eMedicine Specialties > Endocrinology > Pituitary Gland

Prolactinoma

Author: Venkatesh Babu Segu, MD, MBBS, DM, Associate Director of Diabetes Care Center, Department of Internal Medicine, St Mark's Hospital of Salt Lake City
Contributor Information and Disclosures

Updated: Sep 28, 2009

Introduction

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).

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).1,2,3,4,5

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.6 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).7

Clinical

History

Prolactinomas can cause symptoms secondary to the hormonal effects of excess PRL and to the space-occupying effects of the tumor itself.

The clinical features of sustained hyperprolactinemia (which vary with the duration and degree of the condition, as well as with the age and sex of the patient) are as follows1,5 :

  • Reproductive-aged females can present with menstrual disturbance and/or infertility.8 The usual menstrual aberration in these women is oligomenorrhea, amenorrhea, or the occurrence of irregular menstrual cycles. Occasionally, if the prolactinoma occurs in a person of younger age, delayed menarche can result.
  • Galactorrhea can be spontaneous or expressive (only upon squeezing of the nipples). Galactorrhea is observed in 30-80% of these women and can be quite distressing for the patient.
  • Other features of hypoestrogenism include vaginal dryness, dyspareunia, and a decline in bone mineral density (ie, osteopenia or osteoporosis).4
  • Men with prolactinoma have 1 or more features of hypogonadism, which may include decreased libido, erectile dysfunction, or infertility.7 Gynecomastia is very unusual in these men. Galactorrhea is much less common in men than it is in women, and demonstrating galactorrhea in a male may require vigorous breast manipulation.
  • If a prolactinoma develops prepubertally, hyperprolactinemia may result in a female body habitus and small testicles.
  • If the prolactinoma is large enough to compress the surrounding normal hormone-secreting pituitary cells, it may result in deficiencies of 1 or more hormones (eg, thyroid-stimulating hormone [TSH], GH, adrenocorticotropic hormone).

Correlating with the size of the tumor, the space-occupying effects of prolactinoma are as follows:

  • Larger tumors are frequently associated with headache secondary to stretching of the pain-sensitive structures around the pituitary gland.
  • Encroachment of surrounding tissues may result in visual problems in the form of field defects. Visual problems range from bitemporal hemianopsia (from compression of the optic chiasm), which is common, to total vision loss and ophthalmoplegia (from compression of cranial nerves III, IV, or VI).
  • Postmenopausal women and elderly men frequently present only with the space-occupying effects of the tumor.

Physical

  • In women, focus the physical examination on assessment for galactorrhea and the identification of clinical signs of estrogen deficiency.
  • In men, examine testicular size and consistency, as well as the pattern of hair on the body. Also assess for the rare occurrence of gynecomastia and/or galactorrhea.
  • In male and female patients, assess visual acuity and visual fields (by the confrontation method) and perform a cranial nerve examination at the bedside to help determine if the tumor has caused any mass effect.

More on Prolactinoma

Overview: Prolactinoma
Differential Diagnoses & Workup: Prolactinoma
Treatment & Medication: Prolactinoma
Follow-up: Prolactinoma
References
Further Reading
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References

  1. 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].

  2. Serri O. Progress in the management of hyperprolactinemia. N Engl J Med. Oct 6 1994;331(14):942-4. [Medline].

  3. Molitch ME. Prolactinoma. In: Melmed S, ed. The Pituitary. Boston, Mass: Blackwell Scientific; 1995:443-7.

  4. 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].

  5. Mancini T, Casanueva FF, Giustina A. Hyperprolactinemia and prolactinomas. Endocrinol Metab Clin North Am. Mar 2008;37(1):67-99, viii. [Medline].

  6. 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].

  7. 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].

  8. Schlechte JA. Clinical practice. Prolactinoma. N Engl J Med. Nov 20 2003;349(21):2035-41. [Medline].

  9. 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].

  10. Honbo KS, van Herle AJ, Kellett KA. Serum prolactin levels in untreated primary hypothyroidism. Am J Med. May 1978;64(5):782-7. [Medline].

  11. 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.

  12. 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].

  13. 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].

  14. 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].

  15. 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].

  16. Molitch ME. Pharmacologic resistance in prolactinoma patients. Pituitary. 2005;8(1):43-52. [Medline].

  17. 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].

  18. Foyouzi N, Frisbaek Y, Norwitz ER. Pituitary gland and pregnancy. Obstet Gynecol Clin North Am. Dec 2004;31(4):873-92, xi. [Medline].

  19. Raymond JP, Goldstein E, Konopka P, et al. Follow-up of children born of bromocriptine-treated mothers. Horm Res. 1985;22(3):239-46. [Medline].

  20. 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].

  21. 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].

  22. 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].

  23. 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].

  24. 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].

  25. 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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Keywords

prolactinoma, prolactin, pituitary, pituitary gland, pituitary tumor, pituitary adenoma, pituitary tumors, bromocriptine, cabergoline, high prolactin levels, prolactin-secreting adenoma, hormone-secreting pituitary tumor, hyperprolactinemia, pituitary adenoma, growth hormone tumor, microprolactinoma, macroprolactinoma

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Contributor Information and Disclosures

Author

Venkatesh Babu Segu, MD, MBBS, DM, Associate Director of Diabetes Care Center, Department of Internal Medicine, St Mark's Hospital of Salt Lake City
Venkatesh Babu Segu, MD, MBBS, DM is a member of the following medical societies: American Association of Clinical Endocrinologists, American Diabetes Association, and Endocrine Society
Disclosure: Nothing to disclose.

Medical Editor

Robert A Gabbay, MD, PhD, Associate Professor of Medicine, Division of Endocrinology, Diabetes and Metabolism, Laurence M Demers Career Development Professor, Penn State College of Medicine; Director, Diabetes Program, Penn State Milton S Hershey Medical Center; Executive Director, Penn State Institute for Diabetes and Obesity
Robert A Gabbay, MD, PhD is a member of the following medical societies: American Association of Clinical Endocrinologists, American Diabetes Association, and Endocrine Society
Disclosure: Novo Nordisk Honoraria Speaking and teaching; Merck Honoraria Speaking and teaching

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

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.

CME Editor

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.

 
 
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