adds strength to the notion that late-night salivary cortisol (LNSC) catches recurrent Cushing’s that’s missed by urinary free cortisol, even though UFC remains a standard screening approach in some places.

The study is tiny and retrospective, but at the joint meeting of the International Congress of Endocrinology and the Endocrine Society, lead investigator Dr. Ty Carroll explained why the findings still matter, and also why two LNSC measurements are better than one.

Video: http://www.clinicalendocrinologynews.com/home/article/video-use-late-night-salivary-cortisol-to-catch-recurrent-cushings/d7fad98e9289f9402034e73455b7560c.html

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Clinical effectiveness of metyrapone monotherapy in 195 patients with Cushing’s syndrome

Posted on June 21, 2014 by MaryO

From Day 1 of the 16th International Congress of Endocrinology and the Endocrine Society’s 96th Annual Meeting and Expo »

Chicago, IL – June 21, 2014

E Daniel, SJB Aylwin, SG Ball, K Boelaert, D Cuthbertson, C Daousi, JR Davis, W Drake, AB Grossman, M Gurnell, N Karavitaki, T Kearney, K Meeran, A Rees, PJ Trainer, JDC Newell-Price

Summary: Metyrapone is widely used in the UK for the control of cortisol excess in Cushing’s syndrome, but its use is not standardised. The few published reports on metyrapone use pertain to limited patient numbers. In this report, the largest report on metyrapone use, metyrapone was effective in achieving eucortisolemia in over 70% of patients without any other cortisol-lowering intervention, with a satisfactory safety profile. A variety of monitoring regimens were used, but greater standardisation of practice and more active dose titration is needed.

Methods:

  • A retrospective survey was conducted across 13 tertiary centres in England and Wales.
  • Using a standardised proforma, extensive data including monitoring and safety information were collected for patients with Cushing’s syndrome on metyrapone therapy between 1997 and 2013.
  • Eucortisolemia was defined according to the monitoring test used as a mean cortisol ‘day curve’ value ≤300 nmol/l, a urinary free cortisol bellow the upper limit of normal (ULN) or a 9am serum cortisol

Results:

  • A total of 195 patients received metyrapone (160 as monotherapy). Average age was 49.6 +/-15.7 years: 87.2% had metyrapone in conjunction with other interventions (surgery, radiotherapy or chemotherapy) while 12.8% had cortisol-lowering treatment alone.
  • Dose-titration was used in 81% of patients, whereas 19% had a block-and-replace regimen.
  • A total of 138 patients received metyrapone monotherapy for a mean duration of 162 days before any other intervention took place.
  • The etiology of Cushing’s syndrome in this subgroup was: pituitary-dependent disease [CD, 59% (macroadenoma 32% of CD)], ectopic ACTH syndrome (EAS, 17%), adrenocortical carcinoma (ACC, 4%), adrenal adenoma (AA, 17%) and other benign adrenal disease (3%).
  • Hypokalemia was actively managed with potassium levels increasing during metyrapone therapy (3.90 mmol/L vs 3.68 mmol/L, P=0.0026).
  • In this subgroup, 74% achieved eucortisolemia on varying doses: CD 1370 mg, EAS 2080 mg, AA 1170 mg, ACC 750 mg daily in divided doses.
  • The preferred monitoring method was by cortisol ‘day-curves’, followed by 9am cortisol and urinary free cortisol.
  • Overall, 25.3% of patients developed side effects, most commonly gastrointestinal upset and hypoadrenalism.
  • 88% of adverse events were managed as outpatients; 36% of patients treated for more than one month had ≤2 monitoring assessments and insufficient dose titration.

From MDLinx

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Utility of measurement of dexamethasone levels in the diagnostic testing for Cushing’s syndrome

Posted on June 21, 2014 by MaryO

From Day 1 of the 16th International Congress of Endocrinology and the Endocrine Society’s 96th Annual Meeting and Expo »

Chicago, IL – June 21, 2014

ST Sharma, JA Yanovski, SB Abraham, LK Nieman

Summary: Dexamethasone (dex) suppression tests (DST) are used for screening and differential diagnosis of Cushing’s syndrome (CS). The 1 mg overnight (LD) DST is used to diagnose CS, the dex-suppressed CRH stimulation (Dex-CRH) test to differentiate CS from pseudocushings (PCS) while the 8 mg overnight (HD) DST is used to differentiate Cushing’s disease (CD) from ectopic ACTH syndrome (EAS). Researchers assessed the utility of dex levels in improving the diagnostic accuracy of these tests and they found that low dex and high CBG levels can account for false positive (FP) DST and Dex-CRH test results. Use of a higher dex dose in pts with low dex levels can help decrease FP results.

Methods:

  • This is a retrospective study of patients (pts) with CS, PCS and normal volunteers (NV) who had a dex level measured as part of LDDST, HDDST or Dex-CRH test.
  • A post-dex cortisol (F) level ≥1.8 mcg/dl in the LDDST and a 15 min post-CRH F level ≥1.4 mcg/dl in the Dex-CRH test suggested CS.
  • A ≥69% suppression of F levels in HDDST indicated CD.
  • Dex levels

Results:

  • LDDST (n=77): Post-dex F was abnormal in 44 pts, 37 of these did not have CS on follow-up.
  • Proportion of pts with low dex levels was similar in those with incorrect or correct LDDST results (P=0.7).
  • Three of 5 pts with an abnormal result and low dex levels (44-117 ng/dl) had suppressed post-dex F levels after a 2 mg overnight DST. HDDST (N=56): Results were not consistent with the final diagnosis (CD or EAS) in 13 (23%) pts.
  • Of these, 5 had low dex levels (400-1220 ng/dl).
  • Proportion of pts with low dex levels was similar between those with correct and incorrect HDDST results (P=0.5).
  • HDDST in 1 pt with ACTH-dependent CS suggested EAS (28% suppression) with low dex level.
  • IPSS indicated CD.
  • After a doubled dex dose (16 mg), F levels suppressed by 76%, changing the HDDST result to CD.
  • Dex-CRH (n=139): Results were consistent with the final diagnosis in 133 pts (74 CS, 20 NV, 39 PCS).
  • Six pts with an abnormal result had dex levels
  • Of these, repeat testing with doubled dex dose (1 mg every 6 hours) in 2 pts led to higher dex levels (610, 757 ng/dl) and normal F level in one.
  • Two pts with abnormal result were on OCPs, 1 with a known high cortisol binding globulin (CBG) level.
  • None had CS on follow-up.
  • There was no correlation between dex and post-dex F levels in LDDST, 15 min post-CRH F levels in Dex-CRH test and % suppression of F post-dex in HDDST (P=NS).

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Long-term remission and recurrence rate in a cohort of Cushing’s disease: the need for long-term follow-up

Posted on June 9, 2014 by MaryO

Pituitary. 2014 Apr 19. [Epub ahead of print]


Aranda G1, Enseñat J, Mora M, Puig-Domingo M, Martínez de Osaba MJ, Casals G, Verger E, Ribalta MT, Hanzu FA, Halperin I.

Author information

 Abstract

OBJECTIVE:

Transsphenoidal surgery is the procedure of choice in Cushing disease (CD), with immediate post-operative remission rates ranging between 59 and 94 % and recurrence rates between 3 and 46 %, both depending upon the definition criteria and the duration of the follow-up. Our aim was to assess the rate of remission, recurrence and persistence of the disease after the first treatment and to identify predictors of remission in the CD population of our center.

METHODS:

Retrospective cohort study of the patients diagnosed of CD and with follow-up in our center between 1974 and 2011. We analyzed 41 patients (35 women and 6 men) with a mean age at diagnosis of 34 ± 13 years. The mean follow-up was 14 ± 10 years (range 1-37 years) and the median of follow-up period was 6.68 years.

RESULTS:

Thirty-five (85.4 %) patients underwent transsphenoidal surgery as first treatment option. Histopathological evidence of a pituitary adenoma was registered in 17 (48.5 %) patients. Thirty-two (78 %) patients achieved disease remission after the first treatment, 21 (65.6 %) of them presented disease recurrence. Persistent disease was observed in 9 (22 %) patients. Twelve (29.3 %) subjects developed post-surgical adrenal insufficiency, 7 of which (70 %) achieved stable remission. Two parameters were found to be significant predictors of remission after the first treatment: age at disease diagnosis and the development of adrenal insufficiency (cortisol ❤ μg/dl) in the immediate post-operative state.

CONCLUSIONS:

We report a high recurrence rate, at least partially attributable to the long follow-up time. Early post-surgery adrenal insufficiency predicts remission. Hypopituitarism was also very prevalent, and strongly associated with radiotherapy. These results lead us to the conclusion that CD needs a life-long strict follow-up.

PMID:

 

24748528

 

[PubMed – as supplied by publisher]

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Global Pituitary ACTH Hypersecretion (Cushing’s Disease) Therapeutics Pipeline Review 2014

Posted on June 3, 2014 by MaryO

DUBLIN–(BUSINESS WIRE)–Research and Markets (http://www.researchandmarkets.com/research/zp4qhh/pituitary_acth) has announced the addition of the “Pituitary ACTH Hypersecretion (Cushing’s Disease) – Pipeline Review, H1 2014” report to their offering.

“Pituitary ACTH Hypersecretion (Cushing’s Disease) – Pipeline Review, H1 2014”

This report provides comprehensive information on the therapeutic development for Pituitary ACTH Hypersecretion (Cushing’s Disease), complete with comparative analysis at various stages, therapeutics assessment by drug target, mechanism of action (MoA), route of administration (RoA) and molecule type, along with latest updates, and featured news and press releases. It also reviews key players involved in the therapeutic development for Pituitary ACTH Hypersecretion (Cushing’s Disease) and special features on late-stage and discontinued projects.

The report enhances decision making capabilities and help to create effective counter-strategies to gain competitive advantage. It strengthens R&D pipelines by identifying new targets and MOAs to produce first-in-class and best-in-class products.

Scope

  • The report provides a snapshot of the global therapeutic landscape of Pituitary ACTH Hypersecretion (Cushing’s Disease)
  • The report reviews key pipeline products under drug profile section which includes product description, MoA and R&D brief, licensing and collaboration details & other developmental activities
  • The report reviews key players involved in the therapeutics development for Pituitary ACTH Hypersecretion (Cushing’s Disease) and enlists all their major and minor projects
  • The report summarizes all the dormant and discontinued pipeline projects
  • A review of the Pituitary ACTH Hypersecretion (Cushing’s Disease) products under development by companies and universities/research institutes based on information derived from company and industry-specific sources
  • Pipeline products coverage based on various stages of development ranging from pre-registration till discovery and undisclosed stages
  • A detailed assessment of monotherapy and combination therapy pipeline projects
  • Coverage of the Pituitary ACTH Hypersecretion (Cushing’s Disease) pipeline on the basis of target, MoA, route of administration and molecule type
  • Latest news and deals relating related to pipeline products

Companies Involved in Therapeutics Development

  • Isis Pharmaceuticals, Inc.
  • Ipsen S.A.
  • Novartis AG
  • Corcept Therapeutics Incorporated
  • HRA Pharma, SA
  • Cortendo Invest AB
  • Orphagen Pharmaceuticals, Inc.
  • ElexoPharm GmbH

Drug Profiles

  • mifepristone
  • ketoconazole
  • pasireotide LAR
  • LCI-699
  • DG-3173
  • ISIS-GCCRRx
  • Next Generation Cortisol Inhibitor
  • Small Molecule to Inhibit CYP11B1 for Cushing Disease
  • Peptides to Antagonize ACTH Receptor for Cushing Syndrome
  • Steroidogenic Factor-1 Antagonists
  • Drug to Inhibit Melanocortin Receptor 2 for Cushing Disease

For more information visit http://www.researchandmarkets.com/research/zp4qhh/pituitary_acth

Contacts

Research and Markets
Laura Wood, Senior Manager.
press@researchandmarkets.com
U.S. Fax: 646-607-1907
Fax (outside U.S.): +353-1-481-1716
Sector: Pharmaceuticals

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