Pituitary Tumors

Removal of a pituitary tumor through the nose with the operative microscope

Introduction . . .

Side view showing tumor compressing optic nerves

Front view showing compression of the optic nerves and chiasm

Pituitary tumors arise from the pituitary gland within the base of the skull. These tumors are almost always benign. Symptoms arise when these tumors secrete hormones or become large enough to compress adjacent structures. Rarely, these tumors may spontaneously hemorrhage. As these tumors enlarge, the normal pituitary function is destroyed. This produces various

Primary Reference: Fizgerald, P.A. and Klonoff, D.C. Hypothalamic and Pituitary Hormones, in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, pp 603-618.

The adrenals are two crescent-shaped glands that sit on top of each kidney. The adrenal glands secrete hormones directly into the bloodstream. They are divided anatomically and functionally into two main parts: the medulla (middle) and the cortex (rind) (Clayman 1989). Additionally, each division of an adrenal gland consists of internal layers that produce different hormones. The inner part, or adrenal medulla, manufactures epinephrine and norepinephrine, also known as commonly known as adrenaline and noradrenaline. These hormones are the "fight or flight" hormones that are released in potentially life-or-death situations. Their release increases one's heart rate , and blood pressure , and diverts more blood to the brain, heart, and skeletal muscles. This is important when discussing stress. The adrenal cortex surrounds the adrenal medulla and responds to a different type of stress. This is where the steroid hormones are made. These include cortisone, hydrocortisone, testosterone, estrogen, 17-hydroxy-ketosteroids, DHEA, pregnenolone, aldosterone, androstenedione, progesterone, and some other intermediate hormones. Many of these hormones are also made elsewhere in the body, but aldosterone, cortisone, and hydrocortisone are made only in the adrenal glands. The hormone aldosterone, together with the kidneys, regulates the balance of sodium and potassium in the body. This regulation is critical to many areas o f physiological function, including the ability to react to stress, maintain fluid balance, and regulate blood pressure. Two disorders often associated with impaired function of the adrenal glands are Addison's disease and Cushing's syndrome. Addison's Disease: Adrenal Insufficiency Addison's disease is a profound chronic adrenal failure caused by damage or disease of the adrenal gland, resulting in a deficiency of cortisol. This disease is sometimes called chronic adrenal insufficiency or hypocortisolism. The most important job of cortisol is to help the body respond to stress. Among its other vital tasks, cortisol is partly responsible for:

Maintaining blood pressure and cardiovascular function Balancing the effects of insulin in breaking down sugar for energy Slowing the immune system's inflammatory response Regulating the metabolism of proteins, carbohydrates, and fats

Addison's disease is characterized by muscle weakness, reduced blood sugar, nausea, loss of appetite, weight loss, and low blood pressure, which can impact the act of standing, causing dizziness or fainting. Skin changes also are common in Addison's disease, with areas of hyperpigmentation or dark tanning that are mostly visible on scars, skin folds, toes, lips, mucous membranes, and pressure points, such as the elbows, knees, and knuckles. Cushing's Syndrome: Overproduction of Cortisol The overproduction of cortisol by the adrenal glands leads to Cushing's syndrome (Clayman 1989). Cushing's syndrome also results when glucocorticoid drug hormones (such as hydrocortisone, prednisone, methylprednisolone, or dexamethasone) are taken in excess for a prolonged period of time. These steroid hormones are often used to treat inflammatory-related illnesses such as asthma, rheumatoid arthritis, systemic lupus erythematosus, and some allergies. The overproduction of cortisol in the adrenal glands can happen in two ways. A pituitary tumor could be producing too much ACTH (adrenocorticotropic hormone, produced by the pituitary gland), stimulating the adrenals to grow and to produce too much cortisol, or a benign or malignant tumor outside the pituitary such as in the lung, thymus gland, pancreas, or other organs can produce too much ACTH. The pituitary form is classically called Cushing's disease. Cushing's syndrome is characterized by central obesity; sparing of the arms and legs (thin extremities); a round, reddish moon face; buffalo hump; and a protuberant abdomen. Many people with Cushing's syndrome experience severe fatigue, weak muscles, ulcers, thin skin, high blood pressure, and high blood sugar. Irritability, anxiety, and depression are also very common. Women with Cushing's syndrome will usually have excess hair growth (hirsuitism) on their face, necks, chests, abdomens, and thighs. Their menstrual periods may become irregular or stop. Men may have decreased fertility and desire for sex. Adrenal Fatigue Constant stress and poor nutrition can weaken the adrenal glands. When stress continues over prolonged periods of time, the adrenal glands can deplete the body's hormonal and energy reserves, and the glands may either shrink in size or hypertrophy (enlarge). The overproduction of adrenal hormones caused by prolonged stress can weaken the immune system and inhibit the production of white blood cells that protect the body against foreign invaders (in particular lymphocytes and lymph node function). Adrenal dysfunction can disrupt the body's blood sugar metabolism, causing weakness, fatigue, and a feeling of being run down. It can also interfere with normal sleep rhythms and produce a wakeful, unrelaxing sleep state, making a person feel

worn out even after a full night's sleep. If a person succumbs easily to allergies and infections, feels constantly drained and exhausted, and experiences low blood sugar and blood pressure, the culprit may be weak adrenals. Adrenal insufficiency is sometimes linked to chronic fatigue. In some fatigued patients, thyroid problems may overlap adrenal problems. In these cases, the status of the adrenal glands and the thyroid gland must be assessed. The appropriate treatment should be undertaken only after this determination is made. If adrenal fatigue is suspected, the patient should be evaluated by a physician with experience in recognizing and treating adrenal fatigue and issues of the relative Addisonian state. It is very important to make sure that full-blown Addison's disease is not the problem, since it must be treated vigorously (Ehlert et al. 2001; Tsigos et al. 2002). In most communities, a qualified internist or internal medicine subspecialist will begin the investigation. Diagnosis

Factors that May be Overlooked in Diagnosis

If disturbed adrenal function is suspected, the levels of hormones such as hydrocortisone, aldosterone, epinephrine, and ACTH may be measured in blood, plasma, and urine. There are also tests (by injection) to measure the effects of substances that normally modify the production of a specific hormone. One test is called the ACTH challenge test. When ACTH is injected, there should be an increase in adrenal hormone output. If this does not happen, adrenal fatigue is probable. These tests are also helpful in localizing the underlying cause of a particular disorder (e.g., to distinguish between Cushing's syndrome caused by an adrenal tumor from that caused by pituitary disease). Conversely, a very high potency corticosteroid (dexamethasone) can be used to assess the suppressability of cortisone production in Cushing's syndrome. If disease of the adrenal glands is suspected, imaging studies (abdominal x-ray, MRI, CT scan, arteriography, radionuclide scanning, and IV scanning of the position of kidneys using an IV dye) may show the presence of adrenal calcification, a tumor, atrophy, or the overgrowth of a gland. Factors that May be Overlooked in Diagnosis Cortisone is produced mainly in a reversible reaction from cortisol; it is also secreted in small amounts from the adrenal cortex. The term hydrocortisone refers to both naturally produced cortisone and the pharmaceutical preparation used to treat various inflammatory disorders. Naturally produced hydrocortisone is a glucocorticoid, meaning that it helps to regulate normal blood glucose concentration by converting amino acids and fatty acids to glucose, when needed, in a process called gluconeogenesis. Synthetic hydrocortisone drugs (corticosteroids) became available in the late 1940s and were heralded as a miraculous treatment for rheumatoid arthritis due to their suppression of the immune system. However, it did not take long to learn that there was a serious price to pay for

chronic corticosteroid use. People taking synthetic hydrocortisone developed many symptoms and physical abnormalities such as the symptoms of Cushing's syndrome, resulting from the body's overexposure to corticosteroids. As a result of these adverse reactions, an often irrational approach developed in the medical community to the question of relative adrenal function. A person who has total failure of the adrenal glands is said to have Addison's disease even though low steroid levels can also be caused by failure of the hypothalamus , thalamus, and pituitary areas of the brain. In this case, the adrenal glands still function. In the case of Cushing's syndrome, the disease may manifest due to physical abnormality or as the result of corticosteroid use. When a physician evaluates a patient relying solely upon laboratory data, the patient is considered either normal or having Addison's disease or Cushing's syndrome. There may be no analysis of other contributing factors. This protocol is directed only at the function of the adrenal glands. However, just as in thyroid dysfunction (see the Thyroid Deficiency protocol), normal laboratory tests do not exclude what some physicians refer to as adrenal fatigue (or relative Cushing's or Addisonian states). The association of impaired immune function and the administration of synthetic corticosteroids ha ve s blurred an important fact. Decreased levels of corticosteroids also impair immune function. What further complicates the matter is the fact that it is now thought that the continual overproduction of cortisol, not in the range that would produce Cushing's syndrome, contributes to immune suppression, atherosclerosis, brain cell injury, and accelerated aging. Drug Treatments

Addison's Diseases Cushing's Syndrome

Addison's Disease

Adrenal Cortical Extract Hydrocortisone

Adrenal Cortical Extract A few physicians recommend adrenal cortical extract (ACE), which contains all the corticosteroids in the proper proportions. ACE used to be widely available in this country, but at the present time it is not. Complementary physicians may have had experience with it. At times of increased stress, the addition of adrenal glandulars may be advisable but must be monitored carefully. Long-term use is not recommended and is likely hazardous. (The FDA removed all products containing adrenal cortex from market in 1997 due to concerns regarding

contamination.) Hydrocortisone Cortisol is usually replaced orally with hydrocortisone tablets. The doses of this medication are adjusted to meet the needs of individual patients. During a critical stage, when blood pressure and blood sugar are dangerously low and potassium levels are high, therapy can involve the injection of hydrocortisone, saline, and dextrose. Cushing's Syndrome Treatment of Cushing's syndrome will depend upon the cause of the disorder. If the disorder is caused by long-term corticosteroid use, the drug must be slowly decreased and the patient weaned under medical supervision. If it is caused by a pituitary or adrenal tumor, surgery is necessary to remove it. In Cushing's syndrome caused by an ectopic ACTH-secreting tumor, the tumor is resected. For a year after cessation of high-dose corticosteroid therapy, even minor illnesses can cause a full-blown Addisonian collapse. If the tumor is malignant and has metastasized and resection is not possible, treatment may include a combination of chemotherapy, immunotherapy, and radiation therapy. Drugs such as ketoconazole, aminoglutethimide, or metyrapone may also be given to suppress cortisol metabolism and secretion. The European drug KH3 (the active ingredient is procaine), which can block some of the cell-damaging effects of cortisol and help protect against cortisol toxicity, is beneficial for Cushing's disease. KH3 has been also known for its beneficial effects in aging and depressed people (Cohen et al. 1974; Hall et al. 1983). A suggestion would be to take 1-2 KH3 capsules in the morning on an empty stomach and 1-2 KH3 capsules in mid-afternoon, also on an empty stomach.

Box 4.27Causes of hypoadrenalism

Common (~ >99%) Rare (~ <1%) Primary (Addison's disease) Autoimmunity Infection (e.g. tuberculosis or fungal infections) Hemorrhage Metastases Drugs - e.g. etomidate, ketoconazole, metyrapone etc. Secondary (any pituitary disease causing Abrupt cessation of exogenous sources of glucocorticoids

hypopituitarism) Tertiary (any hypothalamic disease causing hypopituitarism)

Box 4.25Congenital adrenal hyperplasia (CAH) - CYP21A2 deficiency

21-hydroxylase (CYP21A2) deficiency is the most common form of CAH accounting for 90% of all such cases. Common in Alaskan Eskimos (~1 in 700 live births) but less common in most Western countries (between 1 in 5000 and 1 in 15 000 live births). Clinical manifestations vary according to the sex of the patient but result from a loss of aldosterone and cortisol metabolism with precursors being shunted into androgen synthesis (see Box 4.26 ). Total ablation of enzyme activity (e.g. deletion or nonsense mutations) results in salt-wasting disease (loss of aldosterone) and virilization and ambigous genitalia of a female infant (increased testosterone production). Salt wasting results in severe dehydration in the first 14 days of life with hypotension and death if untreated Children with mutations resulting in 12% normal enzyme activity (e.g. missense mutations) have virilization but not saltwasting Mutations resulting in 2060% normal enzyme activity give the so-called non-classical presentations similar to that of Clinical Case 4.5 Boys without salt-wasting may present with precocious sexual development Treatment is with oral glucocorticoid therapy (monitored to result in suppression of the high concentrations of precursors such as 17-hydroxyprogesterone) together with mineralocorticoids (monitored by blood pressure and by assays of serum renin)

Classification of Adrenocortical Hormone

Translated By: Joe Hing Kwok Chu Section 1: Classification of adrenocortical hormone
There are more than fifty kinds of steroids produced by the adrenal glands. Not all of them are secreted into the blood stream. The more important ones are those that exist in the veins of the adrenal glands and possess physiological functions. There are nine

different kinds of steroid found in the veins of the adrenal glands.

I. Classification by structures
According to their chemical structures, they can be classified into three categories: 1. steroid of having twenty-one -carbon atoms pregnehydroxy as basic structure: cortisol (hydrocortisone), 11-deoxycortisol, corticosterone, 11-deoxycorticosterone and aldosterone. 2.steroid of having nineteen carbon atoms male hydroxy as basic structure: dehydroepiandrosterone, delta4-androstenedione, and 11-hydroxy-delta4hydroxyandrosterone. 3. steroid of having eighteen carbon atoms female hydroxy as basic structure: estrone and estradiol. The table below describes the individual classifications: Secretion in 24 hours in Adult (mg) 15~23 2~5 0.05~0.1 5 0.1 0.34

Classification

Names of Hormone

cortisol corticosterone aldosterone deoxycorticosterone deoxycortisol

dehydroepiandoster one 15~30 delta4androstenedione 11-hydroxydelta4androstenedio ne 0~10 0~10

estrone estradiol

trace trace

II. Classification by medical functions and the relationship of their structures:

1. Glucocorticoid Includes cortisol and corticosterone. Glucocorticoid moderates the metabolism of sugar, fat, and protein and can raise the resistance to the adverse stimulation of the body. Clinically applied steroids belong to this group, like cortisone, hydrocortisone, and their pharmaceutical derivatives: prednisone, dexamethasone etc. It is called glucocorticoid because of the early discovery of its function on the metabolism of sugar. In structure they possess the common characteristics of being able to affect physiological functions which beside require d4-213,20-prednenolone- 21- sterol-3,20 diketone basic structure, and in site 11th possess oxygen base (like hydroxy base of hydrocortisone, and acetone base of cortisone). If in site 17th, a replacement by hydroxy as glucocorticoid the action will be much stronger than corticosterone.

Translator's note: In America sometimes glucocorticoid and cortisol are used interchangeably. Cortisol also has some mineralocorticoid effect of retaining sodium and excreting potassium. Although the strength of cortisol and aldosterone in sodium retention is about 0.3:2,500; and the strength of potassium excretion is about 24:500, usually 200 times more cortisol than aldosterone is secreted. Therefore cortisol has an important overall influence on sodium retention. In fact, cortisol insufficiency is diagnosed clinically by using a water load challenge. A subject is given 1 L of water to drink. In a normal individual this load will be cleared in 1-2 hour, but not for at least 12 hours in those with cortisol insufficiency. 2. Mineralocorticoid Mineralocorticoid inncludes aldosterone, 11deoxycorticosterone, 11-deoxycortisol. Mineralocorticoid helps the body to retain sodium and expel potassium. It is an essential hormone in maintaining the balance of electrolytes and body fluid. It also possess the d4-21- 3,20-prednenolone basic structure; but on the 11th position it lacks oxygen (like deoxycorticosterone and deoxycortisol), or on the 18th position it contain (-CHO) (like aldosterone). The 18th position of (-CHO) can obviously increase the mineralocorticoid effect; thus the retaining sodium effect of aldosterone is 25 times stronger than that of 11-deoxycorticosterone. But, if on the 17th position, a-CHO is added, the effect is weaker. Thus sodium retention effect of 11-deoxycortisol is only 3% of that of 11deoxycorticosterone.

3. Sex Hormone Sex hormone can be classified into 19 carbon androgen and 18 carbon estrogen a. androgen b. estrogen

Types
Adrenal gland tumors may present as benign, meaning they grow slowly and fail to invade any other tissues, or cancerous, also known as malignant, meaning they grow quickly and can spread to other tissues in the body. MedLine Plus and the National Institutes of Health report that most adrenal tumors are noncancerous. Both benign and cancerous tumors can cause health problems as the tumor may cause the gland to increase hormone production and secretion.

Tumors
Several types of cancerous or benign tumors can form in the adrenal gland. Adrenocortical carcinoma describes a rare type of cancer that forms in the adrenal cortex, according to the National Cancer Institute. Because this type of tumor develops in the adrenal cortex, it increases the level of cortisol, aldosterone and sex hormones such as estrogen. Neuroblastoma, a type of cancer that begins in nerve tissue, most commonly affects the adrenal gland. Pheochromocytoma, a rare benign tumor, describes a tumor that develops in the adrenal medulla.

Symptoms
Symptoms of adrenal tumors depend upon the type of tumor and which hormones the tumor affects. Adrenocortical carcinoma affects the levels of cortisol and steroids, resulting in a fatty hump on the neck, a flush rounded face, obesity, stunted growth and masculine features, according to MedLine Plus. Tumors of the adrenal medulla, such as pheochromocytoma, produce high blood pressure, rapid heartbeat, profound sweating, abdominal pain, anxiety and weight loss, according to MayoClinic.com.

Treatment
Small adrenal tumors may cause few symptoms, allowing doctors to observe the tumor without the need for specific treatment. Larger tumors, however, require treatment. Many of the symptoms caused by adrenal tumors can be treated with medications, such as beta blockers to lower blood pressure. The best way to treat all the symptoms is to remove the tumor

either through a minimally invasive laparoscopic procedure or through open surgery.

Read more: http://www.livestrong.com/article/237654-aboutandrenal-tumors/#ixzz1YKU15ut7