Familial isolated pituitary adenoma (AIP study)

Professor Márta Korbonits is the Chief Investigator for the NIHR Clinical Research Network supported familial pituitary adenomas study (AIP) which is investigating the cause, the clinical characteristics and family screening of this relatively recently established disease group.

Please tell us about the condition in layman’s terms?
Pituitary adenomas are benign tumours of the master gland of the body, the pituitary gland. It is found at the base of the brain. The most commonly identified adenoma type causing familial disease makes excess amounts of growth hormone, and if this starts in childhood the patient have accelerated growth leading them to become much taller than their peers. This condition is known as gigantism.

How rare is this condition?
Pituitary adenomas cause disease in 1 in a 1000 person of the general population. About five to seven percent of these cases are familial pituitary adenomas.

How it is normally diagnosed?
There are different types of pituitary adenomas causing quite varied diseases. Gigantism and its adult counterpart acromegaly is usually diagnosed due to rapid growth, headaches, joint pains, sweating, high blood pressure and visual problems. Pituitary adenomas grow slowly and it usually takes 2-10 years before they get diagnosed. The diagnosis finally is made by blood tests measuring hormones, such as growth hormone, and doing an MRI scan of the pituitary area.

What is the study aiming to find out?
The fact that pituitary adenomas can occur in families relatively commonly was not recognised until recently. Our study introduced testing for gene alterations in the AIP (Aryl Hydrocarbon Receptor Interacting Protein) gene in the UK, and identified until now 38 families with 160 gene carriers via screening. We also aim to identify the disease-causing genes in our other families as well.

How will it benefit patients?
The screening and early treatment of patients can have a huge benefit to patients as earlier treatment will lead to less complications and better chance to recovery. We hope we can stop the abnormal growth spurts therefore avoiding gigantism. Patients that are screened will find out if they carry the AIP gene and whether they are likely to pass on the gene to their families. For most patients, knowing they have a gene abnormality also helps them to understand and accept their condition.

How will it change practice?
As knowledge of the condition becomes more understood, genetic testing of patients to screen for AIP changes should be more commonplace. Patients can be treated knowing they have this condition, and family members who are carriers of the gene can benefit from MRI scans to monitor their pituitary gland and annual hormone tests.

How did the NIHR CRN support the study?
The familial pituitary adenoma study is on the NIHR CRN Portfolio. The study’s association with NIHR has allowed the widespread assessment of the patients, has incentivised referrals from clinicians and raised awareness of both our study and the familial pituitary adenoma condition itself.

For more information contact NIHR CRN Communications Officer, Damian Wilcock on 020 3328 6705  or email damian.wilcock@nihr.ac.uk

From https://www.crn.nihr.ac.uk/blog/case_study/national-rare-disease-day-2016-familial-isolated-pituitary-adenoma-aip-study/

What Genes are Related to Cushing’s Disease?

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

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