History and physical examination can distinguish among most physiologic, pharmacologic, or pathologic causes of an elevated serum prolactin level (SPL) (strength of recommendation [SOR]: C, expert opinion). Patients with unexplained elevations of serum prolactin or with a level
 above 200 ng/mL should undergo imaging of
 the sella turcica (SOR: C, expert opinion). Mildly elevated SPL due to physiologic causes may be managed expectantly (SOR: B, cohort studies) and pharmacologic elevations may be treated by discontinuing the causative medication (SOR: C, expert opinion). Elevated SPL due to pathologic
 causes requires both monitoring for complications and treatment of the underlying condition (SOR: C, expert opinion)

Jackson, Jo

Safranek, Sarah

University of Missouri: MOspace

VOL 54, NO 10 / OCTOBER 2005 897w w w. j f p o n l i n e . c o mCLINICAL INQUIRIESE V I D E N C E - B A S E D A N S W E RWhat is the recommended evaluation andtreatment for elevated serum prolactin?■ Evidence summaryAn expert guideline recommends a historyand physical examination to determinewhether an elevated SPL is due to physio-logic, pharmacologic, or pathologic causes(TABLE).1 The fasting morning SPL is leastvariable and correlates best with a diseasestate.1 Clinical correlation is necessary toreveal false positives (due to biologicallyinactive forms of prolactin) or false nega-tives (due to very high SPLs that exceed theability of the assay). If an elevated SPL issuspected despite a normal laboratoryreport, retesting with serum diluted 1:100can identify a false-negative value.2A detailed drug history is importantsince drug-induced elevated SPL is com-mon.1 Laboratory evaluation includes thy-roid-stimulating hormone, blood ureanitrogen, and creatinine, as well as preg-nancy testing when applicable. If no causeof elevated SPL is identified by initial clin-ical evaluation or if the SPL is greater than200 ng/mL, experts recommend imagingof the sella turcica with computed tomog-raphy or magnetic resonance imaging.1Physiologic causes. For patients with amildly elevated SPL due to a physiologicHistory and physical examination can distinguishamong most physiologic, pharmacologic, or pathologic causes of an elevated serum prolactinlevel (SPL) (strength of recommendation [SOR]:C, expert opinion). Patients with unexplained elevations of serum prolactin or with a levelabove 200 ng/mL should undergo imaging of the sella turcica (SOR: C, expert opinion). Mildlyelevated SPL due to physiologic causes may bemanaged expectantly (SOR: B, cohort studies)and pharmacologic elevations may be treated bydiscontinuing the causative medication (SOR: C,expert opinion). Elevated SPL due to pathologiccauses requires both monitoring for complicationsand treatment of the underlying condition (SOR:C, expert opinion). Dopamine agonists are effective for patientsrequiring drug treatment (SOR: B, systematicreview of cohort studies), and cabergoline is more effective and better tolerated thanbromocriptine (SOR: B, randomized controlledtrial [RCT]). Surgery is reserved for symptomaticpatients not controlled medically (SOR: C, expert opinion).Jo Jackson, MD University of Washington, SeattleSarah Safranek, MLIS Health Sciences Library, University of Washington, SeattleC L I N I C A L C O M M E N T A R YPatients with mildly elevated SPLs can be safelywatched with testing and symptom monitoring Most elevated prolactin levels in my practice havebeen mild and often secondary to medication,though there are a host of causes, as listed in theTABLE. This Clinical Inquiry reassures us thatpatients with mildly elevated SPLs can be safelywatched with serial testing and monitoring symptoms. Obtaining SPLs only on fasting specimens can help improve test accuracy. Thefeared risk of vision loss due to a macroadenomaseems to be quite small. Patients with significantlyelevated SPLs with amenorrhea or infertility deserve referral to clinicians comfortable withusing dopamine agonists because of the high rateof success with this treatment. Allen Daugird, MDUniversity of North Carolina at Chapel HillJFP_1005_CI.finalREV2  9/23/05  10:19 AM  Page 897898 VOL 54, NO 10 / OCTOBER 2005  THE JOURNAL OF FAMILY PRACTICECLINICAL INQUIRIEScause, experts recommend expectant man-agement. Patients should be monitored forsymptoms of hypogonadism (amenorrhea,infertility, or sexual dysfunction) and haveSPL measured at 6- to 12-month intervals.1In cohort studies, treatment of the under-lying cause of elevated SPL reverses second-ary physiologic changes of low estrogen ortestosterone, and hypogonadism.3–5Pharmacologic causes. Eliminating apharmacologic cause may lead to normal-ization of SPL, although experts recom-mend psychiatric consultation before dis-continuing neuroleptic medications.1Pathologic causes. Experts advise treat-ing the underlying cause of a pathologic ele-vation of SPL. Patients with microadenomashould have SPLs monitored to preventcomplications of decreased bone mineraldensity and sexual dysfunction due to per-sistently elevated SPL. Patients with amacroadenoma (>1 cm) are at risk fortumor growth and require serial imagingstudies in addition to treatment of SPL,according to expert opinion.1–3Medical therapy. Medical therapy witha dopamine agonist is indicated for patientswith either symptoms of hypogonadism dueto elevated SPL, or neurologic symptomsdue to the size of a macroadenoma.1 In areview of 13 cohort studies, bromo-criptineimproved symptoms and reduced SPLs tonormal for 229 of 280 women (82%).6 Acohort study of 27 patients with macroade-nomas treated with bromocriptine found10% to 50% reductions of tumor size.7 Arandomized controlled trial treating 459women having hyperprolactinemic amenor-rhea with either cabergoline or bromocrip-tine achieved a stable normal SPL in 83%and 59%, respectively (P<.001). Adverseeffects were common but were less commonwith cabergoline (68% vs 78%) and result-ed in fewer discontinuations (3% vs 12%).8Surgical therapy. Surgery is indicatedfor patients unresponsive to or intolerantof medical therapy, or who have visualfield loss, cranial nerve palsy, or headachedue to macroadenoma.1 A retrospectivereview of patients who underwent surgicalresection found a 40% recurrence rate.9Recommendations from othersWilliams Textbook of Endocrinologyincludes the recommendations above andadvises seeking consultation for patientswith mass effects of macroadenomas such asvisual field loss, cranial nerve palsy, orheadaches; for patients with progressive ele-vation of SPL despite medical treatment; andfor pregnant women.4 Conventional antipsy-chotic agents are commonly associated withelevated prolactin due to dopamine agonistactivity. Some atypical antipsychotics maylead to lower levels of elevated prolactin,transient elevations or marked elevations.10Experts recommend following serial SPLs, ifantipsychotics are truly needed. Psychiatricconsultation may assist in making decisionsabout medication selection. Patients withT A B L EPHYSIOLOGICPregnancyEctopic pregnancyLactationNipple stimulationStressSleep disorderPHARMACOLGICDopamine receptor antagonists: phenothiazines, butyrophenones,thioxanthene, risperidone, metoclopramide, sulpiride, pimozideDopamine-depleting agents: α-methyldopa, reserpineHormones: estrogens, antiandrogensOthers: danazol, isoniazid, verapamil, cyproheptadine, opiates, H2-blockers (cimetidine), cocaine and marijuana, tricyclic antidepressantsPATHOLOGICAcromegalyAlcoholic cirrhosisChest wall trauma or tumorHerpes zosterHypothalamic and pituitary stalk diseaseHypothyroidismPituitary tumors: prolactinomas, adenomasPolycystic ovarian syndromeRenal failureSarcoidosisPhysiologic, pharmacologic, and pathologic causes of an elevated serum prolactin level1C O N T I N U E DJFP_1005_CI.finalREV  9/20/05  2:39 PM  Page 898Evaluation and treatment for elevated serum prolactin ▲symptoms (galactorrhea, amenorrhea,headaches, visual disturbances, sexual dys-function) or levels of 200 or more, shouldundergo an MRI or CT. Experts recommendmonitoring levels every 1 to 3 months.1R E F E R E N C E S1. Biller BM, Luciano A, Crosignani PG, et al. Guidelinesfor the diagnosis and treatment of hyperprolactinemia.J Reprod Med 1999; 44(12 Suppl):1075–1084.2. Barkan AL, Chandler WF. Giant pituitary prolactinomawith falsely low serum prolactin: the pitfall of the “highhook effect”: Case report. Neurosurgery 1998;42:913–915.3. Sanfilippo JS. Implications of not treating hyperpro-lactinemia. J Reprod Med 1999; 44(12Suppl):1111–1115. 4. Melmed S, Kleinberg D. Physiology and disorders ofthe pituitary hormone axes. In: Williams RH, LarsenPR. Williams Textbook of Endocrinology. 10th ed.Philadelphia, Pa: Saunders; 2003: 200–212.5. Schlechte J, Dolan K, Sherman B, Chapler F, Luciano A.The natural history of untreated hyperprolactinemia: aprospective analysis. J Clin Endocrinol Metab 1989;68:412–4186. Vance ML, Evans WS, Thorner MO. Drugs five yearslater. Bromocriptine. Ann Intern Med 1984; 100:78–91.7. Molitch ME, Elton RL, Blackwell RE, Caldwell B, ChangRJ, Jaffe R et al. Bromocriptine as primary therapy forprolactin-secreting macroadenomas: results of aprospective multicenter study. J Clin Endocrinol Metab1985; 60:698–705.8. Webster J, Piscitelli G, Polli A, Ferrari C, Ismail I,Scanlon MF. A comparison of cabergoline andbromocriptine in the treatment of hyperprolactinemicamenorrhea. N Engl J Med 1994; 331:904–909.9. Abrahamson M, Snyder P. Treatment of hyperprolactindue to lactotroph adenomas and other causes.UpToDate [database]. Waltham, Mass: UpToDate;2004.10. Smith S. Effects of antipsychotics on sexual andendocrine function in women: implications in clinicalpractice. J Clin Psychopharmacol 2003; 23(3 Suppl1):S27–S32.901V O L .  1 ,  N O .  3  /  M A Y - J U N E  2 0 0 5■ New design with reader-friendly text■ Enhanced search, making it easier to find what you need■ Online purchase of subscriptions or single articles ■ Plus more article options—■  view full text or PDF ■  add to favorites■  print this article ■  e-mail this articleWhether you’re a first-time or frequent visitor—there’s lots more to see at the new JFPonline.com!THE JOURNAL OF FAMILY PRACTICE website has added many new features, making it even more useful and informative:And you can still access all the practice opportunities, supplements with CME credit, and other resources you’ve come to depend on at JFPonline.comVisit the New JFPonline.com!JFP_1005_CI.finalREV  9/20/05  2:39 PM  Page 901

What is the recommended evaluation and treatment for elevated serum prolactin?

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