Pituitary Macroadenomas Workup

Laboratory tests include basal hormone levels and dynamic hormone measurements depending on the tumor studied.

All tumors should have screening basal hormone measurements, which may include prolactin, thyrotropin, thyroxine, adrenocorticotropin, cortisol, LH, FSH, estradiol, testosterone, growth hormone, insulinlike growth factor-1 (IGF-1), and alpha subunit glycoprotein.

Dynamic hormone tests are performed to assess the functionality of a tumor and assist in differential diagnosis. They also can be used to assess anterior pituitary reserve.

Thyrotropin-releasing hormone (TRH) causes elevation of serum prolactin and thyrotropin. Prolactinomas, hyperprolactinemic states, hyperthyroidism, and panhypopituitarism exhibit a blunted response. Gonadotropinomas respond paradoxically to TRH (LH, FSH, LH-beta, and alpha subunit should be measured).

GHRH produces an elevation in growth hormone. This response is blunted in growth hormone deficiency, Cushing disease, and hypothyroidism. Other agents that may be used for this test include insulin, L-dopa, arginine, and clonidine. Acromegaly may produce a paradoxical reduction in growth hormone.

Hyperglycemia suppresses serum growth hormone. This suppression does not occur in pituitary tumors secreting growth hormone, ectopic growth hormone–releasing tumors, Cushing syndrome, and anorexia nervosa. A paradoxical rise in growth hormone may be observed in acromegaly, acute illness, and chronic renal failure. Many people with acromegaly also show paradoxical growth hormone response to TRH and occasionally to GnRH.

CRH causes a rise in corticotropin. This response is exaggerated in Cushing disease but blunted in other causes of Cushing syndrome. When combined with inferior petrosal sinus sampling, this test may assist in differentiating Cushing disease from benign ectopic adrenocorticotropic hormone (ACTH) syndrome.

Insulin-induced hypoglycemia causes a rise in corticotropin, cortisol, and growth hormone. A blunted response is observed in Cushing syndrome, growth hormone deficiency, hypothyroidism, and hyperthyroidism.

Metyrapone causes a rise in morning serum 11-deoxycortisol and urinary 17-hydrocorticosteroids (17-OH steroids). An exaggerated response occurs in Cushing disease, but no response is observed in other causes of Cushing syndrome.

Dexamethasone suppression testing is used in Cushing syndrome evaluation. An overnight 1-mg dexamethasone dose fails to suppress morning serum cortisol in Cushing syndrome but is only a screening test. Low-dose and high-dose dexamethasone suppression tests assist, respectively, in establishing the diagnosis of Cushing syndrome and differentiating between Cushing disease and ectopic production of corticotropin.

Cosyntropin testing and corticotropin infusion testing assist in assessing the hypothalamic-pituitary-adrenal axis for adrenocortical insufficiency.

GnRH causes an increase in LH and FSH levels. This response is blunted in pituitary hypogonadism but exaggerated in primary hypogonadism. Test results, however, are not very dependable.

Pituitary imaging is important in confirming the diagnosis of pituitary macroadenoma and also for determining the differential diagnoses of other sellar lesions. Plain skull radiographs are poor at delineating soft tissues and so have been replaced by CT scanning and MRI.

CT scanning is better at depicting bony structures and calcifications within soft tissues than either plain radiography or MRI. Differential diagnoses of tumors with calcification, such as germinomas, craniopharyngiomas, and meningiomas, are better determined with CT scanning. CT scans are valuable when MRI is contraindicated, such as in patients with pacemakers or metallic implants in the brain or eyes. Drawbacks include less optimal soft tissue imaging compared to MRI, use of intravenous contrast media that is needed to enhance images, and exposure to radiation. This makes MRI the modality of choice for pituitary imaging.

MRI is more expensive than CT scans but is the preferred imaging study for the pituitary because it provides better visualization of soft tissues and vascular structures. No exposure to ionizing radiation occurs. Images are generated based upon the magnetic properties of the hydrogen atoms. With spin-echo, T1-weighted images, fat produces high–signal intensity images. Structures such as fatty marrow and orbital fat show up as bright images. T2-weighted images of structures with high water content, such as cerebrospinal fluid and cystic lesions, produce high-intensity signals, while structures with high fat content present with low-intensity signals. At least a 1.5-T magnet should be used for MRI of the pituitary.

Visual field testing should be performed, especially in tumors involving the optic chiasm. The severity of visual defects may dictate a more aggressive treatment course.

The histology of pituitary macroadenomas shows varying levels of neoplastic activity. Frozen sections are usually not dependable for definitive diagnosis. Hormonal immunohistochemical stains for neuroendocrine markers are useful, especially in the nonfunctioning tumors.