Pituitary Macroadenomas 

  • Author: James R Mulinda, MD, FACP, FACE; Chief Editor: George T Griffing, MD   more...
 
Updated: Oct 17, 2011
 

Background

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.

Recent studies

In a prospective, randomized study, Mao et al investigated whether treatment with lanreotide prior to transsphenoidal surgery for macroadenomas would improve cure rates in patients with newly diagnosed acromegaly. The study included 49 patients who were administered 4 months of preoperative lanreotide treatment and 49 patients who underwent transsphenoidal surgery without pretreatment. The authors reported a 49% cure rate (24 patients) in the pretreatment group following surgery and an 18.4% cure rate (9 patients) in the nonlanreotide group. Mao et al concluded that in patients with growth hormone – secreting pituitary adenomas, preoperative lanreotide treatment increases cure rates from transsphenoidal surgery.[1]

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Pathophysiology

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.[2]

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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Epidemiology

Frequency

United States

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.

Mortality/Morbidity

Morbidity in pituitary macroadenomas varies from incidentally discovered nonfunctioning tumors to disabling macroadenomas. 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.

Race

No racial predilection exists for pituitary macroadenomas.

Sex

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.

Age

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

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Contributor Information and Disclosures
Author

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

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

Disclosure: Nothing to disclose.

Specialty Editor Board

Dimitris A Papanicolaou, MD  Assistant Professor, Department of Medicine/Endocrinology, Emory University

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

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: Medscape Salary Employment

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 Research, and Endocrine Society

Disclosure: Nothing to disclose.

Mark Cooper, MBBS, PhD, FRACP  Head, Diabetes & Metabolism Division, Baker Heart Research Institute, Professor of Medicine, Monash University

Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD  Professor 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, American College of Medical Practice Executives, American College of Physician Executives, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical Research, Endocrine Society, International Society for Clinical Densitometry, and Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

References

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  2. Chahal HS, Stals K, Unterlander M, et al. AIP mutation in pituitary adenomas in the 18th century and today. N Engl J Med. Jan 6 2011;364(1):43-50. [Medline].

  3. Greenman Y, Stern N. How should a nonfunctioning pituitary macroadenoma be monitored after debulking surgery?. Clin Endocrinol (Oxf). Jun 2009;70(6):829-32. [Medline].

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  14. Hwang YC, Chung JH, Min YK, et al. Comparisons between macroadenomas and microadenomas in Cushing's disease: characteristics of hormone secretion and clinical outcomes. J Korean Med Sci. Feb 2009;24(1):46-51. [Medline]. [Full Text].

  15. Fernandez-Balsells MM, Murad MH, Barwise A, et al. Natural history of nonfunctioning pituitary adenomas and incidentalomas: a systematic review and metaanalysis. J Clin Endocrinol Metab. Apr 2011;96(4):905-12. [Medline].

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  18. Biller BM, Molitch ME, Vance ML, Cannistraro KB, Davis KR, Simons JA, et al. Treatment of prolactin-secreting macroadenomas with the once-weekly dopamine agonist cabergoline. J Clin Endocrinol Metab. Jun 1996;81(6):2338-43. [Medline].

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