Conditions and Treatments

PITUITARY GLAND DISORDERS OVERVIEW

What is the Pituitary Gland?
The pituitary gland is a small gland that sits in the head, just below the brain and behind the nose. The pituitary gland acts as the master gland of the body, producing hormones and controlling other glands in the body. Hormones travel in the blood throughout the body to many tissues and organs and carry out important functions necessary for life.

Within the pituitary gland are different types of cells, each of which makes a specific hormone. The hormones produced in pituitary gland cells include:

  • Prolactin – needed for production of breast milk and lactation
  • Growth hormone (GH) – necessary for normal growth in childhood and important for metabolism and other functions in adults.
  • Adrenocorticotropin (ACTH) –stimulates the adrenal glands (two glands located just above the kidneys) to produce Cortisol, which is a hormone that is essential for life as it helps keep blood pressure normal and blood sugar normal
  • Thyroid-stimulating hormone (TSH) – stimulates the thyroid gland, to make thyroid hormone (thyroxine) which is also necessary for life and important for metabolism, growth and other functions.
  • Luteinizing hormone (LH) and Follicle-stimulating hormone (FSH) – necessary for normal function of the testes in men and ovaries in woman and thus normal fertility and reproduction.
  • Posterior pituitary – releases a hormone Antidiuretic hormone (ADH) (also called vasopressin) that is necessary for maintaining normal water balance in the body.

What disorders can occur in the pituitary gland?
There are many causes of pituitary disease. The most common cause is a pituitary tumor. Up to 20% of people have a pituitary tumor that might be found if they were to have a pituitary MRI, but most of these are small anddo not get recognized or need medical attention. Many pituitary tumors produce no symptoms, but are found by chance on a pituitary MRI done for an unrelated reason. These are called “incidentalomas”.

Pituitary tumors can come to medical attention because of physical signs or symptoms caused by hormone excess produced by the tumor or symptoms of low hormones (hypopituitarism) caused by disturbance of the normal pituitary gland. Large tumors can also put pressure on other structures surrounding the pituitary gland such as the nerves of vision producing visual changes or headaches.

Pituitary tumors are growths of pituitary gland cells. These tumors are almost always benign (i.e. not cancer). In the tumor, the cells multiply and produce a ball of cells of one type. Each tumor takes on characteristics of the cell of its origin. Many pituitary tumors originate in hormone producing cells and these tumors are called hormone-secreting. The most common type of hormone secreting pituitary tumors are prolactinomas, these are tumors made up of prolactin cells. Prolactinomas lead to high level of prolactin in the blood (link to prolactinomas section below). Other pituitary tumors are made up of growth hormone (GH) producing cells, a disease called Acromegaly.  In Acromegaly high levels of GH and a hormone produced by GH, IGF-1 (insulin like growth factor 1) are found in the blood and patients experience many ill effects of these hormone excesses. Other tumors originate in ACTH producing cells leading to high levels of cortisol in the body and a disease called Cushing’s disease. Many pituitary tumors do not appear to produce a high level of a hormone in the blood and are termed nonfunctioning or non-secreting tumors. Some of these tumors originate in LH or FSH cells, but very few produce high levels of these hormones in the blood. Some pituitary tumors are TSH producing and lead to overactive thyroid function in the body.

Pituitary tumors can cause problems due to hormone over-production, with the nature of the changes in the body depending on the hormone. Pituitary tumors can also cause problems due to pressure on the structures surrounding the pituitary gland and the normal pituitary when they grow large. The nerves of vision sit just above the pituitary gland and pituitary tumors can lead to loss of vision, in particular loss of vision on the sides of the visual field. Pituitary tumors can also cause pressure on the normal pituitary gland which can gets compressed to the side or above the tumor. Function of the normal pituitary gland can then become compromised, a condition called hypopituitarism. Pituitary tumors can also cause headache, in particular if they growth rapidly or if some bleeding occurs in the tumor, a condition cause apoplexy. Tumors less than 1 centimeter (cm) in size are called microadenomas and tumors 1 cm or larger are called macroadenomas. The larger the tumor, the more likely it is to cause pressure symptoms.

Other types of tumors and cysts can grow in the pituitary region and disrupt pituitary function.  Some tumors originate in cells that line the pituitary area. Cysts of the pituitary are common. The most common of these are Rathke’s cleft cysts. Another type of tumor that can grow in the pituitary region is a craniopharyngioma, which also often contains cysts.

Other types of disorders can affect the pituitary.  Some inflammatory conditions such as sarcoidosis can involve the pituitary gland.  Inflammation can also involve the pituitary and produce lymphocytic hypophysitis.

What should you do if you are found to have a pituitary tumor?
Whether the pituitary abnormality is found on MRI done for another reason or a doctor suspects a hormone problem and then begins your evaluation, a detailed Endocrine evaluation that tests your hormones is a necessary initial step. Your Endocrinologist will look for signs on your physical examination or clues from your history of a possible hormone problem and will perform a series of blood tests that will test all your hormones. The Endocrinologist will test for high hormones, evaluating for a possible hormone producing or secreting tumors and for low hormone levels, thus evaluating you for hypopituitarism.  You may need treatment with hormone supplements depending on the results of your tests. If you have not already had one, you will need a MRI that looks specifically at your pituitary with thin cuts through the pituitary. Depending on the size and location of your tumor your doctor may ask you to have Visual Field Testing which will determine whether or not your fields of vision are compromised by the tumor.

Depending on the type of tumor and the symptoms you have you may be referred to a Neurosurgeon who specializes in pituitary gland surgery. Prolactinomas are the one type of pituitary tumor that is best initially treated with medication (see below), even if very large. Some pituitary tumors that are not altering your hormones or causing vision disturbance can just be followed with repeat MRI and pituitary hormone testing over time. Most tumors that are hormone secreting and tumors that are threatening or causing a vision problem require transsphenoidal surgery.

Non-functioning (non-secretory) Pituitary Adenomas
Many pituitary tumors are called non-functioning or non-secretory because they do not appear to release an excess of a hormone into the blood. Most of these tumors originate in a cell type that does not produce a hormone, but some come from LH or FSH cells, but these very rarely produce high levels of these hormones in the blood.

Non-secretory tumors do not cause the changes in the body that hormone producing tumors do. Rather, when they become large, they get diagnosed because of problems related to pressure on the structures surrounding the pituitary gland and the normal pituitary. These problems include loss of vision, at first peripheral vision and later more widespread vision loss, pituitary gland insufficiency (hypopituitarism) and headache. Pituitary tumors can also cause headache, in particular if they growth rapidly or if some bleeding occurs in the tumor, a condition cause apoplexy.

Not all growths that appear to be nonfunctioning pituitary adenomas require surgical intervention. A growth in the pituitary can be found when a MRI is done to evaluate an unrelated problem such as neck pain or dizziness. When a pituitary growth is detected in these cases it is called an “incidentaloma”. A lesion found  “incidentally” on the pituitary is often a nonfunctioning pituitary adenoma. Such growths do need to be fully evaluated with a physical examination, history and blood tests. In these cases where the growth or tumor is small and not producing any symptoms or hormone excess it can often be followed over time.  Surgery would be recommended if symptoms develop or the tumor grows rapidly.

Nonfunctioning pituitary tumors are treated with transsphenoidal microsurgery to remove the tumor when the tumor causes pressure on structures around the pituitary or when vision is threatened. This surgery is performed through the nasal sinuses. After surgery, visual field problems improve in most patients.

After surgery, pituitary MRIs need to be repeated over time to watch for any tumor regrowth. Some tumors do regrow even if all visible tumor is removed by surgery. If surgery cannot remove a large piece of tumor because of the location and size of the tumor or the tumor regrows, another surgery and/or radiation therapy may be needed.

ACROMEGALY
Acromegaly is a rare disease causes by a GH producing pituitary tumor.  These tumors are made up of GH producing pituitary cells that produce an excess of GH, which leads to high levels of GH in the blood. GH leads to the production of high levels of another hormone, insulin-like growth factors 1(IGF-1). Establishing the diagnosis of acromegaly requires demonstrating high levels of GH and IGF-1 in the blood. Another way to diagnose acromegaly is with an oral glucose tolerance test. In this test, GH levels in the blood are measured after a sugar containing drink.  GH levels drop very low (or become suppressed) after glucose normally, but in acromegaly GH levels do not fall and may rise after glucose.

High levels of GH and IGF-1 produces may changes in the body from changes in physical appearance to changes in organs and metabolism. Often, the physical changes occur so gradually that they go unnoticed by people who see the patient every day, even the patient’s regular physician. A relative or physician who has not seen the patient in a long time may notice the changes.

Most patients with acromegaly are diagnosed between 40 and 50 years of age, but the physical changes and symptoms may be present as long as 10 years before the diagnosis is made.

The most common physical changes are enlargement of the hands and feet and because of this acromegaly patients often enlarge their rings or get wider shoes. Facial appearance can change with coarsening of the facial features, thickening of the lips and enlargement of the bones of the forehead and the lower jaw. Patients can have a change in their bite and increased spacing of the teeth. Patients often have excess sweating, oily skin and acne. Many patients with acromegaly develop high blood pressure and diabetes mellitus. Many patients have joint pain, arthritis or numbness and tingling of the fingers due to carpal tunnel syndrome. Snoring is common and sleep apnea (breathing repeatedly stops and starts during sleep) can develop. Colon polyps are more common in patients with acromegaly.

In children, acromegaly is very rare, but if it occurs before puberty and before the growth plates of the bones have closed, the child can grow very tall due to the excess GH stimulating growth. This is called Gigantism.

Some patients with acromegaly also have prolactin elevation, which can lead to loss of menstrual periods in woman and low testosterone levels in men. Some patients with acromegaly have pituitary insufficiency, which can produce symptoms of low thyroid, low cortisol (from the adrenal glands) or dysfunction of the ovaries in women or testes in men which can include menstrual disorders, reduced sexual desire or infertility.

Patients with acromegaly, as with any type of pituitary tumor, can have symptoms due to pressure on structures surrounding the pituitary such as vision problems such as peripheral vision loss and headaches.

Acromegaly is treated initially by removal of the pituitary tumor by transsphenoidal microsurgery. Surgery is the most effective treatment for acromegaly because it removes the tumor mass thus relieving pressure on surrounding structures and protecting from future vision loss, it results in rapid reduction in GH and IGF-1 levels with improvement in symptoms and produces long term normalization of hormone levels in most patients. Surgery can lead to remission of acromegaly in most patients, but not all patients can be cured. The chance of remission after surgery depends on the size and location of the tumor.  In some cases where medical problems make surgery unsafe, initial treatment may be given with medication such as a somatostatin analog.

After surgery, patients undergo detailed testing of their IGF-1 level and GH after the glucose drink to determine whether levels are normal or not. For patients with persistent elevations of GH and IGF-1 after surgery a number of medications are available including long-acting somatostatin analogs and a GH receptor antagonist. Some patients are also treated with radiotherapy to the remaining pituitary tumor. Treatment with medication will be necessary until radiation therapy takes effect, which usually takes years. Some patients need a number of therapies to achieve remission. Many of the problems experienced by patients get better and some can completely resolve with effective treatment of acromegaly. Headache can improve rapidly as can abnormal glucose levels, sweating. Much of the thickening of tissues in the hands and feet will reduce in size gradually after treatment. Bone changes such as enlargement of the lower jaw will not reverse.

Cushing’s Disease

Prolactinomas

Craniopharyingiomas

Rathke’s cleft cysts