Monday, April 22, 2013

Treating Nelson's Syndrome after BLA









Sustained improvements in plasma ACTH and clinical status in a patient with Nelson's syndrome treated with pasireotide LAR, a multireceptor somatostatin analog

Laurence Katznelson, MD
Stanford School of Medicine, Departments of Neurosurgery and Medicine, 875 Blake Wilbur Dr. MC 5821, Stanford, CA 94305-5821

Address all correspondence and requests for reprints to: Laurence Katznelson, MD, Stanford School of Medicine, Departments of Neurosurgery and Medicine, 875 Blake Wilbur Dr. MC 5821, Stanford, CA 94305-5821lkatznelson@stanford.edu, tel: (650) 721-1020, fax: (650) 736-8100.


Abstract

Context: Nelson's syndrome refers to aggressive pituitary corticotroph adenoma growth after bilateral adrenalectomy (BLA) for treatment of Cushing's disease (CD). Pasireotide, a novel somatostatin analog, has been effective in treating CD. Here, the first case report of a patient with Nelson's syndrome treated with pasireotide is presented.
Case Presentation: A 55 yo female was diagnosed with CD in 1973 at age 15 y and underwent BLA 1 year later. She subsequently developed Nelson's syndrome and underwent multiple surgeries, and radiotherapy for adenoma growth.
Following presentation with ocular pain, third cranial nerve palsy, and finding of suprasellar tumor enlargement with hemorrhage, she began pasireotide LAR 60 mg/28 days IM. At baseline, fasting plasma ACTH was 42,710 pg/mL (normal, 5–27) and fasting plasma glucose was 98 mg/dL. After 1 month, ACTH declined to 4,272 pg/mL and has remained stable over 19 months of follow up. Hyperpigmentation progressively improved. MRI scans show reduction in the suprasellar component. Fasting plasma glucose increased to 124 mg/dL and she underwent diabetes management.
Evidence Acquisition and Synthesis:In this clinical case seminar, the current understanding of the treatment of Nelson's syndrome, including use of pasireotide in Cushing's disease, are summarized.
Conclusion: A case of Nelson's syndrome with clinically significant and dramatic biochemical and clinical responses to pasireotide administration is reported. Hyperglycemia was noted following pasireotide administration. Pasireotide may represent a useful tool in the medical management of Nelson's syndrome. Further study of the potential benefits and risks of pasireotide in this population is necessary.
Received February 22, 2013.
Accepted March 25, 2013.
Copyright © 2013 by The Endocrine Society

Cushing’s syndrome increased risk for coronary arterial atherosclerosis

Ok. Here is a new article describing cardiovascular damage that Cushing's causes.

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Cushing's syndrome increased risk for coronary arterial atherosclerosis

Neary NM. Clin Endocrinol Metab. 2013;doi:10.1210/jc.2012-3754.

  • April 19, 2013

In a recent study supported by the NIH, researchers determined that patients with Cushing's syndrome have a greater risk for developing coronary arterial atherosclerosis, increasing their rate of cardiovascular morbidity. These findings were published in theJournal of Clinical Endocrinology & Metabolism.

The researchers conducted a prospective case-control study of 15 consecutive patients with adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome who were matched with 15 controls (aged 32 to 66 years) with at least one risk factor for cardiac disease (ie, diabetes, hypertension, hyperlipidemia, family history of early-onset coronary artery disease and previous or current smoking).

Researchers used a multidetector CT (MDCT) coronary angiogram scan to measure calcified and noncalcified coronary plaque volume and Agatston scores. Additional variables included fasting lipids, BP, history of hypertension or diabetes and 24-hour urine free cortisol excretion.

According to data, patients with Cushing's syndrome had significantly greater noncalcified plaque volume and Agatston scores compared with controls (noncalcified plaque volume median [interquartile ranges]: 49.5 vs. 17.9, P<.001; Agatston score: 70.6 vs. 0, P<.05).

Patients with Cushing's syndrome also demonstrated higher systolic (143 mm Hg) and diastolic (86 mm Hg) BP compared with controls (systolic: 134 mm Hg, diastolic: 76 mm Hg).

The limitations of the study include the small cohort of patients and potential selection bias due to ectopic ACTH secretion. However, the researchers wrote that these findings demonstrate a significant difference between the two groups included in the study.

"Overall, the findings point to the possible causes of cardiovascular morbidity in patients treated with exogenous steroids and indicate the need for further studies of that population," they wrote.

Disclosure: The researchers report no relevant financial disclosures.

PERSPECTIVE
Alice C. Levine, MD

Alice C. Levine

  • It has long been recognized that endogenous hypercortisolism (Cushing's syndrome) and administration of supraphysiologic doses of glucocorticoids are associated with increased mortality, primarily due to cardiovascular disease. Excess glucocorticoids induce all of the features of the metabolic syndrome including obesity with central weight gain, hypertension, impaired glucose tolerance/diabetes mellitus and dyslipidemia, all of which increase cardiovascular risk. In this small but well-designed study, the authors attempt to determine whether excess glucocorticoids have a direct adverse effect on the coronary vasculature. Utilizing multidetector computerized tomographic (MDCT) coronary angiography, a validated noninvasive method of assessing calcified and noncalcified coronary plaques, they compared measurements of coronary plaques (Agatston score) in 15 patients with ACTH-dependent Cushing's syndrome (CS) vs. 15 age-, sex- and body weight-matched controls with at least one risk factor for cardiac disease. They found significantly greater coronary calcifications and noncalcified coronary plaque volumes in patients with active or previous hypercortisolism.

    There are obvious limitations to the study; most notably the small sample size, the predominance of patients with CS due to ectopic ACTH (14/15) and significantly more hypertension in the CS vs. the control group. However, other than the HTN, the groups were well-matched and there was no statistical difference in the Framingham risk scores between groups. This is the first study to demonstrate direct effects of CS on coronary plaque burden.

    The findings, while unsurprising, underscore several important features of CS which endocrinologists need to consider. Firstly, as there were no statistical differences in plaque burden in patients with CS who were eucortisolemic (4/15) vs. those who were hypercortisolemic (11/15) at the time of study, the effects of CS on the coronary vasculature may persist even after biochemical cure. Many previous studies in larger cohorts have similarly demonstrated that the adverse effects of high glucocorticoids on cardiovascular, metabolic, psychiatric and neurocognitive function may be only partially reversible with disease remission. Secondly, even adjusting for all the confounding variables, hypercortisolism seems to be an independent risk factor for the development of coronary artery disease. The possible mechanisms underlying this observation are discussed and include increases in prothrombotic factors, circulating levels of vascular endothelial growth factor (VEGF) and angiogenesis. It is also plausible that cortisol increases atherosclerosis through the mineralocorticoid rather than the glucocorticoid receptor, suggesting the possibility of treating this particular deleterious effect of hypercortisolism with a mineralocorticoid-receptor blocker such as spironolactone.

    Within the CS group, no significant correlations were observed between the coronary plaque volumes and the duration of CS or urinary free cortisol (UFC) either at presentation or at the time of MDCT. Although this lack of correlation may also be attributable to the small sample size, it is well known that the onset of Cushing's syndrome is often insidious and it is impossible to pinpoint the exact duration of the abnormality in most patients. This study's finding of direct, adverse and possibly irreversible effects of hypercortisolism on the coronary vasculature should make endocrinologists even more vigilant in diagnosing and treating the disease as early as possible in its course.

    • Alice C. Levine, MD
    • Professor of medicine, division of endocrinology, diabetes and bone diseases
      Co-Director of The Adrenal Center
      Icahn School of Medicine
      Mount Sinai, New York, NY
  • Disclosures: Levine reports no relevant financial disclosures.
http://www.healio.com/endocrinology/adrenal/news/online/%7B23128043-7B9B-4EDC-85E1-3D98F0BD48E5%7D/Cushings-syndrome-increased-risk-for-coronary-arterial-atherosclerosis-

Long-term elevated cortisol may be important cardiovascular risk factor

Not about Cushing's exactly, but this article does underscore cardiovascular risk that Cushies face, particularly why diagnosis is critically important to prevent associated diseases.

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Diabetes / Endocrinology News

  • Hair Analysis Can Show Elevated Cortisol Levels

    Hair analysis reveals longer-term cortisol levels; may be helpful in CV risk assessment



    Elevated levels of the stress hormone cortisol, detectable in hair samples, is associated with increased risk of cardiovascular disease, according to a study published online April 17 in the Journal of Clinical Endocrinology & Metabolism.

FRIDAY, April 19 (HealthDay News) -- Elevated levels of the stress hormone cortisol, detectable in hair samples, is associated with increased risk of cardiovascular disease, according to a study published online April 17 in the Journal of Clinical Endocrinology & Metabolism.

Laura Manenschijn, M.D., from the Erasmus Medical Center in the Netherlands, and colleagues randomly selected 283 community-dwelling elderly participants (median age, 75 years) from a population-based cohort. Three centimeter hair segments were used to measure cortisol.

The researchers found that hair cortisol levels were significantly lower in women than in men (21.0 pg/mg hair versus 26.3 pg/mg hair). There was a significantly increased cardiovascular risk associated with high hair cortisol levels (odds ratio, 2.7) as well as a significantly increased risk of type 2 diabetes mellitus (odds ratio, 3.2). Hair cortisol levels were not found to be associated with non-cardiovascular diseases.

"The increased cardiovascular risk we found is equivalent to the effect of traditional cardiovascular risk factors, suggesting that long-term elevated cortisol may be an important cardiovascular risk factor," the authors write.


http://www.pri-med.com/pmo/MedicalNewsDetail.aspx?id=9128&topic=mc-topic::KA8A584VY&printview=true&tabIndex=



High Long-Term Cortisol Levels, Measured in Scalp Hair, Are Associated With a History of Cardiovascular Disease


 Authors
  1. E. F. C. van Rossum
  1. Department of Internal Medicine (L.M., J.W.K., E.F.C.v.R.), Erasmus MC, 3000 CA Rotterdam, The Netherlands; Department of Epidemiology and Biostatistics (L.S., N.M.v.S., S.v.d.P., G.M.E.E.P., P.L.), EMGO Institute for Health and Care Research, VU University Medical Center, 1081 HZ Amsterdam, The Netherlands; University of Queensland (G.M.E.E.P.), Schools of Human Movement Studies and Population Health, Brisbane 4029, Queensland, Australia; and Department of Endocrinology (P.L.), VU University Medical Center, 1081 HZ Amsterdam, The Netherlands
  1. Address all correspondence and requests for reprints to: Laura Manenschijn, Erasmus MC, Department of Internal Medicine, Room Ee-542, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. E-mail: l.manenschijn@erasmusmc.nl.

Abstract

Background: Stress is associated with an increased incidence of cardiovascular disease. The impact of chronic stress on cardiovascular risk has been studied by measuring cortisol in serum and saliva, which are measurements of only 1 time point. These studies yielded inconclusive results. The measurement of cortisol in scalp hair is a novel method that provides the opportunity to measure long-term cortisol exposure. Our aim was to study whether long-term cortisol levels, measured in scalp hair, are associated with cardiovascular diseases.

Methods: A group of 283 community-dwelling elderly participants were randomly selected from a large population-based cohort study (median age, 75 y; range, 65–85 y). Cortisol was measured in 3-cm hair segments, corresponding roughly with a period of 3 months. Self-reported data concerning coronary heart disease, stroke, peripheral arterial disease, diabetes mellitus, and other chronic noncardiovascular diseases were collected.

Results: Hair cortisol levels were significantly lower in women than in men (21.0 vs 26.3 pg/mg hair; P < .001). High hair cortisol levels were associated with an increased cardiovascular risk (odds ratio, 2.7; P = .01) and an increased risk of type 2 diabetes mellitus (odds ratio, 3.2; P = .04). There were no associations between hair cortisol levels and noncardiovascular diseases.

Conclusions: Elevated long-term cortisol levels are associated with a history of cardiovascular disease. The increased cardiovascular risk we found is equivalent to the effect of traditional cardiovascular risk factors, suggesting that long-term elevated cortisol may be an important cardiovascular risk factor.

  • Received October 19, 2012.
  • Accepted February 22, 2013.