Pituitary Microadenomas Workup

Updated: Nov 07, 2022
  • Author: Andre E Manov, MD, MSHM, FACP, CPE; Chief Editor: George T Griffing, MD  more...
  • Print

Laboratory Studies

Individualizing the evaluation of microadenomas with an evidence-based approach while considering signs, symptoms, size of the lesion, imaging characteristics, and patient factors is key. Endocrine Society clinical practice guidelines recommend a complete biochemical assessment even in asymptomatic patients. [1]

Autonomous secretion by a tumor usually leads to an inappropriate relationship between the level of the hormone secreted by the peripheral gland (thyroid, adrenal, gonadal) and the amount of stimulating pituitary hormone (TSH, corticotropin, gonadotropin). That is, the normal decrease or suppression of the stimulating hormones found in conjunction with the rise of the peripheral gland hormones would not be demonstrated.

Hormonal hypersecretion in the setting of a sellar mass is typically caused by a pituitary adenoma, with the most frequent secretory microadenomas being the prolactin-secreting form. [3]  The prolactin level may correlate with the size of the adenoma; [3]  prolactin concentrations of more than 250 ng/mL are usually associated with macroadenomas and would warrant further imaging follow-up. The prolactin level can also be elevated as a result of factors such as pregnancy, breastfeeding, renal failure, cirrhosis of the liver, and primary hypothyroidism and with certain concomitant medications (antipsychotics/neuroleptics, antidepressants, antiemetics); elevation can also result from the stalk effect, in which a non-functioning adenoma compresses the pituitary stalk, leading to hyperprolactinemia. The prolactin level in the above instances is usually less than 100 ng/mL. However, certain medications, including risperidone and metoclopramide, can elevate the level above 200 ng/mL. 

A thorough history and a review of ongoing medication use are very important. Because excess secretion of growth hormone does not always produce the expected clinical phenotype, especially early on, evaluation of the serum IGF-1 level, age and gender adjusted, is recommended in all cases. Equivocal values warrant further serum growth hormone level measurement after an oral glucose load test.

A patient with Cushing disease may have an elevated or normal (non-suppressed) corticotropin level. Screening for Cushing syndrome with an overnight dexamethasone suppression test is advised. If positive, increased midnight salivary cortisol, the test for which needs to be repeated on a separate day, confirms the diagnosis of Cushing syndrome. Another possibility for the confirmation of Cushing syndrome is a grossly abnormal 24-hour urinary free cortisol test, which also needs to be repeated for confirmation on a separate day. This test usually becomes positive in more advanced cases of Cushing syndrome.

ACTH-secreting tumors can be as small as 5 mm or less in diameter. [14] The incidental finding of nonsecreting microadenomas is sufficiently common that the diagnosis of a corticotropin-secreting adenoma after positive clinical and biochemical testing may require specialized tests such as petrosal sinus sampling to confirm the Cushing disease diagnosis. This is especially appropriate if the microadenoma is less than 6 mm.

Thyrotroph adenomas characteristically lead to elevated serum free thyroxin (T4) and triiodothyronine (T3), with an inappropriately normal or elevated serum TSH level. Such patients may have hyperthyroidism without TSH suppression; however, it is necessary in these cases to differentiate between the presence a thyrotroph adenoma and thyroid hormone resistance.

Evaluation for hormonal hyposecretion is generally conducted in the presence of macroadenomas, since these larger tumors can destroy the hypophyseal gland, leading to the hyposecretion.


Imaging Studies

Microadenomas are generally confined to the pituitary gland/sella, and, given its high sensitivity and specificity, MRI is the imaging modality of choice for workup of these lesions. 

On MRI scans, normal pituitary tissue and pituitary adenomas have a signal that is similar to or slightly greater in intensity than that of CNS tissue. Enhancement with gadolinium improves the detection rate for pituitary adenomas. Microadenomas are isointense to the normal pituitary gland tissue on T1- and T2-weighted images. With contrast, however, these growths enhance at a slower rate than normal pituitary tissue does; dynamic enhanced images can detect this early enhancement difference and confer higher sensitivity for microadenoma detection. Rapid sequential images obtained during the first-pass arterial phase help to detect a microadenoma as a region of non-enhancing tissue, in contrast to the normally enhancing pituitary tissue surrounding it. These enhancement differences can be useful when adenomas are suspected (especially ACTH-secreting tumors) but conventional imaging is negative. [15]

Cystic lesions, such as Rathke cleft cysts, typically have a low-intensity signal on T1-weighted images but may have a high-intensity signal on T2-weighted images. [16]  Pituitary hemorrhage results in a high-intensity signal on both T1- and T2-weighted images.

Meningiomas typically have a brighter and more homogeneous signal than pituitary adenomas. They also have a suprasellar, rather than a sellar, epicenter and a dural-based attachment best seen after contrast enhancement 

Computed tomography (CT) scans are not very specific or sensitive for microadenomas. High-resolution CT scanning is complementary and may be used primarily if MRI is contraindicated. For best spatial resolution, CT scanning can be performed with 1-mm axial thin slices with contrast.

MRI showing a nonenhancing area in the pituitary c MRI showing a nonenhancing area in the pituitary consistent with a microadenoma, in a patient with hyperprolactinemia.



Other Tests

Other tests are dictated by the clinical picture of hormonal excess or, very rarely, hormonal deficiency. In contrast to macroadenomas, pituitary function testing is generally not needed for microadenomas. In addition, unlike pituitary macroadenomas, microadenomas rarely cause visual-field defects, and if there is no involvement of the optic chiasm on MRI, there is no need to perform the associated test.


Histologic Findings

If the tumor is removed surgically, immunohistochemical staining for secretory granules is advisable. If the test is negative and if it is clinically indicated, transcription factor immunostaining may identify the cell of origin for the adenoma. [17]



Staging is determined primarily by the size of the microadenoma. By definition, all are less than 10 mm and are likely to be confined to the sella.