Pituitary Adenoma

Pituitary adenoma is a benign neoplasm arising from the anterior pituitary gland. It is the commonest cause of a sellar mass lesion.

Adenomas are classified by size: microadenoma, under 1 cm, versus macroadenoma, 1 cm or above. Macroadenomas carry greater risk of local mass effect and hypopituitarism.

They are also classified by hormonal secretory status. Functioning adenomas produce a recognisable clinical hormonal excess syndrome, covered under hyperprolactinaemia, acromegaly and Cushing disease. Clinically non-functioning adenomas may still secrete hormone subunits detectable on immunohistochemistry, without producing an overt clinical hormonal syndrome.

Evaluation of any pituitary adenoma requires assessment for hormonal hypersecretion. For macroadenomas, also assess mass effect on surrounding structures and hypopituitarism from compression of normal pituitary tissue.

Pathophysiology and classification

• Clinically non-functioning adenomas are the commonest subtype among macroadenomas. They typically present with mass effect, given the absence of a clinically apparent hormonal excess syndrome.
• They are frequently identified only once large enough to compress the optic chiasm or surrounding normal pituitary tissue. They therefore tend to present at a larger size than functioning adenomas, which are identified earlier by their hormonal symptoms even while small.
• Prolactinomas are the commonest functioning pituitary adenoma subtype overall (see hyperprolactinaemia).
• Growth hormone secreting adenomas cause acromegaly, and adrenocorticotropic hormone secreting adenomas cause Cushing disease. Both are important functioning subtypes.
• Thyroid stimulating hormone secreting adenomas are a rare cause of hyperthyroidism, with inappropriately normal or elevated, rather than suppressed, thyroid stimulating hormone.
• Pituitary apoplexy is an acute complication comprising sudden haemorrhage or infarction within a pituitary adenoma. It is an endocrine and neurosurgical emergency.
• It risks acute, severe hypopituitarism, particularly adrenocorticotropic hormone deficiency with risk of adrenal crisis, together with acute mass effect and visual and neurological complications.

• Mass effect symptoms are the characteristic local manifestations of a sufficiently large adenoma. The most classic is bitemporal hemianopia, from compression of the optic chiasm by a suprasellar extending macroadenoma.
• Headache also occurs. Ophthalmoplegia occurs where lateral tumour extension affects cranial nerves within the cavernous sinus.
• Hypopituitarism reflects compression of normal pituitary tissue by an enlarging adenoma. It can affect any or all of the anterior pituitary hormone axes.
• Hormonal loss follows a generally recognised, though not invariable, order. Growth hormone and gonadotropin deficiency typically occur earliest. Adrenocorticotropic hormone and thyroid stimulating hormone deficiency generally occur later, with more extensive compression.
• The clinical features of functioning adenomas reflect the hormone hypersecreted, as in hyperprolactinaemia and acromegaly.
• Pituitary apoplexy presents with sudden, severe headache (often the most prominent feature), visual disturbance and ophthalmoplegia. In more severe cases there is altered consciousness and features of acute adrenal insufficiency.
• This dramatic, acute presentation contrasts clearly with the typically gradual, insidious presentation of an adenoma growing slowly over an extended period.

• Magnetic resonance imaging of the pituitary region is the essential imaging investigation. It characterises size, extent of any suprasellar or lateral cavernous sinus extension, and relationship to the optic chiasm and surrounding structures, informing diagnosis and treatment planning.
• Full anterior pituitary hormonal assessment is essential for every confirmed pituitary adenoma. One axis may be hypersecreted while other axes are deficient from compression of the surrounding normal gland.
• Assess hormonal hypersecretion with prolactin and insulin like growth factor 1 (a screening test for growth hormone excess). Where clinical features suggest Cushing disease, screen for cortisol excess.
• Assess for hypopituitarism as detailed under that condition.
• Formal visual field assessment is essential for any macroadenoma with suprasellar extension in proximity to the optic chiasm. It characterises any current visual field deficit and provides a baseline for monitoring treatment response.
• Pituitary apoplexy diagnosis is supported by magnetic resonance imaging showing haemorrhage or infarction within the adenoma.
• Arrange urgent, full pituitary hormonal assessment, including immediate cortisol measurement. It is critical to promptly identify and treat any associated acute adrenocorticotropic hormone deficiency.

• Clinically non-functioning microadenomas without significant mass effect, and small, asymptomatic, hormonally inactive incidental findings, may be managed with periodic surveillance imaging and hormonal reassessment alone, given their generally indolent, slow growing natural history.
• Transsphenoidal surgical resection is the primary treatment for macroadenomas causing significant mass effect (visual field compromise, significant hypopituitarism). It is also used for functioning adenomas not amenable to, or not controlled by, medical therapy.
• The role of medical therapy varies substantially by functioning subtype (see the individual conditions). This minimally invasive surgical approach is generally preferred for the great majority of pituitary adenomas, given lower morbidity than historical craniotomy based approaches.
• Medical therapy is first line for prolactinoma specifically, given the excellent response of this tumour type to dopamine agonist therapy. This contrasts clearly with the generally surgery first approach for other functioning and non-functioning adenoma subtypes.
• Radiotherapy (conventional fractionated or, increasingly, stereotactic radiosurgery) is reserved for residual or recurrent disease following surgery, or for patients not suitable for or declining surgery.
• Radiotherapy has delayed onset of therapeutic effect, often taking months to years for full benefit. It carries a recognised long term risk of subsequent hypopituitarism, so irradiated patients need ongoing, long term hormonal surveillance.
• Pituitary apoplexy management requires immediate high dose intravenous hydrocortisone. Give it empirically, without waiting for formal cortisol results, given the potentially catastrophic consequences of untreated acute adrenal insufficiency.
• Arrange urgent neurosurgical assessment for consideration of emergency surgical decompression, particularly with significant, acute visual compromise or deteriorating consciousness. Individualise the urgency and necessity of surgery according to the severity and trajectory of the neurological and visual features.
• Full, ongoing endocrinology follow up underpins long term management across functioning and non-functioning subtypes. It includes regular hormonal reassessment (for persistent or recurrent hypersecretion and for evolving hypopituitarism) and periodic surveillance imaging.
• Multidisciplinary input comes from neurosurgery, ophthalmology (for visual field monitoring) and, where radiotherapy is used, oncology, supporting coordinated care.