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Test ID: PLPMA Prolactin, Pituitary Macroadenoma, Serum

Reporting Name

Prolactin, Pituitary Macroadenoma

Useful For

Quantifying prolactin in serum specimens where the high-dose hook effect is suspected (eg, presence of pituitary tumor with symptoms of prolactinoma, and lower than expected serum prolactin concentration)

Clinical Information

Prolactin-secreting macroadenomas (>10 mm in diameter) can sometimes produce exceedingly high serum prolactin concentrations that may paradoxically result in falsely low prolactin concentrations when measured by immunometric assays. In such situations, very high concentrations of prolactin saturate both the capture and signal antibodies in the assay, block formation of the capture antibody-prolactin-signal antibody "sandwich," and result in falsely decreased prolactin results (referred to as the high-dose hook effect). With such tumors, serum prolactin levels may be falsely decreased into the normal reference interval, potentially resulting in inappropriate patient management. Dilution of the specimen eliminates the analytic artifact in these cases.


Prolactin is secreted by the anterior pituitary gland and controlled by the hypothalamus. The major chemical controlling prolactin secretion is dopamine, which inhibits prolactin secretion from the pituitary. Prolactin is released from the pituitary in response to thyrotropin-releasing hormone and other factors.


Prolactin is the principal hormone that controls the initiation and maintenance of lactation. In normal individuals, prolactin concentrations increase in response to physiologic stimuli such as sleep, stress, exercise, sexual intercourse, and hypoglycemia, and are also elevated during pregnancy, lactation, postpartum, and in the newborn infant.


Hyperprolactinemia is the most common hypothalamic-pituitary disorder encountered in clinical endocrinology. Pathologic causes of hyperprolactinemia include prolactin-secreting pituitary adenoma (prolactinoma, which is more frequent in females than males, and accounts for approximately 40% of all pituitary tumors), functional and organic disease of the hypothalamus, primary hypothyroidism, compression of the pituitary stalk, chest wall lesions, renal insufficiency, polycystic ovarian disease, and ectopic tumors.


In general, serum prolactin concentrations parallel tumor size in patients with prolactinomas. Macroadenomas (>10 mm in diameter) are typically associated with serum prolactin concentrations >250 ng/mL and a concentration >500 ng/mL is diagnostic of a macroprolactinoma. Moderately increased concentrations of serum prolactin are not a reliable guide for determining whether a prolactin-producing pituitary adenoma is present.


Multiple medications can cause increased prolactin concentration including estrogens, dopamine receptor blockers (eg, phenothiazines), dopamine antagonists (eg, metoclopramide, domperidone), alpha-methyldopa, cimetidine, opiates, antihypertensive medications, and other antidepressants and antipsychotics.


Hyperprolactinemia often results in loss of libido, galactorrhea, oligomenorrhea or amenorrhea, and infertility in premenopausal females; and loss of libido, impotence, infertility, and hypogonadism in males. Postmenopausal and premenopausal women, as well as men, can also suffer from decreased muscle mass and osteoporosis.


Prolactinomas may rarely present in childhood or adolescence. In girls, disturbances in menstrual function and galactorrhea may be seen, whereas in boys, delayed pubertal development and hypogonadism are often present. The treatment options are the same as in adult patients.


If no high-dose hook effect is observed, the following report comment will be included with the prolactin result: 10-, 100-, and 400-fold dilutions produced results consistent with the absence of high-dose hook effect. Total prolactin was measured using the Roche Cobas e immunoassay analyzer.


If a high-dose hook effect is observed, which is demonstrated by significantly increasing concentrations of prolactin obtained after dilution of the serum, an interpretive comment will be included with the prolactin result.


The Roche Cobas Prolactin II assay should demonstrate no high-dose hook effect at prolactin concentrations up to approximately 12,500 ng/mL).

Testing Algorithm

A pituitary adenoma should be identified by imaging studies prior to ordering this test.

Report Available

Same day/1 to 2 days

Day(s) Performed

Monday through Sunday

Clinical Reference

1. Winter WE, McCormack A, Bertholf RL: Chapter 65: Pituitary function and pathophysiology. In Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. Sixth edition. Edited by N Rafai, AR Horvath, CT Wittwer. Elsevier, 2018, pp 1492-1529

2. Schoft C, Schofl-Siegert B, Hinrich Karstens J, et al: Falsely low serum prolactin in two cases of invasive macroprolactinoma. Pituitary 2002;5:261-265

3. Casaneuva FF, Molitch ME, Schlecte JA, et al: Guidelines of the Pituitary Society for the diagnosis and management of prolactinomas. Clin Endocrinol 2006;65:265-273

4. Melmed S, Casanueva FF, Hoffman AR, et al: Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011 Feb;96(2):273-288

Method Name

Electrochemiluminescent Immunoassay

Specimen Type


Ordering Guidance

For initial patient assessment; order PRL / Prolactin, Serum as the screening test.

Necessary Information

Patient's age and sex are required.

Specimen Required

Collection Container/Tube:

Preferred: Serum gel

Acceptable: Red top

Submission Container/Tube: Plastic vial

Specimen Volume: 2 mL

Collection Instructions: Centrifuge and aliquot serum into a plastic vial.

Specimen Minimum Volume

1.75 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Serum Refrigerated (preferred) 7 days
  Frozen  90 days
  Ambient  24 hours

Reference Values


<18 years: not established

≥18 years: 4.0-15.2 ng/mL



<18 years: not established

≥18 years: 4.8-23.3 ng/mL 

Test Classification

This test has been cleared, approved, or is exempt by the US Food and Drug Administration and is used per manufacturer's instructions. Performance characteristics were verified by Mayo Clinic in a manner consistent with CLIA requirements.

CPT Code Information


LOINC Code Information

Test ID Test Order Name Order LOINC Value
PLPMA Prolactin, Pituitary Macroadenoma 20568-2


Result ID Test Result Name Result LOINC Value
PRLR Prolactin, S 20568-2
CMT89 Comment 48767-8


If not ordering electronically, complete, print, and send an Oncology Test Request (T729) with the specimen.

Mayo Clinic Laboratories | Endocrinology Catalog Additional Information: