Prolactin, Reflex to Macroprolactin
Code:9018|CPT:84146|LOINC:2842-3, 42607-2, 51441-4
| Includes | Prolactin Macroprolactin Reflex |
|---|
Analysis details
Methodology
- Electrochemiluminescence immunoassay (ECLIA)
- Polyethylene glycol precipitation (PEG)
Expected Turnaround Time
1 day
Special Instructions
- For infants younger than 1 year, withhold feeds for 30–40 minutes before collection.
- For children 1–5 years, avoid food for 2–3 hours before collection.
- Adults should fast for 12 hours; water is permitted.
- With clinician approval, stop estrogens and androgens 48 hours before collection.
- With clinician approval, avoid all medications for 24 hours before collection if feasible.
- Avoid strenuous physical activity and significant emotional stress for 24 hours before collection.
- Do not smoke for 3 hours before collection.
- If prolactin exceeds the reference range, testing will reflex to macroprolactin at additional charge.
- If date of birth and/or sex are not provided, testing will reflex to macroprolactin regardless of prolactin results.
How to use
The Prolactin, Reflex to Macroprolactin test supports the evaluation of hyperprolactinemia in contexts such as galactorrhea, amenorrhea, anovulation, infertility, and suspected prolactin-secreting pituitary adenomas. It is appropriate for both women and men when symptoms suggest disordered prolactin physiology. Reflex testing for macroprolactin (macro PRL, big-big prolactin) is indicated when prolactin is elevated but symptoms are minimal or absent, to exclude macroprolactinemia and to identify true excess of bioactive monomeric prolactin. Findings guide the need for pituitary imaging, therapeutic choices, and prognosis, and help rule out macroprolactinemia as a contributor to menstrual disturbance and infertility in women and men.
Limitations
Circulating prolactin consists predominantly of monomeric prolactin (~85%), which is bioactive, with smaller fractions of dimeric prolactin (~10%) and macroprolactin (~5%). Macroprolactin is an approximately ~200 kDa prolactin–IgG complex with low biological activity. Prolactin is produced by pituitary lactotrophs and is under tonic dopaminergic inhibition. Hyperprolactinemia may result from disruption of hypothalamic–pituitary regulation, primary hypothyroidism, chronic kidney disease, or pituitary adenomas. Medication-related hyperprolactinemia typically reflects dopamine antagonism. In women, manifestations include menstrual dysfunction, anovulation, and galactorrhea; in men, decreased libido and erectile dysfunction are common. Large adenomas can cause headaches or visual symptoms. Macroprolactinemia often shows markedly increased total prolactin concentrations due to reduced renal clearance, yet produces limited clinical symptoms because macroprolactin is poorly bioactive. Menstrual irregularity is the most frequent clinical feature, whereas galactorrhea and infertility are less common. Pituitary adenomas are detected less often and, when present, are usually microadenomas in macroprolactinemia. Because clinical presentation alone cannot reliably differentiate macroprolactinemia from true hyperprolactinemia, reflex testing for macroprolactin is recommended when prolactin is elevated.
| Reference interval |
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| Indications | Assessment of elevated prolactin in women presenting with oligomenorrhea or amenorrhea, Workup of galactorrhea, Evaluation of female infertility or anovulation, Assessment of hyperprolactinemia in men with reduced libido or erectile dysfunction, Evaluation of male infertility, Investigation of asymptomatic hyperprolactinemia, Differentiation of true hyperprolactinemia from macroprolactinemia, Diagnostic evaluation of secondary amenorrhea |
Possible Causes of Abnormal Results
Increased levels
- lactation
- pregnancy
- sexual activity
- stress
- strenuous exercise
Specimen Requirements
| Specimen | Serum |
|---|---|
| Container | Gold/Tiger Top (SST, Gel Separator) |
| Volume | 2 mL (min 1 mL) |
| Storage Instructions | Room temperature, Refrigerated, Frozen |
References
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Fahie-Wilson MN, Soule SG. Macroprolactinemia: contribution to hyperprolactinemia in a district general hospital and evaluation of a screening test based upon precipitation with polyethylene glycol. Ann Clin Biochem. 1997 May;34(Pt 3):252-258. PubMed 9158821
Gibney J, Smith TP, McKenna TJ. Clinical relevance of macroprolactin. Clin Endocrinol (Oxf). 2005 Jun;62(6):633-643. PubMed 15943822
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. PubMed 21296991
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Shlomo Melmed et al. Diagnosis and Treatment of Hyperprolactinemia: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2011 Feb;96(2):273-88.
Wallace IR, Satti N, Courtney CH, et al. Ten-Year Clinical Follow-Up of a Cohort of 51 Patients with Macroprolactinemia Establishes It as a Benign Variant. J Clin Endocrinol Metab. 2010 Jul;95(7):3268-3271.
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McCudden CR, Sharpless JL, Grenache DG. Comparison of multiple methods for identification of hyperprolactinemia in the presence of macroprolactin. Clin Chim Acta. 2010 Feb;411(3-4):155-160.
Beltran L, Fahie-Wilson MN, McKenna TJ, Kavanagh L, Smith TP. Serum Total Prolactin and Monomeric Prolactin Reference Intervals Determined by Precipitation with Polyethylene Glycol: Evaluation and Validation on Common Immunoassay Platforms. Clin Chem. 2008;54(10):1673–1681.