Anatomical Diagnosis

Central to the preoperative evaluation of patients in whom a pituitary tumor is suspected is an appropriate anatomical or radiological diagnosis and a thorough endocrinological work-up. Gadolinium-enhanced magnetic resonance imaging (MRI) has supplanted skull radiographs and computed tomography (CT) in establishing an anatomical diagnosis and is over 90% sensitive in the detection of microprolactinomas. Fine-cut CT scans of the sella remain useful in cases of difficult re-operations in patients originally operated on elsewhere. Magnetic resonance imaging not only delineates the anatomy of mass lesions but also aids in the visualization of the relationship of tumor to the neighboring carotid arteries, optic chiasm, and to the parasellar region. MRI coupled with magnetic resonance angiography (MRA) may also confidently exclude the possibility that a sellar mass represents an aneurysm. Additionally, radiographical suggestion of craniopharyngioma or an infiltrative process—both of which are more likely to lead to panhypopituitarism and diabetes insipidus (DI) after their surgical resections—may make the neurosurgeon more vigilant as to alterations in endocrinological aberrations after surgery.

Although MRI establishes an anatomical diagnosis, the functional consequences of a lesion near the optic chiasm should also be investigated. Formal visual field testing should be performed and should certainly be done in patients with preoperative visual complaints or deficits.

Endocrinological Diagnosis

Knowledge of the particular subtype of pituitary lesion is important because lesions such as prolactinoma are best treated by medical means as first-line therapy. The pituitary endocrinology team performs the crucial preclinical evaluation before consideration of the patient for surgical management. The need for additional testing is ascertained before the patient’s visit to the clinic so that studies can be scheduled with the laboratory and with interventional radiology as indicated. Most commonly these additional tests involve high-dose dexamethasone suppression testing or inferior petrosal sinus sampling (IPSS). Other testing, such as a cardiac evaluation in the patient with acromegaly or oral glucose tolerance testing, can be arranged for the same day the patient is seen in the pituitary clinic. Extracranial imaging may be required in cases of suspected Cushing’s syndrome and acromegaly to exclude ectopic sources of endocrinopathy.

The routine preoperative laboratory workup consists of a complete blood count to assess for the presence of anemia or other hematological abnormalities, a metabolic panel to evaluate for the presence of hyponatremia, hypercalcemia, hyperglycemia, and other metabolic abnormalities. Cushing’s syndrome may produce abnormalities in the standard metabolic panel and blood count, such as hypokalemic metabolic alkalosis, hyperglycemia, and leukocytosis. The endocrinological evaluation involves measurement of pituitary and target gland hormones, including a thyroid panel (T4, TSH), cortisol, ACTH, IGF-1, testosterone, luteinizing hormone (LH)/ follicle-stimulating hormone (FSH), α-subunit, and prolactin (PRL). Laboratory evaluation is critical in patients with prolactin-secreting macroadenoma; in a macroadenoma (>1 cm), PRL should be greater than 200 μg/L to be considered a true prolactinoma, thereby indicating medical and not surgical therapy. One should bear in mind that macroadenomas may have moderately elevated PRL because of interference with dopamine inhibition of lactotrope cells—the so-called “stalk effect.” Medical treatment options for other secretory tumors are listed in Table 4-1 . Serum calcium and glycated hemoglobin are also assessed to detect patients who may have MEN-I. If the patient is a surgical candidate and has no history of undue bleeding or risk factors for bleeding, a prothrombin time (PT)/partial thromboplastin time (PTT) is not typically obtained, but blood typing is performed.

The particular type of secretory tumor has implications for preoperative management. Specifically, patients with TSH-secreting tumors, Cushing’s syndrome, and acromegaly necessitate particular attention paid to attendant extracranial medical problems arising in the setting of these endocrinopathies. Diagnostically, a low T4 and normal or suppressed thyroid-stimulating hormone (TSH) may suggest secondary hypothyroidism, whereas elevated T4 and normal or increased TSH indicates a TSH-producing tumor. Hyperthyroidism from a TSH-secreting tumor, although rare, requires treatment to reduce the risk of perioperative cardiac arrhythmias.

Patients with Cushing’s disease and acromegaly may warrant special attention secondary to the physiological effects of glucocorticoid or growth hormone excess. As many as 80% of patients with Cushing’s disease have systemic hypertension and 50% of untreated patients with Cushing’s disease have a diastolic blood pressure greater than 100 mm Hg. As might be expected in patients with systemic hypertension, ECG abnormalities are common in patients with Cushing’s disease. High voltage QRS complexes and inverted T waves suggesting left ventricular hypertrophy and left ventricular strain have been described. Obstructive sleep apnea (OSA) is also common among patients with Cushing’s disease. Glucose intolerance occurs in at least 60% of patients with Cushing’s disease, with overt diabetes mellitus present in up to one third of all patients. Nephrolithiasis is common in Cushing’s disease, with approximately 50% of active, untreated patients having detectable stones.

In patients with elevated cortisol and suspected Cushing’s syndrome, a 24-hour urinary free cortisol of more than 400 μg/day in a patient is diagnostic ; these patients will also have an elevated midnight plasma cortisol, which under normal physiological conditions is at low levels. The low-dose dexamethasone suppression test establishes the diagnosis of Cushing’s syndrome. Elevated corticotropin (>10 pg/mL) suggests a corticotropin-secreting tumor, while subnormal levels (<5 pg/mL) confirms a corticotropin-independent Cushing’s syndrome. Dynamic testing is required to identify the source of hormonal excess in cases of elevated or normal corticotropin and elevated cortisol. A high-dose dexamethasone suppression test assists in the determination of a pituitary or ectopic source of corticotropin.

Inferior petrosal sinus sampling (IPSS) for corticotropin after stimulation with Corticotropin Releasing Hormone (CRH), while invasive, is a reliable and accurate method of discerning pituitary from nonpituitary corticotropin-dependent Cushing’s syndrome. Although MRI and laboratory analysis have obviated the need for IPSS in most patients, it is a particularly useful discriminatory tool in concert with CRH administration in patients with classic clinical and laboratory Cushing’s disease but in whom MRI findings are negative or equivocal; equivocal results are obtained from suppression and stimulation tests; and in whom a compelling clinical presentation exists. A ratio of inferior petrosal sinus to peripheral ACTH of greater than 3.0 is diagnostic of central Cushing’s disease. Eighty percent of Cushing’s syndrome patients have a pituitary adenoma and Cushing’s disease; 5% to 10% have an ectopic source of ACTH, such as carcinoid tumor; and a small fraction have cortical excess from an adrenal source.

Acromegaly is accompanied by skeletal and soft tissue overgrowth, deformities, and cardiac, respiratory, neuromuscular, endocrine, and metabolic complications. The cardiovascular and respiratory sequelae are particularly important to bear in mind in the care of the acromegalic patient. Atherosclerosis, hypertension, premature CAD, and arrhythmias leading to CHF may develop, and more than 20% of patients have cardiac disease at the time of diagnosis. Indeed, the most frequent cause of death in untreated acromegaly is cardiovascular demise, with 50% of patients dying before the age of 50. Echocardiography may reveal an increase in left ventricular mass, stroke volume, cardiac output, or isovolemic relaxation time, all of which contribute to a poorly compliant left ventricle and the accompanying need for high filling pressures. Given the potential for cardiac morbidity in acromegalic patients, a careful history and physical examination with close attention to the patient’s cardiac status should be routinely performed. Complaints consistent with congestive heart failure warrant preoperative cardiology consultation. Additional considerations include obstructive tissue thickening along the upper respiratory tract complicating intubation and possibly requiring an awake fiberoptic intubation. They may also be unable to tolerate nasal packing and have exacerbations of obstructive sleep apnea. Growth hormone excess causes insulin resistance in 20% to 30% of patients. Preoperative laboratory testing in patients with acromegaly includes measurement of GH and IGF-1 as useful adjuncts in establishing a diagnosis but also includes the oral glucose tolerance test (OGTT), most useful in comparing preoperative and postoperative effects of glucose stimulation on growth hormone (GH) suppression. Overall, life expectancy is reduced by 10 years in acromegalic patients when compared with age-matched controls; reducing GH levels to less than 2.5 μg/L may normalize life expectancy.