Lower health-related quality of life observed in patients with Addison’s disease, Cushing’s syndrome

Patients with hypothalamic-pituitary-adrenal axis dysregulations report health-related quality of life that is far lower than that of the general population, according to findings of a prospective study.

“In most centers, both patients with adrenal deficiency and patients with Cushing’s syndrome are managed by the same team,” Charlotte De Bucy, of the Center for Rare Adrenal Diseases at Cochin Hospital in Paris, and colleagues wrote. “Despite the usual perception that both types of diseases alter quality of life, few studies have similarly investigated the impact of cortisol dysregulations on [health-related quality of life]. Such studies are important, however, to identify meaningful differences that would be important to consider to improve management and outcome.”

De Bucy and colleagues analyzed data from 343 patients with Addison’s disease or Cushing’s syndrome followed in routine practice at a single center in France between September 2007 and April 2014 (78% women; mean age, 48 years; mean length of time since diagnosis, 7.8 years; 61% married). All participants completed the short-form health survey (SF-36), a survey of health-related quality-of-life measures and the 12-item general health questionnaire (GHQ-12), a measure of psychological well-being or distress. Questionnaires were completed at baseline and at 6, 12, 24 and 36 months. Patients with Cushing’s syndrome were also assessed for cortisol status at baseline and at follow-up evaluations.

Within the cohort, 206 had Cushing’s syndrome of pituitary origin, 91 had Cushing’s syndrome of adrenal origin and 46 patients had Addison’s disease; 16% were included in the study before any treatment was initiated.

Researchers found that mean standard deviation scores for psychological and physical dimensions of the SF-36 were “well below” those of the general population, but diagnosis, cortisol status and time since treatment initiation all influenced individual scores. Cushing’s syndrome of pituitary origin was associated with worse health-related quality of life, especially for physical functioning, social functioning and mental health. In Cushing’s syndrome, health-related quality of life was generally worse during periods of hypercortisolism, but scores for these patients were lower than those of patients with Addison’s disease even during periods of hypocortisolism or eucortisolism, according to the researchers.

“The differences were particularly large for physical functioning and role-physical subscales,” the researchers wrote.

They also found that mental health scores for patients with Cushing’s syndrome decreased during periods of hypocortisolism, whereas other adrenal conditions were associated with higher mental health scores.

More than half of patients, regardless of diagnosis and cortisol status, had psychological distress requiring attention, according to the GHQ-12 survey.

“Our findings are important for clinical practice,” the researchers wrote. “The consequences of cortisol dysregulation on [health-related quality of life] should be considered in the management of adrenal insufficiency and even more (in) Cushing’s syndrome patients, and these consequences can be long term, affecting apparently cured patients. Early information on these consequences might be helpful for patients who often perceive a poor quality of life as the result of inadequate disease control or treatment. Even if this possibility exists, knowing that adrenal diseases have long-lasting effects on [health-related quality of life] may be helpful for patients to cope with them.” – by Regina Schaffer

Disclosure: L'association Surrénales supported this study. The researchers report no relevant financial disclosures.

From http://www.healio.com/endocrinology/adrenal/news/in-the-journals/%7B842655ce-e710-4476-a3c2-2909b06434ed%7D/lower-health-related-quality-of-life-observed-in-patients-with-addisons-disease-cushings-syndrome

Cushing’s Disease and Idiopathic Intracranial Hypertension

Gabriel Zada, Amir Tirosh, Ursula B. Kaiser, Edward R. Laws and Whitney W. Woodmansee

Department of Neurosurgery (G.Z., E.R.L.) and Division of Endocrinology, Diabetes, and Hypertension (A.T., U.B.K., W.W.W.), Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115

Address all correspondence and requests for reprints to: Gabriel Zada, M.D., 15 Francis Street, PBB3, Boston, Massachusetts 02115. E-mail: gzada@usc.edu.

Abstract

Case Illustration: A 33-yr-old woman with Cushing’s disease underwent successful surgical resection of a pituitary adenoma and developed IIH 11 months later after inadvertent withdrawal of oral glucocorticoids.

Methods: A review of the literature was conducted to identify previous studies pertaining to IIH in association with neuroendocrine disease, focusing on reports related to HPA axis dysfunction.

Results: A number of patients developing IIH due to a relative deficiency in glucocorticoids, after surgical or medical management for Cushing’s disease, withdrawal from glucocorticoid replacement, or as an initial presentation of Addison’s disease, have been reported. Hypotheses regarding the underlying pathophysiology of IIH in this context and, in particular, the role of cortisol and its relationship to other neuroendocrine and inflammatory mediators that may regulate the homeostasis of cerebrospinal fluid production and absorption are reviewed.

Conclusion: In a subset of patients, dysfunction of the HPA axis appears to play a role in the development of IIH. Hormonal control of cerebrospinal fluid production and absorption may be regulated by inflammatory mediators and the enzyme 11ß-hydroxysteroid dehydrogenase type 1. Further study of neuroendocrine markers in the serum and cerebrospinal fluid may be an avenue for further research in IIH.

Read the entire article at http://jcem.endojournals.org/content/95/11/4850.full

Disturbances of the hypothalamic-pituitary-adrenal axis and plasma electrolytes during experimental sepsis.

Michael A Flierl, Daniel Rittirsch, Sebastian Weckbach, Markus Huber-Lang, Kyros Ipaktchi, Peter A Ward and Philip F Stahel

 

Annals of Intensive Care 2011, 1:53 doi:10.1186/2110-5820-1-53

Published: 30 December 2011

 

Background

Sepsis continues to be a poorly understood syndrome with a high mortality rate. While we are beginning to decipher the intricate interplay of the inflammatory response during sepsis, the precise regulation of the hypothalamic-pituitary-adrenal (HPA) axis and its impact on electrolyte homeostasis during sepsis remains incompletely understood.

Methods

Sepsis was induced in adult male Sprague-Dawley rats by cecal ligation and puncture (CLP). Plasma samples were obtained as a function of time (6-48 hrs) after CLP and compared to healthy animals (neg ctrl). Samples were analyzed for adrenocorticotropin (ACTH), corticosterone, and aldosterone levels as well as concentrations of sodium (Na+), potassium (K+), chloride (Cl-) and magnesium (Mg2+).

Results

ACTH levels were found to be significantly reduced 6-24 hrs after CLP in comparison to baseline levels and displayed gradual recovery during the later course (24-48 hrs) of sepsis. Plasma corticosterone concentrations exhibited a bell-shaped response, peaking between 6 and 12 hrs followed by rapid decline and concentrations below negative control levels 48 hrs after injury. Aldosterone levels in septic animals were continuously elevated between 6 and 48 hrs. While plasma Na+ levels were found to be persistently elevated following CLP, levels of K+, Cl- and Mg2+ were significantly reduced as a function of time and gradually recovered during the later course of sepsis.

Conclusion

CLP-induced sepsis resulted in dynamic changes of ACTH, corticosterone and aldosterone levels. In addition, electrolyte levels showed significant disturbances following CLP. These electrolyte perturbations might be evoked by a downstream effect or a dysfunctional HPA-axis response during sepsis and contribute to severe complications during sepsis.

 

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

From http://www.annalsofintensivecare.com/content/1/1/53/abstract

 

 

A Pill That Stops Stress In Your Brain Before You Feel It

Stress makes many of us miserable — but it can also kill you. Besides just causing horrible anxiety and depression, the physiological basis for stress has also been linked to diseases as varied as obesity, postpartum depression, Cushing's syndrome, epilepsy, and osteoporosis. But what if we could just turn your brain's stress response off?

Now, researchers from Tufts claim to have pinpointed the way that stress hormones hit specific receptors in your brain — and they've even been able to block them. This could lead to the next great psychopharmaceutical breakthrough.

The Tufts researchers discovered that stress pathways are activated by neurosteroids acting on corticotrophin-releasing hormone neurons in what's known as the Hypothalamus-Pituitary-Adrenal axis. By blocking the synthesis of the neurosteroids, they stopped the elevation of corticosterone, and prevented anxiety in mice.

"We have identified a novel mechanism regulating the body's response to stress by determining that neurosteroids are required to mount the physiological response to stress. Moreover, we were able to completely block the physiological response to stress as well as prevent stress-induced anxiety," said author Jamie Maguire, PhD.

Now the team is focusing on modulating the neuroreceptors to treat some of the diseases that accompany stress — be they depression, anxiety, or epilepsy.

From http://io9.com/5867762/a-pill-that-stops-stress-in-your-brain-before-you-feel-it