eMedicine Specialties > Endocrinology > Pituitary Gland

Prolactinoma: Differential Diagnoses & Workup

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

Differential Diagnoses

Hypothyroidism
Pituitary Macroadenomas
Pituitary Microadenomas
Polycystic Ovarian Disease (Stein-Leventhal Syndrome)

Other Problems to Be Considered

If a female patient has amenorrhea, primary or secondary, consider other possible causes of the condition in the differential. If a patient (male or female) presents with infertility, consider all other causes of infertility in the differential.

If a patient has an elevated PRL level, other causes of hyperprolactinemia must be sought. These include the following:

  • Drugs - Such as phenothiazines, haloperidol, metoclopramide, methyldopa, reserpine, verapamil, tricyclic antidepressants, chronic opiate abuse, and cocaine9
  • Pituitary or hypothalamic causes - Including GH-secreting adenoma, nonfunctioning adenoma, pituitary stalk compression, empty sella syndrome, craniopharyngioma, meningioma, dysgerminoma, lymphocytic hypophysitis, other granulomatous conditions causing pituitary stalk distortion, and prior radiation to the area
  • Pregnancy
  • Primary hypothyroidism10
  • Chronic renal failure
  • Cirrhosis
  • Adrenal insufficiency
  • Chest wall lesions
  • Breast stimulation
  • Spinal cord lesions
  • Idiopathic causes

Workup

Laboratory Studies

  • Hormone testing11
    • Serum PRL - Measure serum PRL levels on 1 or more occasions, especially if the elevation is modest. Do not measure the PRL level directly after performing a breast examination, because the breast examination may cause a physiological PRL elevation.
    • Serum pregnancy test - Always consider the possibility of pregnancy in reproductive-aged females, because this is the most common cause of secondary amenorrhea in this group.
    • Serum TSH - Measure TSH levels to exclude the possibility of an elevated PRL level occurring secondary to an elevated TRH level. TRH is one of the PRFs. If the TSH level is elevated, confirm the finding by measuring the free thyroxine level.
  • Measurement of other pituitary hormones
    • In a male presenting with symptoms of hypogonadism, measure serum testosterone or bioavailable testosterone levels.
    • In a patient with a history suggestive of adrenal insufficiency, measure basal and cosyntropin-stimulated cortisol levels.
    • In a person with features consistent with acromegaly, measure serum insulinlike growth factor-1 levels.
  • Exclude other possible systemic causes for hyperprolactinemia, such as chronic renal failure or cirrhosis, using appropriate laboratory tests as warranted.

Imaging Studies

  • After performing biochemical testing, order a magnetic resonance imaging (MRI) scan of the pituitary hypothalamic area (with gadolinium enhancement) or a computed tomography (CT) scan of the region (with contrast) to determine if a mass lesion is present.
    • MRI is better for soft-tissue delineation and for the identification of a small lesion. CT scanning is better for the identification of any bone distortion or destruction. Special attention is given to the size of the tumor and its encroachment on surrounding structures (eg, the optic chiasm, other cranial nerves) and resulting effects (eg, bony destruction).
    • Good correlation exists between the size of the prolactinoma and the degree of elevation of the serum PRL. A serum PRL value of 200 ng/mL or greater in the presence of a macroadenoma (>10 mm) is virtually diagnostic of prolactinoma. However, if the serum PRL value is less than 200 ng/mL in the presence of a large pituitary mass lesion, this is more suggestive of hyperprolactinemia occurring secondary to stalk compression by the lesion; it could also indicate the occurrence of the hook effect, which is an artifact in the lab method used to measure prolactin.12 Immunoassays used to measure PRL, such as immunoradiometric assay (IRMA), enzyme immunoassay (EIA), and immunochemiluminometric assay (ICMA), employ a "sandwich" (2-antibody) technique. When the PRL level is markedly elevated, the excess antigen (PRL) is washed off in the liquid phase of the sandwich assay and thereby results in gross underestimation of antigen levels in the specimen. When this is suspected, serial dilutions of the serum sample will reveal the actual hormonelevel.
    • Repeat scans are obtained postoperatively and during follow-up examinations thereafter, or they are obtained after medical treatment to help determine if the tumor has progressed or regressed. The frequency with which repeat imaging scans are performed is individualized to the patient. For instance, in patients with microprolactinoma, pituitary MRI could be performed 1 year after treatment start and then every few years thereafter, less frequently than such scanning would be performed in patients undergoing treatment for macroprolactinoma.

Other Tests

  • When the tumor is large and is in close vicinity of the optic chiasm, formal visual-field (VF) testing by an ophthalmologist is performed prior to any therapy. The same testing is repeated after treatment is begun, to monitor the patient's response to treatment.

Procedures

  • If a pituitary/hypothalamic lesion other than a prolactinoma (such as lymphocytic hypophysitis or a granulomatous condition) is considered, biopsy of the lesion by a neurosurgeon is indicated.

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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