Pituitary Adenomas: Current Methods of Diagnosis and Treatment

Introduction

Pituitary adenomas comprise 10% to 15% of all intracranial tumors in adults.[1] In addition, 10% of normal adults have asymptomatic abnormalities on MRI that are consistent with a pituitary adenoma, and perhaps 20% or more are found to have an asymptomatic adenoma on autopsy.[1,2] Patients requiring intervention have a characteristic constellation of signs and symptoms that are easily recognized by the astute primary care physician. Furthermore, these signs and symptoms are critical gauges for the specialist neurosurgeon, endocrinologist, and radiation oncologist in recommending appropriate management.

Once a pituitary adenoma is suspected, diagnostic evaluation with hormonal and neuroradiologic studies is indicated. These studies, along with patient status, preference, and symptoms, guide decisions about medical, surgical, or radiotherapeutic management. Each of these therapies has distinct and characteristic profiles of response and toxicity that influence the recommended treatment plan. In nearly all cases of benign tumors, the possibility of cure exists. This probability of cure should be maximized at the time of primary diagnosis and treatment because multiple recurrences of benign tumors may lead to increased morbidity with further treatment and perhaps, in some cases, to increased mortality from the disease.[3]

Signs and Symptoms

Patients with pituitary adenomas usually have either neurologic or hormonal manifestations of their disease. The most commonly reported neurologic symptoms are headache and visual disturbances. Other cranial nerve palsies and mental deterioration are reported less often but may occur more frequently with giant adenomas.

Endocrinopathies may cause a host of patient complaints, ranging from the polyuria and polydipsia of diabetes insipidus (rare) to menometrorrhagia attributable to abnormal prolactin, luteinizing hormone, or follicle-stimulating hormone levels. Decreased libido and general apathy may be related to luteinizing-hormone deficiency or panhypopituitarism. Skin changes may occur and produce symptoms indicative of imbalances in pituitary hormones, including thyroid and adrenal hormones. Finally, the stigmata of Cushing's disease may lead the patient to complain of a myriad of difficulties, ranging from irritability to a change in body habitus, diabetes, hypertension, or easy bruising. Patients with acromegaly also have characteristic stigmata, which family members may slowly recognize as a change from their former appearance.

Although the development of these symptom complexes is usually insidious from the patient's perspective, the clinicopathologic features of pituitary adenomas often make them readily suspected at the time of diagnosis.

Clinicopathologic syndromes can be identified based on the patient's signs and symptoms and physical findings, as well as the results of biochemical evaluation. These syndromes may be divided into those of primarily neurologic vs hormonal character.

Neurologic Syndromes

Pituitary adenomas frequently extend beyond the sella proper. In general, the path of tumor growth is upward, which pushes the optic chiasm superiorly. Suprasellar extension may also cause headache and pressure on the pituitary stalk, which may cause hormonal abnormalities independent of the tumor's secretory abilities.

Presentations of classic bitemporal hemianopia represent the pure form of this model of injury. More often, however, the patient may have a partial hemianopia and blurred vision in the lateral fields.[4] Rigorous pretherapy ophthalmologic assessment is necessary to accurately gauge the outcome of intervention and the severity of injury at presentation.

Headaches are a common neurologic complaint. These may be due to a direct pressure effect of the tumor, an obstructive hydrocephalus effect (rare), direct hormonal perturbation, or induction of secondary hypertension.[4]

Other cranial nerve palsies may result from direct invasion of the cavernous sinus or, less often, from erosion of the skull base and anterior clivus. Deficits of the oculomotor, abducens, or trigeminal nerves occur most frequently.

More serious deficits than those described above are rare because these tumors generally progress slowly and symptoms of cranial nerve deficits related to vision usually attract medical attention in all but the most stoic of patients. Thus, the majority of patients have one or more of the neurologic clinicopathologic syndromes described above or have hormonal difficulties that lead to diagnosis before gross neurologic dysfunction develops.

Hormonal Syndromes

Adrenocorticotrophic hormone (ACTH) overproduction leads to stigmata of Cushing's disease. These may include diabetes, hypertension, infertility, menstrual irregularity, proximal muscle weakness and atrophy, and skin changes, including easy bruisability, striae, and hirsutism. Changes in body habitus caused by excessive adrenal cortisol include characteristic moon facies, truncal obesity, and humpback appearance, along with wasting and weakness of the proximal extremities. However, the specific manifestations seen in a given patient vary greatly and may sometimes be subtle. Furthermore, the absence of radiographic findings of these macroadenomas often contributes to difficulty in making a diagnosis. Therefore, the clinician must be vigilant for these many signs of disease so as to order appropriate laboratory screening tests. These tests will help locate the origin of hypercortisol production so that appropriate therapy is delivered.

Approximately 5% to 10% of pituitary tumors cause elevated cortisol levels, and an additional 5% are positive for ACTH on immunocytochemistry alone.[1]

Growth Hormone--Pituitary adenoma is the most common cause of acromegaly. Overproduction of growth hormone is the third most common anomaly seen in pituitary adenomas, with nonfunctioning adenomas and prolactinomas occurring more frequently.

Excess production of growth hormone by a pituitary adenoma leads to acromegaly in an adult or gigantism in a child. Stigmata of acromegaly include coarsening of facial features, excess growth and thickening of the distal phalanges, soft-tissue swelling, cardiac hypertrophy, hypertension, diabetes, hirsutism, excessive skin tags, hypertrophic arthropathy, peripheral neuropathy, hyperparathyroidism, hyperprolactinemia, and hypothyroidism. While these stigmata often make the diagnosis obvious to the clinician, their insidious onset often leads to significant delays in diagnosis.

Prolactin--Hypersecretion of prolactin may occur in 60% to 80% of patients with pituitary tumors, although hyperprolactinemia may not be the primary endocrinologic defect in many of these cases.[1,5] Elevation of prolactin secondary to pituitary stalk compression may occur with any mass within or extending out of the sella; however, a prolactin level above 200 ng/ml is usually accepted as evidence of a prolactin-secreting adenoma.[5] Elevated prolactin levels result in diminished levels of estrogen and testosterone. Female patients generally develop menstrual irregularity or frank amenorrhea or galactorrhea. Decreased libido occurs in both men and women.

Depression and mood alterations are associated with prolactin hypersecretion. In general, men are less symptomatic from prolactin-secreting tumors, and therefore, are more likely than women to have neurologic signs and symptoms of disease and a macroadenoma.

Gonadotropins--Aberrant secretion of follicle-stimulating hormone and luteinizing hormone is rare and is most often discovered after pituitary adenomas produce neurologic symptoms. Occasionally, hypogonadism is a presenting complaint.

Thyrotropin--Thyroid-stimulating hormone excess occurs in less than 1% of pituitary adenomas. The resultant hyperthyroidism is often presumed to be of alternative etiology and is treated with thyroid-suppressing therapy. Such treatment may be successful until neurologic symptoms occur. Therefore, these tumors often grow to a large size and extend into adjacent structures, making treatment difficult. Discovery of a microadenoma-secreting, thyroid-stimulating hormone is rare, and this condition may be cured by addressing the pituitary adenoma.