What is the pituitary? The pituitary is a small, pea-sized gland located at the base of the brain that functions as "The Master Gland." From its lofty position above the rest of the body it sends signals to the thyroid gland, adrenal glands, ovaries and testes, directing them produce thyroid hormone, cortisol, estrogen, testosterone, and many more. These hormones have dramatic effects on metabolism, blood pressure, sexuality, reproduction, and other vital body functions. In addition, the pituitary gland produces growth hormone for normal development of height and prolactin for milk production. Is "The Master Gland" connected to the brain? The pituitary hangs from the hypothalamus, a part of the brain located immediately above it, by a thread-like stalk that contains both blood vessels and nerves. Hormones produced in the hypothalamus carry signals or messages to the pituitary gland. The hypothalamus serves as a "switching station" to relay signals from many different parts of the brain to the pituitary gland, which in turn transmits its own signals to various parts of the body. The pituitary is divided into a larger anterior region (adenohypophysis) and a smaller posterior area (neurohypophysis). It sits in a small pocket of bone in the base of the skull called the pituitary fossa, also known as the sella turcica, or Turkish saddle, because of the resemblance. The sella turcica is located deep within the skull, which can be imagined by drawing an imaginary line from the top of the nose through the brain to the back of the head, and from ear to ear. The point at which they intersect is where the pituitary gland sits. Why are pituitary disorders so hard to diagnose? Pituitary disorders can cause a wide spectrum of symptoms, both hormonal and neurological, due to its location near the brain, the intracranial nerves and blood vessels and because of the vital hormonal control that the gland provides. Diagnosis of pituitary disease may be extremely difficult because it's often confused with other disorders. It is dependent on symptoms, signs on examination, blood tests and MRI findings. Direct access to the pituitary can only be reached at surgery. Which hormones are secreted by the anterior pituitary? Thyroid Stimulating Hormone (TSH) causes the thyroid gland to produce and release thyroid hormones. Thyroid hormone controls the basal metabolic rate and plays an important role in growth and maturation. Thyroid hormones affect almost every organ in the body. Growth Hormone (GH) regulates growth and metabolism. Adrenocorticotropic Hormone (ACTH) triggers the adrenals to release the hormone cortisol, which regulates carbohydrate, fat, and protein metabolism and blood pressure. The adrenal glands sit above the kidneys and are also responsible for the body's fight or flight response. Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) control the production of sex hormones (estrogen and testosterone) and sperm and egg maturation and release. Melanocyte-Stimulating Hormone (MSH) regulates the production of melanin, a dark pigment, by melanocytes in the skin. Increased melanin production produces pigmentation or tanning of the skin; in certain conditions excessive production of melanocyte-stimulating hormone can cause darkening of the skin. Prolactin (PRL) stimulates production of breast milk and is necessary for normal milk production during breast feeding. Which hormones are produced and/or controlled by the posterior pituitary or hypothalamus? Oxytocin stimulates contractions of the uterus during labor and the ejection of milk during breast-feeding. Antidiuretic Hormone (ADH) increases reabsorption of water into the blood by the kidneys and therefore decreases urine production. Also referred to as Vasopressin. What happens if the pituitary produces either too much or too little of these hormones? An imbalance occurs, leading to more than a dozen disorders of the endocrine system. Deficiency of thyroid hormone, adrenal cortical hormone (cortisol) or antidiuretic hormone (vasopressin) is rapidly life-threatening. In patients with abnormalities of the other hormones, quality of life is significantly compromised. What causes the pituitary to malfunction? Tumors (overwhelmingly benign), inflammation, infections and injury can cause the gland to malfunction, as well as metastasis or spread of other tumors to the pituitary (rare). Radiation therapy to the brain can also cause normal pituitary cells to malfunction. What is a pituitary Tumor? A pituitary tumor is an abnormal growth of pituitary cells. Pituitary tumors can either be nonfunctional (that is they do not secrete hormones) or produce specific hormones, such as prolactin (causing infertility, decreased libido, and osteoporosis), growth hormone (causing acromegaly), ACTH (causing Cushing's), TSH (causing hypothyroidism), or be nonfunctional (that is they do not produce hormones). These tumors behave according to their cell of origin and are named for the specific cell type affected. For example, if a tumor originates in a prolactin producing cell, the patient develops a prolactinoma-a prolactin secreting pituitary tumor that is common and usually treatable. High prolactin levels suppress production of the pituitary hormones (luteinizing hormone and follicle stimulating hormone) that stimulate production of estrogen or testosterone. Men with these tumors have low testosterone levels and lose their sex drive and eventually their masculine characteristics-hair, muscle, erections, and ability to produce sperm. Women with prolactin producing tumors often do not ovulate, experience low estrogen levels, and cease having menstrual periods. In both cases, patients with low sex hormones develop osteoporosis. It is important to remember that most pituitary tumors are benign and cancer is very rare. They have variable patterns of growth and affect different people in vastly different ways. Some are small and incidental, while others are small but cause hormone excess. Others may be rapidly growing mass lesions. Are they deadly? If diagnosed early enough, the prognosis is typically excellent. If not, some tumors can grow into macroadenomas that press on the optic nerves (causing loss of peripheral vision and, in some cases, blindness), the brain (impacting function) and the pituitary (limiting or eliminating hormone production). Large tumors can also invade the cavernous sinuses, which house the carotid arteries, the veins to drain the eyes, and nerves involved in eye movement. Surgery around the cavernous sinuses is difficult and should be performed by an experienced pituitary surgeon. The tumors can also secrete too much of a hormone, causing hypertension, diabetes, mood disorders, sexual dysfunction, infertility, osteoporosis, arthritis, accelerated heart disease and death. Why is early diagnosis such a problem? The confusing constellation of symptoms that can be produced by pituitary tumors and the difficult to visualize location make diagnosis very tricky. It is not uncommon for patients to have symptoms of either hormonal deficiency (caused by compression of the pituitary or its "stalk") or hormone excess (caused by unregulated production of hormones by the pituitary tumor). In a significant minority of patients diagnosis is not made until the individual has developed debilitating or life-threatening symptoms of heart disease or adrenal (uncommon), gonadal and/or thyroid insufficiency. Even in the 21st century death from a large pituitary tumor or hormonal deficiency still occurs, albeit rarely. Early diagnosis is usually a reflection of a high index of suspicion on the part of a physician. Unfortunately, many doctors have been taught that pituitary disease is rare, so it is not at the forefront of their list of possible diagnoses. How prevalent are pituitary tumors/disease? Autopsy reports and radiologic and MRI evidence from around the globe indicate that one out of every five people worldwide has a pituitary tumor. The earliest study took place in 1936, when Dr. R.T. Costello of the Mayo Foundation conducted a cadaver study and found pituitary tumors in 22.4 % of the population (Costello R.T. Subclinical adenoma of the pituitary gland. Am. J. Pathol. 1936; 12:205-214). Statistics have not changed much ever since. The clinical significance of these findings are critical to determine. Why are these tumors so common? We don't know because funding for benign brain tumor research is virtually nonexistent. That's about to change. In October 2002, Congress passed the Benign Brain Tumor Cancer Registries Amendment Act, which will force hospitals, clinics and doctors to report pituitary tumor incidence rates in the data collection of cancer registries. The problem remains diagnosis. No report of incidence rates is possible without it. Why isn't this common knowledge? There are four main reasons: Pituitary tumors/disease present a vast array of symptoms, and it's often the symptoms that get treated, not the disease. As a result, pituitary patients can spend years being misdiagnosed as their tumors grow. People with undetected pituitary tumors can die of heart attacks, hypothyroidism, adrenal insufficiency or water balance problems, all of which can mask the main cause: a pituitary tumor. dollars spent. As a result, we have failed to answer the most important question: Why are pituitary tumors so common? There is a lack of education within the medical community and among the general public. The insurance industry hasn't caught on to the untold billions of dollars that could be saved through early diagnosis and treatment. Once it becomes clear that it's in everyone's best interest, the word will spread. How are pituitary tumors treated? It depends on the type of tumor and how far it has invaded into the brain, as well as the patient's age and overall health. Three kinds of treatment are used: surgery (removing the tumor during an operation), radiation therapy (using high-dose x-rays/proton beams to kill tumor cells) and drug therapy to shrink and sometimes eradicate the tumor. Drugs can also block the pituitary gland from making too much hormone. A Transphenoidal operation can remove the tumor through a cut in the nasal passage, leaving no external scar. (Sometimes a surgeon prefers to go through an incision under the upper lip instead of the nose, also with no external scarring.) A Craniotomy removes the tumor through a cut in the front of the skull; this is rarely done for large invasive tumors. Is surgery risky? Surgery is a common treatment, and it is almost always successful IF performed by a skilled and specialized neurosurgeon. The smaller the tumor, the greater the chance the surgery will be successful. Large tumors that grow upward (into the nerves that mediate vision) or laterally (into the cavernous sinuses that contain the major arteries to the brain-the carotid arteries) increase the risk of surgery and are generally associated with a lower probability of cure. Early diagnosis and treatment is the key. Is there a long recovery process? In most cases, no. Patients often report immediate relief from symptoms after Transphenoidal Hypophysectomy and little pain. Some leave the hospital the same day. How effective is radiation therapy? Radiation therapy uses high-energy x-rays to kill cancer cells and abnormal pituitary cells and shrink tumors. Radiation for pituitary tumors these days almost always comes from a radiation source outside the body (external radiation therapy). Radiation therapy may be used if medication/surgery fails to control the tumor. There are several different types of radiation therapy. Standard External Beam Radiotherapy uses a radiation source that is nonselective and radiates all cells in the path of the beam; in almost all cases other portions of the brain in the area of the pituitary are in the path of the radiation beam. Proton Beam Treatment employs a specific type of radiation in which "protons", a form of radioactivity, are directed specifically to the pituitary gland. The advantage of this technique is less damage to tissues surrounding the pituitary gland. Gamma Knife Irradiation combines standard external beam radiotherapy with a technique that focuses the radiation through many different ports. This treatment tends to do less damage to tissues adjacent to the pituitary gland. Some clinics are using proton beam therapy; laser-guided MR imaged stereotactic intrasellar tumor localization can be used for selected patients with untreated pituitary tumors, incomplete surgical resection, or tumor recurrence. Are all pituitary tumors created equal? No. There are more than a dozen very different disorders that result from pituitary tumors and disease. For example, if a tumor forms in an ACTH secreting pituitary cell, it could result in the overproduction of cortisol (Cushing's Disease) or the underproduction of cortisol (adrenal insufficiency, often referred to as Secondary Addison's Disease). Cushing's is a condition characterized by excessive fat accumulation in central parts of the body (obesity, including a rounded or fat-filled face), diabetes, hypertension, a low serum potassium, thinning and bruising of skin, and osteoporosis. Symptoms of adrenal insufficiency include dehydration, low blood pressure and sodium level, and excessive weight loss. Primary Addison's Disease is caused when the adrenal glands fail to work on their own, i.e. fail to respond to directions from the pituitary and hypothalamus. If the tumor forms in a growth hormone producing cell, it can overproduce growth hormone. Tumors that form from growth hormone producing cells cause two different clinical pictures. If they occur in children before the growth plates in long bones have closed, excessive growth hormone will cause gigantism. (Do you recall the movie "My Giant" with Billy Crystal and the basketball player?). If the growth hormone excess occurs during adulthood there is excessive enlargement of the hands, feet, and jaw, as well as soft tissue swelling of many tissues (acromegaly). Acromegaly is associated with an increased probability of developing diabetes mellitus, heart attack, hypertension, and certain types of cancer including malignancy of the colon. Most commonly the facial changes develop subtly and may not be noticed by the patient or his/her family. What happens after a tumor is removed/treated? There may be permanent loss of some or all pituitary hormones, an imbalance that can be treated with Hormone Replacement Therapy, which has been inaccurately associated with only one group of patients: post-menopausal women. HRT can replace thyroid, growth, testosterone, or adrenal hormones when those made by the pituitary to stimulate the endocrine glands are no longer produced. It can be lifesaving therapy for the many millions of patients who need to replace hormones they no longer make. How do I get diagnosed? Anyone suffering from a constellation of complaints/clinical findings suspicious for pituitary disease should get blood and urinary hormone levels checked and, if indicated, a brain MRI, keeping in mind that microadenomas may not show up on the x-rays. Combinations of three or more of the following may suggest the possibility of a pituitary tumor: sexual dysfunction, depression, galactorrhea, infertility, growth problems, osteoporosis, obesity (specifically central), severe vision problems, easy bruising, aching joints, carpel tunnel syndrome, disrupted menses, early menopause, muscle weakness, fatigue. Where do I go to get tested? It is important to go to a hospital with a Neuroendocrine Unit or Pituitary Testing Facility, preferably both. (This may necessitate plane travel, but it would be worth every penny.) Pituitary blood tests can be very complicated and must be performed by specially trained technicians who can conduct dynamic hormone testing and precisely-timed blood sampling, administer testing agents, and have special expertise in measuring pituitary hormones. Tests that require special attention include ACTH (Cortrosyn) stimulation, bilateral inferior petrosal sinus ACTH sampling, Insulin tolerance, growth hormone stimulation, TRH stimulation, GnRH stimulation, Oral glucose tolerance, and GHRH/arginine testing for growth hormone reserve. Where do I go to get treated? Ideally you want to be seen by a pituitary endocrinologist associated with a neuroendocrine or pituitary unit with a pituitary testing facility. The interpretation of complex blood tests can result in misdiagnoses. This can be associated with microadenomas (very small tumors) that do not show up on an MRI of the brain. It often takes a real expert to get the right answers and avoid pitfalls.