If One Partner Has Cushing’s Syndrome, Can The Couple Still Get Pregnant?

Posted on May 12, 2015 by MaryO

Cushing’s syndrome can affect fertility in both men and women.

Women

The high levels of cortisol in Cushing’s syndrome disrupt a woman’s ovaries. Her menstrual periods may stop completely or become irregular. As a result, women with Cushing’s syndrome almost always have difficulty becoming pregnant.5,6,7 For those who do become pregnant, the risk of miscarriage is high.5,6,7

In rare cases, usually when a woman’s Cushing’s syndrome is caused by a benign adrenal tumor, pregnancy can occur, but it brings high risk for the mother and fetus.5,6,7

After a woman is treated for Cushing’s syndrome, her ovaries often recover from the effects of too much cortisol. Her regular menstrual cycles will return, and she can become pregnant.8

In some women, regular periods do not return after they are treated for Cushing’s syndrome. This occurs if surgery removes the part of the pituitary gland involved in reproduction.4 An infertility specialist can prescribe hormone therapy to bring back regular periods, ovulation, and fertility.8

Men

A man diagnosed with Cushing’s syndrome may have a decline in sperm production and could have reduced fertility.9 He also might experience a lowered sex drive as well as impotence (pronounced IM-puh-tuhns). In addition, some medications used to treat Cushing’s syndrome can reduce fertility.10 However, fertility usually recovers after Cushing’s syndrome is cured and treatment has stopped.9

Does Cushing’s syndrome affect pregnancy?

Cushing’s syndrome can cause serious and potentially life-threatening effects for the mother and the fetus during pregnancy.11,12 For example, Cushing’s syndrome raises a woman’s risk of developing pregnancy-related high blood pressure (called preeclampsia, pronounced pree-i-KLAMP-see-uh, or eclampsia) and/or pregnancy diabetes, which also is called gestational (pronounced je-STEY-shuhn-ul) diabetes). Infection and slow healing of any wounds are more likely, as is heart failure. When the syndrome is caused by a tumor, it will be surgically removed as early as possible to reduce any threat.13

  1. Margulies, P. (n.d.). Adrenal diseases—Cushing’s syndrome: The facts you need to know. Retrieved May 21, 2012, from National Adrenal Diseases Foundation website http://www.nadf.us/adrenal-diseases/cushings-syndrome/ External Web Site Policy
  2. Nieman, L. K., & Ilias, I. (2005). Evaluation and treatment of Cushing’s syndrome. Journal of American Medicine, 118(12), 1340-1346. PMID 16378774.
  3. American Cancer Society. (n.d.). Fact sheet on pituitary tumors. Retrieved May 19, 2012, fromhttp://documents.cancer.org/acs/groups/cid/documents/webcontent/003133-pdf.pdf (PDF – 171 KB). External Web Site Policy
  4. Biddie, S. C., Conway-Campbell, B. L, & Lightman, S. L. (2012). Dynamic regulation of glucocorticoid signalling in health and disease. Rheumatology, 51(3), 4034-4112. Retrieved May 19, 2012, from PMID: 3281495.
  5. Abraham, M. R., & Smith, C. V. (n.d.). Adrenal disease and pregnancy.Retrieved April 8, 2012, fromhttp://emedicine.medscape.com/article/127772-overview – aw2aab6b6. External Web Site Policy
  6. Pickard, J., Jochen, A. L., Sadur, C. N., & Hofeldt, F. D. (1990). Cushing’s syndrome in pregnancy. Obstetrical & Gynecological Survey, 45(2), 87-93.PMID 2405312.
  7. Lindsay, J. R., Jonklaas, J., Oldfield, E. H., & Nieman, L. K. (2005). Cushing’s syndrome during pregnancy: Personal experience and review of the literature. Journal of Clinical Endocrinology and Metabolism, 90(5), 3077.PMID 15705919.
  8. Klibansky, A. (n.d.). Pregnancy after cure of Cushing’s disease. Retrieved April 27, 2012, fromhttp://03342db.netsolhost.com/page/pregnancy_after_cure_of_cushings_disease.php. External Web Site Policy
  9. Jequier, A.M. Endocrine infertility. In Male infertility: A clinical guide (2nd ed.). Cambridge University Press, 2011: chap 20, pages 187-188. Retrieved May 19, 2012, from http://books.google.com/books?id=DQL0YC79uCMC&pg=PA188&lpg=PA188&dq=male+infertility+causes+and+treatment+Cushing&source=bl&ots=k1Ah5tVJC7&sig=WJR4N0wUawlh0Rant31QMPq6ufs&hl=en&sa=X&ei=hGe5T-LrHYSX6AHgrvmzCw&ved=0CGoQ6AEwAQ#v=onepage&q=male%20infertility%20causes%20and%20treatment%20Cushing&f=false. External Web Site Policy
  10. Stewart, P. M., & Krone, N. P. (2011). The adrenal cortex. In Kronenberg, H. M., Shlomo, M., Polonsky, K. S., Larsen P. R. (Eds.). Williams textbook of endocrinology (12th ed.). (chap. 15). Philadelphia, PA: Saunders Elsevier.
  11. Abraham, M. R., & Smith, C. V. Adrenal disease and pregnancy. Retrieved April 8, 2012, from http://emedicine.medscape.com/article/127772-overview – aw2aab6b6. External Web Site Policy
  12. Buescher, M. A. (1996). Cushing’s syndrome in pregnancy. Endocrinologist, 6, 357-361.
  13. Ezzat, S., Asa, S. L., Couldwell, W. T., Barr, C. E., Dodge, W. E., Vance M. L., et al. (2004). The prevalence of pituitary adenomas: A systematic review.Cancer, 101(3), 613-619. PMID 15274075.

From https://www.nichd.nih.gov/health/topics/cushing/conditioninfo/pages/faqs.aspx

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Genetics Research Demystifies Fatal Glandular Disease (Cushing’s)

Posted on December 10, 2014 by MaryO

Researchers at Tokyo Institute of Technology have identified genetic mutations responsible for Cushing’s disease, a potentially fatal glandular condition.

Symptoms of Cushing’s disease include weight gain, muscular weakness, mood and reproductive problems, and if untreated patients can die from the resulting infections and cardiovascular problems. Although first described by Harvey Cushing back in 1932, as Martin Reincke and colleagues in Germany and Japan point out in their latest Nature Genetics report, the mechanism causing the disease “has remained obscure since its first description”. Now by sequencing the tissues responsible the researchers have identified clusters of mutations that cause Cushing’s disease as well as how these mutations bring the disease into effect.

The disease arises from benign tumours on glandular pituitary tissue – corticotroph adenomas – which excessively secrete the hormone adrenocorticotropin (ACTH). Previous studies sought to identify mutations that might cause the disease through sequencing candidate genes and microarray studies, but these made little progress. Instead, the researchers applied a particular type of DNA sequencing known as ‘exome sequencing’ to the pituitary corticotroph adenoma.

The collaboration included researchers from Ludwig-Maximilians-Universität Munich, the University of Würzburg, the Max Planck Institute, the Helmholtz-Center Munich, Universität Hamburg , Universität Erlangen in Germany and Tokyo Institute of Technology in Japan. The research team exome-sequenced samples from 10 patients with Cushing’s disease and noticed a small number of protein altering mutations in the adenoma tissue. The researchers further identified the gene harbouring the mutations as ubiquitin-specific protease 8 (USP8), and were able to pinpoint the region of USP8 prone to mutation in Cushing’s disease.

Previous research observations of Cushing’s disease have highlighted strong expression of another gene, epidermal growth factor receptor (EGFR). By examining EGFR in HeLa cells expressing USP8, the researchers behind this latest research demonstrated that this was the result of USP8 mutations inhibiting downregulation of EGFR.

The researchers conclude that their results “not only identify the first of so far enigmatic driver mutations in corticotroph adenomas but also elucidate a novel mechanism by which the EGFR pathway is constitutively activated in human tumours.” Further research will be required for a more detailed understanding of genetic onset of the disease.

Reference

Martin Reincke etal, Nature Genetics, Advance Online Publication 9 December 2014

Background

Cushing’s disease adenomas

The adenomas that cause Cushing’s disease are benign tumours of epithelial tissue that grow on the pituitary gland. The tumours comprise corticotroph cells, a hormone producing cell that secretes asdrenocorticotropin (ACTH). While the pathological role of ACTH hypersecretion was already known, previous studies had been unable to identify the molecular mechanisms behind these hormone processes that lead to Cushing’s disease.

Exome sequencing

When RNA is processed by splicing, parts of the RNA – the introns – are removed. The remaining RNA, the exons, are collectively referred to as the exome.

While DNA sequencing finds the sequence of proteins for the whole DNA, by focusing on the exons, exome sequencing provides information specifically on the protein-coding genes. Changes to these genes are more likely to have significant ramifications on the organism.

Ubiquitination and USP8

Ubiquitination is a reversible protein modification process that occurs by means of a small protein called ubitquitin, which is found in all eukaryotic cells (cells containing a nucleus and other structures enclosed within a membrane). Ubiquitination regulates the fate and function of proteins.

USP8 is a ubiquitin-specific protease enzyme that can remove ubitquitin molecules from target proteins. The discovery of a high number of mutations in the USP8 gene in Cushing’s disease prompted the researchers to make further investigations on the mutant USP8 enzymes at biochemical and cellular levels. From these studies they could identify the mechanisms behind the mutations and the effect on epidermal growth factor receptor (EGFR), a gene that mediates the synthesis of an ACTH precursor.

Figure (click to view larger)

corticotroph

Figure caption: Schematic representation showing the proposed mechanisms how USP8 mutations lead to increased ACTH secretion and tumorigenesis in corticotroph.

Further information

Yukiko Tokida, Asuka Suzuki

Center for Public Affairs and Communications, Tokyo Institute of Technology

2-12-1, Ookayama, Meguro-ku, Tokyo 152-8550, Japan

E-mail: media@jim.titech.ac.jp

URL: http://www.titech.ac.jp/english/

Tel: +81-3-5734-2975     Fax: +81-3-5734-3661

About Tokyo Institute of Technology

As one of Japan’s top universities, Tokyo Institute of Technology seeks to contribute to civilization, peace and prosperity in the world, and aims at developing global human capabilities par excellence through pioneering research and education in science and technology, including industrial and social management. To achieve this mission, we have an eye on educating highly moral students to acquire not only scientific expertise but also expertise in the liberal arts, and a balanced knowledge of the social sciences and humanities, all while researching deeply from basics to practice with academic mastery. Through these activities, we wish to contribute to global sustainability of the natural world and the support of human life.

 

Source: Tokyo Institute of Technology, Center for Public Affairs and Communications: http://www.healthcanal.com/genetics-birth-defects/58155-tokyo-institute-of-technology-research-genetics-research-demystifies-fatal-glandular-disease.html

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Mutation of ARMC5 gene characterized as the cause of meningeal tumour growth

Posted on October 13, 2014 by MaryO

Scientists at the Luxembourg Centre for Systems Biomedicine (LCSB) of the University of Luxembourg have published their findings that mutations in a gene known as “ARMC5” promote the growth of benign tumours in the adrenal glands and on the meninges: ARMC5 appears to belong to the group of so-called tumour suppressor genes. It is the first time in years that scientists have characterized such a gene.

The ARMC5 gene was discovered by independent workgroups studying – so-called adrenal adenomas – in connection with Cushing’s syndrome. In this disease, the body produces too much of the . Now, for the first time, a mutation of ARMC5 has been characterized as the cause behind the growth of meningeal tumours. The results on this tumour syndrome, obtained by the group of Dr. Patrick May and PD. Dr. Jochen Schneider together with colleagues from Charité Berlin (Dr. Ulf Elbelt) and the Universities of Würzburg (Prof. Dr. Bruno Allolio) and Cologne (Dr. Michael Kloth), have been published recently in the Journal of Clinical Endocrinology Metabolism.

Cortisol is an important hormone. It influences many metabolic pathways in the body and has a suppressing effect on the immune system. Accordingly, it is commonly employed as an anti-inflammatory medication. Prolonged, elevated levels of cortisol in the body can lead to obesity, muscular dystrophy, depression and other symptoms. To maintain the correct concentration in the blood, the body has a refined regulation system: Certain areas of the brain produce the hormone corticotropin as a stimulator of cortisol release; the actual formation of cortisol takes place in the . As the concentration of cortisol in the blood rises, the brain reduces the production of corticotropin.

In search of the causes of Cushing’s syndrome, scientists recently encountered certain genetic causes of benign tumours of the adrenal cortex. Growth of these adrenal cortex adenomas is based on a combination of hereditary and spontaneous mutations: It affects people in whom one of two “alternative copies” – one of the so-called alleles – of the ARMC5 gene is mutated from birth. If the second allele of ARMC5 later also undergoes a spontaneous mutation in the adrenal cortex, then the gene no longer functions. “What is interesting is that the failure of ARMC5 has no direct influence on cortisol production. However, because the tumour cells multiply faster than other body cells, and the number of cells in the tumour increases, the blood cortisol level rises in the course of the disease”, says Dr Schneider. Then, the level in the body rises and ultimately results in the onset of Cushing’s syndrome.

When other scientific workgroups discovered that further benign tumours – in this case meningeal tumours – occur more often in ARMC5-Cushing families, the group of Patrick May and Jochen Schneider sequenced the ARMC5 gene and studied it using bioinformatic techniques. “We demonstrated for the first time, in a patient with an adrenal cortex tumour and simultaneously a meningeal tumour, that somatic, that is non-hereditary, ARMC5 mutations are present in both tumours. This observation suggests that ARMC5 is a true tumour-suppressor gene.”

It must now be explored, Schneider continues, to what extent patients with adrenal cortex tumours ought to be screened for simultaneous presence of meningioma, and in which other types of tumour ARMC5 mutations are responsible for tumour growth: “Building upon that, we can learn whether the gene and the metabolic pathways it influences offer new approaches for treating the tumour syndrome.”

Explore further: Are you carrying adrenal Cushing’s syndrome without knowing it?

More information: “Molecular and Clinical Evidence for an ARMC5 Tumor Syndrome: Concurrent Inactivating Germline and Somatic Mutations are Associated with both Primary Macronodular Adrenal Hyperplasia and Meningioma.” Journal of Clinical Endocrinology Metabolism, October 2014. DOI: 10.1210/jc.2014-2648

Journal reference: Journal of Clinical Endocrinology & Metabolism search and more info website

Provided by University of Luxembourg search and more info

From http://medicalxpress.com/news/2014-10-mutation-armc5-gene-characterized-meningeal.html

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Differences Between Cushing’s Syndrome and Cushing’s Disease

Posted on August 28, 2013 by MaryO

What’s the difference between Cushing’s Disease and Cushing’s Syndrome?

disease-syndrome

Cushing’s syndrome is a hormonal disorder

Cortisol is a normal hormone produced in the outer portion of the adrenal glands. When functioning normally, cortisol helps the body respond to stress and change. It mobilizes nutrients, modifies the body’s response to inflammation, stimulates the liver to raise blood sugar, and helps control the amount of water in the body. Cortisol production is regulated by the adrenocorticotrophic hormone (ACTH), produced in the pituitary gland. Spontaneous overproduction of cortisol in the adrenals is divided into two groups – those attributed to an excess of ACTH and those that are independent of ACTH.

Cushing’s syndrome is the term used to describe a group of symptoms that occur when a persons’ cortisol levels are too high (known as hypercortisolism) for too long. The majority of people have Cushing’s syndrome because they are regularly taking certain medicine(s) that continually add too much cortisol to the body. Doctors call this an “exogenous” (outside the body) cause of Cushing’s syndrome. Other people have Cushing’s syndrome because something is causing the adrenal gland(s) to overproduce cortisol. Doctors call this an “endogenous” (inside the body) cause of Cushing’s syndrome.

Cushings-causes.png

Cushing’s disease is a form of Cushing’s syndrome

Cushing’s disease is the most common form of endogenous Cushing’s syndrome. It is caused by a tumor in the pituitary gland that secretes excessive amounts of a hormone called Adrenocorticotropic hormone, or ACTH. Fortunately, this type of tumor is typically benign. Unlike a cancerous (malignant) tumor, a benign tumor stays in its original location and will not spread. After you are diagnosed with Cushing’s syndrome, it is important that your doctor continues the diagnostic process to determine the cause of hypercortisolism.

From the message boards It is not only a tumor that causes Cushings Disease—many of us have the rarer form of this rare disease which is Pituitary Hyperplasia. It also causes CD and may be nodular (shown on MRI s a tumor) or dispersed (meaning spread throughout the gland).

How a pituitary tumor causes Cushing’s disease

Pituitary.jpg

ACTH is a hormone produced in your pituitary gland. ACTH travels to your adrenal glands and signals them to produce cortisol.

Pituitary adenomas are benign tumors of the pituitary gland which secrete increased amounts of ACTH, causing excessive cortisol production. Most patients have a single adenoma. First described in 1912 by neurosurgeon Harvey Cushing in his book The Pituitary Body and its Disorders, Cushing’s disease is the most common cause of spontaneous Cushing’s syndrome, accounting for 60 to 70 percent of cases.

If a person has Cushing’s disease, it means that a group of abnormal cells has built up in the pituitary gland to form an ACTH-producing pituitary tumor. These abnormal cells produce ACTH, just as normal pituitary gland cells do—only far too much. The excess ACTH travels to adrenal glands. The adrenal glands are then bombarded with signals to produce more and more cortisol. As a result, the adrenal glands continuously secrete too much cortisol.

Ectopic ACTH Syndrome

Some benign or malignant (cancerous) tumors that arise outside the pituitary can produce ACTH. This condition is known as ectopic ACTH syndrome. Lung tumors cause more than 50 percent of these cases. Other less common types of tumors that can produce ACTH are thymomas, pancreatic islet cell tumors, and medullary carcinomas of the thyroid.

Adrenal Tumors

Adrenal glands.jpg

An abnormality of the adrenal glands such as an adrenal tumor may cause Cushing’s syndrome. Most of these cases involve non-cancerous tumors called adrenal adenomas, which release excess cortisol into the blood.

Adrenocortical carcinomas, or adrenal cancers, are the least common cause of Cushing’s syndrome. Cancer cells secrete excess levels of several adrenal cortical hormones, including cortisol and adrenal androgens. Adrenocortical carcinomas often cause very high hormone levels and rapid onset of symptoms.

Familial Cushing’s syndrome

Most cases of Cushing’s syndrome are not genetic. However, some individuals may develop Cushing’s syndrome due to an inherited tendency to develop tumors of one or more endocrine glands. In Primary Pigmented Micronodular Adrenal Disease, children or young adults develop small cortisol-producing tumors of the adrenal glands. In Multiple Endocrine Neoplasia Type I (MEN I), hormone secreting tumors of the parathyroid glands, pancreas and pituitary occur. Cushing’s syndrome in MEN I may be due to pituitary, ectopic or adrenal tumors.

Risk factors

Obesity, type 2 diabetes, poorly controlled blood glucose (blood sugar levels), and high blood pressure may increase the risk of developing this disorder.

Adapted from http://www.cushiewiki.com/index.php?title=Cushing%27s_Disease_or_Syndrome

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Researchers May Have Found the Cause of Cushing’s Disease

Posted on June 3, 2013 by MaryO

A team of researchers may have zeroed in on the cause of Cushing’s disease, a condition that leads to diabetes, obesity and the risk of premature death.

Location of the pituitary gland in the human brain

Location of the pituitary gland in the human brain (Photo credit: Wikipedia)(TR4). By reducing the TR4 in lab mice, they were able to reverse tumor growth and excess ACTH production.

More women than men get the disease, which begins usually between 20 and 50 with mostly benign tumors in the pituitary gland. It’s known that that condition results in excess production of adrenocorticotrophic hormone (ACTH). But until now, scientists haven’t been sure what drives the production of ACTH.

Now, UCLA researchers and their colleagues have zeroed in on the culprit: excessive production of testicular orphan nuclear receptor (TR4). By reducing the TR4 in lab mice, they were able to reverse tumor growth and excess ACTH production.

The findings, published in the journal Proceedings of the National Academy of Sciences, could point the way to targeted treatment of Cushing’s.

From http://www.thirdage.com/medical-care/researchers-find-the-cause-of-cushing-s-disease

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