Pituitary adenoma/PitNET

Last revised by Naqibullah Foladi on 22 May 2023

Pituitary adenomas or pituitary neuroendocrine tumors (PitNET) are primary neuroendocrine tumors that occur in the pituitary gland and are one of the most common intracranial neoplasms.

Depending on their size they are broadly classified into:

Although this distinction is largely arbitrary, it is commonly used and does highlight an important fact: small intrapituitary lesions (microadenomas) present differently and have different surgical and imaging challenges from larger lesions (macroadenomas) that extend into the suprasellar region. As such, it is not unreasonable to discuss them separately. This article is a general overview.

Pituitary adenomas and pituitary carcinomas are in fact neuroendocrine tumors and should be referred to as pituitary neuroendocrine tumors (PitNET). Gradually terminology is shifting to reflect this. In the 5th edition (2021) of the WHO classification of CNS tumors, "PitNET" has been added to a pituitary adenoma (rather than replacing it) 13 and it is almost certain that the 5th edition of the WHO classification of tumors of endocrine organs will adopt this new terminology as well 11,12

For the time being, until widespread adoption and recognition of this new terminology occurs, it seems prudent to continue to use the word adenoma, or at the very least include it in brackets. 

Pituitary adenomas are common, with rates varying widely depending on the definition: population prevalence is approximately 0.1%; autopsy prevalence is around 15% 2. They account for approximately 10% of all intracranial neoplasms and 30-50% of all pituitary region masses 3

Pituitary macroadenomas are approximately twice as common as microadenomas 3

A minority of tumors are associated with multiple endocrine neoplasia type I (MEN I)multiple endocrine neoplasia type IV (MEN4)Carney complex, McCune-Albright syndrome, and familial isolated pituitary adenoma.

Pituitary adenomas present either due to hormonal imbalance (both microadenomas and macroadenomas) or mass effect on adjacent structures (macroadenomas), classically the optic chiasm. Rarely presentation can be catastrophic, due to pituitary apoplexy

Over half of all adenomas are secretory 2, although even when this is the case this may not be the cause of presentation. A lack of libido or even galactorrhea may not lead to presentation and as such many secreting tumors are only diagnosed when mass effect occurs (see below). 

Hormones secreted include:

  • secretory: ~65% 

    • prolactin: ~50% 

    • growth hormone (GH): 10%

    • adrenocorticotropin (ACTH): 6% 

    • thyrotropin (TSH): 1% 

    • mixed

  • non-secretory: ~35%; most tend to be macroadenomas

It is also important to note that larger tumors can lead to hormonal imbalance due to mass effect rather than secretion. Hypopituitarism or moderately elevated prolactin are both seen, the latter due to the so-called stalk effect; prolactin release (unlike other pituitary hormones) is tonically inhibited by prolactin inhibitory hormone (PIH - a.k.a. dopamine) and as such, compression of the pituitary infundibulum can result in elevation of systemic prolactin levels due to interruption of normal inhibition. Keep in mind, though, that numerous drugs that act as dopamine antagonists will also elevate prolactin - see elevated prolactin (differential) 9.  

Most of the cases presenting due to mass effect are due to non-secreting macroadenomas 3 and the most common structure to be compressed by a macroadenoma is the optic chiasm. Invasion into the cavernous sinus is also encountered, with occasional compression of the oculomotor (CN III) nerve or, less frequently, the abducens (CN VI) nerve. Uncommonly, large tumors may result in hydrocephalus (by compressing the midbrain or distorting the third ventricle), orbital or sinonasal symptoms. 

Very rarely, pituitary adenomas may be seen in ectopic (i.e. extrasellar) locations, most commonly within the sphenoid sinus. It may also be found in the suprasellar region, cavernous sinus, parasellar region, clivus, nasal cavity, nasopharynx, temporal bone, and third ventricle.10

Radiographic features are discussed separately:

Treatment of pituitary adenomas depends on a number of factors:

  • size and presence of symptoms related to mass effect: these will often necessitate surgical decompression, regardless of cell type

  • cell type: prolactin and growth hormone-secreting tumors can often be treated medically

The most commonly employed approach to pituitary masses is transsphenoidal, whereby the floor of the pituitary fossa is accessed via the nasal cavity. In large tumors, other approaches may be necessary (e.g. craniotomy). 

Medical management of prolactinomas relies on administering a dopamine receptor agonist (e.g. bromocriptine or cabergoline). Although it can dramatically reduce the size of a macroadenoma, it has been associated with an increased incidence of hemorrhage into the tumor 4.  

Growth hormone-secreting tumors are usually surgically resected; however, in recurrent cases or in patients who are not able to undergo surgery, they can be treated with octreotide (a long-acting somatostatin analog). This can result in both reduction of the size of the tumor and reduction in the serum levels of growth hormone 4,5.  

There is no treatment required for the asymptomatic microprolactinoma14.

Radiosurgery is also occasionally used. Its main complication is hypopituitarism (seen in up to 70% of cases). Less common complications include damage to the optic apparatus (optic nerves, chiasm, optic tracts), cranial nerves, and internal carotid arteries 7

Recurrent symptoms requiring further intervention is relatively common, with 18% of patients with non-functioning tumors and 25% of patients with prolactinomas eventually requiring further treatment 6

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