Pituitary Incidentalomas

Definition, Etiology, PathogenesisTop

A pituitary incidentaloma (PI) is generally defined as a pituitary lesion identified on brain imaging performed for an unrelated reason. The prevalence of pituitary adenomas varies widely; autopsy studies report a prevalence between 3% and 27%, while imaging studies report a prevalence of ~10%. By convention masses <1 cm are called microadenomas, while those >1 cm are called macroadenomas.

The true pathologic etiology of most PIs remains unknown, since most PIs do not require surgical intervention. Of those that require surgery, up to 90% are pituitary adenomas, while the rest include etiologies such as Rathke cleft cysts, meningiomas, craniopharyngiomas, germinomas, and metastases (Table 1). The pathogenesis of PIs is believed to be a multistep process, through genetic and epigenetic mechanisms conferring growth advantage to a particular type of cells, resulting in their increase through clonal expansion.

Clinical FeaturesTop

PIs can cause symptoms through mass effect or by affecting hormone production. Roughly half (55%) of PIs are nonfunctioning in that they do not produce excessive pituitary hormones but can still cause symptoms due to secondary hormone deficiencies or local compressive symptoms. Adenomas that secrete excessive pituitary hormones can cause symptoms due to excessive secretion of a particular hormone or hormones in addition to compressive effects and secondary hormone deficiencies (Table 2). While prolactinomas and lesions leading to Cushing syndrome and acromegaly are seen more frequently, tumors secreting functionally active thyroid-stimulating hormone (TSH), luteinizing hormone (LH), or follicle-stimulating hormone (FSH) are exceedingly rare.

Local compressive symptoms may include periorbital headaches, visual field deficits due to compression of the optic chiasm, or less commonly ophthalmoplegia due to involvement of the cavernous sinus affecting cranial nerves III, IV, and VI.

DIAGNOSISTop

Clinical Assessment

All patients presenting with PIs should undergo clinical assessment for an excess or deficiency of anterior and posterior pituitary hormones as well as for symptoms due to mass effects. These assessments could help in determining the need for biochemical, radiographic, or visual field evaluation, as delineated below.

Diagnostic Tests

1. Biochemical testing for an excess or a deficiency of pituitary hormones should be carried out in patients presenting with PIs based on lesion size or presence of symptoms and signs. Pituitary hormone deficiencies are rare in microadenomas, suggesting the need for testing for hormonal deficiencies only in patients presenting with symptoms. However, testing for hormone deficiency should be done in all patients presenting with macroadenomas. Biochemical tests for hormonal oversecretion and undersecretion: Table 3.

In addition, testing for primary hypothyroidism (TSH) should also be done to exclude thyrotroph hyperplasia masquerading as a macroadenoma and responsive to medical therapy with levothyroxine, which does not require surgical treatment. It can present with hyperprolactinemia from stimulation of prolactin by thyrotropin-releasing hormone (TRH) in response to hypothyroidism. Prolactin should also be checked in all patients with PIs to determine if the lesion is a prolactinoma, which is usually medically treated.

2. Formal visual field testing should be considered in patients in whom the PI is close to, or abuts, the optic nerves or chiasm on magnetic resonance imaging (MRI).

3. Imaging: A dedicated MRI of the sella should be performed at baseline in patients diagnosed with a PI using computed tomography (CT).

TREATMENTTop

Indications for Surgery

Patients with PIs who have evidence of hormonal hypersecretion (except for a prolactinoma, which is usually medically treated) should have surgery at the time of initial diagnosis, if possible. In addition, patients with visual field deficits, neurologic deficits due to compressive effects, visual disturbances due to pituitary apoplexy, or lesions abutting the optic nerves or chiasm should also be referred for surgery.

FOLLOW-UPTop

Follow-up for patients who do not undergo surgery or do not have pituitary hormone hypersecretion at initial diagnosis:

1) In patients with a microadenoma or macroadenoma, clinical assessment of pituitary deficiency should be undertaken 12 or 6 months after initial testing, respectively, and yearly thereafter.

2) Biochemical assessment for hypopituitarism should be carried out if there is a change in symptoms or increase in the size of the tumor.

3) MRI should be performed at 6 months in those with a macroadenoma and at 12 months in those with a microadenoma. If the lesion is stable, this interval can be changed to every year for those with a macroadenoma and every 1 to 2 years for those with a microadenoma in the 3 years post diagnosis, and the interval can be increased thereafter if the lesion remains stable until 5 years for a microadenoma and up to 10 years for a macroadenoma.

4) Visual field testing should be undertaken in patients whose PIs enlarge to abut or compress the optic nerves or chiasm on repeat imaging.

TableSTop