#513  Pituitary Incidentalomas

February 2, 2026 | By Matthew Watto, MD

Audio

Video

Transcript available via YouTube

Dr. Fleseriu schools us on managing the unexpected

Become a master of pituitary incidentalomas. Learn about the hormonal workup and management of pituitary microadenomas, macroadenomas and empty sella syndrome and when surgery may be needed. We’re joined by Dr. Maria Fleseriu, @MariaFleseriu (Oregon Health and Science University)

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Show Segments

• Intro
• Rapid fire questions/Picks of the Week
• Case 1
• Defining Pituitary Incidentalomas
• What is the difference between micro adenoma, macroadenoma and functional vs non-functional adenomas
• Hormonal workup of microadenoma (assessing for hypopituitarism and hormonal excess)
• Decided when to reimage patients and long term follow up of microadenomas
• Case 2
• Hormonal workup for pituitary macroadenoma
• Deciding when surgery should be considered
• Discussing the role of visual field testing
• Case 3
• Defining empty sella syndrome
• Discussing hormonal assessment of empty sella syndrome
• Treatment options for hyperprolactinemia caused by empty sella syndrome
• Outro

Disclosures

Dr. Fleseriu reports no relevant financial disclosures. The Curbsiders report no relevant financial disclosures. 

Pituitary Incidentaloma Pearls

1. Regardless of the pituitary adenoma size, patients should be evaluated for hormonal deficiencies and hormone excess
2. Check TSH, free T4, IGF-1, AM cortisol, ACTH, LH, FSH and either testosterone or estrogen based on patient sex to assess for hypopituitarism
3. Every patient with a pituitary adenoma should be screening for a prolactinoma with a prolactin level and acromegaly with IGF-1 level and consider Cushing testing if suspected clinically
4. MRI with pituitary protocol is the imaging of choice for incidentalomas and repeat imaging should consider the size of the adenoma and the proximity to the optic chiasm
5. Testing for Cushing disease includes a late night salivary cortisol test, 24-hour urine free cortisol test, or 1 mg dexamethasone suppression test, however, each test has its own caveats
6. Empty sella syndrome can cause hypopituitarism so assess for hormonal deficiencies
7. Empty sella syndrome can also cause hyperprolactinemia due to stalk effect and may also rarely represent a previous adenoma that was secreting ACTH or growth hormone so consider testing for Cushing and acromegaly if clinically suspected

Pituitary Incidentalomas Show Notes

Pituitary incidentalomas are defined as lesions in the sella or parasellar region that are found incidentally on an imaging study, not when we are looking for a pituitary pathology (Fleseriu et al. 2025). These can include pituitary adenomas, other tumors (e.g. meningiomas), vascular lesions, empty sella, Rathke’s cleft cysts, infiltrative diseases, and infections. Detection is becoming more common as more of the population is receiving more brain imaging, and autopsy studies suggest an 11% prevalence.

Classifying Pituitary Adenomas

Patients presenting with adenomas can be classified as having micro, macro, or giant adenomas based on size. The size cutoffs, though arbitrary, are as follows: less than 1 cm is a microadenoma, 1 cm or greater is a macroadenoma, and 4cm or greater is a giant adenoma (Fleseriu et al. 2025, Iglesias 2018).

The relation of the adenoma to the optic chiasm is very important, regardless of size, due to the concern of adenoma growth and compression of the chiasm. When defining functionality, a functional adenoma is one that secretes excessive amounts of one or more hormones which can be shown on pathology based off of staining for these hormones and looking for transcription factors. Non-functioning pituitary adenomas (NFPAs) show no overt signs or symptoms of hormonal hypersecretion and show no hormone secretory activity on biochemical testing (Fleseriu et al. 2025).

Hormonal Workup for Pituitary Microadenomas

For all pituitary lesions we should be screening both for evidence of hormonal hypersecretion and insufficiency. For hypersecretion this includes sending a prolactin level and screening for acromegaly using an insulin-like growth factor 1 (IGF1) level for all lesions. We are seeing that patients with acromegaly may not be presenting with the typical features we are often taught, and screening with IGF1 can ensure cases are not missed (Fleseriu et al. 2025). Screening for Cushing disease should also be considered in patients who have features (weight gain, worsening of blood glucose control, easy bruising, unexplained thrombosis etc.). Per Dr. Fleseriu you may not have all the characteristic features, and if you do have a clinical suspicion you should test!

In terms of looking for hormone deficiencies/hyposecretion we can screen for adrenal insufficiency with a morning cortisol and adrenocorticotropic hormone (ACTH) level and growth hormone deficiency with IGF-1 level, with additional dynamic testing if needed. Hypogonadism can be screened for with LH and FSH levels and estrogen or testosterone based on the patient’s sex (Fleseriu et al. 2025). You should also screen for central hypothyroidism with a TSH AND free T4. The free T4 is particularly important as TSH levels can be normal in patients with secondary hypothyroidism. Treatment response for secondary hypothyroidism is monitored using free T4 (Iglesias 2025). 

Screening for Cushing Disease

Screening for Cushing disease can involve a low-dose dexamethasone suppression test, 24-hour urine free cortisol level, and late night salivary cortisol test (Riencke 2023). Dr. Fleseriu utilizes the late night salivary cortisol as her first-line test of choice as some research indicates it has a higher specificity than other tests when it comes to Cushing disease (Tritos and Miller 2023, Fleseriu et al. 2021). Her test of choice for hypercortisolism secondary to an adrenal source is the 1 mg dexamethasone suppression test as it is the test of choice to detect even mild autonomous cortisol secretion (Prete and Bancos 2024). All of these tests have caveats that need to be considered when interpreting testing.

Performing the dexamethasone suppression test can be difficult given women who are on estrogen as OCPs can have falsely elevated cortisol values due to increased cortisol binding globulin (Neiman 2025, Riencke 2023). Additionally, patients have to take dexamethasone at 11 PM and ideally obtain blood work at 8 AM which can be difficult to obtain if the lab is not open or the patient runs late. You need a dexamethasone level as well for most patients to ensure the patient has received an adequate dose of dexamethasone to suppress normal endogenous cortisol secretion (Riencke 2023).

A 24-hour urine cortisol level is a sensitive test, albeit lower than others, to help determine cortisol excess however may be difficult to collect for some patients. A late-night salivary cortisol level uses the concept that cortisol is usually secreted in a diurnal manner in normal patients (Newell-Price 2019). Normal cortisol production is typically highest in the morning and it typically is lowest close to midnight. In patients who work night shifts, this changes, given cortisol is usually highest close to the time you wake up (Neiman 2025). With a late-night salivary cortisol, patients place a swab at the side of their mouth near their cheek to collect saliva and place it into a salivette. Per Dr. Fleseriu, it can be collected just before they go to sleep to avoid a false positive test due to the stress of having to wake up later at night. 

Monitoring for Adenoma Growth

Per Dr. Fleseriu, we do not know what features in a microadenoma make it more likely to progress to a macroadenoma. Although previous Endocrine Society Guidelines suggested a 6 mm cutoff in microadenomas that made them higher risk of progression, this has not been seen in further research and the new 2025 Pituitary Society Guidelines do not suggest this cutoff anymore (Fleseriu et al. 2025).

We also keep a closer eye on patients with lesions closer to the optic chiasm, given a higher chance of chiasm compression as compared to lesions further from the chiasm.  

In stable patients with a pituitary microadenoma, you can extend imaging to 2-3 years after the initial imaging if it is are ≥5 mm away from the optic chiasm (Fleseriu et al. 2025). We are not really sure when to definitively stop following these lesions, and Dr. Fleseriu notes you can consider repeat imaging in 5 years time to ensure there is no growth. This is also debated in the guidelines with some experts arguing for longer follow up of lesions than others (Fleseriu et al. 2025). 

For patients with headaches, Dr. Fleseriu notes to consider referring to neurology if you suspect the adenoma may be associated with symptoms.

For macroadenomas, the imaging interval should be more frequent and should also include visual field testing at baseline and for follow up (Fleseriu et al. 2025). If macroadenomas are noted to be less than 5 mm from the optic chiasm, guidelines suggest imaging 6-12 months after initial imaging and 1 year if the adenoma is greater than 5 mm from the optic chiasm (Fleseriu et al. 2025). If there is growth on follow up imaging or the lesion extends closer to the chiasm (grows to less than 5 mm from the optic chiasm), imaging is recommended in 1-2 years (Fleseriu et al. 2025). If there is no growth noted and the lesion remains greater than 5 mm from the chiasm, follow up imaging can be extended to 2-3 years (Fleseriu et al. 2025). 

Dr. Fleseriu also uses formal visual field evaluations as a tool between imaging to assess tumor growth. Visual field testing is indicated if the patient has visual symptoms or there is radiologic evidence suggesting the lesion is abutting the optic chiasm (Fleseriu et al. 2025). Per the Pituitary Society guidelines, repeat visual field testing performed in 6 months for lesions with suprasellar extension, 6-12 months if the lesion if <5 mm from the optic chiasm, and 1-2 years if the lesion is ≥5 mm from the optic chiasm (Fleseriu et al. 2025). Repeat hormonal workup looking for hypopituitarism can also be used to screen for growth of the adenoma as, due to the mass effect leading to new deficiencies, it can indicate adenoma growth in between our imaging follow up (Fleseriu et al. 2025).

The Pituitary Society international consensus guideline statement includes an algorithm as below (Fleseriu et al. 2025). 

Management of Pituitary Macroadenomas

For these lesions you need a formal visual field test to assess for any visual field deficits(Fleseriu et al. 2025). A brain MRI is still an excellent imaging modality to assess pituitary macroadenomas, however, according to expert opinion, if there is suspicion for apoplexy a CT scan without contrast may be able to pick up hemorrhage which may be missed by MRI.

These patients should be assessed for hormonal deficiencies and excess just as it is recommended for pituitary microadenomas (Fleseriu et al. 2025). These patients are more likely to have hormonal deficiencies due to mass effect. In terms of which hormones are most likely to be deficiency, the gonadotropins and growth hormones are most likely to be deficient however with more advanced disease, secondary hypothyroidism and adrenal insufficiency can occur. Per Dr. Fleseriu, if there is any concern for adrenal insufficiency, draw the cortisol level and empirically start steroids while pending results due to the risk for adrenal insufficiency.

Make sure to assess all of the hormones at once, as supplementing one hormone that is deficient can affect the levels of other hormones. When supplementing thyroid hormone in particular before replacing glucocorticoids in patients with both secondary hypothyroidism and secondary adrenal insufficiency, it can worsen adrenal insufficiency (Yousef et al. 2025).  Per Dr. Fleseriu, patients with panhypopituitarism can adapt to chronic hormone deficiencies and may not present with all the typical signs and symptoms of hypopituitarism.

Additional consideration for hormonal testing is making sure the prolactin is diluted to ensure there is no hook effect which is assay interference which can occur when the levels are very high. If the prolactin is only slightly elevated this may be a stalk effect–the mass compressing the stalk causes decreased dopamine to reach the anterior pituitary, thus decreasing the suppression of prolactin.

It is important to get the neurosurgeon involved early in the care of the patient to assess whether surgery may be indicated. In older individuals, comorbidities and functional status need to be considered, particularly when assessing for surgery versus observation. It takes a multidisciplinary team when it comes to making the decision regarding surgery.

Management of Empty Sella Syndrome

Empty sella syndrome is when the pituitary gland, housed in the “sella turcica” appears flattened or shrunken, often due to cerebrospinal fluid filling the space, leading to the gland appearing absent on scans (Fleseriu et al. 2025). Obesity and idiopathic intracranial hypertension predispose patients to developing this condition but it could also be idiopathic. The initial hormonal workup is the exact same as with a pituitary incidentaloma with morning cortisol, ACTH, TSH, free T4, prolactin, LH, FSH and testosterone or estrogen based off patient sex (Fleseriu et al. 2025). You can have stalk effect in these patients leading to elevated prolactin and menstrual irregularities in women.

In terms of hormonal follow up in these patients, you can consider repeating hormonal testing, however as of right now there is no recommendation for repeat imaging as we are not sure whether progression of empty sella will lead to future hormonal deficiencies.

Per Dr. Fleseriu, sometimes empty sella syndrome can indicate a previously functional pituitary adenoma that underwent infarction. These can be prolactinomas, growth hormone, or even ACTH secreting adenomas. 

In these patients with stalk effect with elevated prolactin, you can still consider dopamine agonists or oral contraceptive pills to ensure the patient still has regular periods in women and make sure that they have enough estrogen to prevent osteoporosis long term (Lundholm 2024). Testosterone replacement may also be needed occasionally in men.

Links

1. Transylvania Tourism
2. Pituitary Society
3. Endocrine Society

Goal

Listeners will develop an approach to the assessment of pituitary incidentalomas, in particular the management of pituitary microadenomas, macroadenomas, and empty sella syndrome. 

Learning objectives

After listening to this episode listeners will…  

1. Understand the initial hormonal and imaging workup for pituitary adenomas
2. Know when to consider closer monitoring of adenomas and when to consider visual field testing and potentially surgical referral
3. Be able to evaluate patients with empty sella syndrome with hormonal testing

Citation

Ahmad M, Fleseriu M, Williams PN, Watto MF. “#513 Pituitary Incidentalomas”. The Curbsiders Internal Medicine Podcast. thecurbsiders.com/category/curbsiders-podcast Feb 2, 2026.