Background
Prolactinomas are the most common hormone-secreting pituitary tumors. Based on its size, a prolactinoma can be classified as a microprolactinoma (< 10 mm diameter) or a macroprolactinoma (>10 mm diameter).
Pathophysiology
Tumor formation is due to neoplastic transformation of anterior pituitary lactotrophs, resulting in excess synthesis and secretion of prolactin (PRL). Linkage to aryl hydrocarbon-interacting protein gene (AIP) mutation has been identified in some families with prolactinoma and in childhood-onset pituitary adenomas.[1]
Physiologically, PRL, a polypeptide hormone consisting of 199 amino acids, is regulated by hypothalamic factors. These include prolactin-releasing factors (PRFs) and prolactin-inhibitory factors (PIFs).
Dopamine (DA) is the principal PIF, and thyrotropin-releasing hormone (TRH), vasoactive intestinal peptide, and peptide histidine methionine are the putative PRFs. The physiologic role of these PRFs is not established. A delicate balance between the PRFs and PIFs normally keeps the serum PRL level within a physiologic range. Moreover, the interplay of various neurohormonal factors results in a pulsatile secretion of PRL from the pituitary.
Prolactinoma is one of the several causes of pathologic hyperprolactinemia (see Other Problems to Be Considered).[2, 3, 4, 5, 6]
Epidemiology
Frequency
United States
The exact frequency with which prolactinomas occur in the general population is not clearly established. In nonselected surgical series, this tumor accounts for approximately 25-30% of all pituitary adenomas. Some growth hormone (GH) – producing tumors also cosecrete PRL. Microprolactinomas are much more common than macroprolactinomas.
International
In a study of 81,449 inhabitants of Banbury, Oxfordshire, in the United Kingdom, Fernandez et al determined the incidence of pituitary adenomas there to be 77.6 cases per 100,000 population, with the majority of cases (57%, or 44.4 persons per 100,000 population) being prolactinomas.[7] It was also determined that prolactinomas accounted for most pituitary adenomas in persons up to age 60 years, the incidence being 75% of pituitary adenomas occurring in persons up to age 20 years, and 61% of pituitary adenomas in persons between the ages of 20 and 60 years. Moreover, prolactinomas accounted for 76% of pituitary adenomas in females, although in males, the majority of pituitary adenomas (57%) were nonfunctioning lesions.
The incidences of nonprolactinoma pituitary adenomas were as follows: nonfunctioning pituitary adenomas, 28%; adenomas associated with acromegaly, 11%; corticotroph adenomas, 2%; and adenomas of unknown functional status, 2%.
Sex
Among patients with prolactinomas, as many as 60% of the males present with macroprolactinomas, while 90% of the females present with microprolactinomas. This may partially be due to the fact that the male patients often present much later (for clinical evaluation of hypogonadism) than do the female patients (for clinical evaluation of amenorrhea).[8]
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Schlechte J, Dolan K, Sherman B, et al. The natural history of untreated hyperprolactinemia: a prospective analysis. J Clin Endocrinol Metab. Feb 1989;68(2):412-8. [Medline].
Serri O. Progress in the management of hyperprolactinemia. N Engl J Med. Oct 6 1994;331(14):942-4. [Medline].
Molitch ME. Prolactinoma. In: Melmed S, ed. The Pituitary. Boston, Mass: Blackwell Scientific; 1995:443-7.
Zadrozna-Sliwka B, Bolanowski M, Jawiarczyk A, et al. The role of cyclase activating (CAP) and cyclase inhibiting (CIP) parathormone fractions in the assessment of bone metabolism disturbances in women with hyperprolactinemia of various origin. Neuro Endocrinol Lett. Feb 2008;29(1):178-84. [Medline].
Mancini T, Casanueva FF, Giustina A. Hyperprolactinemia and prolactinomas. Endocrinol Metab Clin North Am. Mar 2008;37(1):67-99, viii. [Medline].
Fernandez A, Karavitaki N, Wass JA. Prevalence of pituitary adenomas: a community-based, cross-sectional study in Banbury (Oxfordshire, UK). Clin Endocrinol (Oxf). Jul 24 2009;[Medline].
Carter JN, Tyson JE, Tolis G, et al. Prolactin-screening tumors and hypogonadism in 22 men. N Engl J Med. Oct 19 1978;299(16):847-52. [Medline].
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Hoffer ZS, Roth RL, Mathews M. Evidence for the partial dopamine-receptor agonist aripiprazole as a first-line treatment of psychosis in patients with iatrogenic or tumorogenic hyperprolactinemia. Psychosomatics. Jul-Aug 2009;50(4):317-24. [Medline].
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Frantz AG. Endocrine diagnosis of prolactin-secreting pituitary tumors. In: Black PM, Zervas NT, Ridgway EC, et al, eds. Secretory Tumors of the Pituitary Gland. New York, NY: Raven Press; 1984:45-53.
Frieze TW, Mong DP, Koops MK. "Hook effect" in prolactinomas: case report and review of literature. Endocr Pract. Jul-Aug 2002;8(4):296-303. [Medline].
Rivera JL, Lal S, Ettigi P, et al. Effect of acute and chronic neuroleptic therapy on serum prolactin levels in men and women of different age groups. Clin Endocrinol (Oxf). May 1976;5(3):273-82. [Medline].
Colao A, Di Sarno A, Sarnacchiaro F, et al. Prolactinomas resistant to standard dopamine agonists respond to chronic cabergoline treatment. Clin Endocrinol Metab. 1997;82(3):876-83. [Full Text].
Webster J, Piscitelli G, Polli A, et al. A comparison of cabergoline and bromocriptine in the treatment of hyperprolactinemic amenorrhea. Cabergoline Comparative Study Group. N Engl J Med. Oct 6 1994;331(14):904-9. [Medline]. [Full Text].
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Swords F, Monson J, Besser GM, et al. Gamma knife radiosurgery: a safe and effective salvage treatment for pituitary tumors not controlled despite conventional radiotherapy. Eur J Endocrinol. Sep 22 2009;[Medline].
Foyouzi N, Frisbaek Y, Norwitz ER. Pituitary gland and pregnancy. Obstet Gynecol Clin North Am. Dec 2004;31(4):873-92, xi. [Medline].
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Kreutzer J, Buslei R, Wallaschofski H, et al. Operative treatment of prolactinomas: indications and results in a current consecutive series of 212 patients. Eur J Endocrinol. Jan 2008;158(1):11-8. [Medline].
Tyrrell JB, Lamborn KR, Hannegan LT, et al. Transsphenoidal microsurgical therapy of prolactinomas: initial outcomes and long-term results. Neurosurgery. Feb 1999;44(2):254-61; discussion 261-3. [Medline].
Kars M, Pereira AM, Smit JW, et al. Long-term outcome of patients with macroprolactinomas initially treated with dopamine agonists. Eur J Intern Med. Jul 2009;20(4):387-93. [Medline].
van der Klaauw AA, Kars M, Biermasz NR, et al. Disease specific impairments in quality of life during long-term follow-up of patients with different pituitary adenomas. Clin Endocrinol (Oxf). Apr 29 2008;[Medline].
Zhang F, Chen J, Lu Y, et al. Manifestation, management and outcome of subclinical pituitary adenoma apoplexy. J Clin Neurosci. Oct 2009;16(10):1273-5. [Medline].
Vaneckova M, Seidl Z, Hana V, et al. Macroprolactinomas: retrospective follow up study in the MR imaging and correlation with clinical symptomatology. Neuro Endocrinol Lett. Dec 2007;28(6):841-5. [Medline].
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