Pituitary disorders

Authors : Drs Anne Peters and Pejman Cohan USC Westside Center for Diabetes and Beverly Hills

2008-07-19

Pituitary gland

INTRODUCTION

The pituitary is a small, bean-shaped gland located below the brain in the skull base, in an area called the pituitary fossa or sella turcica. The pituitary gland is an endocrine gland regulated by a region of the brain called the hypothalamus, to which it is connected by a thin connection called the pituitary stalk or infundibulum. Weighing less than one gram and measuring one centimeter in width, the pituitary gland is often called the "master gland" since it controls the secretion of many of the body’s hormones. When released by the pituitary into the blood stream, these substances have a dramatic and broad range of effects on growth and development, sexuality and reproductive function, metabolism, the response to stress, and overall quality of life. The pituitary gland is thus at the anatomical and functional crossroads of the brain, mind, and body.

Structurally, the pituitary gland is divided into a larger anterior (front) region (termed the adenohypophysis) and a smaller posterior (back) region (termed the neurohypophysis). Directly above the pituitary gland are the crossing fibers of the visual nerves, called the optic chiasm. On each side of the pituitary gland is the cavernous sinus, a channel of veins through which runs the large carotid arteries that carry blood to the brain, and important nerves that control eye movements and facial sensation. Because of the close proximity of the pituitary gland to these major nerves and blood vessels, as well as the vital hormonal control the pituitary gland provides, disorders of the pituitary can cause a wide spectrum of symptoms, from headaches to sexual dysfunction to abnormal growth.

PITUITARY HORMONES

The specific hormones produced by the pituitary along with their principal functions are listed below:

●Growth Hormone (GH): This is the principal hormone that, among many other functions, regulates body and brain development, bone maturation, metabolism, and is essential for healthy muscles.

●Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH): These hormones control the production of sex hormones (estrogen and testosterone) as well as sperm and egg maturation and release.

 ●Prolactin (PRL): This hormone stimulates secretion of breast milk.

●Thyroid Stimulating Hormone (TSH): This hormone stimulates the thyroid gland to release thyroid hormones. Thyroid hormones control basal (basic) metabolic rate and play an important role in growth and maturation. Thyroid hormones affect almost every organ in the body.

●Adrenocorticotropic Hormone (ACTH): This hormone triggers the adrenal glands (located above the kidneys) to release cortisol which in turn, regulates carbohydrate, fat, and protein metabolism, and is essential in the stress response.

●Vasopressin – Also called anti-diuretic hormone (ADH): This hormone promotes water to be reabsorbed by the kidneys and is thus essential in water and electrolyte balance. Note, this hormone is actually produced by the hypothalamus and then stored in the pituitary gland until it is ready to be released into the circulation.

 In disease states, the pituitary gland may under- or over-produce hormones. Decreased or absent hormone production from the pituitary gland is called hypopituitarism (otherwise termed Pituitary Failure). Common symptoms and treatments for pituitary failure are listed in the table below:

Hormone Deficient	Symptoms	Treatment
GH	Children: Growth delay Adults: Decreased muscle mass, increased body fat, elevated cholesterol, low bone density (osteoporosis), impaired psychological well-being, poor quality of life	Recombinant Human Growth Hormone- Given once daily as an injection under the skin
LH / FSH	Decreased libido, erectile dysfunction, irregular or absent menses, decreased body hair, decreased muscle strength, hot flashes, mood changes	Men: Testosterone- Given as either topical gel or patch or injections Women: Estrogen + Progesterone-Given as either topical patch or pills
ACTH	Poor appetite, nausea, weakness, vomiting, low blood sugar, low blood pressure, dizziness, body aches	Hydrocortisone or Prednisone-Given as daily pills
TSH	Fatigue, weakness, cold intolerance, dry skin, constipation, heavy/painful menses, weight gain, memory loss, mood disturbance	Levothyroxine – Given as daily pills (some examples include Synthroid or Levoxyl or Levothroid or Armour Thyroid)
Prolactin	Inability to lactate	No treatment available
Vasopressin (ADH)	Increased thirst and frequent urination	DDAVP- Given either as daily pills or nasal spray

PITUITARY TUMORS

Pituitary tumors are the most common disorders of the pituitary gland. The vast majority (greater than 99%) of pituitary tumors is benign (non-cancerous). These non-cancerous tumors are also called adenomas. Although they are not cancerous, these tumors can result in hormonal overproduction causing serious endocrine disturbances such as acromegaly (excess GH), cushing’s disease (excess ACTH), or prolactinoma (excess prolactin). In other instances, pituitary tumors may be non-functional, meaning that they do not produce excess hormones. Nevertheless, as these non-functional tumors grow, they can cause compression of the normal pituitary gland leading to decreased or absent hormone production (a condition called hypopituitarism or pituitary failure), visual loss from optic chiasm or optic nerve compression, and headaches. Pituitary failure may also result from pituitary surgery or from pituitary radiation therapy. In rare circumstances, a large pituitary tumor may spontaneously hemorrhage. This spontaneous hemorrhage is called pituitary apoplexy and often leads to pituitary failure. Pituitary apoplexy is further discussed below. Pituitary adenomas can also be classified on the basis of their size. Tumors measuring less than 1 cm are called micro-adenomas; tumors measuring greater than 1 cm are referred to as macroadenomas.

Other non-pituitary tumors may also arise near the pituitary gland and can impact pituitary hormonal function. These include Rathke’s cleft cysts, craniopharyngiomas, meningiomas, chordomas, gliomas and epidermoid cysts. Each of these types of pituitary tumors and disorders will be individually described below.

ACROMEGALY  

Acromegaly is a disease caused by a pituitary tumor (adenoma) that secretes too much growth hormone (GH). This overproduction of GH results in overgrowth of various tissues and many other metabolic problems. The high GH levels in turn stimulate the liver to make excessive amounts of another protein called insulin-like growth factor-1 (IGF-1). High levels of GH and IGF-1 can lead to diabetes, high blood pressure, carpal tunnel syndrome, arthritis and sleep apnea, heart failure, among other things. Because of the serious changes resulting from GH excess, treatment is essential. Untreated acromegaly is a serious condition that can cause dramatic bone and soft tissue changes and serious cardiovascular problems.  If the GH producing tumor develops before bone growth is completed in adolescence, gigantism is the result. The famous wrestler, Andre Rene Roussimoff (better know as “Andre the Giant”), is an example of a person with gigantism.  Andre died in his forties, probably from the cardiac complications of Acromegaly.  Death is approximately doubled in acromegaly compared with the normal population.  

SYMPTOMS AND SIGNS:  Hand enlargement (usually detected as an increase in ring size)  Foot (usually detected as an increased shoe size)  Forehead enlargement (medically termed frontal bossing)  Jaw enlargement (medically termed prognathism)  Underbite/Spreading of teeth  Tongue enlargement  Excessive snoring  Sleep Apnea  Carpel tunnel syndrome  Headaches  Changes in vision  Fatigue  Sexual problems  Irregular menstrual cycles  Milky breast discharge (medically termed galactorrhea)  High blood pressure (Hypertension)  Diabetes Mellitus  Colon tumors     Since these physical changes develop gradually over many years, comparing old and recent photographs will often demonstrate dramatic changes in body appearance.    

DIAGNOSIS:  Acromegaly is diagnosed by documenting elevated levels of both GH and insulin-like growth factor-1 (IGF-1). IGF-1 is a hormone made by the liver under the influence of GH. Therefore, in states of GH excess, IGF-1 will also be elevated. An oral glucose tolerance test is often used to confirm excess GH production. This test is done by administering a standardized amount of a sugary beverage to the patient and then measuring GH levels.  Normally, GH levels decline after intake of the sugary drink. However, in Acromegaly, the GH levels do not decrease and may even increase in response to sugar ingestion.  Following hormonal testing that confirms acromegaly, an MRI of the pituitary should be performed to confirm the presence of a pituitary adenoma.  In very rare cases, Acromegaly can result from tumors located outside of the pituitary gland (such as the pancreas or lung. This rare cause of Acromegaly is called ectopic Acromegaly.  

TREATMENT:  The goals of treatment are to remove the pituitary tumor and to restore normal GH levels. Surgery to remove the pituitary tumor is considered the treatment of choice for most patients with Acromegaly. This surgery is performed through the nostril (termed transsphenoidal surgery). The success of surgery depends on the size of the tumor and the skill of the surgeon. Remission may not be possible in patients with large or invasive adenomas. In such instances, medical therapy and/or radiotherapy (treatment with radiation) may be necessary to shrink the residual tumor and control GH levels. In general, the higher the pre-operative GH level, the lower the chance for cure. Long-term remission of acromegaly after surgery is possible in 80-90% of patients with tumors measuring less than 1 cm (microadenomas) and in 50-60% of patients with macroadenomas.  Patients with persistent GH elevation after surgery, may be treated with medications and/or radiotherapy.  Medications included octreotide (name brand Sandostatin LAR®), lanreotide (name brand Somatuline®) or pegvisomant (brand name Somavert®).  Octreotide or lanreotide (given by once monthly injection) achieves long-acting suppression of GH in about 70% of patients. These drugs lead to some tumor shrinkage in 30-50% of patients, and often improve soft tissue swelling, headache, joint pains, and sleep apnea. Preoperative use of octreotide may facilitate tumor removal and lessen risks of general anesthesia. Side effects may include loose stools, malabsorption (inadequate absorption of nutrients), gallstones, and local pain at the injection site. Pegvisomant®, a GH receptor blocker, is also effective in lowering IGF-1 levels, although it does cause an elevation in GH levels and will not shrink the tumor. Pegvisomant is a daily injection.  Bromocriptine and Cabergoline are oral medications that are called "dopamine agonists." These medications lower GH secretion in only about 15% of acromegalic patients and may cause some tumor shrinkage in only 10-15% of patients.  Radiation is also an effective treatment for acromegaly.  Radiation is now primarily delivered using stereotactic techniques. Stereotactic techniques mean that the radiation beam is accurately focused and directed at the tumor through the use of computers and scanning devices that create a three-dimensional picture. When a high dose of radiation is given in a single treatment, it is termed Stereotactic Radiosurgery (SRS). Gamma knife is another term that is used to refer to SRS. When the radiation is delivered in multiple small doses over a period of weeks, it is called Stereotactic Radiotherapy (SRT).  Both SRS (one dose) and SRT (multiple doses) are effective in lowering GH and IGF-1 levels and stopping tumor growth in 60-70% of patients. However, the lowering of GH and IGF-1 levels takes longer with SRT (average 7 years) compared with SRS (average 18 months). Pituitary gland failure often occurs in the years after either SRS or SRT. Other complications such as visual loss are rare with either SRS or SRT.

CUSHING’S DISEASE  

Cushing's disease is a serious condition caused by a pituitary tumor (adenoma) that is over-producing the hormone, ACTH. Cushing’s disease is a subset of Cushing’s syndrome, which refers to elevated blood cortisol levels of any cause. Cushing's syndrome results from tumors of the pituitary, adrenal glands, or from tumors elsewhere in the body (ectopic ACTH-producing tumors). The cause of Cushing's syndrome is a pituitary adenoma in more than 70% of patients. Most ACTH adenomas are microadenomas. Cushing's disease is relatively uncommon, affecting 10-15 of every million people each year, and most commonly in adults aged 20-50 years old; women account for more than 70% of cases. Since Cushing’s disease causes so many common problems affecting the general population such as obesity, hypertension, and diabetes, it is possible that many patients with Cushing’s disease are undiagnosed for years or perhaps never diagnosed.  

SYMPTOMS AND SIGNS:  Weight gain (especially in the abdomen)  Rounding and flushing of the face (referred to as “moon face”)  Fat deposits behind the neck (referred to as buffalo hump  Thinning and bruising of the skin  Purplish stretch marks (referred to stria)  Excess hair growth on the face and body (termed hirsutism)  Muscle weakness and muscle wasting.  Fatigue  Irregular or absent menstruation  Sexual problems  Depression  High blood pressure  Diabetes  Osteoporosis  Kidney stones  Since these physical changes may develop gradually over many years, comparing old and recent photographs will often demonstrate dramatic changes in body appearance.    

DIAGNOSIS:  Unfortunately, the diagnosis of Cushing's disease is often long delayed. An endocrinologist should always supervise the evaluation for Cushing's disease since many of the clinical features of Cushing’s disease can be non-specific and deceptive.  The diagnosis of Cushing’s disease rests on documenting high levels of the hormone cortisol.  This is usually accompanied through various blood and urine tests.  To complicate matters, there is considerable overlap in the lab results of patients with Cushing’s syndrome and those without.  The most commonly done tests include 24-hour urinary free cortisol collection, midnight salivary cortisol test, and/or a low-dose dexamethasone suppression test. If blood ACTH levels are elevated or normal, then the Cushing’s is term ACTH-dependent and the source is from either an ACTH-secreting pituitary adenoma or an ectopic (elsewhere in the body) ACTH-producing tumor. A high-dose dexamethasone suppression test and/or petrosal sinus sampling are tests used to distinguish between ectopic ACTH production and pituitary ACTH production (Cushing's disease). Petrosal sinus sampling is highly specialized and invasive procedure during which a small tube is inserted into the veins of the groin and then threaded up to the pituitary gland in order to measure ACTH levels. Petrosal sinus sampling should never be performed before the diagnosis of ACTH-dependent Cushing's syndrome is established.  Once the diagnosis of Cushing's syndrome is made and it confirmed that the Cushing’s is ACTH-dependent, then a pituitary MRI may be done. If the MRI is focused on the pituitary and done with and without contrast, it can detect an adenoma in about 50% of cases. If the Cushing’s syndrome is ACTH-independent, then a CT scans of the adrenal glands are very useful for determining the presence or absence of an adrenal tumor causing Cushing's syndrome.  

TREATMENT:  Like Acromegaly, transsphenoidal Surgery is considered the treatment of choice for Cushing’s syndrome. Surgical remission rates range from 80-90% for microadenomas and from 30-70% for macroadenomas and invasive adenomas. Long-term follow-up with testing of 24-hour urinary free cortisol levels every 6 months is essential to monitor for tumor recurrence, which can occur in 5-10% of patients.  In patients who have persistent Cushing’s disease after surgery, medications such as ketoconazole and aminoglutethimide may be used. These medications inhibit steroid (cortisol) production in the adrenal glands. They are initially effective but have many side effects, and the overall long-term control of Cushing’s disease with these drugs is rather poor. For patients whose Cushing's disease is not controlled with surgery, stereotactic radiotherapy (SRT) or stereotactic radiosurgery (SRS) are effective in controlling cortisol levels and tumor growth in 50-70% of patients  Radiation is now primarily delivered using stereotactic techniques. Stereotactic techniques mean that the radiation beam is accurately focused and directed at the tumor through the use of computers and scanning devices that create a three-dimensional picture. When a high dose of radiation is given in a single treatment, it is termed Stereotactic Radiosurgery (SRS). Gamma knife is another term that is used to refer to SRS. When the radiation is delivered in multiple small doses over a period of weeks, it is called Stereotactic Radiotherapy (SRT).   However, the lowering of cortisol levels generally takes significantly longer with SRT compared to SRS. Also, SRT and SRS often result in loss of normal pituitary function over 5 to 10 years. Other complications such as visual loss are rare with either SRS or SRT.


PROLACTINOMAS

Prolactinomas are benign pituitary tumors that secrete excessive amounts of the hormone prolactin. They are the most common of all the pituitary adenomas. The normal blood prolactin level is typically less than 20-25 ng/ml. Patients with prolactinomas can have prolactin levels in the hundreds to even the thousands. In general, the prolactin level correlates with the size of the prolactinoma. In most women, prolactinomas are detected when they are smaller (microadenomas) and the prolactin level is moderately elevated (50-300 ng/ml). In contrast, in men prolactinomas are typically detected when they are larger (macroadenomas), and the prolactin level may be considerably higher.  

SIGNS AND SYMPTOMS:  Irregular or absent menstrual cycles  Breast milk production (medically termed galactorrhea)  Low testosterone level in men (medically termed hypogonadism)  Low estrogen level in women (medically termed hypogonadism)  Low sex drive  Infertility  Weight gain  Mood changes  Headaches  Visual changes  Brest enlargement (medically termed gynecomastia)

DIAGNOSIS:  A prolactinoma is diagnosed by documenting elevated blood prolactin levels. A prolactin level of over 150-200 ng/ml is almost always due to a prolactinoma. However, moderate prolactin elevations (30-200 ng/ml) can occur from other causes such as pregnancy, stress (discomfort, exercise), low thyroid function (hypothyroidism), kidney or liver failure, and certain medications (e.g., medications to treat nausea or depression). An additional cause of high prolactin level is the so called "stalk compression effect.” The stalk effect refers to a mild elevation of the prolactin (generally between 40 – 100 ng/mL) due to pressure on the pituitary stalk from a pituitary or other brain tumor. In the situation of the stalk effect, the tumor is not actually secreting prolactin. Examples of tumors that may cause stalk effect are craniopharyngiomas. After documenting high prolactin level, an MRI is done with and without contrast to visual the tumor.

TREATMENT:  In general, the first line of treatment for patients with a prolactinoma is oral medications. Approximately 80% of patients will have prolactin levels restored to normal with dopamine agonist therapy and many will have marked tumor shrinkage. The most commonly used agent is cabergoline (Dostinex) which has replaced bromocriptine (Parlodel®) as the drug of choice given cabergoline’s higher success rate and lower side-effect rate. Most women have return of menses and many become fertile again. Tumor shrinkage will often result in rapidly improved vision and headache resolution. Cabergoline is taken only twice per week and generally has few side effects. It is also effective in patients whose prolactinomas are resistant to bromocriptine therapy. The usual starting dose is 0.5 mg twice per week and may be increased up to 1.0 mg twice per week. Bromocriptine, if used, should be started at a low dose to minimize nausea and other gastrointestinal side effects, usually 2.5 mg tablet per day at mealtime. The dose is then increased over several days or weeks to a daily maximum usually no exceeding 10 mgs.  Recent reports indicate that long-term, high-dose therapy with a dopamine agonist like cabergoline or bromocriptine can result increased risk of injury to the valves of the heart. Although the risk of valvular heart disease appears to be low with standard doses of cabergoline and bromocriptine used to treat prolactinomas, it remains a potential risk.  Transsphenoidal Surgery to remove the pituitary tumor is a reasonable first-line therapy in patients with micro-prolactinomas that do not invade the cavernous sinus and whose prolactin level is less than 250 ng/ml. In these patients, long term remission is generally 80-90%. Surgery is also effective for lowing prolactin levels in patients intolerant of cabergoline. However, for macroadenomas, the cure rate is generally low. In men with large invasive prolactinomas, it averages less than 30%. Even in patients with long-standing visual loss, dopamine agonist therapy can be tried first. However, if visual loss has occurred rapidly over less than 2 weeks, or if the MRI shows hemorrhage or degeneration in the tumor, endonasal surgery is generally recommended. For the minority of patients who do not respond well to dopamine agonist therapy with cabergoline, surgery should generally be performed within 6 months of starting therapy. After more than 6 months of such therapy, the tumor may become more scarred and difficult to remove.  Because most patients with prolactinomas respond so well to dopamine agonist therapy and/or surgery, radiation therapy is rarely required.



NON-FUNCTIONAL (ENDOCRINE-INACTIVE) ADENOMAS  

Non-functional adenomas are pituitary tumors that do not result in excess hormone production. Instead, they typically cause symptoms due to pressure on the normal pituitary gland and/or on structures near the pituitary such as the optic nerves and optic chiasm.  Almost all symptomatic endocrine-inactive adenomas are macroadenomas. Occasionally, they grow quite large and into the cavernous sinus, and may also compress the optic nerves. Some patients with large tumors may have hemorrhage into the tumor (this is referred to as pituitary apoplexy) causing rapid onset of headache, vision loss, double vision, and/or pituitary failure.    

SYMPTOMS:  Pituitary failure  Visual changes  Headaches  Fatigue  Decreased mental function  Weight gain,  Loss of sex drive  Infertility  Irregular periods  

DIAGNOSIS:  Endocrine-inactive adenomas are diagnosed by imaging studies and hormonal testing. An MRI of the pituitary gland provides the most detail, although a brain MRI or brain CT scan will reveal most pituitary macroadenomas. Hormonal testing is also essential to evaluate for pituitary gland failure (i.e., hypopituitarism). A complete pituitary hormonal analysis should be performed as described above and is ideally overseen by an endocrinologist.  

TREATMENT:  Transsphenoidal Surgery is considered the first-line treatment for symptomatic endocrine-inactive adenomas or incidentally discovered macroadenomas larger than 15 mm or those that contact the optic nerves or optic chiasm. The long-term surgical remission or cure rate is approximately 70-80% overall. The total tumor removal rate is higher for smaller tumors and those that do not invade the cavernous sinus. Conversely, the total tumor removal rate is lower for larger tumors (over 3 cm) or those that invade the cavernous sinus. Transsphenoidal tumor removal improves visual acuity and visual field deficits in 75-90% of patients and headache resolution is seen in 80-90% of patients. Pituitary function is restored in only 20-50% of patients. Patients who do not have hormonal recovery after surgery will require hormone replacement therapy. Because transsphenoidal surgery is so effective and relatively safe, it is rare that even large macroadenomas warrant a transcranial operation as the initial procedure.  For patients who have residual tumor after the initial transsphenoidal surgery, focused radiation may be needed to control tumor growth. Radiation is now primarily delivered using stereotactic techniques. Stereotactic techniques mean that the radiation beam is accurately focused and directed at the tumor through the use of computers and scanning devices that create a three-dimensional picture. When a high dose of radiation is given in a single treatment, it is termed Stereotactic Radiosurgery (SRS). Gamma knife is another term that is used to refer to SRS. When the radiation is delivered in multiple small doses over a period of weeks, it is called Stereotactic Radiotherapy (SRT).  Both SRT and SRS halt tumor growth in at least 85-90% of patients. However, SRT and SRS may result in loss of normal pituitary function over 5 to 10 years. Neurologic complications such as visual loss and temporal lobe damage rarely occur with SRT and SRS. There is no effective medical therapy that reliably halts growth of endocrine-inactive adenomas.     


TSH-SECRETING PITUITARY TUMOR (THYROTROPINOMA)  

Pituitary tumors that secrete thyroid-stimulating hormone (TSH) are quite rare and represent only about 1-2% of all pituitary adenomas that are surgically removed. In these tumors, over-production of TSH results in over-stimulation of the thyroid gland and excessive thyroid hormone production (hyperthyroidism). Because many patients first have thyroid treatment of some sort, these pituitary tumors are often aggressive and invasive in their growth pattern. Most patients who have not had prior anti-thyroid therapy will have an elevated thyroxine (T4) and a markedly elevated TSH level. MRI and CT of the pituitary without and with contrast agents typically demonstrate the adenoma. First-line therapy is transsphenoidal removal. Invasive and very large tumors may require additional therapy including thyroid ablation along with pituitary radiation therapy, preferably with stereotactic radiotherapy (SRT).   


CRANIOPHARYNGIOMA  

Craniopharyngiomas are benign brain tumors that arise near the pituitary gland and pituitary stalk and are typically both cystic and solid in structure. They occur most commonly in childhood and adolescence and in later adult life, after age 50. They account for 10-15% of sellar and suprasellar tumors (tumors that occur in and above the pituitary gland) and 50-60% of sellar and suprasellar tumors in children. They are usually not discovered until they impinge upon important structures around them, and are frequently quite large (over 3 cm) when detected. Although they are benign (not malignant) tumors, these tumors tend to become adherent to structures around the pituitary gland and stalk, including the optic nerves, optic chiasm, intracranial arteries, and the brain itself. They are thought to arise from remnants of embryological development. They are thought to be closely related to Rathke’s Cleft cysts (RCCs).  

SYMPTOMS:  Craniopharyngiomas can cause a variety of symptoms depending upon their location. If the tumor compresses the pituitary stalk or gland, the tumor can cause partial or complete pituitary failure. This may lead to growth failure, delayed puberty, loss of normal menstrual function or sexual desire, increased sensitivity to cold, fatigue, constipation, dry skin, nausea, low blood pressure, and depression. Pituitary stalk compression can also cause diabetes insipidus (DI), and increased prolactin levels causing a milky discharge from the breast (galactorrhea). If the tumor compresses the optic chiasm or nerves, then visual loss can result. Involvement of the hypothalamus, an area at the base of the brain, may result in obesity, increased drowsiness, and temperature regulation abnormalities. Other symptoms especially with larger tumors may include personality changes, headache, confusion, and vomiting.  DIAGNOSIS:  A craniopharyngioma is typically diagnosed with an MRI of the pituitary region. Many craniopharyngiomas will also be well seen on a CT scan especially since some are partially calcified (containing calcium deposits). A complete pituitary hormonal blood evaluation should also be performed. Other possible diagnoses to consider with a cystic pituitary mass is a cystic pituitary adenoma or an arachnoid cyst.  

TREATMENT:  Surgery: The best initial treatment for a craniopharyngioma is surgical removal by either the transsphenoidal approach (i.e., through the nostril) or by a supra-orbital “eyebrow craniotomy (i.e., through an incision along the eyebrow).  The goal of surgery is to completely remove the tumor while improving vision and brain function. Because of their tendency to be adherent to the optic chiasm, other nerves and important blood vessels, complete tumor removal may not be possible in up to 50% of patients.  Radiosurgery (SRS) or Stereotactic Radiotherapy (SRT): With incomplete removal, stereotactic radiotherapy (SRT) or stereotactic radiosurgery (SRS), are typically used to prevent further tumor growth. Additionally, because of the tendency for craniopharyngiomas to recur, repeat MRIs or CT scans should be obtained at least every 6 months for the first 5 years after surgery or radiation therapy and then at least annually thereafter.  Hormonal Replacement Therapy: Many patients with a craniopharyngioma will develop pituitary hormone deficiencies because of the tumor itself, surgery or as a consequence of radiotherapy. Such patients will require hormone replacement therapy such thyroid, cortisol, testosterone (men), estrogen (women), and/or DDAVP for diabetes insipidus. Because hormonal deficiencies can develop many years after radiation treatment, patients treated with radiation should have periodic hormonal evaluations throughout their lifetimes. Regular follow-up with an endocrinologist is recommended for all patients with a craniopharyngioma.  


RATHKE’S CLEFT CYSTS  

Rathke’s Cleft Cysts are benign cysts; they are not true tumors or neoplasms. Rathke’s pouch forms as part of normal development and eventually forms the anterior lobe, pars intermedia, and pars tuberalis of the pituitary gland. This pouch normally closes in fetal development, but a remnant often persists as a cleft (indentation or gap) that lies between the anterior and posterior lobes of the pituitary gland. Occasionally, this remnant enlarges to form a cyst. RCCs can cause pituitary failure, headaches, and in some instances, vision loss.  SYMPTOMS:  Symptomatic RCCs are relatively common pituitary lesions, accounting for 5-10% of surgically removed pituitary masses. RCCs can be seen at any age, although most are identified in adults. Intrasellar RCCs are usually asymptomatic and are found incidentally at autopsy or on a magnetic resonance imaging (MRI) scan. However, larger RCCs may cause visual disturbances, symptoms of pituitary dysfunction, and headaches.  DIAGNOSIS:  The typical means of visualizing a RCC is with an MRI or a computer tomography (CT) scan of the pituitary region performed without and with contrast. A complete pituitary hormonal blood evaluation should also be performed. Other possible diagnoses to consider when a cystic mass is seen in the area of the pituitary include a cystic pituitary adenoma, craniopharyngioma or arachnoid cyst.  TREATMENT:  The standard treatment for a symptomatic RCC causing pituitary failure, headache, or visual loss is surgical removal through the transsphenoidal approach. The goal of surgery is to completely remove the cyst contents while improving or preserving pituitary function vision and alleviating headache and visual loss if present. Attempts to remove the cyst lining should be avoided because this can result in pituitary gland damage. A complete removal of RCCs is possible in 80-95% of cases although they can recur at a rate of 5-15% over 5 to 10 years. 

OTHER PITUITARY DISORDERS  

Lymphocytic Hypophysitis:  

Lymphocytic Hypophysitis (LH) is an autoimmune condition in which the body’s immune system inappropriately mounts an “attack” against the pituitary gland and the pituitary stalk. This immune reaction can result in pituitary failure (hypopituitarism). One or more pituitary hormones may become deficient. Moreover, infiltration of immune cells in the area of the pituitary gland can also place pressure on surrounding structures and result in headaches and visual disturbance. LH has a characteristic appearance on MRI in which the pituitary gland and/or the pituitary stalk are enlarged and thickened, but there is no pituitary tumor. Biopsy may be necessary to confirm the diagnosis. Once believed to be a rare condition that occurred primarily in young women in the context of pregnancy, LH is now increasingly recognized as a cause of pituitary failure. The exact immunological mechanisms that lead to LH are poorly understood. It is sometimes associated with other immune disorders (such as Hashimoto’s Thyroiditis). There is no single effective treatment for LH and treatment needs to be tailored to the particular patient and his or her symptoms. In some cases, steroids (i.e., Prednisone) are administered to dampen the autoimmune reaction. However, steroids have many potential side effects, and some patients do not show improvement even with high-dose steroid therapy. In those that do respond to steroids, the symptoms may recur once the steroids are either tapered or stopped. In cases where the immune reaction against the pituitary gland is severe and results in headaches or visual disturbance, transsphenoidal surgery may be done to relieve pressure within the pituitary gland. Regardless of the treatment chosen, the patient suspected of having LH must have their pituitary function carefully tested and any pituitary hormone deficiencies must be replaced.  

Pituitary Apoplexy:  

Pituitary apoplexy occurs when a pituitary tumor spontaneously bleeds. This may occur if the tumor outgrows it blood supply. The use of blood thinners in a person with a pituitary tumor may predispose to pituitary apoplexy. The relatively sudden change in tumor size causes compression of the normal pituitary gland, the optic nerves, and the nerves that control eye movements. All types of pituitary adenomas discussed above can be associated with apoplexy, particularly larger tumors (macroadenomas). Symptoms often include headache, nausea, visual loss, and double vision. If bleeding extends into the cerebrospinal fluid spaces, severe headache, neck stiffness, and fever may occur. Many patients also have pituitary hormone insufficiency. Pituitary apoplexy is best diagnosed with an MRI scan of the brain, with special attention to the pituitary. A computerized tomography (CT) scan of the pituitary gland also shows an abnormality in most cases. Effective treatment of pituitary apoplexy requires rapid administration of high-dose steroids (hydrocortisone), and careful monitoring of fluid and electrolyte levels. In many cases, urgent transsphenoidal surgery is necessary to evacuate (empty) the blood and remove the underlying tumor. 

Sheehan’s Syndrome:  

Sheehan’s syndrome (also referred to as post-partum pituitary necrosis) is a condition in which the pituitary gland is injured as result of heavy blood loss during complicated childbirth. This heavy loss of blood deprives the pituitary gland of oxygen and other nutrients and leads to necrosis (death) of pituitary tissue and therefore pituitary failure (hypopituitarism). Failure to produce breast milk after delivery (due to lack of the pituitary hormone prolactin) may be a presenting sign of Sheehan’s syndrome. Fortunately, Sheehan’s syndrome is now rare cause of pituitary failure, particularly in developed countries as a result of improved obstetric care.

 

Empty Sella Syndrome:

Empty sella syndrome is a radiological finding where spinal fluid is found within the space created for the pituitary. The most common cause is a large opening in the diaphragma sellae, a membrane which sits on top of the pituitary and protects it in its socket within the bones at the base of the skull. When this opening is large, the spinal fluid pressure is transmitted to the pituitary and flattens it out within the sella. Generally, in this situation, pituitary function is normal, but a number of patients have headaches, mild hyperprolactinemia, galactorrhea, and irregular menses. In most cases, however, the pituitary functions normally. Some patients have empty sella syndrome as a result of other processes such as pituitary tumors that have degenerated, etc. Rare patients have a congenital empty sella and a coexisting pituitary tumor.

Metastatic Brain Tumors: 

Metastatic brain tumors (also known as secondary brain tumors) arise from a cancer from another part of the body that then spreads to the pituitary gland. These are the most common type of brain tumor occurring 5-10 times more commonly than primary brain tumors. The most frequent types of cancer that metastasize to the brain are lung, breast, melanoma, colon, kidney and thyroid.  Symptoms of a metastatic tumor or tumors are variable and depend on the location; common complaints include headache, seizures, weakness, numbness, imbalance or in-coordination, confusion, and personality changes. Such tumors may also result in pituitary failure, commonly diabetes insipidus. The diagnosis of these tumors is typically made by a brain MRI with and without contrast which will show the exact location and number of metastatic tumors. Treatment of metastatic brain tumors may involve surgical removal, radiotherapy or chemotherapy. In many instances, all 3 of these treatments are needed. Although the prognosis for patients with a metastatic brain tumor can be poor, treatments are continually improving.  

Post-Head Trauma Hypopituitarism: 

Head trauma is an increasingly recognized cause of pituitary damage or pituitary failure. Pituitary failure after head trauma has been reported even in the absence of skull fracture or loss of consciousness. Most patients are young men involved in motor vehicle accidents, and there is often a lag of many years from the time of head injury to the diagnosis of hypopituitarism.
 

 SUMMARY  

In summary, pituitary conditions are now felt to be increasingly common and can cause a variety of symptoms that range from fatigue to headaches to visual changes to sexual dysfunction. Many effective treatments are now available to effective treat most pituitary disorders and thereby improve quality of life. Patients with pituitary tumors benefit most by a multi-disciplinary team of health care providers that include endocrinologists, neurosurgeons, ophthalmologists, radiation therapists, psychologists, and psychiatrists.  The following internet websites provide additional useful information:   

 

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