Long-term Cognitive Effects of Glucocorticoid Excess in Cushing’s Syndrome

Posted on June 7, 2016 by MaryO

Psychoneuroendocrinology. 2016 Mar;65:26-33. doi: 10.1016/j.psyneuen.2015.11.020. Epub 2015 Nov 30.

Forget H1, Lacroix A2, Bourdeau I2, Cohen H3.

Abstract

CONTEXT AND OBJECTIVE:

We previously found that patients with Cushing’s syndrome (CS) scored lower than controls in several domains of cognitive function and that correction of hypercortisolism is not necessarily correlated with short-term improvement in intellectual performance. Here, we examined the long-term outcome in patients treated for CS by assessing the extent to which the detrimental effects of glucocorticoid (GC) excess on cognition can be reversed three years after corrective surgery.

DESIGN:

A battery of neuropsychological tests, including tests of attention, visuospatial processing, learning and memory, and executive functioning were administered pre-treatment and 12, 24 and 36 months post-treatment.

PATIENTS AND CONTROL SUBJECTS:

We included 18 patients with endogenous CS recruited before surgical treatment and 18 controls matched for age, sex and education.

RESULTS:

CS patients performed worse than controls on tests of attention, executive functioning and nonverbal aspects of memory. Moreover, at 36 months following eucortisolism, executive function performance and, to a lesser extent, attention tasks showed limited change compared to pre-treatment testing.

CONCLUSION:

Chronic hypercortisolism is accompanied by a deleterious impact on aspects of cognitive function. This negative effect on attention, executive performance and nonverbal memory seen in patients with CS suggests a differential effect of excess GCs upon different brain areas and networks. This influence persists years after the return to normal cortisol secretion levels.

Copyright © 2015 Elsevier Ltd. All rights reserved.

KEYWORDS:

Attention; Cognitive functions; Endogenous Cushing’s syndrome; Glucocorticoids; Hypercortisolism; Memory

PMID:
26708069
[PubMed – in process]

From http://www.ncbi.nlm.nih.gov/pubmed/26708069

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Masked renal dysfunction in patients with adrenal Cushing’s syndrome manifested by adrenalectomy

Posted on May 31, 2016 by MaryO

INTRODUCTION AND OBJECTIVES

Many patients with primary aldosteronism (PA) exhibit a decline in renal function after adrenalectomy. Excessive aldosterone secretion causes glomerular hyperfiltration, and cancellation of this excessive secretion manifests the masked renal dysfunction. Considering the mineralocorticoid effect of cortisol as with aldosterone, excessive cortisol secretion may also mask the renal dysfunction of patients with adrenal Cushing’s syndrome (CS). However, postoperative changes in renal function in patients with CS have not been evaluated. We evaluated changes in renal function after adrenalectomy in patients with functional adrenal tumor.

METHODS

A total of 164 consecutive patients underwent adrenalectomy for unilateral functional adrenal tumor at our institution between January 2004 and October 2014. Of the 164 patients, we retrospectively analyzed 118 patients (PA/CS/subclinical Cushing’s syndrome [SCS]/pheochromocytoma [PCC]: n = 51/21/13/33, respectively) who were followed up for over 6 months and whose change in renal function was evaluable. Laboratory data, including baseline hormone levels before medical treatment, were collected from medical records. Estimated glomerular filtration rate (eGFR) values were obtained using the 3-variable Japanese equation. Renal dysfunction was defined as a 20% reduction in eGFR from baseline to within 3 times average during the 6 months post-operation. The change in eGFR before and after the operation was analyzed in each adrenal tumor.

RESULTS

The mean change in eGFR before and after the operation was -14% (range, -55%-18%) in patients with PA, -9% (-48%-23%) in patients with CS, -2% in patients with SCS, and -2% in patients with PCC. The eGFR decline in patients with PA and CS was significant (p < 0.0001 and p = 0.0171, respectively), while there was no significant change in patients with SCS and PCC. After the operation, 39% (20/51) and 24% (5/21) of patients with PA and CS manifested renal dysfunction, respectively, while none of the patients with SCS and PCC manifested renal dysfunction. Preoperative renal function was not correlated with manifested renal dysfunction. Multivariate analysis identified older age and higher levels of plasma aldosterone concentration as independent predictors of renal dysfunction manifestation in patients with PA, while no clinical predictor was identified in patients with CS.

CONCLUSIONS

This is the first report that has shown a decline in eGFR after adrenalectomy in patients with CS. Possible masked renal damage should be considered in patients with CS as well as PA.

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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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Addison’s disease: Primary adrenal insufficiency

Posted on May 2, 2016 by MaryO

Abstract

Adrenal insufficiency, a rare disorder which is characterized by the inadequate production or absence of adrenal hormones, may be classified as primary adrenal insufficiency in case of direct affection of the adrenal glands or secondary adrenal insufficiency, which is mostly due to pituitary or hypothalamic disease.

Primary adrenal insufficiency affects 11 of 100,000 individuals. Clinical symptoms are mainly nonspecific and include fatigue, weight loss, and hypotension. The diagnostic test of choice is dynamic testing with synthetic ACTH.

Patients suffering from chronic adrenal insufficiency require lifelong hormone supplementation. Education in dose adaption during physical and mental stress or emergency situations is essential to prevent life-threatening adrenal crises.

Patients with adrenal insufficiency should carry an emergency card and emergency kit with them.

From http://www.ncbi.nlm.nih.gov/pubmed/27129928

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A Single-Center 10-Year Experience with Pasireotide in Cushing’s Disease: Patients’ Characteristics and Outcome

Posted on April 30, 2016 by MaryO

Pasireotide is the first pituitary-directed drug approved for treating patients with Cushing’s disease (CD). Our 10-year experience with pasireotide in CD is reported here.

Twenty patients with de novo, persistent, or recurrent CD after pituitary surgery were treated with pasireotide from December 2003 to December 2014. Twelve patients were treated with pasireotide in randomized trials and 8 patients with pasireotide sc (Signifor®; Novartis AG, Basel, Switzerland) in clinical practice. The mean treatment duration was 20.5 months (median 9 months; range, 3-72 months).

Urinary free cortisol (UFC) levels mean percentage change (± SD) at last follow-up was-40.4% (± 35.1; range, 2-92%; median reduction 33.3%) with a normalization rate of 50% (10/20). Ten patients achieved sustained normalized late night salivary cortisol (LNSC) levels during treatment. LNSC normalization was associated with UFC normalization in 7/10 patients. Serum cortisol and plasma ACTH significantly decreased from baseline to last follow-up. Body weight decrease and blood pressure improvement during pasireotide treatment were independent from UFC response. Glucose profile worsening was observed in all patients except one. The frequency of diabetes mellitus increased from 40% (8/20) at baseline to 85% (17/20) at last follow-up requiring initiation of medical treatment only in 44% of patients.

Pasireotide treatment was associated with sustained biochemical and clinical benefit in about 60% of CD patients. Glucose profile alteration is a frequent complication of pasireotide treatment; however, it seems to be easy to manage with diet and lifestyle intervention in almost half of the patients.

From http://www.ncbi.nlm.nih.gov/pubmed/27127913

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