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Pituitary Adenomas

Pathology || Signs and Symptoms || Diagnosis || Treatment || Overview ||
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Pathology





Pituitary adenomas are the most common type of pituitary tumor. They are typically “benign” tumors meaning that they do not spread to other parts of the body; however, pituitary adenomas often cause important symptoms secondary to hormone secretion and via compression of important anatomic structures like the optic chiasm, optic nerves, optic tracts, carotid arteries, and cavernous sinuses.

Pituitary adenomas come in several distinct “flavors”. They are usually categorized based on the type of hormone they secrete. These hormones include (in order of decreasing incidence): prolactin, growth hormone, adrenocorticotroph hormone (ACTH), thyroid stimulating hormone (TSH), follicle stimulating hormone (FSH), and luteinizing hormone (LH). It is important to note that many adenomas secrete no hormones at all! In addition, hormone secreted by some tumors may be biologically inactive and produce no symptoms.

Another method for categorizing pituitary adenomas is based on their appearance under a microscope. Tumors may be classified as eosinophilic (prolactin and growth hormone), basophilic (ACTH, TSH, FSH, and LH), or chromophobic. This method of classifying tumors is less common now that hormone type can be readily identified using modern staining techniques.

Additionally, pituitary adenomas are classified based on their size. "Macro"-adenomas are greater than 10mm in greatest diameter. "Micro"-adenomas are anything less than 10mm.

The reasons for why pituitary adenomas form has not yet been elucidated. It is likely that multiple factors play a role. The first includes mutations in genes responsible for cell growth. Genes known as tumor suppressors, which create proteins that inhibit the growth of tumors have been shown to be much less active in pituitary adenomas. In addition, oncogenes (a general term for a gene, that when activated results in tumor growth), such as the “pituitary tumor transforming gene” (PTTG), have been shown to be overactive in pituitary adenomas.

Pituitary adenomas may also run in families; however, sporadic tumor development is more common. Families with syndromes such as multiple endocrine neoplasia (type 1) or Carney complex often have multiple family members with pituitary adenomas. Many of these syndromes also present with other endocrine abnormalities or tumor types, which helps distinguish them from sporadic pituitary adenomas.

Overall, pituitary adenomas have a highly variable etiology that differs from person to person.

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Signs and Symptoms

Pituitary adenomas present with symptoms of hormone over secretion, or as a result of compression of adjacent anatomical structures.

Let’s start by discussing the symptoms related to excess hormone secretion. Patients with prolactin secreting tumors (aka: “prolactinomas”) present with nipple discharge (galactorrhea), missed menstrual cycles (amenorrhea), impotence, and infertility.

Growth hormone secreting tumors cause acromegaly in adults. Acromegaly is characterized by enlargement of the hands, feet, and facial structures. Although the cosmetic features of acromegaly can be disturbing to patients, the real threat is in the growth of soft tissues surrounding the internal organs such as the heart. If left untreated damage to the internal organs can occur. Patients with acromegaly also frequently develop diabetes mellitus and hypertension (ie: high blood pressure).

Growth hormone secreting tumors in children cause gigantism, which is characterized by excessive growth leading to very large stature. Gigantism occurs in children because the bony growth plates have not yet fused. Patients with gigantism are also at risk for soft tissue and internal organ disease similar to that seen in acromegaly.

Excess secretion of adrenocorticotroph hormone (ACTH) by a pituitary adenoma causes Cushing’s disease. Cushing’s disease is a constellation of symptoms that result from the actions of excessive amounts of steroid on the bodies’ tissues. ACTH-secreting pituitary tumors cause the adrenal glands to pump out more cortisol (ie: a natural steroid). The excess cortisol causes the classic features of Cushing’s syndrome including, but not limited to: acne, facial hair, weakness, osteoporosis, cataracts, diabetes mellitus, increased risk of infections, and easy bruising.

Tumors that churn out thyroid stimulating hormone can cause hyperthyroidism, which is characterized by heat intolerance, heart rhythm abnormalities, tremor, and weight loss amongst many other nonspecific symptoms. Tumors that secrete follicle stimulating and/or luteinizing hormone are surprisingly rare, but typically cause disturbances in sexual function and libido.

If large enough pituitary adenomas can also compress important anatomical structures. Compression of the optic chiasm can lead to a bitemporal visual field deficit, in which patients lose peripheral vision in each eye. Invasion into the cavernous sinus (ie: one of the large venous structures in the brain) can lead to compression of the cranial nerves that course through it. The third cranial nerve is most vulnerable and compression can result in a dilated pupil and difficulty with eye movement.

Also, large adenomas may squish the normal pituitary gland and cause numerous hormone deficiencies.

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Diagnosis

MRI of pituitary adenoma

Diagnosis of a pituitary adenoma is made under the appropriate clinical context. Patients with evidence of pituitary dysfunction or hyperactivity should have a thorough medical work-up including prolactin, FSH, LH, TSH, T4, ACTH, GH, IGF-1, prolactin, testosterone, and cortisol levels.

It is very important to measure hormone levels because some adenomas may shrink with medications and obviate the need for surgical removal.

MRI and/or CT scans with contrast are necessary to delineate the size of the tumor, and to see if it is abutting important structures such as the optic chiasm, carotid arteries, or cavernous sinus. CT and MRI imaging are also invaluable when it comes to operative planning.

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Treatment

Treatment is dependent on symptoms and hormone dysfunction.

Adenomas that cause vision problems secondary to compression of the optic chiasm should be surgically removed. Patients with signs/symptoms of Cushing’ s disease, acromegaly, or gigantism, and imaging studies that show a pituitary tumor should also be strongly considered for surgical resection.

Prolactinomas are slightly more complicated because even large tumors may shrink with dopamine agonist medications such as cabergoline and/or bromocriptine. Both of these medications inhibit the secretion of prolactin by the pituitary tumor.

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Overview

Pituitary adenomas are the most common type of pituitary tumor. They come in many different flavors and can cause pituitary dysfunction either via over secretion or under secretion of hormone. Large tumors may cause vision problems. MRI and CT scans are routinely ordered for operative planning purposes. Treatment is usually surgical removal, except for prolactinomas, which may shrink with medications.

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Related Articles

- Diabetes mellitus

- Hypertension

- Meningioma

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References and Resources

(1) Rostad S. Pituitary adenoma pathogensis: an update. Curr Opin Endocrinol Diabetes Obes. 2012 May 22.

(2) Dworakowska D, Grossman AB. The pathophysiology of pituitary adenomas. Best Pract Res Clin Endocrinol Metab. 2009 Oct;23(5):525-41.

(3) Molitch ME. Pituitary tumors: cabergoline versus bromocriptine: a meta analysis? Nat Rev Endocrinol. 2011 May;7(5):254-5.

(4) Baehr M, Frotscher M. Duus' Topical Diagnosis in Neurology: Anatomy, Physiology, Signs, Symptoms. Fourth Edition. Stuttgart: Thieme, 2005.

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An agonist is a medication that binds to, and activates the receptors of the natural compound; in this case dopamine.