Connecting Canine and Human Health to Fight Cushing’s Disease

Cushing’s Disease is common in dogs but rare and hard to diagnose in people. That’s why University of Georgia researchers are leveraging canine treatments to find new solutions to battle the condition in humans. This collaboration between veterinary medicine and human health care is just one example of how UGA uses a Precision One Health approach to find and tailor new medical treatments for people and animals.

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Imagine your body as a well-run newsroom. Each day, the editor-in-chief—in this case, the pituitary gland—provides assignments, keeping everything running smoothly. One day, however, the editor’s role is usurped by a rogue reporter who declares breaking news nonstop, flooding the newsroom with bulletins and sending everyone into overdrive.

This is a bit like Cushing’s Disease. The rogue reporter is a tiny, usually benign tumor, the stress bulletins cortisol. The newsroom—your body—responds with metabolic fluctuations, burnt out muscles, emotional distress, and more. Over the long haul, Cushing’s Disease can cause lasting deterioration of the body: osteoporosis, muscle weakness, high blood pressure and heart disease, diabetes, memory and mood issues, fatigue, and more.

It’s a common disease and easier to detect in canines. In people, however, it is rare and difficult to diagnose. University of Georgia researchers are leveraging canine treatments to find new solutions to battle the condition in humans.

This collaboration between veterinary medicine and human health is just one example of how UGA uses a Precision One Health approach to find and tailor new medical treatments for people and animals.

From https://research.uga.edu/news/connecting-canine-human-health-to-fight-cushings-disease/

Severe Trauma May Damage The Brain as Well as the Psyche

NOTE: This is only a portion of the article.  Read the entire post at http://www.nytimes.com/1995/08/01/science/severe-trauma-may-damage-the-brain-as-well-as-the-psyche.html?pagewanted=all

Cortisol is a major means the body uses, with adrenaline, to arouse itself so quickly; its action, for example, triggers an increase in blood pressure and mobilizes energy from fat tissue and the liver.

“The dark side of this picture is the neurological effects,” said Dr. Sapolsky. “It’s necessary for survival, but it can be disastrous if you secrete cortisol for months or years on end. We’ve known it could lead to stress-exacerbated diseases like hypertension or adult onset diabetes. But now we’re finding the hippocampus is also damaged by these secretions.”

Studies in animals show that when glucocorticoids are secreted at high levels for several hours or days, there is a detectable effect on memory, though no neuronal death. But with sustained release from repeated stress, “it eventually kills neurons in the hippocampus,” said Dr. Sapolsky. “This has been shown solidly in rats, with the cell biology well understood.”

A parallel effect has long been known among patients with Cushing’s disease, a hormonal condition in which tumors in the adrenal or pituitary glands or corticosteroid drugs used for a prolonged time cause the adrenal glands to secrete high levels of a hormone called ACTHm and of cortisol. Such patients are prone to a range of diseases “in any organ with stress sensitivity,” including diabetes, hypertension and suppression of the immune system, said Dr. Sapolsky.

Cushing’s patients also have pronounced memory problems, especially for facts like where a car was parked. “The hippocampus is essential for transferring such facts from short-term to long-term memory,” said Dr. Sapolsky.

In 1993, researchers at the University of Michigan reported that magnetic resonance imaging had shown an atrophy and shrinkage of the hippocampus in patients with Cushing’s disease; the higher their levels of cortisol, the more shrinkage.

In an apparent paradox, low levels of cortisol in post-trauma victims were found in a separate research report, also in the July issue of The American Journal of Psychiatry. Dr. Rachel Yehuda, a psychologist at Mount Sinai Medical School in New York City, found the lower levels of cortisol in Holocaust survivors who had been in concentration camps 50 years ago and who still had post-traumatic symptoms.

“There are mixed findings on cortisol levels in trauma victims, with some researchers finding very high levels and others finding very low levels,” said Dr. Sapolsky. “Biologically speaking, there may be different kinds of post-traumatic stress.”

In a series of studies, Dr. Yehuda has found that those post-trauma patients who have low cortisol levels also seem to have “a hypersensitivity in cell receptors for cortisol,” she said. To protect itself, the body seems to reset its cortisol levels at a lower point.

The low cortisol levels “seem paradoxical, but both too much and too little can be bad,” said Dr. Yehuda. “There are different kinds of cells in various regions of the hippocampus that react to cortisol. Some atrophy or die if there is too little cortisol, some if there is too much.”

Dr. Yehuda added, “In a brain scan, there’s no way to know exactly which cells have died.”

To be sure that the shrinkage found in the hippocampus of trauma victims is indeed because of the events they suffered through, researchers are now turning to prospective studies, where before-and-after brain images can be made of people who have not yet undergone trauma, but are at high risk, or who have undergone it so recently that cell death has not had time to occur.

Dr. Charney, for example, is planning to take M.R.I. scans of the brains of emergency workers like police officers and firefighters and hopes to do the same with young inner-city children, who are at very high risk of being traumatized over the course of childhood and adolescence. Dr. Pitman, with Dr. Yehuda, plans a similar study of trauma victims in Israel as they are being treated in emergency rooms.

Dr. Yehuda held out some hope for people who have suffered through traumatic events. “It’s not necessarily the case that if you’ve been traumatized your hippocampus is smaller,” she said. She cited research with rats by Dr. Bruce McEwen, a neuroscientist at Rockefeller University, showing that atrophied dendritic extensions to other cells in the hippocampus grew back when the rats were given drugs that blocked stress hormones.

Dr. Sapolsky cited similar results in patients with Cushing’s disease whose cortisol levels returned to normal after tumors were removed. “If the loss of hippocampal volume in trauma victims is due to the atrophy of dendrites rather than to cell death, then it is potentially reversible, or may be so one day,” he said.

NOTE: This is only a portion of the article.  Read the entire post at http://www.nytimes.com/1995/08/01/science/severe-trauma-may-damage-the-brain-as-well-as-the-psyche.html?pagewanted=all

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

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

Decreased prefrontal functional brain response in women with Cushing’s syndrome in remission

endo2016

 

April 03, 2016

Poster Session: Cushing’s Syndrome and Primary Adrenal Disorders

Decreased prefrontal functional brain response in women with Cushing’s syndrome in remission

O Ragnarsson, A Stomby, P Dahlqvist, JA Evang, M Ryberg, T Olsson, J Bollerslev, L Nyberg, G Johannsson

Summary: Neuropsychiatric symptoms including impairment of memory, attention, and executive function are important features of Cushing’s syndrome (CS). Notably, patients with CS in remission commonly demonstrate residual cognitive dysfunction, which has been suggested to be linked to incomplete recovery of neuronal function. Researchers sought to assess whether functional brain responses are altered during cognitive testing in patients with CS in remission. During episodic memory, women with CS in long-term remission have reduced functional brain responses in the prefrontal cortex and in the hippocampus.

Methods:

  • Included in this study were 19 women previously treated for CS (14 Cushing’s disease and 5 cortisol producing adrenal adenomas) and 19 controls, matched for age, gender, and education.
  • The median (interquartile range) remission time was 7 (6-10) years.
  • Researchers studied brain activity with functional magnetic resonance imaging during an episodic-memory face-name task.
  • The primary regions of interest were the prefrontal cortex and the hippocampus.
  • A voxel wise comparison of functional brain responses in patients and controls was performed, and an uncorrected P < 0.001 was considered significant.

Results:

  • During memory encoding, patients displayed lower functional brain responses in the left and right prefrontal gyrus (Brodmann areas [BA] 44, 45, and 46) as well as the right inferior occipital gyrus (BA 18) compared to controls (P < 0.001 for all).
  • Patients displayed lower functional brain responses in several brain areas including the prefrontal, parietal, occipital, and cerebellar cortices bilaterally during memory retrieval.
  • The most predominant difference was found in the right prefrontal cortex (BA 46 and 48; P < 0.001).
  • Reduced functional response in left dorsolateral prefrontal cortex was seen for patients during both encoding and retrieval.
  • Researchers compared the functional brain responses in four hippocampal clusters that were significantly activated during memory encoding among all participants (P < 0.05, FDR).
  • Patients had a trend toward lower functional brain responses in the left anterior hippocampus compared to controls (P=0.05).

From http://www.mdlinx.com/endocrinology/conference-abstract.cfm/ZZ6AA1CEC190F5428EA690616DAA054518/56991/?utm_source=confcoveragenl&utm_medium=newsletter&utm_content=abstract-list&utm_campaign=abstract-ENDO2016&nonus=0

Irreversible Effects of Previous Cortisol Excess on Cognitive Functions in Cushing’s Disease | Laika’s MedLibLog

Irreversible Effects of Previous Cortisol Excess on Cognitive Functions in Cushing’s Disease | Laika’s MedLibLog.

If we listen to Cushing patients, who are “cured” and have traded Cushing’s disease for Addison’s disease, we notice that they feel better after their high levels of cortisol have normalized, but not fully cured (see two examples of ex-Cushing patients with longlasting if not irreversible health) problems in my previous post here. [added 2010-04-17)

To realize how this affects daily life, I recommend to read the photo-blog 365 days with Cushing by Robin (also author of Survive the Journey). Quite a few of her posts deal with the continuous weakness (tag muscle atrophy), tiredness (tag fatigue), problems with (short-term) memory (see tag memory)  or both (like here and here).

Scientifically the question is to which extent ex-Cushing patients score worse than other healthy individuals or chronically ill people and, if so, whether this can be attributed to the previous high levels of glucocorticoids….

via Irreversible Effects of Previous Cortisol Excess on Cognitive Functions in Cushing’s Disease | Laika’s MedLibLog.