Pituitary Macroadenomas

Pituitary Macroadenomas

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The sellar region is a site of various types of tumors. Pituitary adenomas are the most common. They arise from epithelial pituitary cells and account for 10-15% of all intracranial tumors. Tumors exceeding 10 mm are defined as macroadenomas, and those smaller than 10 mm are termed microadenomas. Most pituitary adenomas are microadenomas.

All tumors should have screening basal hormone measurements, which may include prolactin, thyrotropin, thyroxine, adrenocorticotropin, cortisol, luteinizing hormone (LH), follicle-stimulating hormone (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.

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 Plain skull radiographs are poor at delineating soft tissues and so have been replaced by computed tomography (CT) scanning and magnetic resonance imaging (MRI).

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 goal of treatment for macroadenoma is complete cure. When this is not attainable, reducing tumor mass, restoring hormone function, and restoring normal vision are attempted using medications, surgery, and radiation. Pituitary macroadenomas often require surgical intervention for cure. The exceptions to this rule are the macroprolactinomas, which usually have an excellent response to medical therapy. The tumor size may be diminished but often does not disappear completely. Medical treatment can play a role in reducing tumor size, controlling hormonal excess, or correcting hormonal deficiency.

Pituitary macroadenomas are benign epithelial neoplasms composed of adenohypophysial cells. Primary malignant tumors of the pituitary are extremely rare. Evidence suggests that pituitary adenoma development occurs in several steps, including an irreversible initiation phase followed by tumor promotion.

Pituitary tumor development is a monoclonal process with several contributing factors. Causal contributors include heredity and hormonal influence and genetic mutations. The monoclonal nature of most pituitary tumors suggests that they arise from a mutated pituitary cell. However, the exact pathophysiologic/molecular mechanisms leading to the development of pituitary adenomas remain unknown.

The role of genetic mutations was highlighted in a report suggesting that patients with pituitary tumors from 4 Irish families share a common mutation with a patient from the 18th century who had pituitary tumor–mediated gigantism. [1]

Some pituitary tumors may occur as part of a clinical syndrome. In multiple endocrine neoplasia type 1 (MEN 1), an autosomal dominant genetic disorder, pituitary adenomas (most often prolactinomas) occur in association with tumors of the parathyroid and pancreatic islet cells.

In McCune-Albright syndrome, skin lesions and polyostotic fibrous dysplasia occur with hyperfunctioning endocrinopathies. This syndrome results from an activating mutation (somatic mutation) of the alpha subunit of the Gs protein and involves tissues whose response to hormonal signals is mediated by adenylate cyclase. The most common pituitary tumor in McCune-Albright syndrome is somatotropinoma, resulting in acromegaly. Interestingly, a significant proportion of somatotropinomas in sporadic cases of acromegaly harbor the same mutations.

Carney complex is an autosomal dominant disorder characterized by primary pigmented nodular adrenal disease, cutaneous pigmented lesions (lentigines, blue nevi), Sertoli cell tumors of the testes, acromegaly, melanocytic schwannomas, and cardiac myxomas.

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Pituitary tumors are found on autopsy in as many as 25% of unselected cases. The annual incidence of pituitary neoplasms varies from 1-7 cases per 100,000 population based on neurosurgical series.

Morbidity in pituitary macroadenomas varies from incidentally discovered nonfunctioning tumors to disabling macroadenomas. [2] Morbidity results from mass effects (eg, bitemporal hemianopsia), hormonal imbalance (pituitary hormone deficiency due to compression of the normal pituicytes or hormonal excess from the tumor), and patient comorbidities. Significant morbidity is also associated with treatment of these tumors.

No racial predilection exists for pituitary macroadenomas.

Autopsy series show an equal distribution of pituitary tumors between men and women. Corticotropinomas are an exception, occurring mainly in women, with a female-to-male ratio of 4:1. In general, women of childbearing age are diagnosed more frequently with pituitary adenomas than men. The reason for this higher rate of diagnosis is unclear but might be related to the clinical presentation of such patients. Amenorrhea (or menstrual irregularities), which is a relatively common symptom in women with macroadenomas, raises the suspicion of a pituitary lesion.

Tumors affect individuals of all ages, but incidence increases with age, peaking between the third and sixth decades of life.

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James R Mulinda, MD, FACP Consulting Staff, Department of Endocrinology, Endocrinology Associates, Inc

James R Mulinda, MD, FACP is a member of the following medical societies: American College of Physicians

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Yoram Shenker, MD Chief of Endocrinology Section, Veterans Affairs Medical Center of Madison; Interim Chief, Associate Professor, Department of Internal Medicine, Section of Endocrinology, Diabetes and Metabolism, University of Wisconsin at Madison

Yoram Shenker, MD is a member of the following medical societies: American Heart Association, Central Society for Clinical and Translational Research, Endocrine Society

Disclosure: Nothing to disclose.

George T Griffing, MD Professor Emeritus of Medicine, St Louis University School of Medicine

George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, International Society for Clinical Densitometry, Southern Society for Clinical Investigation, American College of Medical Practice Executives, American Association for Physician Leadership, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical and Translational Research, Endocrine Society

Disclosure: Nothing to disclose.

Dimitris A Papanicolaou, MD 

Dimitris A Papanicolaou, MD is a member of the following medical societies: American College of Physicians, Endocrine Society, Royal Society of Medicine

Disclosure: Nothing to disclose.

Pituitary Macroadenomas

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