What Genes are Related to Cushing’s Disease?

Posted on July 29, 2015 by MaryO

genetic

 

The genetic cause of Cushing disease is often unknown. In only a few instances, mutations in certain genes have been found to lead to Cushing disease. These genetic changes are called somatic mutations. They are acquired during a person’s lifetime and are present only in certain cells. The genes involved often play a role in regulating the activity of hormones.

Cushing disease is caused by an increase in the hormone cortisol, which helps maintain blood sugar levels, protects the body from stress, and stops (suppresses) inflammation. Cortisol is produced by the adrenal glands, which are small glands located at the top of each kidney. The production of cortisol is triggered by the release of a hormone called adrenocorticotropic hormone (ACTH) from the pituitary gland, located at the base of the brain. The adrenal and pituitary glands are part of the hormone-producing (endocrine) system in the body that regulates development, metabolism, mood, and many other processes.

Cushing disease occurs when a noncancerous (benign) tumor called an adenoma forms in the pituitary gland, causing excessive release of ACTH and, subsequently, elevated production of cortisol. Prolonged exposure to increased cortisol levels results in the signs and symptoms of Cushing disease: changes to the amount and distribution of body fat, decreased muscle mass leading to weakness and reduced stamina, thinning skin causing stretch marks and easy bruising, thinning of the bones resulting in osteoporosis, increased blood pressure, impaired regulation of blood sugar leading to diabetes, a weakened immune system, neurological problems, irregular menstruation in women, and slow growth in children. The overactive adrenal glands that produce cortisol may also produce increased amounts of male sex hormones (androgens), leading to hirsutism in females. The effect of the excess androgens on males is unclear.

Most often, Cushing disease occurs alone, but rarely, it appears as a symptom of genetic syndromes that have pituitary adenomas as a feature, such as multiple endocrine neoplasia type 1 (MEN1) or familial isolated pituitary adenoma (FIPA).

Cushing disease is a subset of a larger condition called Cushing syndrome, which results when cortisol levels are increased by one of a number of possible causes. Sometimes adenomas that occur in organs or tissues other than the pituitary gland, such as adrenal gland adenomas, can also increase cortisol production, causing Cushing syndrome. Certain prescription drugs can result in an increase in cortisol production and lead to Cushing syndrome. Sometimes prolonged periods of stress or depression can cause an increase in cortisol levels; when this occurs, the condition is known as pseudo-Cushing syndrome. Not accounting for increases in cortisol due to prescription drugs, pituitary adenomas cause the vast majority of Cushing syndrome in adults and children.

Read more about familial isolated pituitary adenoma.

 

How do people inherit Cushing disease?

Most cases of Cushing disease are sporadic, which means they occur in people with no history of the disorder in their family. Rarely, the condition has been reported to run in families; however, it does not have a clear pattern of inheritance.

The various syndromes that have Cushing disease as a feature can have different inheritance patterns. Most of these disorders are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

From http://ghr.nlm.nih.gov/condition/cushing-disease

Filed under: adrenal, Cushing's, pituitary | Tagged: , , , , , , , , , , , , | Leave a comment »

Narrowing in on Pituitary Tumors

Posted on July 28, 2015 by MaryO

0276f-pituitary-gland

 

As many as 20 percent of people may have a benign cyst or tumor in their pituitary gland. The vast majority of pituitary tumors are noncancerous, but can cause headaches and profound fatigue, and can also disrupt hormone function.

Currently, surgeons rely on radiologic images and MRIs to gather information about the size and shape of the tumor, but the resolution of such imaging technologies is limited, and additional surgeries to remove more of the tumor may be needed if a patient’s symptoms persist. In a new study published in the Proceedings of the National Academy of Sciences on July 27, investigators from Brigham and Women’s Hospital (BWH) present a new technique that could help surgeons more precisely define the locations of tumors in near real-time.

The new strategy uses a visualization technique (matrix-assisted laser desorption/ionization mass spectrometry imaging – MALDI MSI) that can analyze specific hormones, including growth hormone and prolactin, in tissue. In the newly published study, the researchers find that it’s possible to use MALDI MSI to determine the composition of such hormones in a pituitary sample in less than 30 minutes. This could give surgeons critical information to help distinguish tumor from normal gland.

“Our work is driven by a clinical need: we’ve developed a test specifically tailored for the needs of our neurosurgeon colleagues,” said corresponding author Nathalie Agar, PhD, director of the Surgical Molecular Imaging Laboratory in the Department of Neurosurgery at BWH. “A surgeon may sacrifice half of the pituitary gland in an effort to get the tumor out. Without a tool to distinguish healthy tissue from tumor, it’s hard to know in real-time if the surgery was a success. With this technology, in under 30 minutes a surgeon will be able to know if a sample contains normal pituitary tissue or a pituitary tumor.”

“Patients show up with the clinical symptoms of a pituitary tumor, but the tumor itself may not be visible on an MRI,” said co-author Edward Laws, MD, director of the Pituitary and Neuroendocrine Center at BWH. “This technique, which maps out where excess concentrations of hormone levels are located, has the potential to allow us to confirm that we’ve removed the abnormal tissue.”

“Evaluating whether a piece of pituitary tissue is abnormal can be challenging on frozen section,” said co-author Sandro Santagata, MD, PhD, of BWH’s Department of Pathology. “This approach has wonderful potential for enhancing our diagnostic capabilities. It is clearly an important step toward providing intra-operative molecular characterization of pituitary tissues.”

To test the technique, the research team analyzed hormone levels in 45 pituitary tumors and six normal pituitary gland samples, finding a distinct protein signature unique to the normal or tumor sample.

Mass spectrometry, a technique for measuring chemicals present in a sample, is currently used in the operating room to help inform clinical decisions, but up until now, the focus has been on small molecules – metabolites, fatty acids and lipids – using a different type of approach. By analyzing proteins, MALDI MSI offers a way to visualize hormone levels.

Current methods used to detect hormone levels take too long to fit the time constraints of surgical intervention. Surgeons must either remove a larger amount of potentially healthy pituitary gland or perform follow up surgery if the tumor has not been fully removed.

“We’re hoping that techniques like this one will help move the field toward more precise surgery: surgery that not only removes all of the tumor but also preserves the healthy tissue as much as possible,” said Agar.

In the next phase of their work, Agar and her colleagues plan to test out the technique in BWH’s AMIGO suite and analyze the impact of the technique on clinical decision making.

Other researchers who contributed to this study include David Calligaris, Daniel R. Feldman, Isaiah Norton, Olutayo Olubiyi, Armen N. Changelian, Revaz Machaidze, Matthew L. Vestal and Ian F. Dunn.

This work was funded in part by US National Institute of Health (NIH) Director’s New Innovator Award (1DP2OD007383-01 to N.Y.R.A.), U.S. Army Medical Research/CIMIT (2010A052245), the National Center for Image Guided Therapy grant P41RR019703, NIH K08NS064168, the Pediatric Low Grade Astrocytoma Program at Dana-Farber Cancer Institute, the Brain Science Foundation and the Daniel E. Ponton fund for the Neurosciences at BWH.

Brigham and Women’s Hospital 2015 | 75 Francis Street, Boston MA 02115 | 617-732-5500

From http://www.healthcanal.com/cancers/65676-narrowing-in-on-pituitary-tumors.html

Filed under: Cushing's, Diagnostic Testing, pituitary | Tagged: , , , , , , , , , , , , | Leave a comment »

Crooke’s changes common in patients with Cushing’s syndrome, high cortisol production

Posted on July 9, 2015 by MaryO
Oldfield EH, et al. J Clin Endocrinol Metab. 2015;doi:10.1210/JC.2015-2493.
July 8, 2015

 

Evidence of Crooke hyaline changes in the pituitary gland points to a higher likelihood of Cushing’s syndrome in adults, with the changes in basophil cells occurring in 75% to 80% of patients with the hormonal disorder, according to research in The Journal of Clinical Endocrinology & Metabolism.

In a retrospective review of hospital patient records from adults with Cushing’s syndrome who underwent pituitary surgery, researchers also found that a higher degree of cortisol production, as well as exposure to excess glucocorticoids, are often associated with Crooke’s changes in adults.

“The presence of Crooke’s changes is a clear indication of the presence of Cushing’s syndrome, although the absence of Crooke’s changes does not exclude it,” the researchers wrote.

Edward H. Oldfield, MD, FACS, of the department of neurological surgery at University of Virginia Health System, and colleagues analyzed electronic hospital data from 213 consecutive patients with Cushing’s syndrome who received pituitary surgery between 2008 and March 2014. Researchers reviewed analysis of the normal pituitary tissue included with the specimens obtained at surgery, as well as cortisol production measured by 24-hour urine.

Within the cohort, Crooke’s changes occurred in 74% of patients; Crooke’s changes occurred in 81% of patients with an adrenocorticotropic hormone tumor.

Researchers also found that 91% of patients with an adrenocorticotropic hormone-producing tumor and a urinary free cortisol test at least fourfold the upper limit of normal had evidence of Crooke’s changes vs. 74% of patients with a urine cortisol amount that was less than fourfold the upper limit of normal (P = .008).

“Our results clearly demonstrate a correlation between the degree of cortisol production and the presence of Crooke’s changes,” the researchers wrote. “Patients with cortisol production exceeding fourfold upper limit almost all had Crooke’s changes.”

Researchers said study results indicate that the presence of Crooke’s changes may be used to indicate that a patient has Cushing’s syndrome following a pituitary surgery in which no tumor is found.

“However, the absence of Crooke’s changes does not reliably indicate the absence of Cushing’s syndrome, as 19% of patients with a proven [adrenocorticotropic hormone-producing tumor] did not have Crooke’s changes,” the researchers wrote. – by Regina Schaffer

Disclosure: The researchers report no relevant financial disclosures.

From http://www.healio.com/endocrinology/adrenal/news/online/%7B838a3557-f284-4fda-b93d-73dbb4823667%7D/crookes-changes-common-in-patients-with-cushings-syndrome-high-cortisol-production

Filed under: Cushing's, pituitary, Treatments | Tagged: , , , , , , , | Leave a comment »

Multiple aberrant hormone receptors in Cushing’s Syndrome

Posted on June 26, 2015 by MaryO
Eur J Endocrinol. 2015 May 13. pii: EJE-15-0200. [Epub ahead of print]
Multiple Aberrant Hormone Receptors in Cushing’s Syndrome.
El Ghorayeb N1, Bourdeau I2, Lacroix A3.

Author information

Abstract

The mechanisms regulating cortisol production when ACTH of pituitary origin is suppressed in primary adrenal causes of Cushing’s syndrome include diverse genetic and molecular mechanisms. These can lead either to constitutive activation of the cAMP system and steroidogenesis or to its regulation exerted by the aberrant adrenal expression of several hormone receptors, particularly G-protein coupled hormone receptors (GPCR) and their ligands.

Screening for aberrant expression of GPCR in BMAH and unilateral adrenal tumors of patients with overt or subclinical CS demonstrates the frequent co-expression of several receptors. Aberrant hormone receptors can also exert their activity by regulating the paracrine secretion of ACTH or other ligands for those receptors in BMAH or unilateral tumors.

The aberrant expression of hormone receptors is not limited to adrenal Cushing’s syndrome but can be implicated in other endocrine tumors including primary aldosteronism and Cushing’s disease. Targeted therapies to block the aberrant receptors or their ligands could become useful in the future.

PMID:
25971648
[PubMed – as supplied by publisher]

Filed under: adrenal, Cushing's, pituitary, Rare Diseases | Tagged: , , , , , , , , | Leave a comment »

Value of dynamic MRI imaging in pituitary adenomas Indrajit I K, Chidambaranathan N, Sundar K, Ahmed I – Indian J Radiol Imaging

Posted on June 24, 2015 by MaryO

Objectives : MRI has proven to be the best imaging modality in the evaluation of pituitary tumors. Dynamic Imaging is technically a new tool, which has emerged with lot of promise in the evaluation of pituitary adenomas, particularly in accurate delineation of those microadenomas with no contour abnormality and in differentiating residual/recurrent adenoma from surrounding post operative tissue. Dynamic MR imaging is not only useful in the evaluation of pituitary microadenomas but has an equally important role in the assessment of macroadenoma as well. This study analyses and reviews the value of dynamic MR Imaging in pituitary adenomas and postoperative pituitary tumors.

Materials and Methods : A prospective MR Study was undertaken in twenty-five consecutive patients with suspected pituitary adenomatous lesions. These patients were subjected to dynamic MR imaging at our Department from Jan 1997 to Dec 1998. The study was performed on a 0.5T super conducting MR imaging system with Fast Spin echo technique. Gadodiamide (0.1 mmol/Kg) was administered over sixty seconds by hand injection. Dynamic coronal images were obtained simultaneously from three different portions of the gland. Fifteen images were obtained from each of the three portions at an interval of twenty to thirty seconds between the images.

Result : Dynamic MRI was performed in nineteen patients with microadenoma and six cases of macroadenoma. Dynamic MRI study was of diagnostic value in comparison with routine contrast MRI in eleven of the nineteen patients. Dynamic study did not add to the diagnosis and was merely of confirmatory value in remaining eight patients. Dynamic MRI study was used to identify the optimal time for delineation of the adenomatous tumor, by virtue view of the simultaneous differential contrast enhancement patterns between normal pituitary gland and adenoma. Further the enhancement pattern of the normal pituitary gland, the adenomatous nodule and the optimal delineation were individually assessed. This evaluation revealed the average time in seconds for onset of enhancement and the peak enhancement of normal pituitary gland were 43.1 and 111.9 seconds respectively. In comparison the pituitary adenomatous nodules exhibited an average time of 105.8 seconds for onset of enhancement and 188.1 seconds for peak enhancement. The average time in seconds for optimal tumor delineation was 93.9 seconds.

Conclusion : Dynamic MR Imaging has emerged as a technically refined tool in the evaluation of pituitary adenomas. The key questions in evaluation of pituitary adenomas include the presence or absence of a tumor, the number, the location of adenoma nodule, the invasive effects on adjacent structures and the post therapy status of adenoma. Clearly, dynamic MR Imaging is the foremost imaging modality answering these vital questions in patients with pituitary adenomas.

via Value of dynamic MRI imaging in pituitary adenomas Indrajit I K, Chidambaranathan N, Sundar K, Ahmed I – Indian J Radiol Imaging.

Filed under: Cushing's, pituitary, Rare Diseases | Tagged: , , , , | Leave a comment »

« Previous Page — Next Page »