Nonfunctioning Pituitary Adenomas

Essentials of Diagnosis

• Clinical and biochemical evaluation for pituitary hormone hypersecretion is negative

• MRI shows a pituitary microadenoma (<1 cm diameter) or macroadenoma (≥ 1 cm diameter)

• Headache, visual field compromise and anterior hypopituitarism are common with macroadenomas

• Elevated serum PRL with macroadenomas may be due to stalk compression

General Considerations

• Benign neuroendocrine neoplasms that do not produce symptoms from hormone oversecretion

• Nonfunctioning pituitary microadenomas (< 1 cm) are common, detected as an incidental finding in 4–37% of brain CT or MR imaging

• Account for up to 14–54% of all pituitary adenomas and are more frequent with advancing age

Symptoms and Signs

• Nonfunctioning pituitary macroadenomas

  • Measure 1 cm or larger

  • Tend to be more aggressive than functioning pituitary adenomas

  • Frequently present with mass effect symptoms, including

    • Headache

    • Visual field compromise

    • Cranial nerve palsies affecting extraocular muscles

    • Pituitary apoplexy

• Larger macroadenomas frequently cause some hypopituitarism, particularly hypogonadotropic hypogonadism

• Nonfunctioning pituitary microadenomas are asymptomatic

Differential Diagnosis

• Pituitary craniopharyngiomas

• Gliomas

• Meningiomas

• Skull base osteosarcomas

• Rathke cysts

• Lymphocytic hypophysitis

• Infection

• Metastases

Laboratory Findings

• All patients with a pituitary adenoma require testing for pituitary hormone hypersecretion

  • A serum PRL is obtained to screen for prolactin hypersecretion

  • Women with hyperprolactinemia are tested for pregnancy with a serum hCG.

  • Clinical suspicion should dictate whether to formally test for Cushing disease or acromegaly

• Pituitary macroadenomas

  • All patients require evaluation for anterior hypopituitarism

  • Serum free T₄, thyroid-stimulating hormone (TSH), morning serum testosterone and free testosterone (men)

  • Serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) (men with low serum testosterone, women who are postmenopausal, and younger women with amenorrhea)

  • Serum sodium and glucose

  • A serum IGF-I is drawn to screen for growth hormone (GH) deficiency

  • Younger patients with short stature who have not fused their epiphyses should have a full evaluation for growth hormone deficiency

  • Patients with a macroadenoma that impinges upon the optic chiasm require formal visual field testing

  • A cosyntropin stimulation test is performed for patients with hyponatremia or symptoms of possible hypoadrenalism

Imaging

• Pituitary dynamic contrast-enhanced MRI (3T)

  • Modality of choice for the evaluation and follow-up of pituitary adenomas

  • About 10% of nonfunctioning pituitary microadenomas enlarge over several years, whereas 23% of pituitary nonfunctioning macroadenomas enlarge significantly

  • Nonfunctioning pituitary microadenomas that are < 5 mm require no further MRI follow-up

  • For nonfunctioning pituitary adenomas ≥ 5 mm, repeat MRI is recommended at 6 months then yearly for 3 years

  • If no enlargement is noted, MRI surveillance can be done less frequently

• No treatment needed for asymptomatic pituitary nonfunctioning microadenomas

• Patients need to be monitored closely, however, with periodic MRI surveillance

• Surgery is the main treatment option and should be considered for patients whose adenoma is causing mass effect symptoms, premature development of puberty, hormonal deficiencies, or the emergence of symptomatic hormonal hypersecretion

• Radiation therapy can be used for select individuals with pituitary macroadenomas

Prognosis

• Excellent for patients with nonfunctioning microadenomas < 5 mm diameter

• Patients with larger nonfunctioning microadenomas also have a very good prognosis but follow-up is required

• Persons with nonfunctioning macroadenomas have a much higher risk for tumor growth and for hypopituitarism and are more likely to require surgery with or without radiation therapy