Pituitary Macroadenomas Clinical Presentation

Updated: Aug 11, 2021
  • Author: James R Mulinda, MD, FACP; Chief Editor: George T Griffing, MD  more...
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Patients with pituitary macroadenomas may be asymptomatic or may present with complaints due to hormonal imbalance or mass effects.

Tumors in asymptomatic patients may be discovered when imaging the head for unrelated medical conditions. The frequency of diagnosis of pituitary tumors has increased with widespread use of computed tomography (CT) and magnetic resonance imaging (MRI) scans.

Pituitary hormone effects depend on the hormones involved. Panhypopituitarism may present with a deficiency of all the pituitary hormones, but often some are spared. The larger the tumor, the more likely it is to involve most hormones. Anterior pituitary cells are not equally sensitive to mass effects. The most sensitive are the somatotrophs and the gonadotrophs, whereas corticotrophs and thyrotrophs tend to be more resistant. Distinct clinical syndromes, specifically the following, are the result of the hormonal activity of the tumor:

Hyperprolactinemia presents with hypogonadism, infertility, amenorrhea, and galactorrhea. Hyperprolactinemia can be due to increased hormone production by a prolactinoma, or it can be the result of stalk compression by the macroadenoma regardless of hormone activity. In this regard, it is a very common sequela of a pituitary macroadenoma.

Corticotropin excess presents with Cushing disease. Corticotropinomas are rarely macroadenomas. Corticotropin suppression due to compression of the normal corticotrophs presents with glucocorticoid insufficiency. The clinical picture of secondary glucocorticoid deficiency is much milder than primary adrenal insufficiency, where combined mineralocorticoid and glucocorticoid deficiency occur.

Thyrotropin excess presents with secondary hyperthyroidism. Thyrotropinomas are very rare tumors. They present most frequently as macroadenomas. Whether thyrotropinomas are naturally aggressive or whether the aggressive and invasive behavior is the result of delayed diagnosis is unclear. Biologically inadequate thyrotropin presents with secondary hypothyroidism.

Excess growth hormone presents with acromegaly as the result of a somatotropinoma (often a macroadenoma), while inadequate growth hormone presents with failure to thrive in children but often no complaints in adults.

Gonadotropinomas most often are asymptomatic and usually secrete inactive follicle-stimulating hormone (FSH) and luteinizing hormone (LH)-like glycoproteins and/or alpha subunit. They often are macroadenomas and usually result in hypopituitarism. Rarely, they can lead to testicular enlargement in men and ovarian hyperstimulation in women. Deficiency of gonadotropins presents with hypogonadism and infertility.

Mass effects of the macroadenoma may present with visual deficits, headache, elevated intracranial pressure, or intracranial hemorrhage.

Pituitary apoplexy results from infarction of a pituitary tumor or sudden hemorrhage within. This presents as a medical emergency with a headache, sudden collapse, shock, and death if not treated emergently. This tends to occur in macroadenomas. Administration of stimulatory agents, such as thyroid-stimulating hormone TSH, gonadotropin-releasing hormone (GnRH), and insulin-hypoglycemia, have been postulated to lead to increased metabolic needs by the macroadenoma (which has deficient blood supply), leading to necrosis. In this context, apoplexy may be the presenting symptom of a gonadotropinoma in an elderly men receiving GnRH agonist therapy for prostate cancer.

Nelson syndrome results from treatment of Cushing disease with bilateral adrenalectomy. The lack of negative glucocorticoid feedback is postulated to lead to excessive tumor growth. Such tumors are much more aggressive and locally invasive compared to the usual corticotroph adenomas.



Most patients do not have physical findings associated with macroadenomas. Physical findings may be attributable to the mass effects or hormonal disruption.

When the tumor extends onto the optic chiasm, visual field deficits may be demonstrable. Sudden increase in tumor size, such as can occur with hemorrhage, may lead to elevated intracranial pressure.

Hormonally active tumors might present with symptoms due to target organ stimulation, such as hyperthyroidism, Cushing syndrome, or hyperprolactinemia.



The cause of pituitary macroadenomas is unknown. The most favored theory attributes monoclonal neoplastic transformation of pituitary cells as the cause of tumor initiation and growth. The monoclonal nature of most pituitary tumors and their retention of a response to negative feedback by hormones produced by target organs support this hypothesis.