Kristen Riley , MD
Assistant Professor
Department of Surgery, Division of Neurosurgery

Elizabeth D. Ennis, MD
Clinical Associate Professor of Medicine
Department of Medicine, Division of Endocrinology, Diabetes & Metabolism

The University of Alabama at Birmingham
Birmingham, Alabama

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Results from autopsy series indicate pituitary adenomas occur in up to 20% of the population. Many of these tumors are asymptomatic and not diagnosed during patients’ lives.

Pituitary tumors are classified by size and by the presence or absence of hormone production. Tumors that secrete one or more of the anterior pituitary hormones are characterized as secretory, or functional. Nonfunctional (nonsecretory) pituitary adenomas do not produce hormones, but like functional adenomas, may have clinically significant endocrine implications. Of the more than 400 pituitary operations done at UAB, 80% are for nonfunctional tumors, says UAB neurosurgeon Kristen Riley, MD.

Management, which depends on tumor size, functional status, growth rate, and invasiveness, includes observation, medical therapy, surgery, stereotactic radiosurgery, and radiation.

“Pituitary tumors arise in the sella turcica, located at the base of the skull beneath behind the optic chiasm and optic pathways. Consequently, macro-adenomas, regardless of functional status, can compress the optic nerves and chiasm, causing peripheral vision loss and blindness, and produce significant pituitary hormone dysfunction. Such large adenomas often can be cured by surgery. Macroadenomas are usually slow growing, however, and if vision is stable, observation alone may be indicated,” she says. “Hormonal imbalances caused by functional microadenomas and macroadenomas can lead to a number of disorders, including hyperprolactinemia, acromegaly, and Cushing’s disease.”

Physicians often diagnose pituitary tumors incidentally, for example, when patients present with head trauma or during workup for unrelated headaches. Complaints of vision changes and signs and symptoms of hormone deficiency or hypersecretion also can suggest a pituitary tumor.

Neurosurgeon Richard B. Morawetz, MD, established the UAB Neurosurgical Pituitary Disorders Clinic in 1998. Riley is now clinic director and her multidisciplinary team includes endocrinologist Elizabeth D. Ennis, MD. The clinic provides comprehensive care, including long-term observation and follow-up, to more than 500 patients with pituitary tumors.

Microadenomas, which are not large enough to affect visual pathways or sinus nerves, require surgical intervention only when functional, Riley says. “Patients with small nonfunctional adenomas need yearly ophthalmologic evaluation and observation with magnetic resonance imaging to ensure the tumor is not causing visual field defects or exhibiting invasive properties,” she says. “Nonfunctional microadenomas can produce endocrine complications such as secondary hypothyroidism. These conditions are managed medically, as surgery would not improve secondary pituitary dysfunction.”

In women, hyperprolactinoma can interfere with pulsatile gonadotrophin release, causing amenorrhea and breast milk production in nonpregnant patients. Excess prolactin in men can affect sperm synthesis, morphology, and metabolism, resulting in impotence. Prolactinomas also can have detrimental effects on the skeletal system of both sexes, and patients should have annual bone density evaluation with dual-energy X-ray absorptiometry.

“The first-line treatment for prolactinomas is medical, with daily doses of bromocriptine, or a newer drug, cabergoline, which patients take twice weekly. These drugs decrease prolactin levels and shrink tumors,” Riley says. “We recheck prolactin levels 1 month after initiating therapy and if needed, escalate the dose.” Patients who do not respond to or cannot tolerate drug therapy may require surgical removal of the tumor.

Adrenocorticotropic hormone (ACTH) stimulates adrenal production of glucocorticoids. Excess ACTH causes Cushing’s disease, a condition characterized by truncal obesity, buffalo hump, moon facies, muscle weakness, fatigue, and hirsutism. “Cushing’s patients also can have psychiatric issues, particularly depression, purple striae out of proportion or location to weight gain, amenorrhea, easy bruisability, and newly diagnosed or difficult-to-control hypertension and diabetes,” Riley says.

Physicians must distinguish between central and ectopic ACTH production. “A number of laboratory investigations are undertaken to determine if ACTH secretion is from the pituitary gland. Occasionally, an invasive test, inferior petrosal sinus sampling for ACTH, is required to confirm diagnosis,” she says. “Surgery offers the best chance for cure when patients have confirmed central origin of ACTH secretion.”

Acromegaly is the dominant clinical picture in patients with growth hormone (GH) secreting adenomas, Riley says. “These individuals have acral and soft tissue overgrowth, coarse facial features, degenerative arthropathies, muscle weakness, oily skin, hyperhydrosis, and skin tags.” Acromegalic patients also have an increased risk of colon cancer and need regular colonoscopies. The number of skin tags usually correlates with the number of colon polyps. Acromegaly also increases patients’ risk for obstructive sleep apnea, glucose intolerance, hyperlipidemia, and cardiovascular disease.

“While it is sometimes difficult to distinguish acromegalic changes from normal aging, seeing old pictures of patients or meeting family members who exhibit a markedly different aging pattern can help,” Riley says.

Chronically elevated levels of GH reduce 10-year survival, increasing mortality two- to threefold. Appropriate treatment can normalize mortality within 5 years, Riley says.

“Surgery offers the best chance of cure for growth hormone-secreting tumors; surgical intervention also is often necessary to decompress optic pathways,” she says. “If surgery does not produce a biochemical cure, patients need adjuvant therapies, including medication and radiation.”

These adenomas produce thyrotrophin, which results in hypersecretion of thyroid hormone. Thyrotropin-producing tumors can be large and invasive, and also can produce GH, prolactin, or both. These adenomas usually warrant surgery, and tumor removal is often followed by radiation.

Patients with undiagnosed pituitary adenomas can present with pituitary apoplexy, which occurs when the tumor infarcts or bleeds, Riley says. “Patients with apoplexy may present in emergency departments with sudden visual loss, cranial nerve palsies, and complaints of ‘the worst headache of my life.’ ” Pituitary apoplexy is diagnosed when computed tomography reveals blood in the sella. Acute pituitary apoplexy is a surgical emergency. Riley notes it is not uncommon for patients to report severe headache and other symptoms days or weeks after the events. “This may indicate previous pituitary apoplexy. Yet surgery is only appropriate when apoplexy is diagnosed within 24 to 48 hours. Once the acute event is over, pressure on the cranial nerves is relieved, and surgery typically has no role,” she says.

In patients with visual decline from a pituitary adenoma (other than a prolactinoma) and in those with GH-secreting or ACTH-secreting adenomas, surgery is the treatment of choice, Riley says.

Neurosurgeons can now remove many pituitary adenomas using minimally invasive techniques. Using an endoscope for visualization, a transnasal approach that passes through the sphenoid sinus allows surgeons to access the tumor through the base of the skull. “Patients prefer endoscopic options, which leave no facial scars and produce few neurological complications,” Riley says. “Most tumors can be approached endoscopically. Occasionally, a patient’s unique anatomy or the extent of the tumor may require a transcranial approach, accessing and removing the tumor through a craniotomy.”

At UAB stereotactic radiosurgery is most commonly used as an adjuvant treatment following surgery. In certain cases, such as functional tumors with cavernous sinus involvement and no optic compression, the gamma knife is used as a first-line treatment.

“Although many tumors should be treated surgically, observation is a good option for some patients, depending on tumor physiology. For these individuals, physicians must emphasize the critical importance of follow up, which should include repeat imaging studies and serial ophthalmologic testing.”

For more information:

Dr. Elizabeth Ennis
Dr. Kristen Riley
1-800-UAB-MIST
mist@uabmc.edu

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