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April 30, 2007

Hormone Deficiencies and Pituitary Tumors
By Kim M. Norton
For The Record
Vol. 19 No. 9 P. 32

Pituitary disorders are often overlooked because of the symptoms’ slow progression. However, close attention to the pituitary can alleviate years of misdiagnosis.

A pea—that is the size of one of the most critical glands in the entire body. The pituitary gland, located at the base of the brain, is the body’s conductor, sending signals to specific glands and organs to control functions such as blood pressure, the ability to thrive, metabolism, and fertility, among many others.

As the “master gland,” the pituitary is vital to the communication, control, and coordination of the organs that comprise the endocrine system. The pituitary works in tandem with the entire endocrine system, as well as the nervous system, reproductive system, kidneys, gut, and liver to help maintain and control the body’s energy levels, reproduction, growth and development, and internal balance (homeostasis), according to The Hormone Foundation.

Should the pituitary become damaged, it can affect the way the body functions. The most common cause of a hormonal deficiency is a tumor within the pituitary gland caused by trauma, infection, cancer, and/or radiation therapy. If the tumor is left untreated—which is often the case because the symptoms are so subtle—the pituitary is unable to emit the proper hormones at the required amount or at all. This could result in fatigue, the inability to reproduce, lack of appropriate sex characteristics, lack of horizontal growth, and an inability to thrive, explains Jyotika Fernandes, MD, an endocrinologist with the Medical University of South Carolina in Charleston.

“When the pituitary gland fails to produce a hormone—or does not produce enough of a hormone—the patient has hypopituitarinism. If the gland fails to produce two or more hormones, the diagnosis becomes panhypopituitarinism [panpit],” she explains.

Depending on the lacking hormone and the reason behind the decreased function, there are a number of therapies to rectify the problem. “If the patient has a nonfunctioning tumor, then hormone replacement therapy [HRT] is the treatment of choice. However, if it is a functioning tumor and the patient is having pressure symptoms, then surgical intervention followed by radiation therapy and HRT is required,” says Fernandes. Although radiation is one risk factor of a pituitary tumor, it is an effective treatment to stop the tumor from spreading, she adds.

“It is important to bear in mind that the pituitary is a delicate master control for the human body, and we do not know everything there is to know about it,” Fernandes says. “The hormones that endocrinologists are aware that it produces may not be the only ones. To perform surgery on a tumor in the pituitary is tedious and delicate, an operation that should be left to only the most skilled of surgeons. Routine reevaluation is required to ensure that patients receive the correct dosage of the missing hormone, as well as to identify any other issues that the tumor may be causing.”

The Pituitary Gland
The pituitary is divided into two sections: anterior and posterior. Most hormone deficiencies relate to the anterior pituitary gland, which is the most critical to sustaining life, according to Fernandes. Hormones produced by the anterior pituitary gland are the following:

• The thyroid stimulating hormone (TSH) signals the thyroid gland to produce the hormone that controls the body’s metabolism. TSH affects the functioning of every organ in the body.

• Growth hormone (GH) is responsible for vertical growth, as well as the regulation of the body’s metabolism. In children, GH replacement therapy is essential for the child to reach a certain height. In adults, GH naturally declines around the age of 50, but it can be replaced if the patient is experiencing extreme fatigue and a lack of soft tissue growth.

• The adrenocorticotropic hormone (ACTH) is the regulator of the adrenal gland, which controls the release of cortisol that regulates carbohydrates, fat, protein metabolism, and blood pressure. Without the adrenal gland producing cortisol, the body’s organs would shut down following a stressful event. To replace the hormone, synthetic cortisol or cortical steroids are taken regularly. If a stressor is placed on the body, cortisol can be given in larger doses to ensure that the body’s organs continue to function.

• The luteinizing hormone (LH) and the follicle stimulating hormone (FSH) are responsible for the production of estrogen and testosterone, sperm production, and egg maturation and release. These hormones are generally deficient in patients experiencing infertility.

• Melanocyte-stimulating hormone (MSH) regulates the production of melanin in the skin. Too much MSH produces a darker pigmentation, while too little causes the skin to lose pigmentation.

• Prolactin stimulates the production of breast milk and is necessary for normal milk production during breastfeeding.

The hormones controlled by the posterior pituitary gland are the following:

• Oxytocin stimulates contractions of the uterus during labor. In the event the uterus does not begin to contract, pitocin, the synthetic form of oxytocin, is administered. Oxytocin also controls the ability to eject milk while breastfeeding.

• Antidiuretic hormone (ADH) controls water regulation in the body and causes reabsorption of water into the blood by the kidneys, which decreases urine output. A diuretic is given to counteract any imbalance in ADH production.

Detecting a Problem
In almost all cases, pituitary tumors are benign. The size of the tumor and when it is detected dictates the treatment protocol and the success rate following intervention. Common symptoms of a pituitary tumor include headaches and visual disturbances, says Fernandes. “But the symptoms of a deficiency are slow in progression and once symptoms emerge, the tumor is generally enlarged,” she adds.

It is not unusual for patients to describe other symptoms, such as depression, mood swings, loss of memory, insomnia, sexual dysfunction, eating disorders, lethargy, limb weakness, irregular menstruation, impotence, and unusual hair growth. Other clinical signs of a pituitary disorder include high blood pressure, diabetes, and infertility, according to the Pituitary Network Association (PNA).

Because of the array of issues that a patient can experience, the physician may dismiss the pituitary as the source of the problem and treat the individual symptoms without further investigation of their cause. “Early diagnosis [of pituitary disease] 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,” states the PNA. In cases where a pituitary disorder is overlooked, it is not uncommon for patients to be treated for their symptoms and eventually die from heart disease or a thyroid disorder that can be linked back to a pituitary disorder, according to the PNA.

If a patient presents with headaches and visual disturbances, the first steps to a diagnosis are conducting a vision test and brain MRI. The vision test will help identify any pressure on the optic nerve from a tumor, and the MRI will conclusively identify a tumor, explains Fernandes.

Once a tumor is identified, the next step is to determine whether there is a hormonal deficiency and, if so, how much. Although there is not a specific blood test for detecting a deficiency, it is imperative that the patient is cared for by an endocrinologist, preferably at a hospital with a neuroendocrine unit or pituitary testing facility because pituitary blood tests are complicated and require expertise in measuring pituitary hormone levels. The tests that should be administered are the ACTH (Cortrosyn) stimulation test, bilateral inferior petrosal sinus ACTH sampling, insulin tolerance, growth hormone stimulation, thyrotropin-releasing hormone stimulation, gonadotropin-releasing hormone stimulation, oral glucose tolerance, and growth hormone-releasing hormone/arginine testing for growth hormone reserve.

Depending on the MRI results and the blood and stimulation tests, the endocrinologist can decide the best course of treatment. “If the patient has a large tumor or it is causing pressure symptoms, the best course is to remove the tumor. Depending on its size and if it has invaded other areas of the brain will dictate its success,” explains Fernandes.
Large tumors that have metastasized beyond the pituitary generally have a lower success rate following surgery. Fernandes says an increased tumor size also carries a 15% to 20% recurrence rate.

If surgery or pharmaceutical therapies do not eliminate the tumor, radiation therapy is recommended to kill any remaining cancerous cells and shrink the tumor size. Radiation therapy is sometimes used to complement surgery to eliminate any cancerous cells that were missed during surgery, says Fernandes.

Hormone Replacement Therapy
Whether the hormonal deficiency was caused by a tumor, subsequent surgery and radiation, or another related reason, HRT will likely be required. “Depending on the hormone that is deficient, HRT is necessary. But for those patients who have panpit, all the hormones must be replaced,” explains Fernandes.

Life expectancy for individuals with adult onset panpit is equivalent to that of a person with normal pituitary function. However, “patients with the rare form of congenital panpit likely do not have very good outcomes because of the early misdiagnosis in infancy,” explains Scott J. Whitten, MD, a reproductive endocrinologist with The Nevada Center for Reproductive Medicine in Reno.

Hormone Deficiency and Infertility
Infertility treatments and clinics are gaining popularity as gynecologists and obstetricians become increasingly aware of the pituitary’s effect on fertility. Within the pituitary gland lie not only the mechanics for puberty and distinguishing sexual characteristics but also the ability to procreate. Both males and females with infertility are generally referred to a reproductive endocrinologist when the pituitary is the suspected cause. After evaluating the hormones levels associated with fertility—FSH and LH—the reproductive endocrinologist can supplement the decreased hormone to improve fertility.

“Female patients who have panhypopituitarinism or hypopituitarinism where the FSH and LH are affected, the ovaries are generally normal, but there is no signal [estrogen] from the pituitary gland to signal ovulation. By replacing FSH and/or LH, the woman can become pregnant quite easily,” says Whitten. With HRT, the synthetic hormones will stimulate the ovaries, which will in turn drive the growth of the egg to where it can be fertilized, he adds.

Whitten says if the egg does become fertilized, the pregnancy naturally creates human chorionic gonadotropin (HCG) to sustain the pregnancy without any further HRT. The side effects associated with replacing FSH and LH in women can include multiple eggs resulting in multiple pregnancies and ovarian hyperstimulation syndrome. Both issues can be controlled with careful monitoring, says Whitten.

In men, lack of an LH can affect the production of testosterone, which does not necessarily affect fertility, but it can alter secondary sex characteristics, says Whitten. “If the patient has congenital panpit, the protocol would be to replace the testosterone. But for patients with adult onset panpit, the preferred therapy would be to give HCG injections because it works on the receptors of the Leydig cells, which are responsible for the production of testosterone,” he says.

When sperm production is questioned, the culprit could be an FSH deficiency. A semen analysis can accurately identify a deficiency and guide the endocrinologist concerning how much hormone must be replaced to return to normal levels. “It takes three months of HRT to create sperm, and once that level is reached, the patient will remain on HRT while trying to conceive,” says Whitten.

Side effects in males are limited to replacing too much testosterone. “By replacing testosterone or LH, we are replacing what the body is lacking naturally. Patients will see an increased sex drive and better libido. However, too much testosterone will cause cholesterol abnormalities and excessive androgens,” he notes.

Education Is Key
When confronted with a patient who has a wide array of symptoms, the knowledgeable physician should suspect the pituitary to rule out any hormonal imbalance. Unfortunately, the pituitary is an often-overlooked gland—in children, a hormonal deficiency can be overlooked until puberty.

Regardless of age, the pituitary gland should be assessed for possible traumas to improve the patient’s quality of life and correct any imbalance that may affect the body’s ability to function, says Fernandes. Although the general practitioner is a good starting point, the patient should be referred to an endocrinologist because of the endocrine system’s complexity.

In regard to fertility, patients often do not realize there is a problem until they are frustrated with the inability to get pregnant. “Whether the patient has adult onset panpit, puberty induced pituitary disease, or congenital panpit, these patients have a very realistic chance of achieving pregnancy with HRT,” says Whitten. The most critical step is to see a reproductive endocrinologist to evaluate the pituitary and to replace the proper hormones, he adds.

— Kim M. Norton is a New Jersey-based freelance writer specializing in healthcare related topics for various trade and consumer publications.

Endocrine-related Organs

A number of organs within our bodies which are not part of the endocrine system work together to complement it. These organs assist the endocrine system in producing, storing, and emitting hormones into the blood stream to help maintain a healthy endocrine system.

According to The Hormone Foundation, the following organs are essential to the function of the pituitary and the entire endocrine system:

Skin, Liver, and Kidneys
These three organs work together to synthesize 1,25-dihydroxyvitamin D, the active form of vitamin D, which controls levels of calcium and phosphorus in the blood. In the skin, a modified cholesterol (fatty) molecule is converted into vitamin D by chemical changes through ultraviolet rays from the sun. In the liver, vitamin D3 is converted to 25-hydroxyvitamin D (calcidiol) before going to the kidney, where it is converted to 1,25-dihydroxyvitamin D3 (calcitriol) with the help of parathyroid hormone. Calcitriol acts on the intestine, kidneys, and bones to maintain normal levels of blood calcium and phosphorus. Too little calcium in the diet can lead to rickets in children and osteoporosis in adults.

Stomach and Small Intestine
The digestive tract is the body’s largest endocrine-related organ system. It makes and secretes several different hormones that play a role in the body’s metabolism. Ghrelin and leptin are two such hormones shown to regulate appetite and may be important in obesity and weight loss.

Besides providing a connection between mother and fetus, the placenta is a special endocrine organ. It produces hormones similar to those produced elsewhere in the body. Human chorionic gonadotropin (HCG), estrogens, and progesterone are among the most important of these hormones because they maintain pregnancy and prepare a woman’s mammary glands for nursing.

HCG stimulates the ovary to produce estrogens and progestins and helps control normal development of the fetal genitals. The estrogens in the placenta stimulate breast development, promote normal labor, and help produce a steady rise in prolactin. The progestins stimulate breast development and help reduce uterine muscle contractions. Human placental lactogen is a hormone that decreases the mother’s level of growth hormone and increases the amount of blood glucose and lipids (fatty substances) circulating in the mother’s blood.

— Source: Endo 101: The Endocrine System. The Hormone Foundation (www.hormone.org), the public education affiliate of The Endocrine Society.

The Endocrine Society/The Hormone Foundation
8401 Connecticut Avenue, Suite 900
Chevy Chase, MD 20815-5817
Phone: 800-467-6663
Fax: 301-941-0259

Pituitary Network Association
P.O. Box 1958
Thousand Oaks, CA 91358
Phone: 805-499-9973
Fax: 805-480-0633