eMedicine Specialties > Neurology > Neuro-oncology

Pituitary Tumors: Differential Diagnoses & Workup

Author: Jorge Kattah, MD, Head, Program Director, Professor, Department of Neurology, University of Illinois College of Medicine at Peoria
Contributor Information and Disclosures

Updated: Jan 14, 2009

Differential Diagnoses

Other Problems to Be Considered

A number of other intracranial neoplasms can present as intrasellar tumors. These include craniopharyngiomas, meningiomas, neurofibromas, ectopic germinomas, and, rarely, metastatic tumors.

Granulomatous and infectious disorders can localize to the sellar region or the hypothalamus (eg, sarcoid, tuberculomas).

Carotid artery aneurysm can occur in the intrasellar region.

Lesions in the sphenoid sinus, such as a mucocele, can mimic the clinical picture of a pituitary adenoma.

Hypothalamus compression can cause increased prolactin levels because of a decrease in the prolactin inhibitory factor. Thus, hyperprolactinemia may be seen with non–prolactin-secreting pituitary adenomas and other sellar lesions with hypothalamic compression.

An unusual postpartum lymphocytic inflammatory pituitary lesion can be associated a mass lesion. This is known as lymphocytic hypophysitis.

Acromegaly can result from a nonpituitary source of increased growth hormone.

Differentiating between Cushing disease and Cushing syndrome, which is related to adrenal hyperplasia or tumor, is important.

Other causes of hyperprolactinemia that are unrelated to mass lesions in the pituitary or the hypothalamus include the following:

• Intracranial - Empty sella syndrome, pseudotumor cerebri, status post cranial irradiation
• Pharmacological - Antipsychotics (and other dopamine receptor antagonists), methyldopa, reserpine, verapamil, estrogen, opiates, cimetidine, sulpiride
• Endocrine - Primary hypothyroidism
• Metabolic - Chronic renal failure, cirrhosis
• Other unusual causes - Breast manipulation, chest wall lesions, spinal cord lesions, stress
• In some cases, a specific cause cannot be established.

Workup

Laboratory Studies

• Pituitary mass
  • Visual fields and ophthalmologic evaluation are critical in defining the presence of a chiasmal syndrome.
  • Neuroimaging would be appropriate (see Imaging Studies).
• Prolactinomas
  • Serum prolactin levels should be measured in any patient with a suspected sellar or suprasellar mass. If elevated, investigate the possibility of pharmacologic and other factors prior to ordering extensive neuroimaging studies.
  • Generally, a single elevated prolactin level may confirm the diagnosis. Minor elevations may be somewhat difficult to interpret, since breast manipulation can elevate the serum level. The first level obtained serves as a baseline and guides the course of dopamine-agonist therapy.
  • Serum prolactin level >200 mcg/L in a patient with a macroadenoma greater than 10 mm in size is diagnostic of a prolactinoma. Levels below that range in a macroadenoma suggest hyperprolactinemia secondary to hypothalamic compression.
• Growth hormone abnormalities
  • Growth hormone (GH) levels are elevated in acromegaly but can fluctuate significantly.
  • Intravenous (IV) GH levels every 5 minutes for 24 hours may show consistent elevation of GH. This is not a practical diagnostic method, but does indicate that a single GH value is not sufficient to make a diagnosis.
  • Serum insulinlike growth factor 1 (IGF-1) level is the best endocrinologic test for acromegaly. IGF-1 reflects GH concentration in the last 24 hours. Technical factors may limit its usefulness in some laboratories.
  • Oral glucose tolerance test is the definitive test for the diagnosis of acromegaly; a positive result is the failure of GH to decrease to <1 mcg/L after ingesting 50-100 g of glucose.
    • Thyrotrophin-releasing hormone (TRH), 200 mcg, can be given to increase the test's accuracy. A GH level > 5 mcg/L suggests acromegaly.
    • Failure to decrease the GH concentration to <2 mcg/L after a glucose load and after TRH stimulation is highly suggestive of acromegaly.
• Cushing disease and Cushing syndrome
  • Twenty-four hour urine is collected for free cortisol. Usually 2 baseline values are obtained.
  • Dexamethasone suppression test: The physiological basis of this test is a decrease in adrenocorticotropic hormone (ACTH) secretion by the pituitary because of exogenous glucocorticoid administration. One mg of dexamethasone is administered. Serum cortisol level is measured the next morning; it should be <138 nmol/L (ie, <5 mcg/dL).
  • Standard low-dose dexamethasone: Two-day baseline serum and urine cortisol levels are determined. The patient is then given 4 doses of 0.5 mg of dexamethasone at 6-hour intervals. Normal suppression is a serum cortisol level of <138 nmol/L or a urine level of less than 55 nmol/L.
  • If cortisol levels are increased abnormally, corticotrophin-releasing factor (CRF) in a dose of 100 mcg can be given to differentiate between Cushing disease and other causes of hypercortisolism (ie, Cushing syndrome). With pituitary adenomas, cortisol secretion is increased over the baseline.
  • High-dose dexamethasone suppression confirms diagnosis of a pituitary adenoma. It suppresses the pituitary gland even in the presence of an adenoma. If cortisol levels remain unchanged, the cause of increased cortisol is not a pituitary adenoma.
  • Metyrapone test: Metyrapone inhibits synthesis of cortisol. Patients with pituitary tumors remain responsive to low levels of cortisol, prompted by metyrapone administration, with increased secretion of cortisol precursors (ie, 11-deoxycortisol).
  • Serum levels of ACTH: The serum concentration of ACTH is higher than normal (>5.5 pmol/L at 9 am and >2.2 pmol/L at midnight).
  • At times, venous sampling of ACTH from the petrosal sinuses by means of cerebral venography may be valuable when making the diagnosis is difficult.
  • Baseline petrosal sinus levels of CRF distinguish patients with Cushing disease from those with ectopic ACTH secretion.
• Glycoprotein hormones - Thyroid-stimulating hormone, follicle-stimulating hormone, luteinizing hormone
  • Pituitary adenomas that are associated with thyroid-stimulating hormone (TSH) hypersecretion are uncommon. These patients have increased T3 and T4 levels, hyperthyroidism, and goiter with inappropriately high levels of TSH.
  • Increased follicle-stimulating hormone (FSH) levels may be apparent in the histologic examination of a pituitary adenoma in patients without apparent preoperative endocrine abnormalities and in some patients with hypogonadism.
  • Increased luteinizing hormone (LH) levels also may be seen in patients with hypogonadism. The secreted hormone is not intact LH, and serum testosterone levels are not increased.
  • Free alpha and beta subunits of FSH are secreted by pituitary tumors that are thought to be inactive. A high percentage of these tumors have a paradoxical release of FSH subunits in response to TRH stimulation (200 mcg). Rarely, these tumors are associated with precocious puberty or resumption of bleeding in a postmenopausal woman.
  • The initial screening endocrine tests should include levels of prolactin, IGF-1, LH, FSH, TRH and alpha subunit, cortisol, and T4; men should have testosterone level checked.
• Pituitary apoplexy: CSF may be xanthochromic, with crenated RBCs and high protein level.

Imaging Studies

• MRI of the brain and sellar region with multiplanar thin sections is of critical importance.
  • This provides axial, coronal, and sagittal sections of the sellar contents.
  • Generally, the relationship between the lesion and the optic chiasm and visual pathways is recognized easily.
  • Pregadolinium and postgadolinium images are recommended to ensure that primarily isointense lesions do not escape detection.
• CT scan of the brain with sellar images may be sufficiently specific and can detect tumor calcifications. However, the detail is generally inferior to that of MRI.
• Cerebral angiography is not performed routinely in the workup of sellar mass lesions. It generally is performed when vascular lesions are suspected.

Other Tests

• A final diagnosis generally is not made until the lesion is resected.
• If a granulomatous or infectious process is the primary concern, other systemic and neurological testing may be required.

Procedures

• Visual field testing
• Petrosal sinus venous sampling for ACTH- or TSH-producing adenomas in selective cases

Histologic Findings

The role of pathologic examination of pituitary tumors is critical. Routinely perform standard histologic examination, electromicroscopy, and immunohistochemistry for these lesions. Findings then are correlated with clinical and imaging results. The histologic characteristics of these lesions are discussed in Pathophysiology. At times, the differentiation of hyperplasia from adenoma may be difficult. Other nonpituitary mass lesions may be identified easily by pathologic examination.

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